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Abstract Background Intraoperative testing of colonic anastomoses is routine in assuring anastamotic integrity. We sought to determine the efficacy of the methylene blue enema (MBE) as an intraoperative test for anastomotic leaks. Methods This study is a retrospective review of consecutive colonic operations performed from January 2001 to December 2004 in a community hospital setting by a general surgical group that uses the MBE exclusively. All operations featuring a colonic anastomosis and an intraoperative MBE were studied (n = 229). Intraoperative MBE via a rectal tube was used as the diagnostic test. Intraoperative leak (IOL) rate and clinically significant postoperative leak (POL) rate were the outcome measures. Results The IOL rate was 4.5% for proximal anastomoses, 8% for distal anastomoses, and 7% of total anastomoses. The POL rate was 3% of anastomosis. There were no other testing methods employed. There were no POLs in cases where an IOL led to concomitant intraoperative repair. POL rate for proximal anastomosis was 0.8% and for distal 3%, for stapled 1% and hand sewn 5%. Conclusion MBE IOL rate is comparable to published IOL rates for other methods of intraoperative testing. The MBE can be applied to proximal and distal anastomosis. Patients who were found to have an IOL, and underwent immediate repair, did not develop a clinical POL.

Dysregulation of sleep has widespread health consequences and represents an enormous health burden. Short-sleeping individuals are predisposed to the effects of neurodegeneration, suggesting a critical role for sleep in the maintenance of neuronal health. While the effects of sleep on cellular function are not completely understood, growing evidence has identified an association between sleep loss and DNA damage, raising the possibility that sleep facilitates efficient DNA repair. The Mexican tetra fish, Astyanax mexicanus provides a model to investigate the evolutionary basis for changes in sleep and the consequences of sleep loss. Multiple cave-adapted populations of these fish have evolved to sleep for substantially less time compared to surface populations of the same species without identifiable impacts on healthspan or longevity. To investigate whether the evolved sleep loss is associated with DNA damage and cellular stress, we compared the DNA Damage Response (DDR) and oxidative stress levels between A. mexicanus populations. We measured markers of chronic sleep loss and discovered elevated levels of the DNA damage marker γH2AX in the brain, and increased oxidative stress in the gut of cavefish, consistent with chronic sleep deprivation. Notably, we found that acute UV-induced DNA damage elicited an increase in sleep in surface fish but not in cavefish. On a transcriptional level, only the surface fish activated the photoreactivation repair pathway following UV damage. These findings suggest a reduction of the DDR in cavefish compared to surface fish that coincides with elevated DNA damage in cavefish. To examine DDR pathways at a cellular level, we created an embryonic fibroblast cell line from the two populations of A. mexicanus . We observed that both the DDR and DNA repair were diminished in the cavefish cells, corroborating the in vivo findings and suggesting that the acute response to DNA damage is lost in cavefish. To investigate the long-term impact of these changes, we compared the transcriptome in the brain and gut of aged surface fish and cavefish. Strikingly, many genes that are differentially expressed between young and old surface fish do not transcriptionally vary by age in cavefish. Taken together, these findings suggest that cavefish have developed resilience to sleep loss, despite possessing cellular hallmarks of chronic sleep deprivation.

Brain laterality is a prominent feature in Bilateria, where neural functions are favored in a single brain hemisphere. These hemispheric specializations are thought to improve behavioral performance and are commonly observed as sensory or motor asymmetries, such as handedness in humans. Despite its prevalence, our understanding of the neural and molecular substrates instructing functional lateralization is limited. Moreover, how functional lateralization is selected for or modulated throughout evolution is poorly understood. While comparative approaches offer a powerful tool for addressing this question, a major obstacle has been the lack of a conserved asymmetric behavior in genetically tractable organisms. Previously, we described a robust motor asymmetry in larval zebrafish. Following the loss of illumination, individuals show a persistent turning bias that is associated with search pattern behavior with underlying functional lateralization in the thalamus. This behavior permits a simple yet robust assay that can be used to address fundamental principles underlying lateralization in the brain across taxa. Here, we take a comparative approach and show that motor asymmetry is conserved across diverse larval teleost species, which have diverged over the past 200 million years. Using a combination of transgenic tools, ablation, and enucleation, we show that teleosts exhibit two distinct forms of motor asymmetry, vision-dependent and - independent. These asymmetries are directionally uncorrelated, yet dependent on the same subset of thalamic neurons. Lastly, we leverage Astyanax sighted and blind morphs, which show that fish with evolutionarily derived blindness lack both retinal-dependent and -independent motor asymmetries, while their sighted surface conspecifics retained both forms. Our data implicate that overlapping sensory systems and neuronal substrates drive functional lateralization in a vertebrate brain that are likely targets for selective modulation during evolution.

Evolution in response to a change in ecology often coincides with various morphological, physiological, and behavioral traits. For most organisms little is known about the genetic and functional relationship between evolutionarily derived traits, representing a critical gap in our understanding of adaptation. The Mexican tetra, Astyanax mexicanus, consists of largely independent populations of fish that inhabit at least 30 caves in Northeast Mexico, and a surface fish population, that inhabit the rivers of Mexico and Southern Texas. The recent application of molecular genetic approaches combined with behavioral phenotyping have established A. mexicanus as a model for studying the evolution of complex traits. Cave populations of A. mexicanus are interfertile with surface populations and have evolved numerous traits including eye degeneration, insomnia, albinism, and enhanced mechanosensory function. The interfertility of different populations from the same species provides a unique opportunity to define the genetic relationship between evolved traits and assess the co-evolution of behavioral and morphological traits with one another. To define the relationships between morphological and behavioral traits, we developed a pipeline to test individual fish for multiple traits. This pipeline confirmed differences in locomotor activity, prey capture, and startle reflex between surface and cavefish populations. To measure the relationship between traits, individual F2 hybrid fish were characterized for locomotor behavior, prey-capture behavior, startle reflex, and morphological attributes. Analysis revealed an association between body length and slower escape reflex, suggesting a trade-off between increased size and predator avoidance in cavefish. Overall, there were few associations between individual behavioral traits, or behavioral and morphological traits, suggesting independent genetic changes underlie the evolution of the measured behavioral and morphological traits. Taken together, this approach provides a novel system to identify genetic underpinnings of naturally occurring variation in morphological and behavioral traits., (© 2022 The Authors. Evolution & Development published by Wiley Periodicals LLC.)

The vast accomplishments of the US Department of Veterans Affairs (VA) during the past century have contributed to the advancement of medicine and benefited patients worldwide. This article highlights some of those accomplishments and the advantages in the VA system that promulgated those successes. Through its affiliation with medical schools, its formation of a structured research and development program, its Cooperative Studies Program, and its National Surgical Quality Improvement Program, the VA has led the world in the progress of health care. The exigencies of war led not only to the organization of VA health care but also to groundbreaking, landmark developments in colon surgery; surgical treatments for vascular disease, including vascular grafts, carotid surgery, and arteriovenous dialysis fistulas; cardiac surgery, including implantable cardiac pacemaker and coronary artery bypass surgery; and the surgical management of many conditions, such as hernias. The birth of successful liver transplantation was also seen within the VA, and countless other achievements have benefited patients around the globe. These successes have created an environment where residents and medical students are able to obtain superb education and postgraduate training and where faculty are able to develop their clinical and academic careers.

Audencel is a dendritic cell (DC)-based cellular cancer immunotherapy against glioblastoma multiforme (GBM). It is characterized by loading of DCs with autologous whole tumor lysate and in vitro maturation via "danger signals". The recent phase II "GBM-Vax" trial showed no clinical efficacy for Audencel as assessed with progression-free and overall survival in all patients. Here we present immunological research accompanying the trial with a focus on immune system factors related to outcome and Audencel's effect on the immune system. Methodologically, peripheral blood samples (from apheresis before Audencel or venipuncture during Audencel) were subjected to functional characterization via enzyme-linked immunospot (ELISPOT) assays connected with cytokine bead assays (CBAs) as well as phenotypical characterization via flow cytometry and mRNA quantification. GBM tissue samples (from surgery) were subjected to T cell receptor sequencing and immunohistochemistry. As results we found: Patients with favorable pre-existing anti-tumor characteristics lived longer under Audencel than Audencel patients without them. Pre-vaccination blood CD8+ T cell count and ELISPOT Granzyme B production capacity in vitro upon tumor antigen exposure were significantly correlated with overall survival. Despite Audencel's general failure to induce a significant clinical response, it nevertheless seemed to have an effect on the immune system. For instance, Audencel led to a significant up-regulation of the Th1-related immunovariables ELISPOT IFNγ, the transcription factor T-bet in the blood and ELISPOT IL-2 in a dose-dependent manner upon vaccination. Post-vaccination levels of ELISPOT IFNγ and CD8+ cells in the blood were indicative of a significantly better survival. In summary, Audencel failed to reach an improvement of survival in the recent phase II clinical trial. No clinical efficacy was registered. Our concomitant immunological work presented here indicates that outcome under Audencel was influenced by the state of the immune system. On the other hand, Audencel also seemed to have stimulated the immune system. Overall, these immunological considerations suggest that DC immunotherapy against glioblastoma should be studied further - with the goal of translating an apparent immunological response into a clinical response. Future research should concentrate on investigating augmentation of immune reactions through combination therapies or on developing meaningful biomarkers.

Background: Early identification of critically ill patients who will require prolonged mechanical ventilation (PMV) has proven to be difficult. The purpose of this study was to use machine learning to identify patients at risk for PMV and tracheostomy placement., Materials and Methods: The Multiparameter Intelligent Monitoring in Intensive Care III database was queried for all intensive care unit (ICU) stays with mechanical ventilation. PMV was defined as ventilation >7 d. Classifiers with a gradient-boosted decision trees algorithm were created for the outcomes of PMV and tracheostomy placement. The variables used were six different severity-of-illness scores calculated on the first day of ICU admission including their components and 30 comorbidities. Mean receiver operating characteristic curves were calculated for the outcomes, and variable importance was quantified., Results: There were 20,262 ICU stays identified. PMV was required in 13.6%, and tracheostomy was performed in 6.6% of patients. The classifier for predicting PMV was able to achieve a mean area under the curve (AUC) of 0.820 ± 0.016, and tracheostomy was predicted with an AUC of 0.830 ± 0.011. There were 60.7% patients admitted to a surgical ICU, and the classifiers for these patients predicted PMV with an AUC of 0.852 ± 0.017 and tracheostomy with an AUC of 0.869 ± 0.015. The variable with the highest importance for predicting PMV was the logistic organ dysfunction score pulmonary component (13%), and the most important comorbidity in predicting tracheostomy was cardiac arrhythmia (12%)., Conclusions: This study demonstrates the use of artificial intelligence through machine-learning classifiers for the early identification of patients at risk for PMV and tracheostomy. Application of these identification techniques could lead to improved outcomes by allowing for early intervention., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The purpose of this study was to use natural language processing of physician documentation to predict mortality in patients admitted to the surgical intensive care unit (SICU). The Multiparameter Intelligent Monitoring in Intensive Care III database was used to obtain SICU stays with six different severity of illness scores. Natural language processing was performed on the physician notes. Classifiers for predicting mortality were created. One classifier used only the physician notes, one used only the severity of illness scores, and one used the physician notes with severity of injury scores. There were 3838 SICU stays identified during the study period and 5.4 per cent ended with mortality. The classifier trained with physician notes with severity of injury scores performed with the highest area under the curve (0.88 ± 0.05) and accuracy (94.6 ± 1.1%). The most important variable was the Oxford Acute Severity of Illness Score (16.0%). The most important terms were "dilated" (4.3%) and "hemorrhage" (3.7%). This study demonstrates the novel use of artificial intelligence to process physician documentation to predict mortality in the SICU. The classifiers were able to detect the subtle nuances in physician vernacular that predict mortality. These nuances provided improved performance in predicting mortality over physiologic parameters alone.

Background: The purpose of this study was to compare payment trends between cardiothoracic surgeons and interventional cardiologists using the Open Payments website made available for the public by the Center for Medicare and Medicaid Services., Material and Methods: Data were extracted from the second release of the Open Payments database, which includes payments made between August 1, 2013 and December 31, 2014. Total payments to individual physicians were aggregated based on specialty, region of the country, and payment type. The Gini index was calculated for each specialty to measure income disparity. A Gini index of 1 indicates all the payments went to one individual, whereas a Gini index of 0 indicates all individuals received equal payments., Results: During the study period of interest, data were made available for 3587 (80%) cardiothoracic surgeons compared with 2957 (99%) interventional cardiologists. Mean total payments to cardiothoracic surgeons were $7770 (standard deviation, $52,608) compared with a mean of $15,221 (standard deviation, $98,828) for interventional cardiologists. The median total payments to cardiothoracic surgeons was $1050 (interquartile range, $233-$3612) compared with $1851 (interquartile range, $607-$5462) for interventional cardiologists. The overall Gini index was 0.932, whereas the Gini index was 0.862 for interventional cardiologists and 0.860 for cardiothoracic surgeons., Conclusions: The vast majority of interventional cardiologists and cardiothoracic surgeons received payments from drug and device manufacturers. The mean total payments to interventional cardiologists were higher than any other specialty. However, like cardiothoracic surgery, they were among the most equitably distributed compared with other specialties., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The Grynfeltt-Lesshaft hernia is a rare posterior abdominal wall defect that allows for the herniation of retro- and intraperitoneal structures through the upper lumbar triangle. While this hernia may initially present as a small asymptomatic bulge, the defect typically enlarges over time and can become symptomatic with potentially serious complications. In order to avoid that outcome, it is advisable to electively repair Grynfeltt hernias in patients without significant contraindications to surgery. Due to the limited number of lumbar hernioplasties performed, there has not been a large study that definitively identifies the best repair technique. It is generally accepted that abdominal hernias such as these should be repaired by tension-free methods. Both laparoscopic and open techniques are described in modern literature with unique advantages and complications for each. We present the case of an unexpected Grynfeltt hernia diagnosed following an attempted lipoma resection. We chose to perform an open repair involving a combination of fascial approximation and dual-layer polypropylene mesh placement. The patient's recovery was uneventful and there has been no evidence of recurrence at over six months. Our goal herein is to increase awareness of upper lumbar hernias and to discuss approaches to their surgical management.

Introduction: GATA binding protein 3 (GATA3) is a regulator of mammary luminal cell differentiation, and an estrogen receptor (ER) associated marker in breast cancer. Tumor suppressor functions of GATA3 have been demonstrated primarily in basal-like breast cancers. Here, we focused on its function in luminal breast cancer, where GATA3 is frequently mutated, and its levels are significantly elevated., Methods: GATA3 target genes were identified in normal- and luminal cancer- mammary cells by ChIP-seq, followed by examination of the effects of GATA3 expressions and mutations on tumorigenesis-associated genes and processes. Additionally, mutations and expression data of luminal breast cancer patients from The Cancer Genome Atlas were analyzed to characterize genetic signatures associated with GATA3 mutations., Results: We show that some GATA3 effects shift from tumor suppressing to tumor promoting during tumorigenesis, with deregulation of three genes, BCL2, DACH1, THSD4, representing major GATA3-controlled processes in cancer progression. In addition, we identify an altered activity of mutant GATA3, and distinct associated genetic signatures. These signatures depend on the functional domain mutated; and, for a specific subgroup, are shared with basal-like breast cancer patients, who are a clinical group with regard to considerations of mode of treatment., Conclusions: The GATA3 dependent mechanisms may call for special considerations for proper prognosis and treatment of patients.

Objectives: Development and maintenance of scholarly activity is a challenge for small community-based surgical training programs. The current Accreditation Council for Graduate Medical Education Program Requirements in General Surgery states that, "Residents should participate in scholarly activity," and "The sponsoring institution and program should allocate adequate educational resources to facilitate resident involvement in scholarly activities." We adopted a program designed to improve the quality of research projects pursued by surgical residents and to increase the number of projects submitted for both presentation and publication., Design: We hereby describe a structured step-by-step program to mentor surgical residents through clinical projects from development to publication., Setting: Community hospital with academic affiliation, located in the Southeastern United States., Participants: The Resident Scholarly Activity Program at our facility includes 2 faculty mentors who work in direct contact with all the surgical residents of our program (2 residents/y, postgraduate years 1-5). The faculty members are MD, MPH professionals who specialize in resident education and scholarly activity., Results: Implementation of Resident Scholarly Activity Program instruction and mentoring increased the number of publications in all categories defined. The number of publications and presentations increased from 6 to 28 over a 1-year period., Conclusions: A structured scholarly activity program positively affects the number of clinical projects produced by a small community-based surgical training program. Familiarity with project design and biostatistics, plus one-on-one mentoring improves the quality of research produced. A potential additional benefit is the ability to involve private surgical faculty with the residents' projects., (Copyright © 2014 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Startle disease is an inherited neurological disorder that causes affected individuals to suffer noise- or touch-induced non-epileptic seizures, excessive muscle stiffness and neonatal apnea episodes. Mutations known to cause startle disease have been identified in glycine receptor subunit (GLRA1 and GLRB) and glycine transporter (SLC6A5) genes, which serve essential functions at glycinergic synapses. Despite the significant successes in identifying startle disease mutations, many idiopathic cases remain unresolved. Exome sequencing in these individuals will identify new candidate genes. To validate these candidate disease genes, zebrafish is an ideal choice due to rapid knockdown strategies, accessible embryonic stages, and stereotyped behaviors. The only existing zebrafish model of startle disease, bandoneon (beo), harbors point mutations in glrbb (one of two zebrafish orthologs of human GLRB) that cause compromised glycinergic transmission and touch-induced bilateral muscle contractions. In order to further develop zebrafish as a model for startle disease, we sought to identify common phenotypic outcomes of knocking down zebrafish orthologs of two known startle disease genes, GLRA1 and GLRB, using splice site-targeted morpholinos. Although both morphants were expected to result in phenotypes similar to the zebrafish beo mutant, our direct comparison demonstrated that while both glra1 and glrbb morphants exhibited embryonic spasticity, only glrbb morphants exhibited bilateral contractions characteristic of beo mutants. Likewise, zebrafish over-expressing a dominant startle disease mutation (GlyR α1(R271Q)) exhibited spasticity but not bilateral contractions. Since GlyR βb can interact with GlyR α subunits 2-4 in addition to GlyR α1, loss of the GlyR βb subunit may produce more severe phenotypes by affecting multiple GlyR subtypes. Indeed, immunohistochemistry of glra1 morphants suggests that in zebrafish, alternate GlyR α subunits can compensate for the loss of the GlyR α1 subunit. To address the potential for interplay among GlyR subunits during development, we quantified the expression time-course for genes known to be critical to glycinergic synapse function. We found that GlyR α2, α3 and α4a are expressed in the correct temporal pattern and could compensate for the loss of the GlyR α1 subunit. Based on our findings, future studies that aim to model candidate startle disease genes in zebrafish should include measures of spasticity and synaptic development., (© 2013.)

The discrimination and taxonomic identification of marine species continues to pose a challenge despite the growing number of diagnostic metrics and approaches. This study examined the genetic relationship between two sibling species of the genus Calanus (Crustacea; Copepoda; Calanidae), C. agulhensis and C. sinicus, using a multi-gene analysis. DNA sequences were determined for portions of the mitochondrial cytochrome c oxidase I (mtCOI); nuclear citrate synthase (CS), and large subunit (28S) rRNA genes for specimens collected from the Sea of Japan and North East (NE) Pacific Ocean for C. sinicus and from the Benguela Current and Agulhas Bank, off South Africa, for C. agulhensis. For mtCOI, C. sinicus and C. agulhensis showed similar levels of haplotype diversity (H(d) = 0.695 and 0.660, respectively) and nucleotide diversity (π = 0.003 and 0.002, respectively). Pairwise F(ST) distances for mtCOI were significant only between C. agulhensis collected from the Agulhas and two C. sinicus populations: the Sea of Japan (F(ST) = 0.152, p<0.01) and NE Pacific (F(ST) = 0.228, p<0.005). Between the species, F(ST) distances were low for both mtCOI (F(ST) = 0.083, p = 0.003) and CS (F(ST) = 0.050, p = 0.021). Large subunit (28S) rRNA showed no variation between the species. Our results provide evidence of the lack of genetic distinction of C. sinicus and C. agulhensis, raise questions of whether C. agulhensis warrants status as a distinct species, and indicate the clear need for more intensive and extensive ecological and genetic analysis.

Background: Postoperative visits to the emergency department (ED) instead of the surgeon's office consume enormous cost., Hypothesis: Postoperative ED visits can be avoided., Setting: Fully accredited, single-institution, 617-bed hospital affiliated with the University of Connecticut School of Medicine., Patients: Retrospective analysis of 597 consecutive patients with appendectomies over a 4-year period., Methods: Demographic and medical data, at initial presentation, surgery, and ED visit were recorded as categorical variables and statistically analyzed (Pearson chi(2) test, Fisher exact test, and linear-by-linear). Costs were calculated from the hospital's billing department., Results: Forty-six patients returned to the ED within the global period with pain (n = 22, 48%), wound-related issues (n = 6, 13%), weakness (n = 4, 9%), fever (13%), and nausea and vomiting (n = 3, 6%). Thirteen patients (28%) required readmission. Predictive factors for ED visit postoperatively were perforated appendicitis (2-fold increase over uncomplicated appendicitis) and comorbidities (cardiovascular or diabetes). The cost of investigations during ED visits was $55,000 plus physician services., Conclusions: ED visits during the postoperative global period are avoidable by identifying patients who may need additional care; improving patient education, optimizing pain control, and improving patient office access., (2010 Elsevier Inc. All rights reserved.)

Objective: To evaluate the utility of computed tomography (CT) scans in patients with abdominal pain in the emergency department. We compared focused scans (having a single diagnosis in mind) and screening scans (having no diagnosis or more than one diagnosis in mind) with the hypothesis that focused scans will reveal pathology more often than screening scans. Treatment plans and patient outcomes were also compared between the two populations., Methods: This is a prospective study in which 100 patients who presented to an academic medical center with abdominal pain and underwent an abdominal CT were enrolled in the study. A chart review was later completed to gather ultimate outcome data for each of the enrolled subjects., Results: Of the 61 patients having a focused CT, pathology was identified on 63.9% of the scans, which did not differ significantly from the 65.4% of scans that revealed pathology in the screening group. In the focused group, anticipated admissions were reduced, but the reduction was not significant. The screening group did show a significant difference, with eight fewer patients being admitted than initially planned. The total number of patients deemed to require admission was significantly reduced by 15% following all CT scans., Conclusion: While there was no difference between the focused and screening groups in the rate of identifying pathology, there was a significant decline in number of patients requiring admission to the hospital in the "screening" CT group (when comparing emergency physicians' pre- and post-CT treatment plans).

Introduction: Sigmoid diverticulitis is an infection that resolves with conservative management in 70-85% of patients. Some patients require prolonged hospitalization or surgery during their admission. It has been taught that one should expect clinical improvement within 48 h. In this study, we examined whether basic clinical parameters (the maximum temperature and leukocyte count) of patients would predict improvement and discharge as expected, or prolonged hospitalization., Materials and Methods: Data was acquired from 198 patients admitted with acute sigmoid diverticulitis as confirmed by computed tomography (CT) scanning and physical exam. One hundred sixty-five patients recovered without surgery with an average hospital stay of 4 days: 120 were discharged within 4 days, whereas 45 patients required longer stays. Nineteen patients underwent surgery early during their admission (within 48 h). Fourteen patients did not improve over time and required surgery later during their hospital stay. The daily maximum temperature and leukocyte count of patients with prolonged stays was compared to the patients who were discharged within 4 days using analysis of variance analysis., Results: The average maximum temperature and leukocyte count on admission were not statistically different between the groups; therefore, maximum temperature and leukocyte count on admission alone are not predictive. After the first 24 h, however, one could see a statistically significant difference in maximum temperature (p=0.004). The leukocyte count responded significantly by hospital day 2 (p=0.003). Both trends were significant through hospital day 4., Discussion: Patients with a noticeable drop in leukocyte count and maximum temperature over the first 48 h of medical management were predictably discharged early on oral antibiotics. Patients failing to improve at 48 h required prolonged stays or surgery., Conclusion: By observing early trends in leukocyte count and maximum temperature of patients with diverticulitis, one can predict whether they will recover quickly as expected or if they will likely require prolonged IV antibiotics and/or surgery.

A single-blind, randomized prospective trial was performed at a university hospital to determine if preoperative relaxation training will decrease pain and narcotic demand postoperatively. A convenience sample of 49 patients undergoing lumbar and cervical spine surgery was randomized to receive instruction on relaxation techniques or routine preoperative information before surgery. Pain score and narcotic demand in the first 48 hours after surgery were the primary outcomes. Pain scores were higher in the relaxation (4.8 +/- 1.7) versus the standard preparation group (3.9 +/- 1.7) on postoperative day one (POD) 1, but lower on POD 2 (3.9 +/- 1.9 vs 4.1 +/- 1.9), whereas narcotic use (milligrams of IV morphine per hour) was higher in the relaxation group on POD 1 (1.14 +/- 0.94 vs 0.54 +/- 0.55) and POD 2 (0.86 +/- 0.73 vs 0.50 +/- 0.61). The differences were significant for narcotic demand (P = 0.01) but not for pain (P = 0.94). In conclusion, our results could not support the use of relaxation training for reducing postoperative pain and narcotic demand in this selected surgical population.

Anastomotic disruption is a feared and serious complication of colon surgery. Decades of research have identified factors favoring successful healing of anastomoses as well as risk factors for anastomotic disruption. However, some factors, such as the role of mechanical bowel preparation, remain controversial. Despite proper caution and excellent surgical technique, some anastomotic leaks are inevitable. The rapid identification of anastomotic leaks and the timely treatment in these cases are paramount.

Veterans Administration (VA) medical centers have had a long history of providing medical care to those who have served their country. Over time, the VA has evolved into a facility that has had a major role in graduate medical education. In surgery, this had provided experience in the medical and surgical management of complex surgical disease involving the head and neck, chest, and gastrointestinal tract, and in the fields of surgical oncology, peripheral vascular disease, and the subspecialties of urology, orthopedics, and neurosurgery. The VA provides a venue for the attending physician and resident to work in concert to allow the resident to shoulder increasing accountability in decision-making and delivery of care in the outpatient arena, the operating room, and the intensive care unit. Medical students assigned to a VA hospital are afforded a great opportunity to be exposed to preoperative planning, discussions leading to informed consent for surgery, the actual operation, and postoperative care. Numerous opportunities at the VA are available for novice and experienced medical faculty members to develop and/or enhance skills and abilities in patient care, medical education, and research. In addition, the VA offers unique opportunities for academic physicians and other healthcare professionals to administer its many programs, thereby developing leadership skills and experience in the process. The VA is uniquely situated to design and conduct multicenter clinical trials. The most important aspect of this is the infrastructure provided by the VA Cooperative Studies Program. Of the four missions of the Department of Veterans Affairs, research and education is essential to provide quality, state of the art clinical care to the veteran. The National Surgical Quality Improvement Program (NSQIP) is an example of how outcomes based research can favorably impact on patient outcome. Looking across the horizon of information solutions available to surgeons, the options are limited. This is not the case for the Department of Veterans Affairs. With the congressionally mandated charge for the VA to compare its quality to private clinicians, the advent of the "Surgery Package" became possible. The VA will continue its leadership position in the healthcare arena if it can successfully address the challenges facing it.

Objectives: Examine the epidemiology and clinical characteristics of anal cancer in the State of Connecticut., Materials and Methods: The Department of Health Connecticut Tumor Registry resources were utilized for the years 1980-2000., Results: A total of 646 anal cancers (410 females, 236 males) were diagnosed (mean age: 63.4 years). The most prominent histological type was squamous cell carcinoma, followed by adenocarcinoma and cloacogenic carcinoma. Females predominated in both the first and second decade of the study period. Black males accounted for 2.3% of all cases during the first decade, compared to 5% during the second decade. Surgery alone was the most common treatment modality, followed by radiation alone and a combination of surgery and radiation therapy. Chemotherapy data were not available although it is currently considered an important part of therapy., Conclusions: Anal cancer incidence in Connecticut increased in the 21-year period 1980 to 2000, affecting the rate for African-American men more than other race-specific and gender-specific population subgroups. Anal cancer affects women more often than men. Squamous cell carcinoma is the most common histological type.

Objective: To determine the impact on self-perception, of having residents view their own performance (taped) on mock oral board examinations., Design: Self-evaluation-intervention-self-evaluation design. Third-, fourth-, and fifth-year residents evaluated themselves after each examination(room) during mock oral examinations. Residents reviewed the examination on videotape and re-evaluated themselves., Setting: University Medical Center., Participants: Twenty surgical residents from the third, fourth, and fifth years of training., Main Outcome Measures: Mean scores in 6 categories based on a 5-point Likert scale. Scores by examiners plus pre- and post-video viewing self-scores were compared., Results: We found that residents consistently underestimated their performance on the examination. Viewing their videotapes resulted in revised self-scores, which were more consistent with scores of the examiners. All scores will be presented in sequence as follows: Mean score by examiners, mean self-score pre-tape viewing and mean self-score post-tape viewing. For professionalism, scores were 4.63, 4.15, and 4.43, p = 0.047. For organization, 3.91, 3.27, and 3.63, p = 0.007. For decision making, 4.02, 3.42, and 3.72, p = 0.033. P-values reflect the comparison of resident self-scores pre- and post-tape viewing. Analysis of variance comparison of scores in various rooms (different examiners) revealed no significant difference in scores based on rooms (different examiners). Evaluations according to rooms (different examiners) were not statistically different, supporting inter-rater reliability. There was consistent improvement in knowledge and decision making with advanced years of training, supporting internal validity of the examination., Conclusions: Videotape viewing results in revised resident self-scores, which are more consistent with scores given by the examiners. Tape viewing significantly affected resident self-scores in professionalism, organization, and decision-making.

Helicobacter pylori-neutrophil interactions may play a pathogenic role in H. pylori-induced gastritis and peptic ulcer disease. To understand these interactions, we explored the effects of H. pylori-derived products on neutrophil chemotaxis and superoxide anion production. H. pylori bacteria were cultured and supernatants fractionated. Neutrophil chemotactic activity was confirmed in the crude supernatants and in one fractionated peak corresponding to a previously described neutrophil chemotactic factor. H. pylori-derived crude supernatant, sonicate and all chromatography-derived peaks failed to directly stimulate neutrophil superoxide anion production. However, after pretreatment with sonicate, neutrophils demonstrated increased superoxide anion production (priming) following subsequent exposure to the secretagogue fmet-leu-phe. These results suggest that H. pylori products may attract neutrophils to the gastric mucosa without initially stimulating superoxide anion production or tissue injury. Oxygen radical-mediated gastric mucosal injury may subsequently result when these primed neutrophils undergo additional stimulation by as yet unidentified factors.

Background: During surgery, the balance between thrombosis and fibrinolysis is altered. Methods reported to increase fibrinolysis, such as compression devices, may reduce venous thrombosis. However, there are no prospective studies comparing methods and the effect on fibrinolysis., Materials and Methods: In a prospective study, general surgical patients were randomized to either sequential compression devices (Group 1) or subcutaneous heparin (Group 2), and fibrinolysis factors were measured in order to determine the effect on the fibrinolysis system. Blood samples were drawn at a similar time of the day with the tourniquet off. Specifically, t-PA antigen, plasminogen activator inhibitor-1 (PAI-1), and D-dimer were measured preoperatively (preop) and on Postoperative Days (POD) 1 and 7 by the ELISA method. Fibrinolysis factors were reported as the mean +/- SD and as percentage change from preoperative values. Noninvasive vascular studies were performed preop, and on POD 1, 7, and 30, by an examination of the infrainguinal venous system and external iliac veins in bilateral lower extremities. Nonambulatory patients were excluded from the study and DVT prophylaxis methods were initiated at surgery and used through POD 2., Results: For the 136 patients in the study, there were no differences in clinical characteristics such as age, surgical time (all > 60 min), anesthesia type (general or spinal), type of surgical procedure, or other risk factors for DVT. Two DVTs occurred at POD 1 and 30 (both Group 2), and one pulmonary embolism in each group (POD 7 for Group 1; POD 1 for Group 2). For subjects without thrombosis, D-dimer changes were parallel for both groups, increasing through POD 7. Similarly, t-PA antigen levels rose from baseline on POD 1 in both groups, with a return toward baseline by POD 7. The PAI-1 levels increased on POD 1 in both groups, but severalfold more in Group 1 (compression devices). The elevation in PAI-1 decreased by 50% in Group 1 by POD 7, while values returned to normal in Group 2. These changes were not significant using the Mann-Whitney test. Only three patients had thrombotic episodes so that data on changes in fibrinolysis factors are difficult to compare with the larger group., Conclusions: This is the first report of a prospective, randomized comparison of fibrinolysis factors using sequential compression devices in comparison to low dose unfractionated heparin in general surgical patients, and comparing postoperative values to preop. Both groups showed an enhanced fibrinolysis by elevation in t-PA antigen and D-dimer on POD 1, as expected when fibrinolysis occurs. While PAI-1 and t-PA work in parallel, the marked elevation of PAI-1 on POD 1 (although only slightly above reference values) and continuing into POD 7 for subjects using compression devices requires further inquiry. The elevation of PAI-1 in the face of elevated t-PA and D-dimer has been reported, but the comparison between patients using sequential compression devices and mini-dose heparin has not been reported. The reason for the elevation requires additional study into other influences on the synthesis, secretion, and/or function of PAI-1 that do not affect t-PA.

Objective: To compare postoperative pain after laparoscopic hernia repair and conventional open hernia repair., Design: Prospective, randomized study., Setting: Veterans Affairs Medical Center., Patients: Sixty-two patients scheduled for elective inguinal hernia repair., Interventions: Patients were randomized in the operating room to have a laparoscopic hernia repair (30 patients) or a conventional open hernia repair (32 patients). All operations were performed while the patient was under general anesthesia to avoid anesthesia as a confounding variable., Measures: Postoperative pain following laparoscopic hernia repair and open hernia repair were compared using the McGill Pain Score, the McGill Visual Analogue Pain Scale score, and the number of acetaminophen with 30-mg codeine sulfate (Tylenol 3) tablets needed for pain during the first and second 24-hour periods postoperatively. All of the patients were interviewed and the postoperative pain was evaluated by a special study nurse (P.M.L.) who was blinded to the repair technique., Results: At 24 hours, the patients with laparoscopic hernia repair had 26% less pain by the McGill Pain Score (P = .02) and 31% less pain by the McGill Visual Analogue Scale (P = .006) than those who underwent an open hernia repair. At 48 hours the patients who underwent laparoscopic hernia repair had 28% less pain by the McGill Pain Score (P = .03), 42% less pain by the McGill Visual Analogue Scale (P = .002), and used 42% fewer analgesic tablets (P = .004)., Conclusion: Patients with a laparoscopic hernia repair had significantly less pain postoperatively than those with standard open hernia repairs.

This study was designed to prospectively evaluate a previously published prognostic index for predicting deep venous thrombosis (DVT) in general surgical patients with conventional prophylaxis. Patients undergoing procedures of at least 1 hr duration (abdominal, thoracic, head and neck, inguinal) requiring general or spinal anesthetic were prospectively randomized into the following groups: Group 1, sequential pneumatic compression devices during surgery and 2 days postoperatively; Group 2, subcutaneous heparin (5000 U q 12 hr) starting 1 hr before surgery and for 7 days postop; Group 3, control group. All patients underwent duplex evaluation of bilateral lower extremity deep venous systems preoperatively and on postoperative Days 1, 3, and 30. In addition, a previously developed predictive DVT incidence indicator, the prognostic index (PI), was calculated for each patient. A total of 137 patients were entered into the study with 29 removed for patient/staff reasons. There were no differences in PI among the three groups at the 0.05 level (ANOVA). The distribution of risk factors for DVT including increased age, body size, hemoglobin (Hb), and colorectal procedures were distributed evenly among the groups. Additional factors such as diabetes, COPD, PVD, immobilization, and cancer were also evenly distributed among the groups. The PI predicted a 20% incidence of DVT. For Groups 1 (n = 25), 2 (n = 38), and 3 (n = 45) no DVTs were detected over the 30 days of study. During the study period, 8 DVTs were detected by duplex evaluation in general surgical patients not in the study (1.5%). In conclusion, in a prospective randomized study using sequential pneumatic compression devices, subcutaneous heparin or no prophylaxis in matched general surgical patients at moderate to high risk for thromboembolism, no DVTs occurred for up to 30 days. Furthermore, neither a PI nor other factors associated with DVT accurately predicted the incidence of DVT in this patient population.

In summary, it appears that the role of H. pylori in duodenal ulcerogenesis is not directly associated with acid hypersecretion. Similarly, it seems unlikely that H. pylori-induced autoimmune injury is an important mechanism in duodenal ulcerogenesis. An essential question remaining is whether H. pylori infection of areas of gastric metaplasia in the duodenum is essential to ulcer pathogenesis. The low yield of H. pylori in duodenal biopsy studies argues against this mechanism. It is possible that H. pylori gastritis (present in greater than 90% of duodenal ulcer patients) results in the release of inflammatory mediators into the gastric lumen that wash down to the duodenum with gastric emptying. Such a mechanism would explain both the low recovery rate of H. pylori from duodenal biopsies in ulcer patients and the local IgA response seen in the first part of the duodenum in response to H. pylori antigens. This could also explain the high incidence of H. pylori gastritis in patients with duodenal ulcers. Obviously the four theories discussed in this review are not mutually exclusive. Significant interaction may occur between the mechanisms described. In addition, bacterial strain differences may be more important than variations in host response to H. pylori infection. Genetic studies focused on strain differences regarding mediator production and release will help clarify these issues. In the vast majority of patients with duodenal ulcer, H. pylori infection appears to be required but is not sufficient for pathogenesis of the disease. The mechanisms of ulcerogenesis related to H. pylori remain incompletely understood. Several recently identified animal models including the gnotobiotic piglet and the naturally occurring H. mustelae infection in ferrets hold substantial promise for solving the puzzle of H. pylori disease.

Gangrenous cholecystitis is an advanced form of acute cholecystitis associated with increased morbidity and mortality. We sought to determine the incidence of gangrenous cholecystitis in an urban VA hospital patient population and identify any distinguishing characteristics that may aid in its preoperative diagnosis. We retrospectively reviewed all urgent admissions that underwent cholecystectomy (n = 65) over the past 7 years at the Allen Park VAMC. Using histologic criteria, 17 (26%) of these patients had gangrenous cholecystitis. As a group compared to patients with nongangrenous cholecystitis, patients with gangrenous cholecystitis were statistically older (64 vs 54) and had an elevated WBC (15.4 vs 11.5) and increased serum glucose levels (203 vs 141). Preoperative imaging studies (ultrasound and cholescintigraphy) correctly identified only 31% of the gangrenous cholecystitis patients. We conclude that in an urban VA hospital patient population, the diagnosis of gangrenous cholecystitis cannot be accurately made or ruled out among urgent admissions with acute biliary disease. Considering the high incidence (26%) and difficulty confirming the diagnosis of gangrenous cholecystitis in this setting, we recommend early surgical intervention for this and similar patient populations.

Background: Surgical dictum states that the so-called lateral aberrant thyroid represents metastatic thyroid cancer., Methods and Results: We present sixteen cases of patients with benign ectopic thyroid tissue. Seven cases were discovered during evaluation and treatment of hyperparathyroidism. The remaining nine cases were discovered during the evaluation and treatment of thyroid disorders or cervical nodules. In fifteen cases there is benign histology on the nodules. One case has been followed for 4 years with scans revealing a normal thyroid gland with an unchanging ectopic thyroid nodule in the superior mediastinum. In eight of our cases there have been thyroid resections searching for occult carcinomas. Histologic examination on these eight thyroid glands revealed either normal thyroid or benign nodules., Conclusions: Not all lateral aberrant thyroid tissue is malignant. The histologic condition of the nodule combined with intraoperative examination of the ipsilateral thyroid lobe can reliably guide therapy. The old dictum concerning lateral aberrant thyroid representing metastatic cancer should be removed from or modified in review texts and surgical examinations.

Background: Patients with chronic kidney failure have an increased incidence of gastrointestinal complications, particularly bleeding from the stomach. Diminished mucosal blood flow is thought to be an important etiologic factor for such bleeding., Methods: Eleven patients with kidney failure on maintenance dialysis underwent placement of a gastric tonometer for the determination of gastric intramucosal pH (pHi) before and during dialysis. The arterial pH (pHa), calculated pHi, and pHa-pHi differences were compared with the results in a control group of seven normal volunteers., Results: The patients with chronic kidney failure had a mean (+/- SD) pHa (7.36 +/- 0.04) similar to that found in seven control subjects (7.37 +/- 0.04). However, the gastric mucosal pH in the patients on dialysis (7.20 +/- 0.17) was lower than in the seven control subjects (7.38 +/- 0.06) (p < 0.01). A gastric mucosal pH thought to be predictive of either bleeding from stress ulceration (pHi < 7.32) or mucosal ischemia (pHi-pHa difference > 0.13) was found in nine (82%) of the patients with kidney failure and in only one (14%) of the control subjects (p < 0.001)., Conclusions: This new preliminary finding suggests that the high incidence of gastric bleeding in chronic kidney failure may be related to mucosal ischemia.

The infiltration of an organ or tissue by neutrophils is the hallmark of acute inflammation. Recent work from many laboratories suggests that neutrophils may play a role in the development of tissue injury in a variety of disease states in the gastrointestinal tract. These diseases include gastritis, necrotizing enterocolitis, ileitis, ulcerative colitis, and ischemia reperfusion injuries. In view of this recent interest in the neutrophil and its relationship to GI diseases, it seems timely to review what is known about neutrophil recruitment to the gastrointestinal tract. This review will therefore focus on the sojourn of the neutrophil from the circulation to its destination in the GI tract.

Urinary retention is a known complication of inguinal herniorrhaphy. Bladder distension due to vigorous fluid administration is believed to contribute to this problem. Our hypothesis is that fluid restriction will lower the incidence of urinary retention, post-herniorrhaphy. From January 1989 through March 1991, 113 male patients entered the study. Sixty patients (Group I) received unlimited iv fluids (1294 +/- 58 ml) and 9 patients (15%) developed urinary retention. Fifty-three patients (Group II) received 500 ml or less by protocol (485 +/- 2 ml) and 5 of these patients developed retention (9%). Thus, fluid restriction lowered the incidence of urinary retention post-herniorrhaphy but the difference did not reach statistical significance. In addition age over 60 years approached significance as a risk factor for postoperative urinary retention.

The effect of suture obliteration of the subcutaneous dead space in morbidly obese abdominal wounds was studied in a randomized trial, comparing a pre-fascial retention suture technique (utilized for approximated of the thick panniculus) to controls where the skin was simply closed with staples. The wound infection rates were similar (11.8% for the sutured group versus 12.3% for controls, p 0.4), as were the total wound complication rates (26.5% for sutured group versus 21.9% for controls, p 0.4). Ultrasound study of the wounds closed without suturing the panniculus demonstrated no dead spaces. We conclude that no advantage is to be gained by suturing the subcataneous fat, however thick. The finding is of general application in wound closures involving thick layers of fat.

To study levels of neutrophil chemotactic activity in human gastric secretions, these secretions were collected via the endoscope during elective esophagogastroduodenoscopy. Fresh samples were then prepared for the neutrophil chemotactic assay with the use of human peripheral neutrophils in modified Boyden chambers. Mean maximum chemotactic activity was 45.8% +/- 11.2% in patients with gastric inflammation compared with only 10.1% +/- 4.2% in patients with normal results of endoscopic examination. The chemotactic factors responsible for this chemotactic activity may play a role in the recruitment of neutrophils to areas of gastric mucosal injury.

The effects of salicylate were examined on Na+/H+ exchange by isolated gastric mucosal surface cells loaded with H+ and resuspended in a buffered medium. Choline salicylate (pH 7.4) increases the dissipation of an intracellular proton gradient which was measured using acridine orange. The exchange of extracellular Na+ with intracellular H+ by surface cells not only remains intact but also is enhanced upon exposure to salicylate. This was confirmed by cellular uptake of 22Na and titration of cellular H+ efflux. Salicylate increases Na+/H+ exchange via a pathway predominantly sensitive to amiloride. However, the data also suggest that salicylate dissipates an intracellular proton gradient by an additional mechanism. The latter is independent of extracellular Na+ and not due to a generalized increase in cellular permeability.