17 results on '"Melstrom KA"'
Search Results
2. New perspectives for a new century: implications of pathogen responses for the future of antimicrobial therapy.
- Author
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Melstrom KA Jr., Smith JW, Gamelli RL, Shankar R, Melstrom, Kurt A Jr, Smith, Jason W, Gamelli, Richard L, and Shankar, Ravi
- Published
- 2006
- Full Text
- View/download PDF
3. Thematic analysis of patient perspectives in a randomized controlled trial for a remote perioperative telemonitoring program.
- Author
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Fan D, Esslin P, Okunowo O, Sun V, Kaiser AM, Paz B, Raoof M, Lewis A, Melstrom KA, Lai L, Woo Y, Singh G, Fong Y, and Melstrom LG
- Subjects
- Humans, Female, Male, Middle Aged, Aged, Perioperative Care methods, Patient Satisfaction, Monitoring, Physiologic methods, Adult, Patient Reported Outcome Measures, Telemedicine, Gastrointestinal Neoplasms surgery
- Abstract
Background: Remote patient telemonitoring programs offer the potential to enhance access and communication with medical providers. This study assessed the patient-reported experience during perioperative telemonitoring for gastrointestinal (GI) oncologic surgery., Methods: Between October 2021 and July 2023, patients with GI cancer were enrolled in the remote telemonitoring trial and randomized into the intervention or enhanced usual care arm. Although the enhanced usual care arm adhered to standard protocols for problem reporting, the intervention arm received active nursing support for monitoring data deviations from predetermined thresholds. The program culminated in a 15-minute exit interview comprised 9 total questions to gather insights into the patient experiences with device usage, symptom reporting, and communication with the healthcare team. Thematic analysis was conducted on all responses to present a patient-centric summary., Results: Of the 114 patients completing the study, 100 patients (88%) participated in the exit interview. Most enrolled patients (n = 68) were diagnosed as having colorectal cancer. The intervention arm reported greater ease and accessibility in electronic data reporting and communication with healthcare team compared to the enhanced usual care arm (94% vs 69%). Qualitative analysis identified 3 themes used to describe the program: "instilling an affirmative and proactive mindset toward recovery," "receiving timely attention from healthcare team," and "benefits of device usage and electronic health surveys." The subthemes highlighted an appreciative and empowering mindset among most patients., Conclusion: Most enrolled patients expressed satisfaction with the program to facilitate their postoperative recovery. These positive testimonials present a promising outlook for future implementation from the patient perspective., (Copyright © 2024 Society for Surgery of the Alimentary Tract. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
4. Outcomes of rectal cancer patients who refuse surgery after incomplete clinical response to neoadjuvant therapy.
- Author
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Labadie KP, Olson KA, Sun SH, Ituarte PHG, Hanna M, Zerhouni Y, Lai LL, Sentovich SM, Kaiser AM, and Melstrom KA
- Subjects
- Humans, Male, Female, Middle Aged, Retrospective Studies, Aged, Treatment Refusal statistics & numerical data, Adult, Watchful Waiting, Neoplasm Staging, Treatment Outcome, Aged, 80 and over, Rectal Neoplasms therapy, Rectal Neoplasms pathology, Rectal Neoplasms mortality, Neoadjuvant Therapy, Adenocarcinoma therapy, Adenocarcinoma pathology, Adenocarcinoma mortality
- Abstract
Background and Objectives: Total mesorectal excision (TME) remains the standard of care for patients with rectal cancer who have an incomplete response to total neoadjuvant therapy (TNT). A minority of patients will refuse curative intent resection. The aim of this study is to examine the outcomes for these patients., Methods: A retrospective cohort study of stage 1-3 rectal adenocarcinoma patients who underwent neoadjuvant chemoradiation therapy or TNT at a single institution. Patients either underwent TME, watch-and-wait protocol, or if they refused TME, were counseled and watched (RCW). Clinical outcomes and resource utilization were examined in each group., Results: One hundred seventy-one patients (Male 59%) were included with a median surveillance of 43 months. Twenty-nine patients (17%) refused TME and had shortened overall survival (OS). Twelve patients who refused TME converted to a complete clinical response (cCR) on subsequent staging with a prolonged OS. 92% of these patients had a near cCR at initial staging endoscopy. Increased physician visits and testing was utilized in RCW and WW groups., Conclusion: A significant portion of patients convert to cCR and have prolonged OS. Lengthening the time to declare cCR may be considered in select patients, such as those with a near cCR at initial endoscopic staging., (© 2024 Wiley Periodicals LLC.)
- Published
- 2024
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5. Randomized Controlled Trial of Perioperative Telemonitoring of Patient Generated Health Data in Gastrointestinal Oncologic Surgery: Assessing Overall Feasibility and Acceptability.
- Author
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Limbach K, Esslin P, Sun V, Fan D, Kaiser AM, Paz IB, Raoof M, Lewis A, Melstrom KA, Lai L, Woo Y, Singh G, Fong Y, and Melstrom LG
- Subjects
- Humans, Feasibility Studies, Treatment Outcome, Medical Oncology, Patient Generated Health Data, Telemedicine
- Published
- 2023
- Full Text
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6. Severe Immune-Mediated Colitis Induced by Checkpoint Inhibitors in an Adolescent With Lynch Syndrome.
- Author
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Lee RV, Melstrom KA, Mannan R, Idos GE, and Kidambi T
- Abstract
Lynch syndrome is a hereditary colorectal cancer caused by mutations in DNA mismatch repair genes. Immune checkpoint therapies have shown promise in treating Lynch syndrome-associated cancers but can lead to immune-related adverse events, such as colitis. In this report, we present a severe case of immune-mediated colitis (IMC) induced by checkpoint inhibitors in a young patient with Lynch syndrome. This 20-year-old male with Lynch syndrome and a history of glioblastoma underwent dual checkpoint therapy, after initial treatment with systemic steroids. Despite this, his condition worsened, resulting in complications, such as toxic megacolon and small bowel obstruction. He was subjected to various treatments, including infliximab and vedolizumab, but ultimately required total abdominal colectomy with J-pouch creation. This case highlights the challenges of managing severe IMC in patients with Lynch syndrome. The patient's suboptimal response to standard treatments and the development of complications emphasizes the need for a better understanding and alternative therapeutic options for IMC. This case also calls into question whether a subset of patients with IMC should be "treated to target," even though the current standard of care for IMC is guided by symptom response, and if so, further research is necessary to identify potential therapeutic targets. Further research is also required to understand the mechanisms of IMC and develop effective treatment strategies tailored to patients with Lynch syndrome and immune-related adverse events., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Lee et al.)
- Published
- 2023
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7. First-In-Human Pilot PET Immunoimaging Study of 64 Cu-Anti-Carcinoembryonic Antigen Monoclonal Antibody (hT84.66-M5A) in Patients with Carcinoembryonic Antigen-Producing Cancers.
- Author
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Wong JYC, Yamauchi DM, Adhikarla V, Simpson J, Frankel PH, Fong Y, Melstrom KA, Chen YJ, Salehian BD, Woo Y, Dandapani SV, Colcher DM, Poku EK, Yazaki PJ, Wu AM, and Shively JE
- Subjects
- Humans, Carcinoembryonic Antigen, Pilot Projects, Antibodies, Monoclonal therapeutic use, Thyroid Neoplasms, Rectal Neoplasms
- Abstract
Background: PET imaging using radiolabeled immunoconstructs shows promise in cancer detection and in assessing tumor response to therapies. The authors report the first-in-human pilot study evaluating M5A, a humanized anti-carcinoembryonic antigen (CEA) monoclonal antibody (mAb), radiolabeled with
64 Cu in patients with CEA-expressing malignancies. The purpose of this pilot study was to identify the preferred patient population for further evaluation of this agent in an expanded trial. Methods: Patients with CEA-expressing primary or metastatic cancer received64 Cu-DOTA-hT84.66-M5A with imaging performed at 1 and 2 days postinfusion.64 Cu-DOTA-hT84.66-M5A PET scan findings were correlated with CT, MRI, and/or FDG PET scans and with histopathologic findings from planned surgery or biopsy performed postscan. Results: Twenty patients received64 Cu-DOTA-hT84.66-M5A. Twelve patients demonstrated positive images, which were confirmed in 10 patients as tumor by standard-of-care (SOC) imaging, biopsy, or surgical findings. Four of the 8 patients with negative imaging were confirmed as true negative, with the remaining 4 patients having disease demonstrated by SOC imaging or surgery. All 5 patients with locally advanced rectal cancer underwent planned biopsy or surgery after64 Cu-DOTA-hT84.66-M5A imaging (4 patients imaged 6-8 weeks after completing neoadjuvant chemotherapy and radiation therapy) and demonstrated a high concordance between biopsy findings and64 Cu-DOTA-hT84.66-M5A PET scan results. Three patients demonstrated positive uptake at the primary site later confirmed by biopsy and at surgery as residual disease. Two patients with negative scans each demonstrated complete pathologic response. In 5 patients with medullary thyroid cancer,64 Cu-DOTA-hT84.66-M5A identified disease not seen on initial CT scans in 3 patients, later confirmed to be disease by subsequent surgery or MRI. Conclusions:64 Cu-DOTA-hT84.66-M5A demonstrates promise in tumor detection, particularly in patients with locally advanced rectal cancer and medullary thyroid cancer. A successor trial in locally advanced rectal cancer has been initiated to further evaluate this agent's ability to define tumor extent before and assess disease response after neoadjuvant chemotherapy and radiotherapy. clinical trial.gov (NCT02293954).- Published
- 2023
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8. Metachronous peritoneal metastases following curative resection for colon cancer: Understanding risk factors and patterns of recurrence.
- Author
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Le VH, Thornblade L, Ituarte PHG, Lai LL, and Melstrom KA
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- Aged, Colonic Neoplasms pathology, Female, Follow-Up Studies, Humans, Male, Middle Aged, Neoplasm Recurrence, Local epidemiology, Neoplasm Staging, Neoplasms, Second Primary epidemiology, Peritoneal Neoplasms epidemiology, Retrospective Studies, Risk Factors, Survival Rate, Colectomy adverse effects, Colonic Neoplasms surgery, Neoplasm Recurrence, Local pathology, Neoplasms, Second Primary secondary, Peritoneal Neoplasms secondary
- Abstract
Background: A subset of metachronous colon cancer recurrence manifests as peritoneal metastases (PM). Risk factors for metachronous PM recurrence are not well-defined in patients with stage II or III colon cancers after curative resection and standard adjuvant treatments., Methods: Population data from the California Cancer Registry for patients with Stage II or III colon cancer were collected between 2004 and 2012. Multivariate analysis was used to identify factors associated with metachronous PM., Results: Of the 2077 patients with stage II or III colon cancer, female patients (odds ratio [OR] = 1.84, p = 0.02), T4 primary tumor (OR = 2.36, p = 0.02), mucinous (OR = 3.97, p < 0.01) or signet-ring histology (OR = 6.01, p = 0.01), and right-sided cancer (OR = 2.2, p < 0.01) were found with increased risk of metachronous isolated PM recurrence after curative resection. Median survival after diagnosis for patients without PM recurrence was 22 months, compared with 12 months for PM recurrence (p < 0.001)., Conclusion: PM recurrence groups have a worse overall survival than patients with recurrent disease in other sites. A better understanding of the tumor biology and molecular characteristics of colon cancers likely to recur as PM is needed to explain behavior and identify potential targeted therapy., (© 2020 Wiley Periodicals LLC.)
- Published
- 2021
- Full Text
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9. Separation of color channels from conventional colonoscopy images improves deep neural network detection of polyps.
- Author
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Lai LL, Blakely A, Invernizzi M, Lin J, Kidambi T, Melstrom KA, Yu K, and Lu T
- Subjects
- Colonoscopy, Diagnosis, Computer-Assisted, Humans, Narrow Band Imaging, Neural Networks, Computer, Colonic Polyps diagnostic imaging
- Abstract
Significance: Colorectal cancer incidence has decreased largely due to detection and removal of polyps. Computer-aided diagnosis development may improve on polyp detection and discrimination., Aim: To advance detection and discrimination using currently available commercial colonoscopy systems, we developed a deep neural network (DNN) separating the color channels from images acquired under narrow-band imaging (NBI) and white-light endoscopy (WLE)., Approach: Images of normal colon mucosa and polyps from colonoscopies were studied. Each color image was extracted based on the color channel: red/green/blue. A multilayer DNN was trained using one-channel, two-channel, and full-color images. The trained DNN was then tested for performance in detection of polyps., Results: The DNN performed better using full-colored NBI over WLE images in the detection of polyps. Furthermore, the DNN performed better using the two-channel red + green images when compared to full-color WLE images., Conclusions: The separation of color channels from full-color NBI and WLE images taken from commercially available colonoscopes may improve the ability of the DNN to detect and discriminate polyps. Further studies are needed to better determine the color channels and combination of channels to include and exclude in DNN development for clinical use.
- Published
- 2021
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10. Role of minimally invasive surgery for rectal cancer.
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Melstrom KA and Kaiser AM
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- Humans, Minimally Invasive Surgical Procedures, Digestive System Surgical Procedures, Laparoscopy adverse effects, Proctectomy, Rectal Neoplasms surgery, Robotic Surgical Procedures adverse effects, Transanal Endoscopic Surgery
- Abstract
Rectal cancer is one of the most common malignancies worldwide. Surgical resection for rectal cancer usually requires a proctectomy with respective lymphadenectomy (total mesorectal excision). This has traditionally been performed transabdominally through an open incision. Over the last thirty years, minimally invasive surgery platforms have rapidly evolved with the goal to accomplish the same quality rectal resection through a less invasive approach. There are currently three resective modalities that complement the traditional open operation: (1) Laparoscopic surgery; (2) Robotic surgery; and (3) Transanal total mesorectal excision. In addition, there are several platforms to carry out transluminal local excisions (without lymphadenectomy). Evidence on the various modalities is of mixed to moderate quality. It is unreasonable to expect a randomized comparison of all options in a single trial. This review aims at reviewing in detail the various techniques in regard to intra-/perioperative benchmarks, recovery and complications, oncological and functional outcomes., Competing Interests: Conflict-of-interest statement: Dr. Kaiser reports personal fees from Intuitive Surgical, other from McGraw-Hill Publisher, other from Uptodate, outside the submitted work., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)
- Published
- 2020
- Full Text
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11. Health-related quality of life and oncologic outcomes after surgery in older adults with colorectal cancer.
- Author
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Blakely AM, Chanson D, Wong FL, Eng OS, Sentovich SM, Melstrom KA, Lai LL, Fong Y, and Sun V
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- Aged, Aged, 80 and over, Colorectal Neoplasms mortality, Female, Humans, Male, Middle Aged, Survival Analysis, Treatment Outcome, Colorectal Neoplasms psychology, Colorectal Neoplasms surgery, Quality of Life psychology
- Abstract
Purpose: Data regarding changes in functional status and health-related quality of life (HRQOL) before and after surgery are lacking. We identified colorectal cancer patients from the SEER-Medicare Health Outcomes Survey (MHOS) linked database to evaluate the association between HRQOL and survival., Methods: HRQOL survey data captured physical/mental health, activities of daily living (ADLs), and medical comorbidities. Patients who underwent surgery with HRQOL surveys prior to cancer diagnosis and ≥ 1 year after diagnosis were selected. Patient, disease, and HRQOL measures were analyzed in regard to overall survival (OS), disease-specific survival (DSS), and non-DSS., Results: Of 590 patients included, 55% were female, 75% were Caucasian, and 83% had colonic primary. Disease extent was localized for 52%, regional for 41%, and distant for 7%. Median OS was 83 months. Decreased OS was independently associated with age ≥ 75 (HR 1.7, p < 0.0001), male sex (HR 1.4, p = 0.011), advanced disease (regional-HR 2.0, p < 0.0001; distant-HR 7.0, p < 0.0001), and decreased mental HRQOL (HR 1.4, p = 0.005). Decreased DSS was independently associated with advanced disease (regional-HR 4.1, p < 0.0001; distant-HR 16.5, p < 0.0001) and rectal primary (HR 1.6, p = 0.047). Decreased non-DSS was independently associated with age ≥ 75 (HR 2.2, p < 0.0001), male sex (HR 1.4, p = 0.03), decreased mental HRQOL (HR 1.4, p = 0.02), and increased comorbidities (HR 1.4, p = 0.04)., Conclusions: The potential overall survival benefit of oncologic surgery is diminished by declines in physical and mental health. Early identification of older surgical patients at risk for functional and HRQOL declines may improve survival following colorectal cancer surgery.
- Published
- 2020
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12. Surgical Smoke Exposure in Operating Room Personnel: A Review.
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Limchantra IV, Fong Y, and Melstrom KA
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- Humans, Air Pollutants, Occupational adverse effects, Occupational Exposure adverse effects, Operating Rooms, Smoke adverse effects, Smoke prevention & control
- Abstract
Importance: Smoke generated during surgical procedures has long been thought to be hazardous to hospital personnel; however, the degree of danger has yet to be determined., Observations: The dangers of surgical smoke are associated with the composition of the plume. Small-particulate matter is found in the smoke that is easily inhaled. Particulates deposit in the lungs, circulatory system, and other organs, which may cause numerous health problems. The smoke also contains many gaseous compounds known to cause cancer. The type of tissue and the form of cautery have been shown to alter the composition of the surgical smoke. Well-cited articles have asserted that daily inhaled surgical smoke could be equivalent to smoking dozens of cigarettes. Unsafe levels of cancer-causing compounds have been found in the smoke. However, there is no firm evidence that operating room personnel show increased cancer rates compared with the general population. Data implicating other forms of passively inhaled smoke, such as fumes associated with cooking and wood burning, are likely comparable to the smoke issued during surgical procedures. Most operating rooms do not require smoke evacuation, and the elimination techniques are variable. Most systems rely on dispersion and, possibly, mechanical evacuation and filtration. Newer electric filters show promise but require more development., Conclusions and Relevance: Surgical smoke is dangerous, but the severity of the risk has yet to be determined. Therefore, no safe level is known at this point. Efforts should be made to reduce and possibly eliminate smoke from the operating room. Research into cost-effective forms of smoke evacuation is necessary. Studies of respiratory and cancer sequelae of exposure to operating room smoke in personnel who have had long-term exposure to surgical smoke is also needed.
- Published
- 2019
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13. Robotic surgery trends in general surgical oncology from the National Inpatient Sample.
- Author
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Stewart CL, Ituarte PHG, Melstrom KA, Warner SG, Melstrom LG, Lai LL, Fong Y, and Woo Y
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- Aged, Databases, Factual, Digestive System Surgical Procedures methods, Female, Humans, Laparoscopy trends, Male, Middle Aged, Minimally Invasive Surgical Procedures trends, Postoperative Complications epidemiology, Retrospective Studies, Surgical Oncology methods, Digestive System Surgical Procedures trends, Robotic Surgical Procedures trends, Surgical Oncology trends
- Abstract
Background: Robotic surgery is offered at most major medical institutions. The extent of its use within general surgical oncology, however, is poorly understood. We hypothesized that robotic surgery adoption in surgical oncology is increasing annually, that is occurring in all surgical sites, and all regions of the US., Study Design: We identified patients with site-specific malignancies treated with surgical resection from the National Inpatient Sample 2010-2014 databases. Operations were considered robotic if any ICD-9-CM robotic procedure code was used., Results: We identified 147,259 patients representing the following sites: esophageal (3%), stomach (5%), small bowel (5%), pancreas (7%), liver (5%), and colorectal (75%). Most operations were open (71%), followed by laparoscopic (26%), and robotic (3%). In 2010, only 1.1% of operations were robotic; over the 5-year study period, there was a 5.0-fold increase in robotic surgery, compared to 1.1-fold increase in laparoscopy and 1.2-fold decrease in open surgery (< 0.001). These trends were observed for all surgical sites and in all regions of the US, they were strongest for esophageal and colorectal operations, and in the Northeast. Adjusting for age and comorbidities, odds of having a robotic operation increased annually (5.6 times more likely by 2014), with similar length of stay (6.9 ± 6.5 vs 7.0 ± 6.5, p = 0.52) and rate of complications (OR 0.91, 95% CI 0.83-1.01, p = 0.08) compared to laparoscopy., Conclusions: Robotic surgery as a platform for minimally invasive surgery is increasing over time for oncologic operations. The growing use of robotic surgery will affect surgical oncology practice in the future, warranting further study of its impact on cost, outcomes, and surgical training.
- Published
- 2019
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14. Ductal carcinoma in situ: size and resection volume predict margin status.
- Author
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Melstrom LG, Melstrom KA, Wang EC, Pilewskie M, and Winchester DJ
- Subjects
- Female, Humans, Logistic Models, Middle Aged, Multivariate Analysis, Retrospective Studies, Risk Factors, Carcinoma, Intraductal, Noninfiltrating pathology, Carcinoma, Intraductal, Noninfiltrating surgery, Mastectomy, Segmental, Neoplasm Recurrence, Local prevention & control, Neoplasm, Residual pathology, Neoplasm, Residual prevention & control
- Abstract
Objectives: There is strong evidence that breast conservation surgery (BCS) with negative margins for ductal carcinoma in situ (DCIS) is associated with low rates of recurrence. Our goal was to identify factors associated with positive margins in BCS for DCIS., Methods: A retrospective database review identified 823 patients diagnosed with DCIS. The current analysis included 546 of those patients treated with BCS from 2000 to 2006 with complete data regarding tumor and lumpectomy dimensions. Variables analyzed included tumor size, lumpectomy volume, estrogen and progesterone receptor status, histologic subtype, grade, and age at diagnosis. χ analysis and t tests were used to identify factors that may predict positive margins. A multivariate regression model was developed to determine independent variables predictive of positive margin status., Results: A total of 33% of specimens had positive margins. Lumpectomy volume, tumor size, nuclear grade (low vs. high), and number of slides positive for DCIS were all significant for positive margin status by bivariate analysis. On multivariate analysis, tumor size (P < 0.001; odds ratio, 2.37; 95% confidence interval, 1.712, 3.296) and resection volume (P = 0.0006; odds ratio, 0.48; 95% confidence interval, 0.318, 0.729) remained significantly associated with positive margin status. Age at diagnosis, histologic subtype, tumor grade, and estrogen and progesterone status all were not associated with margin status., Conclusions: Positive margins after BCS for DCIS are associated with larger lesions and a smaller volume of resection. With 33% of patients having positive margins, these data suggest that a more aggressive initial resection may avoid positive margins and thus lower the risk of recurrence or the need for additional surgery.
- Published
- 2010
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15. Cytotoxicity of Pseudomonas secreted exotoxins requires OxyR expression.
- Author
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Melstrom KA Jr, Kozlowski R, Hassett DJ, Suzuki H, Bates DM, Gamelli RL, and Shankar R
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- Animals, Bacterial Proteins genetics, Cell Proliferation drug effects, Dendritic Cells cytology, Dendritic Cells drug effects, Exotoxins pharmacology, Gene Expression Regulation, Bacterial, Genes, Bacterial genetics, Macrophages cytology, Macrophages drug effects, Male, Mice, Mice, Inbred C57BL, Stem Cells cytology, Stem Cells drug effects, Trans-Activators genetics, Bacterial Proteins metabolism, Exotoxins metabolism, Pseudomonas aeruginosa metabolism, Pseudomonas aeruginosa pathogenicity, Trans-Activators metabolism
- Abstract
Background: Nosocomial infections often lead to sepsis and multisystem organ failure in critically injured patients, including burn and trauma patients. A better understanding of the bacterial response to the host immune system is essential to develop better antimicrobials against pathogens. Pseudomonas aeruginosa combats host-initiated oxidant stress through expression of the transactivating factor, OxyR. Here we have tested the premise that OxyR regulates Pseudomonal cytotoxicity through secreted exotoxin production., Materials and Methods: Wild-type P. aeruginosa (PAO1) and a deletion mutant lacking the oxyR gene (Delta oxyR) were grown for 18 h in Luria broth and the supernatant containing the secreted products was removed using centrifugation. Secreted proteins were isolated using ammonium sulfate precipitation. ER-MP20(+) myeloid progenitor cells were harvested from the bone marrow of C57Blk/6J mice. These cells were differentiated into dendritic cells and macrophages. Various concentrations (0-20 microg/100 microL) of the bacterial proteins were added to the medium and cells were allowed to differentiate for 7 days. Cellular viability was then assayed using a proliferation assay. These studies were repeated on two other macrophage cell lines, human U937 and murine P388D1., Results: At a protein concentration of 5 microg/100 microL PAO1 supernatant protein, cellular proliferation was significantly reduced to 4.2 +/- 2.8% compared to untreated controls, while the DeltaoxyR supernatant protein remained at 103.3 +/- 4.0% of untreated controls (P < 0.05). Similar significant results were seen in the U937-, P388D1-, and ER-MP20(+)-derived macrophage cells., Conclusions: Taken together, our data indicate that OxyR regulates the secretion of potent cytotoxic factors by P. aeruginosa.
- Published
- 2007
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16. Mechanisms of skeletal muscle degradation and its therapy in cancer cachexia.
- Author
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Melstrom LG, Melstrom KA Jr, Ding XZ, and Adrian TE
- Subjects
- Adrenal Cortex Hormones pharmacology, Animals, Appetite Stimulants pharmacology, Cachexia etiology, Cachexia therapy, Cytokines antagonists & inhibitors, Cytokines metabolism, Humans, Lysosomes metabolism, Megestrol Acetate therapeutic use, Muscle, Skeletal metabolism, Nutritional Support, Pancreatic Neoplasms metabolism, Peptide Hydrolases metabolism, Proteasome Endopeptidase Complex metabolism, Ubiquitin metabolism, Adrenal Cortex Hormones therapeutic use, Appetite Stimulants therapeutic use, Cachexia drug therapy, Cachexia metabolism, Muscle Proteins metabolism, Muscle, Skeletal drug effects, Pancreatic Neoplasms complications
- Abstract
Severe or chronic disease can lead to cachexia which involves weight loss and muscle wasting. Cancer cachexia contributes significantly to disease morbidity and mortality. Multiple studies have shown that the metabolic changes that occur with cancer cachexia are unique compared to that of starvation. Specifically, cancer patients seem to lose a larger proportion of skeletal muscle mass. There are three pathways that contribute to muscle protein degradation: the lysosomal system, cytosolic proteases and the ubiquitin (Ub)-proteasome pathway. The Ub-proteasome pathway seems to account for the majority of skeletal muscle degradation in cancer cachexia and is stimulated by several cytokines including tumor necrosis factor-alpha, interleukin-1beta, interleukin-6, interferon-gamma and proteolysis-inducing factor. Cachexia is particularly severe in pancreatic cancer and contributes significantly to the quality of life and mortality of these patients. Several factors contribute to weight loss in these patients, including alimentary obstruction, pain, depression, side effects of therapy and a high catabolic state. Although no single agent has proven to halt cachexia in these patients there has been some progress in the areas of nutrition with supplementation and pharmacological agents such as megesterol acetate, steroids and experimental trials targeting cytokines that stimulate the Ub-proteasome pathway.
- Published
- 2007
- Full Text
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17. Progressive changes in adherens junction structure during intestinal adenoma formation in Apc mutant mice.
- Author
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Carothers AM, Melstrom KA Jr, Mueller JD, Weyant MJ, and Bertagnolli MM
- Subjects
- Alleles, Animals, Cadherins metabolism, Cell Adhesion, Cell Membrane metabolism, Cell Nucleus metabolism, Cytoskeletal Proteins metabolism, Cytosol metabolism, Enterocytes metabolism, Female, Gene Deletion, Genes, Dominant, Heterozygote, Immunoblotting, Immunohistochemistry, Mice, Mice, Mutant Strains, Mutation, Phosphorylation, Precipitin Tests, Protein Binding, Subcellular Fractions, Tyrosine metabolism, beta Catenin, Adenoma metabolism, Adenomatous Polyposis Coli Protein genetics, Adherens Junctions chemistry, Trans-Activators
- Abstract
The C57BL/6J-Min/+ (Min/+) mouse bears a mutant Apc gene and therefore is an important in vivo model of intestinal tumorigenesis. Min/+ mice develop adenomas that exhibit loss of the wild-type Apc allele (Apc(Min/-)). Previously, we found that histologically normal enterocytes bearing a truncated Apc protein (Apc(Min/+)) migrated more slowly in vivo than enterocytes with either wild-type Apc (Apc(+/+)) or with heterozygous loss of Apc protein (Apc(1638N)). To study this phenotype further, we determined the effect of the Apc(Min) mutation upon cell-cell adhesion by examining the components of the adherens junction (AJ). We observed a reduced association between E-cadherin and beta-catenin in Apc(Min/+) enterocytes. Subcellular fractionation of proteins from Apc(+/+), Apc(Min/+), and Apc(Min/-) intestinal tissues revealed a cytoplasmic localization of intact E-cadherin only in Apc(Min/+), suggesting E-cadherin internalization in these enterocytes. beta-Catenin tyrosine phosphorylation was also increased in Apc(Min/+) enterocytes, consistent with its dissociation from E-cadherin. Furthermore, Apc(Min/+) enterocytes showed a decreased association between beta-catenin and receptor protein-tyrosine phosphatase beta/zeta (RPTPbeta/zeta), and Apc(Min/-) cells demonstrated an association between beta-catenin and receptor protein-tyrosine phosphatase gamma. In contrast to the Apc(Min/+) enterocytes, Apc(Min/-) adenomas displayed increased expression and association of E-cadherin, beta-catenin, and alpha-catenin relative to Apc(+/+) controls. These data show that Apc plays a role in regulating adherens junction structure and function in the intestine. In addition, discovery of these effects in initiated but histologically normal tissue (Apc(Min/+)) defines a pre-adenoma stage of tumorigenesis in the intestinal mucosa.
- Published
- 2001
- Full Text
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