Opportunities to reduce reoperations and to improve inter-facility profiling after initial breast-conserving surgery for cancer. A report from the NCDB.

BACKGROUND: Repeat operations after breast-conserving surgery (BCS) for cancer have been termed "epidemic." To aid improvement activities, we sought to identify those National Cancer Data Base (NCDB) characteristics that were associated with reoperations. METHODS: A retrospective cohort of patients with invasive breast cancer undergoing initial BCS in the NCDB from 2004 to 2015 were identified. Univariate, multivariate, ranking (effect size and R2), and time-trend methods were used to assess associations between patient, facility, tumor, treatment, and calendar-year characteristics with reoperation. RESULTS: In 1226 facilities, 84,462 (16.1%) of 524,594 patients underwent reoperations after BCS [range 0-75%; 10th/90th performance percentiles = 6.6%/25%]. Of 18 factors associated with reoperations, facility ID was the highest-ranked. Its estimated impact on the odds of reoperation was more than 10 times greater than any other factor considered, followed by tumor size, neo-adjuvant chemotherapy receipt, patient age, cancer histology, and nodal status. Reoperations after the year of the SSO-ASTRO margin guideline declined significantly compared with prior years. Significant inter-facility reoperation variability persisted after risk adjustment for more than a dozen distinct patient, facility, tumor, and treatment characteristics. CONCLUSION: In the NCDB, significant inter-facility variability exists regardless of case volume, case mix, and risk adjustment. There were fewer reoperations after the SSO-ASTRO guideline. An endorsed target rate of 10% was achieved by only 1 in 4 facilities. The most impactful determinant of reoperation was the facility itself. Thus, all stakeholders should consider participation in improvement activities. Such activities will benefit from risk-adjusted profiling; the relevant adjustors were identified.

A Reappraisal of the Comparative Effectiveness of Lumpectomy Versus Mastectomy on Breast Cancer Survival: A Propensity Score-Matched Update From the National Cancer Data Base (NCDB).

BACKGROUND: Recent observational studies are concerning because they document rising mastectomy rates coinciding with more than a dozen reports that lumpectomy has better overall survival (OS) than mastectomy. Our aim was to determine if there were differences in OS of matched breast cancer patients undergoing lumpectomy versus mastectomy in the National Cancer Database (NCDB). PATIENTS AND METHODS: A retrospective cohort of patients with stage I-III breast cancer in the NCDB (2004-2013) was identified. Propensity score matching (PSM), Kaplan-Meier, and multivariate Cox proportional hazards models were used to examine OS by type of surgery. RESULTS: Of 845,136 patients, 464,052 (54.9%) underwent lumpectomy and 381,084 (45.1%) underwent mastectomy. After PSM, the hazard ratio (HR) and confidence interval (CI) for OS in all patients comparing lumpectomy with mastectomy was 1.02 (CI, 1.00-1.04; P = .002). In patients with stage I, II, and III, they were HR 1.27 (CI, 1.23-1.36; P < .001), HR 0.98 (CI, 0.95-1.01; P = .21), and HR 0.83 (CI, 0.80-0.86; P < .001), respectively. In subgroup analyses of all patients by estrogen receptor (ER) status, they were HR 1.05 (CI, 1.03-1.07; P < .001) and HR 1.00 (CI, 0.96-1.03; P = .65) in ER+ and ER- patients. CONCLUSION: In our primary model of all stage I-III matched patients, using the most recent NCDB data and the largest observational sample size to date, the OS after mastectomy was not inferior to lumpectomy. This finding can be reassuring to patients and providers. In subgroup analyses, the association between type of surgery and OS differed by cancer stage and hormone receptor status.

The effect of mupirocin dressings on postoperative surgical site infections in elective colorectal surgery: A prospective, randomized controlled trial.

BACKGROUND: Surgical site infections (SSIs) are the most common nosocomial infection among surgical patients. We hypothesized that mupirocin ointment would decrease SSI rates compared to standard surgical dressings in patients undergoing colorectal surgery. METHODS: A prospective randomized controlled trial was performed, including patients undergoing elective open and minimally invasive colorectal surgery. Patients were randomized 1:1 to receive standard gauze dressings or mupirocin ointment (2%) dressings. The primary outcome was incisional SSI at 30 days postoperative. RESULTS: A total of 192 patients were enrolled; 150 underwent randomization: 75 to the mupirocin arm, and 75 to the standard gauze dressing arm. Three SSIs occurred; one (1%) in the mupirocin group, and two (3%) in the standard gauze group (P = 0.560). There was no significant difference between standard gauze dressings and mupirocin dressings. CONCLUSION: Mupirocin (2%) ointment failed to show a benefit compared to standard dressings for postoperative SSI.

Global trends in the burden of liver cancer.

BACKGROUND: The aim of this study is to describe the influence of geography, socio-economic development, and demographic shift on the trends in global incidence, mortality, and prevalence of liver cancer (LC). METHODS: Data (2012-2030) relating to LC and demographic shifts based on WHO regions and HDI areas were extracted from GLOBOCAN 2012 and analyzed to evaluate trends in incidence, mortality, and prevalence. RESULTS: The results of our study document a rising global burden of LC with the maximum impact in the WPRO region. We did not observe a definite association between LC and higher socio-economic status with the highest burden in the MHD region. For the MHD region, we noticed age reversal in burden from the younger age group currently to the older age group in the future (2030). Another finding is the high burden and early onset of disease in some low-income countries such as Mongolia, Lao PDR, and Vietnam. CONCLUSION: The results of our study demonstrate a rising global burden of LC with some significant but uneven trends based on geography, age, and socio-economic status. This information can be used to shape policy and aid strategic targeting of resources to areas with the highest burden.

An Analysis of Future Publications, Career Choices, and Practice Characteristics of Research Presenters at an American College of Surgeons State Conference: A 15-Year Review.

OBJECTIVES: The Accreditation Council for Graduate Medical Education requires scholarly activity within general surgery residency programs. The association between in-training research presentations and postgraduation publications is unknown. We hypothesized that surgical trainee presentations at an American College of Surgeons (ACS) state chapter meeting resulted in peer-reviewed publications and future scholarly activity. DESIGN: The ACS Wisconsin state chapter meeting agendas from 2000 to 2014 were reviewed to identify all trainees who delivered podium presentations. A literature search was completed for subsequent publications. Program coordinators were queried and an electronic search was performed to determine practice location and type for each residency graduate. SETTING: Wisconsin state chapter ACS meeting. PARTICIPANTS: General surgery residents, fellows, and medical students in Wisconsin. RESULTS: There were 288 podium presentations by trainees (76% residents, 20% medical students, and 4% fellows). Presentations were clinical (79.5%) and basic science (20.5%). There were 204 unique presenters; 25% presented at subsequent meetings. Of these unique presenters, 46% published their research and 31% published additional research after residency. Among presenters who completed residency or fellowship (N = 119), 34% practiced in a university setting, and 61% practiced in a community setting; 31% practiced in Wisconsin. When comparing clinical vs basic science presenters, there was no difference in fellowship completion (37% vs 44%; p = 0.190) or practice type (38% vs 46% in a university setting; p = 0.397). Repeat presenters were more likely to pursue a fellowship vs those presenting once (76% vs 37%; p = 0.001). CONCLUSIONS: Research presentations by surgical trainees at an ACS state chapter meeting frequently led to peer-reviewed publications. Presenters were likely to pursue research opportunities after residency. Repeat presenters were more likely to pursue a fellowship. ACS Wisconsin chapter meetings provide an excellent opportunity for scholarly activity. These outcomes should encourage ACS chapters and ACS members to support trainee research.

Global epidemiological trends and variations in the burden of gallbladder cancer.

BACKGROUND: The aim of this study is to describe the trends and variations in the global burden of gallbladder cancer (GBC) with an emphasis on geographic variations and female gender. METHODS: Data (2012-2030) relating to GBC was extracted from GLOBOCAN 2012 database and analyzed. RESULTS: The results of our study document a rising global burden of GBC with geographic and gender variations. The highest burden was noted in the WPRO region (based on WHO regions), Asia (based on continents) and India, Chile, and China (based on countries). The less developed regions of the world account for the majority of the global burden of GBC. The geographic variations are also present within individual countries such as in India and Chile. Females are afflicted at a much higher rate with GBC and this predilection is exaggerated in countries with higher incidence such as India and Chile. In females, people of certain ethnic groups and lower socio-economic standing are at a higher risk. CONCLUSIONS: Our study demonstrates a rising global burden of GBC with some specific data on geographic and gender-based variations which can be used to develop strategies at the global as well as the high-risk individual country level.

Predictive global trends in the incidence and mortality of pancreatic cancer based on geographic location, socio-economic status, and demographic shift.

BACKGROUND AND OBJECTIVES: Pancreatic Cancer (PC) is a lethal malignancy that accounts for about 4% of cancer-related deaths worldwide. The aim of this study is to describe the influence of geography (based on WHO regions), socio-economic development (based on Human Development Index [HDI]) and demographic shift on the temporal trends in global incidence and mortality of PC. METHODS: Data (2012-2030) relating to the incidence, mortality of PC and demographic shifts based on WHO regions and HDI areas were extracted from GLOBOCAN 2012. Linear regression was used to evaluate trends in total incidence and mortality. RESULTS: We noted a definite association between PC and higher socio-economic status. Advanced age (age ≥65) contributed to the rising burden in all socio-economic regions of the world except in the Low Human Development (LHD) countries where the disease predominantly affected population <65 years of age. CONCLUSIONS: The global burden of PC is expected to rise significantly over the next few decades regardless of geographic location, socio-economic development, age and gender. Advance knowledge of this data can help formulate strategies to specifically target countries and populations that promote public health policy to tackle this lethal disease on the global stage. J. Surg. Oncol. 2016;114:736-742. © 2016 Wiley Periodicals, Inc.

Androgens upregulate Cdc25C protein by inhibiting its proteasomal and lysosomal degradation pathways.

Cdc25C is a cell cycle protein of the dual specificity phosphatase family essential for activating the cdk1/Cyclin B1 complex in cells entering into mitosis. Since altered cell cycle is a hallmark of human cancers, we investigated androgen regulation of Cdc25C protein in human prostate cancer (PCa) cells, including androgen-sensitive (AS) LNCaP C-33 cells and androgen-independent (AI) LNCaP C-81 as well as PC-3 cells. In the regular culture condition containing fetal bovine serum (FBS), Cdc25C protein levels were similar in these PCa cells. In a steroid-reduced condition, Cdc25C protein was greatly decreased in AS C-33 cells but not AI C-81 or PC-3 cells. In androgen-treated C-33 cells, the Cdc25C protein level was greatly elevated, following a dose- and a time-dependent manner, correlating with increased cell proliferation. This androgen effect was blocked by Casodex, an androgen receptor blocker. Nevertheless, epidermal growth factor (EGF), a growth stimulator of PCa cells, could only increase Cdc25C protein level by about 1.5-fold. Altered expression of Cdc25C in C-33 cells and PC-3 cells by cDNA and/or shRNA transfection is associated with the corresponding changes of cell growth and Cyclin B1 protein level. Actinomycin D and cycloheximide could only partially block androgen-induced Cdc25C protein level. Treatments with both proteasomal and lysosomal inhibitors resulted in elevated Cdc25C protein levels. Immunoprecipitation revealed that androgens reduced the ubiquitination of Cdc25C proteins. These results show for the first time that Cdc25C protein plays a role in regulating PCa cell growth, and androgen treatments, but not EGF, greatly increase Cdc25C protein levels in AS PCa cells, which is in part by decreasing its degradation. These results can lead to advanced PCa therapy via up-regulating the degradation pathways of Cdc25C protein.

Toll-like receptor 7 stimulates the expression of Epstein-Barr virus latent membrane protein 1.

Epstein-Barr virus (EBV) is a ubiquitous human herpesvirus. Toll-like receptor 7 (TLR7) is involved in host innate immunity against pathogens, and its aberrant activation is linked to the development of systemic lupus erythematosus (SLE, also called "lupus"). Type I interferons (IFN) are apparently driving forces for lupus pathogenesis. Previously, we found that EBV latent membrane protein 1 (LMP1) primes cells for IFN production. In this report, the relationship among EBV LMP1, TLRs, and IFN production are examined. We find that TLR7 activation increases the expression of EBV LMP1, and IFN regulatory factor 7 (IRF7) is involved in the stimulation process. TLR7 activation did not induce IFNs from EBV-infected cells, but potentiates those cells for IFN production by TLR3 or TLR9 activation. In addition, we find that LMP1 and IFNs are co-expressed in the same cells in some lupus patients. Therefore, the aberrant activation of TLR7 might induce LMP1 expression and LMP1-expression cells may be producing IFNs in lupus patients. These results suggest EBV might be an exacerbating factor in some lupus patients via promoting IFN production.

Kaposi sarcoma-associated herpesvirus degrades cellular Toll-interleukin-1 receptor domain-containing adaptor-inducing beta-interferon (TRIF).

Kaposi sarcoma-associated herpesvirus (KSHV) is a human γ-herpesvirus associated with several human malignancies. The replication and transcription activator (RTA) is necessary and sufficient for the switch from KSHV latency to lytic replication. Toll-interleukin-1 receptor (TIR) domain-containing adaptor-inducing ß-interferon (TRIF, also called TIR-domain-containing adaptor molecule-1 (TICAM-1)) is a signaling adaptor molecule that is critically involved in the Toll-like receptor 3 (TLR-3) and TLR-4 signaling pathways for type I interferon (IFN) production, a key component of innate immunity against microbial infection. In this report, we find a new mechanism by which RTA blocks innate immunity by targeting cellular TRIF. RTA specifically degrades TRIF by shortening the half-life of TRIF protein. This RTA-mediated degradation is at least partially mediated through the ubiquitin-proteasome pathway because proteasome inhibitors as well as knockdown of cellular ubiquitin expression alleviate the degradation. RTA may not directly interact with TRIF and may activate TRIF degradation indirectly through an unknown mediator(s). RTA targets multiple regions of TRIF and may use its ubiquitin ligase domain for the degradation. In addition, physiological levels of TRIF protein are down-regulated during KSHV lytic replication when RTA is expressed. Finally, RTA down-regulates double-stranded RNA-initiated activation of TLR-3 pathway, in the absence of degradation of IFN regulatory factor 7 (IRF-7). Taken together, these data suggest that KSHV employs a novel mechanism to block the innate immunity by degrading TRIF protein. This work may contribute to our understandings on how KSHV evades host immunity for its survival in vivo.