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Imaging technologies (e.g., magnetic resonance imaging [MRI]) have been proposed as noninvasive alternatives to surgical biopsy techniques in the follow-up of women with suspicious primary breast lesions. This article is a synopsis of a systematic review by the Blue Cross and Blue Shield Association Technology Evaluation Center. According to the best available evidence, the sensitivity and specificity of MRI ranged from 91% to 99% and from 31% to 91%, respectively. Predictive values were calculated by using three likely scenarios of diagnostic performance and disease prevalence. The potential harm of failing to diagnose or delaying diagnosis of breast cancer in patients with false-negative MRI results is of significant concern. We conclude that the potential benefit of sparing some patients from unnecessary biopsy by using noninvasive imaging does not outweigh the potential harm of a missed or delayed diagnosis of breast cancer. [ABSTRACT FROM AUTHOR]

PURPOSES: This systematic review addressed the following key questions on managing small cell lung cancer (SCLC): the sequence, timing, and dosing characteristics of primary thoracic radiotherapy (TRTx) for limited-stage disease; primary TRTx for extensive-stage disease; effect of prophylactic cranial irradiation (PCI); positron emission tomography (PET) for staging; treatment of mixed histology tumors; surgery; and second-line and subsequent-line treatment for relapsed/progressive disease. METHODS: The review methods were defined prospectively in a written protocol. We primarily sought randomized controlled trials that compared the interventions of interest. RESULTS: Robust evidence was lacking for all questions except PCI, for which a patient-level metaanalysis showed that PCI improves survival of SCLC patients who achieved complete response after primary therapy from 15.3 to 20.7% (p = 0.01). The case for concurrent over sequential radiation delivery rests largely on a single multicenter trial. Support for early concurrent therapy comes from one multicenter trial, but two other multicenter trials found no advantage. Metaanalysis did not find significant reductions in 2-year and 3-year mortality rates for early TRTx. Favorable results from a single-center trial on TRTx for extensive stage disease need replication in a multicenter setting. Relevant comparative studies were nonexistent for management of mixed histology disease and surgery for early limited SCLC. PET may be more sensitive in detecting extracranial disease than conventional staging modalities, but studies were of poor quality. CONCLUSIONS: PCI improves survival among those with a complete remission to primary therapy. A research agenda is needed to optimize the effectiveness of TRTx and its components. [ABSTRACT FROM AUTHOR]

Background: The value of dental radiographs to oral health care decision making must be balanced with radiation safety to minimize patient exposure and occupational risk of oral health care providers. This review summarizes recommendations and regulatory guidance regarding dental radiography and cone-beam computed tomography. An expert panel presents recommendations on radiation safety, appropriate imaging practices, and reducing radiation exposure., Types of Studies Reviewed: A systematic search run in Ovid MEDLINE, Embase, and Cochrane Database of Systematic Reviews identified relevant topical systematic reviews, organizational guidelines, and regulatory reviews published in the peer-reviewed literature since 2010. A supplemental search of the gray literature (eg, technical reports, standards, and regulations) identified topical nonindexed publications. Inclusion criteria required relevance to primary oral health care (ie, general or pediatric dentistry)., Results: A total of 95 articles, guidance documents, and regulations met the inclusion criteria. Resources were characterized as applicable to all modalities, operator and occupational protection, dose reduction and optimization, and quality assurance and control., Practical Implications: Understanding factors affecting imaging safety and applying fundamental principles of radiation protection consistent with federal, state, and local requirements are essential for limiting patient ionizing radiation exposure, in conjunction with implementing optimal imaging procedures to support prudent use of dental radiographs and cone-beam computed tomographic imaging. The regulatory guidance and best practice recommendations summarized in this article should be followed by dentists and other oral health care providers., Competing Interests: Disclosures Ms. Aerne-Bowe received an honorarium ($500) for participating in multiple components of the dental radiography update project. None of the other authors reported any disclosures., (Copyright © 2024 American Dental Association. Published by Elsevier Inc. All rights reserved.)

Bile acids (BAs) are steroid detergents in bile that contribute to the absorption of fats and fat-soluble vitamins while shaping the gut microbiome because of their antimicrobial properties 1-4 . Here we identify the enzyme responsible for a mechanism of BA metabolism by the gut microbiota involving amino acid conjugation to the acyl-site of BAs, thus producing a diverse suite of microbially conjugated bile acids (MCBAs). We show that this transformation is mediated by acyltransferase activity of bile salt hydrolase (bile salt hydrolase/transferase, BSH/T). Clostridium perfringens BSH/T rapidly performed acyl transfer when provided various amino acids and taurocholate, glycocholate or cholate, with an optimum at pH 5.3. Amino acid conjugation by C. perfringens BSH/T was diverse, including all proteinaceous amino acids except proline and aspartate. MCBA production was widespread among gut bacteria, with strain-specific amino acid use. Species with similar BSH/T amino acid sequences had similar conjugation profiles and several bsh/t alleles correlated with increased conjugation diversity. Tertiary structure mapping of BSH/T followed by mutagenesis experiments showed that active site structure affects amino acid selectivity. These MCBA products had antimicrobial properties, where greater amino acid hydrophobicity showed greater antimicrobial activity. Inhibitory concentrations of MCBAs reached those measured natively in the mammalian gut. MCBAs fed to mice entered enterohepatic circulation, in which liver and gallbladder concentrations varied depending on the conjugated amino acid. Quantifying MCBAs in human faecal samples showed that they reach concentrations equal to or greater than secondary and primary BAs and were reduced after bariatric surgery, thus supporting MCBAs as a significant component of the BA pool that can be altered by changes in gastrointestinal physiology. In conclusion, the inherent acyltransferase activity of BSH/T greatly diversifies BA chemistry, creating a set of previously underappreciated metabolites with the potential to affect the microbiome and human health., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

This prospective observational study aimed to evaluate the association of metabolomic alterations with weight loss outcomes following sleeve gastrectomy (SG). We evaluated the metabolomic profile of serum and feces prior to SG and three months post-SG, along with weight loss outcomes in 45 adults with obesity. The percent total weight loss for the highest versus the lowest weight loss tertiles (T3 vs. T1) was 17.0 ± 1.3% and 11.1 ± 0.8%, p < 0.001. Serum metabolite alterations specific to T3 at three months included a decrease in methionine sulfoxide concentration as well as alterations to tryptophan and methionine metabolism ( p < 0.03). Fecal metabolite changes specific to T3 included a decrease in taurine concentration and perturbations to arachidonic acid metabolism, and taurine and hypotaurine metabolism ( p < 0.002). Preoperative metabolites were found to be highly predictive of weight loss outcomes in machine learning algorithms, with an average area under the curve of 94.6% for serum and 93.4% for feces. This comprehensive metabolomics analysis of weight loss outcome differences post-SG highlights specific metabolic alterations as well as machine learning algorithms predictive of weight loss. These findings could contribute to the development of novel therapeutic targets to enhance weight loss outcomes after SG.

Background: Surgery is an outcome-based specialty where maintaining peak performance is crucial to patient care. There are a variety of identified surgeon stressors that can have an impact on performance, but one factor unique to surgical residents is the observation by an attending surgeon. This study explored how the perceived authority of the observer had an impact on the participants' physiologic markers of stress and task completion times., Methods: Eighteen general surgery residents performed the Fundamentals of Laparoscopic Surgery skills intracorporeal knot-tying and peg transfer tasks in a crossover study design while under the observation of an attending and a neutral observer. Heart rate variability, mean R-R interval, the time between R spikes on an EKG, minimum heart rate, maximum heart rate, average heart rate, and time to task completion were recorded. Analyses were completed via 2 × 2 analysis of variance with repeated measures., Results: When observed by an attending, participants demonstrated higher minimum, average, and maximum heart rates (P = .046, = .007, and &lt; .001, respectively) than when observed by a neutral observer. Attending observation also significantly shortened time to task completion, relative to neutral observation (P = .022)., Conclusion: Attending observation is linked to increased objective measures of stress at the time of performance with decreased task completion times. Educational efforts to optimize the response to stress during learning may lead to better outcomes., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: The purpose of this systematic review was to examine whether dental intervention involving bone or soft-tissue manipulation preradiotherapy (pre-RT) is associated with lower rates of osteoradionecrosis of the jaw (ORNJ) in patients with head and neck cancer (HNC)., Types of Studies Reviewed: The authors included relevant studies from MEDLINE, Embase, and Cochrane Library, including observational studies published from 2007 through 2021 and involving adults who underwent dental intervention pre-RT for HNC. Authors assessed evidence certainty by using the Grading of Recommendations Assessment, Development, and Evaluation approach. Random-effects models were used to calculate pooled relative risk estimates and hazard ratios. When meta-analysis was not possible, study-level measures of association and narrative summaries of the evidence were reported., Results: Twenty-two studies were included. From the pooled, unadjusted analysis, patients undergoing pre-RT extractions may have a 55% increased risk of experiencing ORNJ (relative risk, 1.55; 95% CI, 0.85 to 2.86; very low certainty); the unadjusted pooled hazard ratio was 3.19 (95% CI, 0.99 to 10.31; very low certainty), corresponding to a possible increased hazard of developing ORNJ (very low certainty). Findings for other pre-RT procedures manipulating bone or tissue relied on limited, observational studies with low or very low certainty evidence., Conclusions: Mostly very low certainty evidence suggests that patients with HNC who need pre-RT dental intervention may have an increased risk of developing ORNJ compared with those who do not., Practical Implications: Maintaining optimal oral health may help reduce the need for urgent pre-RT dental treatment, potentially reducing ORNJ risk and minimizing delay of oncologic treatment in patients with HNC., (Copyright © 2022 American Dental Association. Published by Elsevier Inc. All rights reserved.)

Background: Standards for preoperative bariatric patient selection include a thorough psychological evaluation. Using patients "red-flagged" during preoperative evaluations, this study aims to identify trends in long-term follow-up and complications to further optimize bariatric patient selection., Methods: A multidisciplinary team held a case review conference (CRC) to discuss red-flagged patients. A retrospective chart review compared CRC patients to control patients who underwent bariatric surgery in the same interval. Patients under 18 years old, undergoing revisional bariatric surgery, or getting band placement were excluded. High-risk characteristics causing CRC inclusion, preoperative demographics, percent follow-up and other postoperative outcomes were collected up to 5 years postoperatively. If univariate analysis revealed a significant difference between cohorts, multivariable analysis was performed., Results: Two hundred and fifty three patients were red-flagged from 2012 to 2013, of which 79 underwent surgery. After excluding 21 revisions, 3 non-adult patients, and 6 band patients, 55 red-flagged patients were analyzed in addition to 273 control patients. Patient age, sex, initial BMI, ASA, and co-morbidities were similar between groups, though flagged patients underwent RYGB more frequently than control patients. Notably, percent excess BMI loss and percent follow-up (6 months-5 years) were similar. In multivariable analysis, minor complications were more common in flagged patients; and marginal ulcers, endoscopy, and dilation for stenosis were more common in flagged versus control patients who underwent RYGB. Perforation, reoperation, revision, incisional hernia, and internal hernia were statistically similar in both groups, though reoperation was significantly more common in patients with multiple reasons to be flagged compared to controls., Conclusion: Bariatric patients deemed high risk for various psychosocial issues have similar follow-up, BMI loss, and major complications compared to controls. High-risk RYGB patients have greater minor complications, warranting additional counseling of high-risk patients., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: We sought to compare the performance of the 2008 Centers for Disease Control and Prevention Pediatric criteria for ventilator-associated pneumonia, the 2013 Adult Ventilator-Associated Condition criteria, the new Draft Pediatric Ventilator-Associated Condition criteria, and physician-diagnosed ventilator-associated pneumonia in a cohort of PICU patients., Design: Secondary analysis of a previously conducted prospective observational study., Setting: PICU within a tertiary care children's hospital between April 1, 2010, and April 1, 2011., Patients: Patients between 31 days and 18 years old, mechanically ventilated via endotracheal tube for more than 72 hours and no limitations of care., Interventions: None., Measurements and Main Results: Ventilator-associated pneumonia criteria applied in real time and ventilator-associated condition criteria applied retrospectively. Outcomes assessed between cases and noncases within criteria. Of the 133 eligible participants, 24 (18%) had ventilator-associated pneumonia by 2008 Pediatric criteria and 27 (20%) by physician diagnosis. Sixteen (12%) and 10 (8%) had ventilator-associated condition by 2013 Adult and Draft Pediatric criteria, respectively. We found significant overlap between cases identified with 2008 Pediatric criteria and physician diagnosis (p = 0.549), but comparisons between the other definitions revealed that the newer criteria identify different patients than previous Centers for Disease Control and Prevention ventilator-associated pneumonia criteria and physician diagnosis (p < 0.01). Although 20 participants were diagnosed with ventilator-associated pneumonia by 2008 Pediatric criteria and physician diagnosis, only three participants were identified by all four criteria. Three subjects uniquely identified by the Draft Pediatric criteria were noninfectious in etiology. Cases identified by all criteria except Draft Pediatric had higher ratios of actual ICU length of stay to Pediatric Risk of Mortality III-adjusted expected length of stay compared with noncases., Conclusions: The Draft Pediatric criteria identify fewer and different patients than previous ventilator-associated pneumonia criteria or physician diagnosis, potentially missing patients with preventable harms, but also identified patients with potentially preventable noninfectious respiratory deteriorations. Further investigations are required to maximize the identification of patients with preventable harms from mechanical ventilation.

Objective: To assess the variation between racial/ethnic groups in emergency department (ED) treatment of asthma for pediatric patients., Methods: This study was a cross-sectional analysis of pediatric (2-18 years) asthma visits among 6 EDs in the Upper Midwest between June 2011 and May 2012. We used mixed-effects logistic regression to assess the odds of receiving steroids, radiology tests, and returning to the ED within 30 days. We conducted a subanalysis of asthma visits where patients received at least 1 albuterol treatment in the ED., Results: The sample included 2909 asthma visits by 1755 patients who were discharged home from the ED. After adjusting for demographics, insurance type, and triage score, African American (adjusted odds ratio [aOR], 1.78; 95% confidence interval [CI], 1.40-2.26) and Hispanic (aOR, 1.64; 95% CI, 1.22-2.22) patients had higher odds of receiving steroids compared with whites. African Americans (aOR, 0.58; 95% CI, 0.46-0.74) also had lower odds of radiological testing compared with whites. Asians had the lowest odds of 30-day ED revisits (aOR, 0.26; 95% CI, 0.08-0.84), with no other significant differences detected between racial/ethnic groups. Subgroup analyses of asthma patients who received albuterol revealed similar results, with American Indians showing lower odds of radiological testing as well (aOR, 0.47; 95% CI, 0.22-1.01)., Conclusions: In this study, children from racial/ethnic minority groups had higher odds of steroid administration and lower odds of radiological testing compared with white children. The underlying reasons for these differences are likely multifactorial, including varying levels of disease severity, health literacy, and access to care.

Emergency department (ED) utilization by American Indian (AI) children is among the highest in the nation. Numerous health disparities have been well documented in AI children, but limited information is available on parental experiences of care for AI children in the ED. Our objective was to understand parental attitudes towards ED care for AI children. Focus groups were held with AI parents/caregivers at five sites in the Upper Midwest. Traditional content analysis was used to identify themes. A total of 70 parents participated in ten focus groups. Three main themes were identified: healthcare environment, access to care, and interaction with providers. Healthcare environment issues included availability of specialists, wait times, and child-friendly areas. Transportation and financial considerations were major topics in access to care. Issues in interaction with providers included discrimination, stereotyping, and trust. This is one of the first studies to assess parent perspectives on ED use for AI children. Obtaining parental perspectives on ED experiences is critical to improve patient care and provide important information for ED providers.

Background: Children who leave the emergency department (ED) without complete evaluation or care (LWCET) have poorer outcomes in general. Previous studies have found that American Indian (AI) children have higher rates of LWCET than other racial or ethnic groups. Therefore, this study aims to examine LWCET in AI children by exploring differences by ED location and utilization patterns., Methods: This is a retrospective cohort study of five EDs in the upper Midwest between June 2011 and May 2012. We included all visits by children aged 0-17 who identified as African American (AA), AI or White. Logistic regression was used to determine differences in LWCET by race and ED location controlling for other possible confounding factors including sex, age, insurance type, triage level, distance from ED, timing of visit, and ED activity level., Results: LWCET occurred in 1.73% of 68,461 visits made by 47,228 children. The multivariate model revealed that AIs were more likely to LWCET compared to White children (Odds Ratio (OR) = 1.62, 95% Confidence Interval (CI) = 1.30-2.03). There was no significant difference in LWCET between AA and White children. Other factors significantly associated with LWCET included triage level, distance from the ED, timing of visit, and ED activity level., Conclusion: Our results show that AI children have higher rates of LWCET compared to White children; this association is different from other racial minority groups. There are likely complex factors affecting LWCET in AI children throughout the upper Midwest, which necessitates further exploration.

Background: Effective pain management is a priority in dental practice. Government and private agencies highlight the need to provide optimal pain relief, balancing potential benefits and harms of both opioid and nonopioid analgesic agents. The purpose of this study is to summarize the available evidence on the benefits and harms of analgesic agents, focusing on preexisting systematic reviews., Types of Studies Reviewed: An overview of systematic reviews was conducted to evaluate the efficacy or reported adverse events associated with orally administered medication or medication combinations for relief of acute pain. Reviews were inclusive of all age populations but were limited to those that evaluated medication and medication combinations marketed in the United States and had moderate or high methodological quality according to the A MeaSurement Tool to Assess systematic Reviews (AMSTAR) 2 tool., Results: Five reviews were found eligible for inclusion. The data identified combinations of ibuprofen and acetaminophen as having the highest association with treatment benefit in adult patients and the highest proportion of adult patients who experienced maximum pain relief. Diflunisal, acetaminophen, and oxycodone were found to have the longest duration of action in adult patients. Medication and medication combinations that included opioids were among those associated most frequently with acute adverse events in both child and adult-aged patient populations., Practical Implications: The best available data suggested that the use of nonsteroidal medications, with or without acetaminophen, offered the most favorable balance between benefits and harms, optimizing efficacy while minimizing acute adverse events., (Copyright © 2018 American Dental Association. Published by Elsevier Inc. All rights reserved.)

Introduction: Obesity accelerates the development and progression of pancreatic cancer, though the mechanisms underlying this association are unclear. Adipocytes are biologically active, producing factors such as hepatocyte growth factor (HGF) that may influence tumor progression. We therefore sought to test the hypothesis that adipocyte-secreted factors including HGF accelerate pancreatic cancer cell proliferation., Material and Methods: Murine pancreatic cancer cells (Pan02 and TGP-47) were grown in a) conditioned medium (CM) from murine F442A preadipocytes, b) HGF-knockdown preadipocyte CM, c) recombinant murine HGF at increasing doses, and d) CM plus HGF-receptor (c-met) inhibitor. Cell proliferation was measured using the MTT assay. ANOVA and t-test were applied; p < 0.05 considered significant., Results: Wild-type preadipocyte CM accelerated Pan02 and TGP-47 cell proliferation relative to control (59 ± 12% and 34 ± 12%, p < 0.01, respectively). Knockdown of preadipocyte HGF resulted in attenuated proliferation vs. wild type CM in Pan02 cells (35 ± 5% vs. 68 ± 14% greater than control; p < 0.05), but proliferation in TGP-47 cells remained unchanged. Recombinant HGF dose-dependently increased Pan02, but not TGP-47, proliferation (p < 0.05). Inhibition of HGF receptor, c-met, resulted in attenuated proliferation versus control in Pan02 cells, but not TGP-47 cells., Conclusions: These experiments demonstrate that adipocyte-derived factors accelerate murine pancreatic cancer proliferation. In the case of Pan02 cells, HGF is responsible, in part, for this proliferation., (Copyright © 2016 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved.)

Background: Obesity accelerates pancreatic cancer growth; the mechanisms underlying this association are poorly understood. This study evaluated the hypothesis that obesity, rather than high-fat diet, is responsible for accelerated pancreatic cancer growth., Methods: Male C57BL/6J mice were studied after 19 weeks of high-fat (60 % fat; n = 20) or low-fat (10 % fat; n = 10) diet and 5 weeks of Pan02 murine pancreatic cancer growth (flank)., Results: By two-way ANOVA, diet did not (p = 0.58), but body weight, significantly influenced tumor weight (p = 0.01). Tumor weight correlated positively with body weight (R (2) = 0.562; p < 0.001). Tumors in overweight mice were twice as large as those growing in lean mice (1.2 ± 0.2 g vs. 0.6 ± .01 g, p < 0.01), had significantly fewer apoptotic cells than those in lean mice (0.8 ± 0.4 vs 2.4 ± 0.5; p < 0.05), and greater adipocyte volume (3.7 vs. 2.2 %, p < 0.05). Apoptosis (R (2) = 0.472; p = 0.008) and serum adiponectin correlated negatively with tumor weight (R = 0.45; p < 0.05)., Conclusions: These data suggest that body weight, and not high-fat diet, is responsible for accelerated murine pancreatic cancer growth observed in this model of diet-induced obesity. Decreased tumor apoptosis appears to play an important mechanistic role in this process. The concept that decreased apoptosis is potentiated by hypoadiponectinemia (seen in obesity) deserves further investigation.

Introduction: Pancreatic enucleation is associated with a low operative mortality and preserved pancreatic parenchyma. However, enucleation is an uncommon operation, and good comparative data with resection are lacking. Therefore, the aim of this analysis was to compare the outcomes of pancreatic enucleation and resection., Material and Methods: From 1998 through 2010, 45 consecutive patients with small (mean, 2.3 cm) pancreatic lesions underwent enucleation. These patients were matched with 90 patients undergoing pancreatoduodenectomy (n = 38) or distal pancreatectomy (n = 52). Serious morbidity was defined in accordance with the American College of Surgeons-National Surgical Quality Improvement Program. Outcomes were compared with standard statistical analyses., Results: Operative time was shorter (183 vs. 271 min, p < 0.01), and operative blood loss was significantly lower (160 vs. 691 ml, p < 0.01) with enucleation. Fewer patients undergoing enucleation required monitoring in an intensive care unit (20% vs. 41%, p < 0.02). Serious morbidity was less common among patients who underwent enucleation compared to those who had a resection (13% vs. 29%, p = 0.05). Pancreatic endocrine (4% vs. 17%, p = 0.05) and exocrine (2% vs. 17%, p < 0.05) insufficiency were less common with enucleation. Ten-year survival was no different between enucleation and resection., Conclusion: Compared to resection, pancreatic enucleation is associated with improved operative as well as short- and long-term postoperative outcomes. For small benign and premalignant pancreatic lesions, enucleation should be considered the procedure of choice when technically appropriate.

Introduction: Obesity is an independent risk factor for severe acute pancreatitis, though the mechanisms underlying this association are unknown. The powerful anti-inflammatory adipokine adiponectin is decreased in obesity. We recently showed that the severity of pancreatitis in obese mice is inversely related to circulating adiponectin levels, and therefore hypothesized that adiponectin upregulation would attenuate the severity of pancreatitis in obese mice., Methods: Forty congenitally obese mice were studied. Seven days prior to study, 20 mice received a single tail vein injection of adenovirus expressing recombinant murine adiponectin (APN; 2 × 10⁸ plaque forming unit (pfu)), and the remainder received a control adenoviral vector expressing β-galactosidase (β-gal; 2 × 10⁸ pfu). Half of the mice in each group had pancreatitis induced by cerulein injection (50 mcg/kg IP hourly for 6 h). The other half received saline on the same schedule. Serum APN concentration and pancreatic tissue concentrations of interleukin (IL)-6, IL-1β, and MCP-1 were measured by ELISA. Histologic pancreatitis score was calculated based on the degree of inflammation (0-4), edema (0-4), and vacuolization (0-4). Data were analyzed by ANOVA and Tukey's tests; p < 0.05 was considered significant., Results: No difference in body weight was observed between groups. Serum APN was significantly upregulated in the APN group compared with the β-gal group. Pancreatic tissue concentration of IL-6 was significantly decreased in the APN group compared with the β-gal group. No change either in pancreatic tissue concentration of IL-1β and MCP-1 or in the severity of histologic pancreatitis were observed., Conclusion: Adiponectin upregulation modulates the pancreatic cytokine milieu but does not attenuate pancreatitis in this model of mild acute pancreatitis.

Background: Choledochal cysts (CC) are rare, congenital anomalies of the biliary tree, associated with the development of biliary malignancies. Small periampullary choledochal diverticula (PCD) are a previously unreported type of biliary anomaly found primarily at ERCP., Objective: The aim of this study was to assess whether PCD are congenital or acquired lesions by comparing the clinical presentation, management, and risk of malignancy between patients with PCD and CC., Design: Retrospective analysis of a medical center database., Setting: Academic tertiary referral center., Patients: Over the study period, data regarding 16 patients with PCD were identified and compared with that of 118 patients with CC., Intervention: Retrospective review of ERCP, surgical pathology, billings, and a diagnostic imaging database from our institution from 1985 to 2009 was done., Main Outcome Measurements: Clinical presentation, investigations, management strategies, complication rates, and long-term outcomes were compared in patients with classic CC and PCD over the same time period., Results: Patients with PCD were less likely to be female (50% vs 81%), older aged (mean 68 vs 28 years), to complain of abdominal pain (88% vs 68%), and were less likely to present with jaundice (0% vs 32%) (P<.05 for all pairs). Patients with PCD also were noted to have lower frequency of anomalous pancreatobiliary junction (0% vs 83%) and biliary neoplasia (0% vs 5%) and more likely to have sphincter of Oddi dysfunction (63% vs 1%). Management of PCD was done with ERCP in 87% of cases and with surgery in 0% of cases, whereas management of CC was done with ERCP in 20% of cases and surgery in 80% of cases (P<.001). Long-term complications at a mean follow-up of 3.7 years after therapy were more common in CC (40% vs 6%, P=.02)., Limitations: Retrospective study. Lack of structured follow up., Conclusion: Small, periampullary, choledochal diverticula are a newly reported, likely acquired anomaly of the biliary tract that are frequently associated with sphincter of Oddi dysfunction and may be secondary to biliary hypertension. These acquired lesions should not be classified as CC., (Copyright © 2011 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.)

Background: Many experimental models of acute pancreatitis suffer from lack of clinical relevance. We sought to validate a recently reported murine model of acute pancreatitis that more closely represents the physiology of human biliary pancreatitis., Methods: Mice (C57BL/6J n=6 and CF-1 n=8) underwent infusion of 50μl of 5% sodium taurocholate (NaT) or 50μl of normal saline (NaCl) directly into the pancreatic duct. Twenty-four hours later, pancreatitis severity was graded histologically by three independent observers, and pancreatic tissue concentration of interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1) were determined by ELISA., Results: Twenty four hours after retrograde injection, the total pancreatitis score was significantly greater in mice infused with NaT than in those infused with NaCl (6.3 ± 1.2 vs. 1.2 ± 0.4, p<0.05). In addition, the inflammatory mediators IL-6 and MCP-1 were increased in the NaT group relative to the NaCl group., Discussion: Retrograde pancreatic duct infusion of sodium taurocholate induces acute pancreatitis in the mouse. This model is likely representative of human biliary pancreatitis pathophysiology, and therefore provides a powerful tool with which to elucidate basic mechanisms underlying the pathogenesis of acute pancreatitis.

The classification of choledochoceles as a type of choledochal cyst stems from the 1959 article by Alonso-Lej and colleagues describing 94 choledochal cysts, only 4 of which were choledochoceles. Even then, Alonso-Lej questioned the propriety of including the choledochocele, stating it was unclear "as to whether or not it originates from the same etiologic factors [as other choledochal cysts]". In 1971, Trout and Longmire also questioned the validity of classifying choledochoceles as choledochal cysts, noting the anatomic position article and variant mucosa of the choledochocele. Wearn and Wiot, in an article titled "Choledochocele: not a form of choledochal cyst", cite the differences in clinical presentation, demographics, and histology as reasons why choledochoceles represent separate entities from choledochal cysts. Over the ensuing decades, numerous investigators have questioned the legitimacy of classifying choledochoceles as choledochal cysts. In our recent series (the only one to our knowledge directly comparing patients with choledochocele and other [type I, II, IV, and V] choledochal cysts), patients with choledochoceles differed from patients with choledochal cysts in their age, gender, presenting symptoms, history of previous cholecystectomy, pancreatobiliary ductal anatomy, management, and most importantly, propensity to developing biliary malignancy. Based on the available cases of choledochoceles found in the literature, combined with the recent series from our institution, we conclude that choledochoceles seem to be distinct entities from choledochal cysts.

Background: Obesity accelerates development and growth of human pancreatic cancer. We recently reported similar findings in a novel murine model of pancreatic cancer in congenitally obese mice. The current experiments were designed to evaluate the effects of diet-induced obesity on pancreatic cancer growth., Methods: Thirty C57BL/6J female mice were fed either control 10% fat (n = 10) or 60% fat diet (n = 20) starting at age 6 weeks. At 11 weeks, 2.5 × 10(5) PAN02 murine pancreatic cancer cells were inoculated. After 6 weeks, tumors were harvested. Serum adiponectin, leptin, insulin, and glucose concentrations were measured. Tumor proliferation, apoptosis, adipocyte content, and tumor-infiltrating lymphocytes were evaluated., Results: The diet-induced obesity diet led to significant weight gain (control 21.3 ± 0.6 g; diet-induced obesity 23.1 ± 0.5 g; p = 0.03). Mice heavier than 23.1 g were considered "Overweight." Tumors grew significantly larger in overweight (1.3 ± 0.3 g) compared to lean (0.5 ± 0.2 g; p = 0.03) mice; tumor size correlated positively with body weight (R = 0.56; p < 0.02). Serum leptin (3.1 ± 0.7 vs. 1.4 ± 0.2 ng/ml) and insulin (0.5 ± 0.2 vs. 0.18 ± 0.02 ng/ml) were significantly greater in overweight mice. Tumor proliferation, apoptosis, and tumor adipocyte volume were similar. T and B lymphocytes were observed infiltrating tumors from lean and overweight mice in similar number., Conclusion: These data show that diet-induced obesity accelerates the growth of murine pancreatic cancer.

Objective: The aim of this analysis was to report a multidisciplinary series comparing choledochoceles to Todani Types I, II, IV, and V choledochal cysts., Summary Background Data: Choledochoceles have been classified as Todani Type III choledochal cysts. However, most surgical series of choledochal cysts have reported few choledochoceles because they are managed primarily by endoscopists., Methods: Surgical, endoscopic, and radiologic records were reviewed at the Riley Children's Hospital and the Indiana University Hospitals to identify patients with choledochal cysts. Patient demographics, presenting symptoms, radiologic studies, associated abnormalities, surgical and endoscopic procedures as well as outcomes were reviewed., Results: A total of 146 patients with "choledochal cysts" including 45 children (31%) and 28 with choledochoceles (18%) were identified, which represents the largest Western series. Patients with choledochoceles were older (50.7 vs. 29.0 years, P < 0.05) and more likely to be male (43% vs. 19%, P < 0.05), to present with pancreatitis (48% vs. 24%, P < 0.05) rather than jaundice (11% vs. 30%, P < 0.05) or cholangitis (0% vs. 21%, P < 0.05), to have pancreas divisum (38% vs. 10%, P < 0.01), and to be managed with endoscopic therapy (79% vs. 17%, P < 0.01). Two patients with choledochoceles (7%) had pancreatic neoplasms., Conclusions: Patients with choledochoceles differ from patients with choledochal cysts with respect to age, gender, presentation, pancreatic ductal anatomy, and their management. The association between choledochoceles and pancreas divisum is a new observation. Therefore, we conclude that classifications of choledochal cysts should not include choledochoceles.

Background: Advances in imaging, minimally invasive techniques, and regionalization have changed pancreatic surgery. Therefore, the aims of this report are to determine whether the pancreatic operations or the spectrum of disease have evolved at a high-volume center., Methods: From 1996 through 2009, 2,004 pancreatic operations were performed at Indiana University Hospital. The operations, pathology, and outcomes for 1996-2003 were compared with 2004-2009., Results: In 2004-2009, more operations/year were performed (215 vs 89; P < .01) and patients were older (58.8 years vs 55.8 years; P < .01). In recent years, more pancreatoduodenectomies (55.0% vs 50.4%) and fewer pancreatojejunostomies (6.2% vs 12.6%) and Beger/Frey procedures (2.6% vs 4.8%) were performed (P < .05). In 2004-2009, pylorus preservation (81.1% vs 64.4%), laparoscopic distal pancreatectomy (33.9% vs 0%), and splenic preservation (25.3% vs 2.2%) were carried out more frequently (P < .001). Pathology review revealed more tumors (68.8% vs 60.4%) and less pancreatitis (29.2% vs 34.4%; P < .01). Thirty-day mortality improved from 2.5% to 1.8%., Conclusion: At a high-volume pancreatic surgery center, the number and age of the patients, the percentage of pancreatic resections, preservation of the pylorus and spleen as well as laparoscopic procedures, and the percentage of patients with tumors all have increased, whereas the outcomes continued to improve., (Copyright © 2010 Mosby, Inc. All rights reserved.)

Objectives: Systematic review of trastuzumab outcomes among breast cancer patients who have negative, equivocal, or discordant HER2 assay results; use of HER2 assay results to predict outcomes of chemotherapy or hormonal therapy regimen for breast cancer; use of serum HER2 to monitor treatment response or disease progression in breast cancer patients; and use of HER2 testing to manage patients with lung, ovarian, prostate, or head and neck tumors. Also, narrative review of concordance of HER2 assays., Data Sources: We abstracted data from: three articles plus one conference abstract on negative, equivocal, or discordant HER2 results; 26 studies on selection of chemotherapy or hormonal therapy; 15 studies on serum HER2; and 26 studies on ovarian, lung, prostate, or head and neck tumors. Foreign-language studies were included., Review Methods: We sought randomized trials or single-arm series (prospective or retrospective) of identically treated patients that presented relevant outcome data associated with HER2 status., Results: HER2 assay results are influenced by multiple biologic, technical, and performance factors. Many aspects of HER2 assays were standardized only recently, so inconsistencies confound the literature comparing different methods. The evidence is weak on outcomes of trastuzumab added to chemotherapy for HER2-equivocal, -discordant, or -negative patients. Evidence comparing chemotherapy outcomes in HER2-positive and HER2-negative patient subgroups may generate hypotheses, but is too weak to test hypotheses. Only a rigorous test can resolve whether HER2-positive patients (but not HER2-negative patients) benefit from an anthracycline regimen. Evidence is available only from uncontrolled series on whether HER2 status predicts complete pathologic response to neoadjuvant chemotherapy. Evidence also is weak regarding differences by HER2 status for outcomes of chemotherapy for advanced or metastatic disease; with most studies lacking statistical power. Data from studies of tamoxifen and aromatase inhibitors suggest that future studies should examine whether HER2 status predicts response to specific hormonal therapies among estrogen-receptor-positive patients. The evidence is weak on whether serum HER2 predicts outcome after treatment with any regimens in any setting, as is the evidence on use of serum or tissue HER2 testing for malignancies of lung, ovary, head and neck, or prostate., Conclusions: Overall, few studies directly investigated the key questions of this systematic review. Going forward, cancer therapy trial protocols should incorporate elements to facilitate robust analyses of the use of HER2 status and other biomarkers for managing treatment.

Objectives: Systematic review of outcomes of three treatments for osteoarthritis (OA) of the knee: intra-articular viscosupplementation; oral glucosamine, chondroitin or the combination; and arthroscopic lavage or debridement., Data Sources: We abstracted data from: 42 randomized, controlled trials (RCTs) of viscosupplementation, all but one synthesized among six meta-analyses; 21 RCTs of glucosamine/chondroitin, 16 synthesized among 6 meta-analyses; and 23 articles on arthroscopy. The search included foreign-language studies and relevant conference proceedings., Review Methods: The review methods were defined prospectively in a written protocol. We sought systematic reviews, meta-analyses, and RCTs published in full or in abstract. Where randomized trials were few, we sought other study designs. We independently assessed the quality of all primary studies., Results: Viscosupplementation trials generally report positive effects on pain and function scores compared to placebo, but the evidence on clinical benefit is uncertain, due to variable trial quality, potential publication bias, and unclear clinical significance of the changes reported. The Glucosamine/Chondroitin Arthritis Intervention Trial (GAIT), a large (n=1,583), high-quality, National Institutes of Health-funded, multicenter RCT showed no significant difference compared to placebo. Glucosamine sulfate has been reported to be more effective than glucosamine hydrochloride, which was used in GAIT, but the evidence is not sufficient to draw conclusions. Clinical studies of glucosamine effect on glucose metabolism are short term, or if longer (e.g., 3 years), excluded patients with metabolic disorders. The best available evidence for arthroscopy, a single sham-controlled RCT (n=180), showed that arthroscopic lavage with or without debridement was equivalent to placebo. The main limitations of this trial are the use of a single surgeon and enrollment of patients at a single Veterans Affairs Medical Center. No studies reported separately on patients with secondary OA of the knee. The only comparative study was an underpowered, poor-quality trial comparing viscosupplementation to arthroscopy with debridement., Conclusions: Osteoarthritis of the knee is a common condition. The three interventions reviewed in this report are widely used in the treatment of OA of the knee, yet the best available evidence does not clearly demonstrate clinical benefit. Uncertainty regarding clinical benefit can be resolved only by rigorous, multicenter RCTs. In addition, given the public health impact of OA of the knee, research on new approaches to prevention and treatment should be given high priority.

Full-field digital mammography (FFDM) is proposed as an alternative to screen-film mammography (SFM). The ability to separate and optimize the acquisition, storage, and display of images may allow greater visualization of breast cancers at equal or lower radiation doses, especially in younger women and those with denser breasts. This is a synopsis of a systematic review by the Blue Cross Blue Shield Association Technology Evaluation Center. This updated systematic review primarily incorporated the results of the ACR Imaging Network(R) Digital Mammographic Imaging Screening Trial (DMIST), which provided results on 42,760 asymptomatic women who underwent both FFDM and SFM and showed with reasonable certainty that there was no difference in the accuracy of the 2 modalities for asymptomatic women in general, with some advantages of FFDM in certain subgroups. There were no strong, new studies on the use of digital mammography compared with film mammography in a diagnostic population. However, the DMIST results indicated that tumors detected by FFDM, but not by SFM, were likely to be invasive carcinomas or medium-grade to high-grade ductal carcinoma in situ. On the basis of the suppositions that these are the cancers of greatest interest and the ones more likely to be found in a diagnostic population and that the diagnostic population may be younger on average than the screening population, it was concluded that there is sufficient evidence to support the use of FFDM for diagnostic purposes.

Objectives: This is a systematic review of evidence on issues in managing small cell lung cancer (SCLC). Key questions addressed are: the sequence, timing, and dosing characteristics of primary thoracic radiotherapy (TRTx) for limited-stage disease; primary TRTx for extensive-stage disease; effect of prophylactic cranial irradiation (PCI); positron emission tomography (PET) for staging; treatment of mixed histology tumors; surgery; and second- and subsequent-line treatment for relapsed/progressive disease., Data Sources: MEDLINE, EMBASE, and the Cochrane Register, Review Methods: The review methods were defined prospectively in a written protocol. We sought randomized controlled trials that compared the interventions of interest. Where randomized trials were limited or nonexistent, we sought additional studies. We performed meta-analysis of studies that compared early and late TRTx., Results: The strongest evidence available for this report is a patient-level meta-analysis showing that PCI improves survival of SCLC patients who achieved complete response following primary therapy from 15.3 percent to 20.7 percent (p=0.01). No other question yielded evidence so robust. The case for concurrent over sequential radiation delivery rests largely on a single multicenter trial. Support for early concurrent therapy comes from one multicenter trial, but two other multicenter trials found no advantage. Our meta-analysis did not find significant reductions in 2- and 3-year mortality for early TRTx. Favorable results from a single-center trial on TRTx for extensive stage disease need replication in a multicenter setting. For other questions (i.e., management of mixed histology disease; surgery for early limited SCLC), relevant comparative studies were nonexistent. PET may be more sensitive in detecting disease outside the brain than conventional staging modalities, but studies were of poor quality and reliable estimates of performance are not possible., Conclusions: PCI improves survival among those with a complete response to primary therapy. A research agenda is needed to optimize the effectiveness of TRTx and its components. PET for staging may be useful, but its role awaits clarification by rigorous studies. No relevant evidence was available to address management of mixed histology disease or surgery for early limited SCLC.

Wireless capsule endoscopy is proposed in the management of patients with obscure gastrointestinal (GI) bleeding, defined as persistent or recurrent GI bleeding without a cause identified on routine endoscopy. Obscure GI bleeding often originates from a small-intestinal abnormality, which presents diagnostic and therapeutic challenges because the small intestine is not easily visualized on conventional workup. This is a synopsis of a systematic review by the Blue Cross Blue Shield Association Technology Evaluation Center. Limited evidence shows that capsule endoscopy identified small-bowel lesions generally beyond the reach of push enteroscopy in 25% to 50% of patients and revealed additional diagnostic findings in 25% of patients compared with small-bowel barium radiographic studies. The authors conclude that in some cases, the information provided by capsule endoscopy in this specific patient population with obscure GI bleeding not diagnosed via conventional workup can lead to changes in management that would improve net health outcome.

Evidence-based technology assessment can help answer critical questions concerning the safety, effectiveness, and appropriate uses of medical technologies. This practice can be used to avoid the promotion of ineffective technologies and the premature diffusion of technologies that have not been demonstrated to improve patient-oriented health outcomes, both of which draw resources from effective and appropriate medical care. This article describes the process of such evaluation as undertaken by the Blue Cross Blue Shield Association Technology Evaluation Center. The key components of the assessment process are described, including the problem formulation and evaluation of study quality, as well as the process by which the available evidence is judged against the five Technology Evaluation Center criteria.