Anesthetic choices and breast cancer recurrence: A retrospective cohort study of risk factors

Background: The impact of anesthetic techniques for breast cancer surgery traditionally has been centered on the incidence of acute pain syndromes and complications immediately after surgery. Evaluating anesthesia management beyond short-term effects is an emerging science. Several animal studies have concluded that regional anesthesia independently reduces cancer recurrence and metastasis. A small number of retrospective clinical studies indicate that reductions in cancer recurrence are attributable to anesthesia technique; however, individual risk factors need to be taken into consideration. ^ Purpose: The aims were to: 1) investigate differences in patient, disease and treatment factors between women who received surgical treatment for breast cancer with paravertebral regional and general anesthesia compared to women who received general anesthesia alone; 2) explore patient, disease and treatment factors associated with recurrence of breast cancer; and 3) test the association between type of anesthesia and breast cancer recurrence and survival over 22–46 months following surgery. ^ Methods: This retrospective cohort study included 358 patients with stage 0-III disease who received a partial or total mastectomy without axillary node dissection between October 2006 and October 2008 at a large academic cancer center. Follow-up ended in August 2010 with a median follow-up time of 28.8 months. ^ Results: The patient demographics were equally represented across anesthesia groups. Mean BMI (kg/m2) was greater for the patients who received general anesthesia (GA) alone (29±6.8) compared to those that received paravertebral regional block (PVB) with GA (28±5.1), p=0.001. The PVB with GA group had more advanced stages of disease (p=0.01) and longer surgeries (p=0.01) than the GA only group. Breast cancer recurrence was detected in only 1.7% of the study population. The mean age was 51±18 in those who had a recurrence compared to 58±11 in the non-recurrent group (p=0.06). Overall, no association between anesthesia type and recurrence was found (p=0.53), with an unadjusted estimated hazard ratio of 1.84 (95% CI 0.34–10.08). ^ Conclusions: In contrast to previous retrospective studies in cancer patients receiving surgical and anesthesia treatment, this study was unable to detect a difference in relating type of anesthesia with decreased breast cancer recurrence. Nonetheless, a significant association between BMI and type of anesthesia was observed and should be taken into account in future studies. Because the overall rate of recurrence was very small in this population, a larger study would be needed to detect any differences in rates of recurrence attributable to type of anesthesia. ^

Pathologic Markers of Prognosis in Ampullary Carcinoma

Ampullary cancer is a rare gastrointestinal malignancy that can be curable with surgical resection of localized disease. The benefit of adjuvant therapy, however, remains unknown in these patients partly because of difficulty in stratifying which patients are at high risk for recurrence. To better identify those patients who may benefit from adjuvant therapy, I conducted a retrospective analysis the pathology reports from 176 patients with surgically resected ampullary cancer who had not received any neoadjuvant therapy, the systemic therapy given, and the patient outcomes. A tissue microarray (TMA) of 95 surgically resected ampullary specimens was also constructed to examine whether there is a correlation between classical immunohistochemical profiles for intestinal and pancreaticobiliary tumors and their histologic classification. In this study, I confirmed the prognostic value of advanced T-stage, nodal metastases, and lymphovascular invasion. Patients whose tumors had “high risk” features had a significantly worse overall survival (p=.002). Furthermore, my research highlighted the importance of histology and its impact on survival, with pancreaticobiliary-like features being a negative prognostic factor (p=0.001). Importantly, patients whose tumors have pancreaticobiliary histology appear to benefit from adjuvant therapy, further implicating histology as an important pathologic marker (p=0.053). In addition, the TMA confirmed a correlation between classical immunohistochemical profiles for intestinal and pancreaticobiliary tumors and histologic classification. My research findings suggest that histology subtypes, T-stage, nodal metastases, and lymphovascular invasion should all be taken into consideration when determining which patients with ampullary cancer may benefit from further adjuvant therapy.

Learning What Works: Demonstrating Practice Effectiveness with Children and Families Through Retrospective Investigation

Intensive family preservation services (IFPS), designed to stabilize at-risk families and avert out-of-home care, have been the focus of many randomized, experimental studies. Employing a retrospective “clinical data-mining” (CDM) methodology (Epstein, 2001), this study makes use of available information extracted from client records in one IFPS agency over the course of two years. The primary goal of this descriptive and associational study was to gain a clearer understanding of IFPS service delivery and effectiveness. Interventions provided to families are delineated and assessed for their impact on improved family functioning, their impact on the reduction of family violence, as well as placement prevention. Findings confirm the use of a wide range of services consistent with IFPS program theory. Because the study employs a quasi-experimental, retrospective use of available information, clinical outcomes described cannot be causally attributed to interventions employed as with randomized controlled trials. With regard to service outcomes, findings suggest that family education, empowerment services and advocacy are most influential in placement prevention and in ameliorating unmanageable behaviors in children as well as the incidence of family violence.

Retrospective assesment of the levonorgestrel intrauterine device to treat complex atypical hyperplasia and early endometrioid endometrial cancer

Objective: The primary objective of this project was to describe the efficacy of the Levonorgestrel Intrauterine Device (LIUD) for treatment of Complex Endometrial Cancer (CAH) and Grade 1 Endometrial Cancer (G1EEC) in terms of rate of Complete Response (CR) and Partial Response (PR) after 6 months of therapy. Finally, we assessed if any clinical or pathologic features were associated with response to the LIUD. ^ Methods: This study was a retrospective case series designed to report the response rate of patients with CAH or G1EEC treated with LIUD therapy. In addition, this study has a laboratory component to assess molecular predictors of response to LIUD therapy. Retrospective data already collected from patients diagnosed with CAH or EEC grade 1 and treated with LIUD therapy at MD Anderson Cancer Center (MDACC) were used for this study. Patients from all ethnic and race groups were included. A Complete Response (CR) was defined in patients diagnosed with CAH if pathologic report at 6 months demonstrated either no evidence of hyperplasia or no atypia in the setting of simple or complex hyperplasia. Partial Response (PR) was recorded if disease downgraded to only CAH from G1EEC. No Response (NR) was recorded if pathologic report demonstrates no change (Stable Disease, SD) or progression to cancer (Progressive Disease, PD). We calculated the proportion of patients with complete response to LIUD therapy with 95% confidence interval. We compared the response rates (CR/PR vs NR) by obesity status (Obese if BMI > 40 kg/m2 vs non-obese if BMI <= 40 kg/m2) as well as other clinical and pathologic factors, such as age, uterine size (median size), and presence of exogenous progesterone effect. ^ Results: There were 39 patients diagnosed with either CAH or G1EEC treated with the LIUD. Of 39 patients, 12 did not have pathological results of biopsy at 6months time period. Of 27 evaluable patients, 17 were diagnosed with CAH and 10 with G1EEC. Overall response rate (RR) was 78% (95% CI = 62-94%) at 6 months, 18 patients had CR (4 in G1EEC; 14 in CAH), 3 patients had PR (3 in G1EEC), 3 had SD (1 in CAH; 2 in G1EEC), 3 had PD (2 in CAH; 1 in G1EEC). After histology stratification, RR at 6 months was 82.35% (14/17; 95%CI = 67.4-97.3%) in CAH and 70% (7/10; 95% CI = 41-98.4%) in G1EEC. ^ There was no difference in response (R) and no response (NR) based on BMI (p=0.56). He observed a trend showing association between age with response (p=0.1). There was no association between uterine size and response to therapy (p=0.17). We recorded strong association between exogenous progesterone effect and response. ^ Conclusion: LIUD therapy for the treatment of CAH and G1EEC may be effective and safe. Presence of exogenous progesterone effect may predict the response to LIUD therapy at earlier time points. There is need of further studies with larger sample size to explore the relationship of response with other clinical and pathologic factors^

Impact of racial differences in medical care on breast cancer survival: Findings from a large nationwide and retrospective cohort study

Background: No studies have attempted to determine whether nodal surgery utilization, time to initiation and completion of chemotherapy or surveillance mammography impact breast cancer survival. ^ Objectives and Methods: To determine whether receipt of nodal surgery, initiation and completion of chemotherapy, and surveillance mammography impact of racial disparities in survival among breast cancer patients in SEER areas, 1992-2005. ^ Results: Adjusting for nodal surgery did not reduce racial disparities in survival. Patients who initiated chemotherapy more than three months after surgery were 1.8 times more likely to die of breast cancer (95% CI 1.3-2.5) compared to those who initiated chemotherapy less than a month after surgery, even after controlling for known confounders or controlling for race. Despite correcting for chemotherapy initiation and completion and known predictors of outcome, African American women still had worse disease specific survival than their Caucasian counterparts. We found that non-whites underwent surveillance mammography less frequently compared with whites and mammography use during a one- or two-year time interval was associated with a small reduced risk of breast-cancer-specific and all-cause mortality. Women who received a mammogram during a two-year interval could expect the same disease-specific survival benefit or overall survival benefit as women who received a mammogram during a one-year interval. We found that while adjustment for surveillance mammography receipt and physician visits reduced differences in mortality between blacks and whites, these survival disparities were eliminated after adjusting for the number of surveillance mammograms received. ^ Conclusions: The disparities in survival among African American and Hispanic women with breast cancer are not explained by nodal surgery utilization or chemotherapy initiation and chemotherapy completion. Surveillance mammograms, physician visits and number of mammograms received may play a major role in achieving equal outcomes for breast cancer-specific mortality for women diagnosed with primary breast cancer. Racial disparities in all-cause mortality were explained by racial differences in surveillance mammograms to certain degree, but were no longer significant after controlling for differences in comorbidity. Focusing on access to quality care and post treatment surveillance might help achieve national goals to eliminate racial disparities in healthcare and outcomes. ^

Retrospective analysis of Methicillin-Resistant Staphylococcus Aureus (MRSA) skin and Soft-Tissue Infections (SSTI) in a university hospital emergency department (ED)

Study Objective: Identify the most frequent risk factors of Community Acquired-MRSA (CA-MRSA) Skin and Soft-tissue Infections (SSTIs) using a case series of patients and characterize them by age, race/ethnicity, gender, abscess location, druguse and intravenous drug-user (IVDU), underlying medical conditions, homelessness, treatment resistance, sepsis, those whose last healthcare visit was within the last 12 months, and describe the susceptibility pattern from this central Texas population that have come into the University Medical Center Brackenridge (UMCB) Emergency Department (ED). ^ Methods: This study was a retrospective case-series medical record review involving a convenience sample of patients in 2007 from an urban public hospital's ED in Texas that had a SSTI that tested positive for MRSA. All positive MRSA cultures underwent susceptibility testing to determine antibiotic resistance. The demographic and clinical variables that were independently associated with MRSA were determined by univariate and multivariate analysis using logistic regression to calculate odds ratios (OR), 95% confidence intervals, and significance (p≤ 0.05). ^ Results: In 2007, there were 857 positive MRSA cultures. The demographics were: males 60% and females 40%, with the average age of 36.2 (std. dev. =13) the study population consisted of non-Hispanic white (42%), Hispanics (38%), and non-Hispanic black (18.8%). Possible risk factors addressed included using recreational drugs (not including IVDU) (27%) homelessness (13%), diabetes status (12.6%) or having an infectious disease, and IVDU (10%). The most frequent abscess location was the leg (26.6%), followed by the arm and torso (both 13.7%). Eighty-three percent of patients had one prominent susceptibility pattern that had a susceptibility rate for the following antibiotics: trimethoprim/sulfamethoxazole (TMP-SMX) and vancomycin had 100%, gentamicin 99%, clindamycin 96%, tetracycline 96%, and erythromycin 56%. ^ Conclusion: The ED is becoming an important area for disease transmission between the sterile hospital environment and the outside environment. As always, it is important to further research in the ED in an effort to better understand MRSA transmission and antibiotic resistance, as well as to keep surveillance for the introduction of new opportunistic pathogens into the population. ^

Study on the effect of metformin in patients of metastatic renal cell cancer with diabetes receiving tyrosine kinase inhibitor therapy

Objective: The primary objective of our study was to study the effect of metformin in patients of metastatic renal cell cancer (mRCC) and diabetes who are on treatment with frontline therapy of tyrosine kinase inhibitors. The effect of therapy was described in terms of overall survival and progression free survival. Comparisons were made between group of patients receiving metformin versus group of patients receiving insulin in diabetic patients of metastatic renal cancer on frontline therapy. Exploratory analyses were also done comparing non-diabetic patients of metastatic renal cell cancer receiving frontline therapy compared to diabetic patients of metastatic renal cell cancer receiving metformin therapy. ^ Methods: The study design is a retrospective case series to elaborate the response rate of frontline therapy in combination with metformin for mRCC patients with type 2 diabetes mellitus. The cohort was selected from a database, which was generated for assessing the effect of tyrosine kinase inhibitor therapy associated hypertension in metastatic renal cell cancer at MD Anderson Cancer Center. Patients who had been started on frontline therapy for metastatic renal cell carcinoma from all ethnic and racial backgrounds were selected for the study. The exclusion criteria would be of patients who took frontline therapy for less than 3 months or were lost to follow-up. Our exposure variable was treatment with metformin, which comprised of patients who took metformin for the treatment of type 2 diabetes at any time of diagnosis of metastatic renal cell carcinoma. The outcomes assessed were last available follow-up or date of death for the overall survival and date of progression of disease from their radiological reports for time to progression. The response rates were compared by covariates that are known to be strongly associated with renal cell cancer. ^ Results: For our primary analyses between the insulin and metformin group, there were 82 patients, out of which 50 took insulin therapy and 32 took metformin therapy for type 2 diabetes. For our exploratory analysis, we compared 32 diabetic patients on metformin to 146 non-diabetic patients, not on metformin. Baseline characteristics were compared among the population. The time from the start of treatment until the date of progression of renal cell cancer and date of death or last follow-up were estimated for survival analysis. ^ In our primary analyses, there was a significant difference in the time to progression of patients receiving metformin therapy vs insulin therapy, which was also seen in our exploratory analyses. The median time to progression in primary analyses was 1259 days (95% CI: 659-1832 days) in patients on metformin therapy compared to 540 days (95% CI: 350-894) in patients who were receiving insulin therapy (p=0.024). The median time to progression in exploratory analyses was 1259 days (95% CI: 659-1832 days) in patients on metformin therapy compared to 279 days (95% CI: 202-372 days) in non-diabetic group (p-value <0.0001). ^ The median overall survival was 1004 days in metformin group (95% CI: 761-1212 days) compared to 816 days (95%CI: 558-1405 days) in insulin group (p-value<0.91). For the exploratory analyses, the median overall survival was 1004 days in metformin group (95% CI: 761-1212 days) compared to 766 days (95%CI: 649-965 days) in the non-diabetic group (p-value<0.78). Metformin was observed to increase the progression free survival in both the primary and exploratory analyses (HR=0.52 in metformin Vs insulin group and HR=0.36 in metformin Vs non-diabetic group, respectively). ^ Conclusion: In laboratory studies and a few clinical studies metformin has been proven to have dual benefits in patients suffering from cancer and type 2-diabetes via its action on the mammalian target of Rapamycin pathway and effect in decreasing blood sugar by increasing the sensitivity of the insulin receptors to insulin. Several studies in breast cancer patients have documented a beneficial effect (quantified by pathological remission of cancer) of metformin use in patients taking treatment for breast cancer therapy. Combination of metformin therapy in patients taking frontline therapy for renal cell cancer may provide a significant benefit in prolonging the overall survival in patients with metastatic renal cell cancer and diabetes. ^

Indeterminate QunatiFERON-TB Gold In-Tube assay results in association with procedural specimen collection in children

BACKGROUND. The development of interferon-gamma release assays (IGRA) has introduced powerful tools in diagnosing latent tuberculosis infection (LTBI) and may play a critical role in the future of tuberculosis diagnosis. However, there have been reports of high indeterminate results in young patient populations (0-18 years). This study investigated results of the QunatiFERON-TB Gold In-Tube (QFT-GIT) IGRA in a population of children (0-18 years) at Texas Children's Hospital in association with specimen collection procedures using surrogate variables. ^ METHODS. A retrospective case-control study design was used for this investigation. Cases were defined as having QFT-GIT indeterminate results. Controls were defined as having either positive or negative results (determinates). Patients' admission status, staff performing specimen collection, and specific nurse performing specimen collection were used as surrogates to measure specimen collection procedures. ^ To minimize potential confounding, abstraction of patients' electronic medical records was performed. Abstracted data included patients' medications and evaluation at the time of QFT-GIT specimen collection in addition to their medical history. QFT-GIT related data was also abstracted. Cases and controls were characterized using chi-squared tests or Fisher's exact tests across categorical variables. Continuous variables were analyzed using one-way ANOVA and t-tests for continuous variables. A multivariate model was constructed by backward stepwise removal of statistically significant variables from univariate analysis. ^ RESULTS. Patient data was abstracted from 182 individuals aged 0-18 years from July 2010 to August 2011 at Texas Children's Hospital. 56 cases (indeterminates) and 126 controls (determinates) were enrolled. Cancer was found to be an effect modifier with subsequent stratification resulting in a cancer patient population too small to analyze (n=13). Subsequent analyses excluded these patients. ^ The exclusion of cancer patients resulted in a population of 169 patients with 49 indeterminates (28.99%) and 120 determinates (71.01%), with mean ages of 9.73 (95% CI: 8.03, 11.43) years and 11.66 (95% CI: 10.75, 12.56) years (p = 0.033), respectively. Median age of patients who were indeterminates and determinates were 12.37 and 12.87 years, respectively. Lack of data for our specific nurse surrogate (QFTNurse) resulted in its exclusion from analysis. The final model included only our remaining surrogate variables (QFTStaff and QFTInpatientOutpatient). The staff collecting surrogate (QFTStaff) was found to be modestly associated with indeterminates when nurses collected the specimen (OR = 1.54, 95% CI: 0.51, 4.64, p = 0.439) in the final model. Inpatients were found to have a strong and statistically significant association with indeterminates (OR = 11.65, 95% CI: 3.89, 34.9, p < 0.001) in the final model. ^ CONCLUSION. Inpatient status was used as a surrogate for indication of nurse drawn blood specimens. Nurses have had little to no training regarding shaking of tubes versus phlebotomists regarding QFT-GIT testing procedures. This was also measured by two other surrogates; specifically a medical note stating whether a nurse or phlebotomist collected the specimen (QFTStaff) and the name and title of the specific nurse if collection was performed by a nurse (QFTNurse). Results indicated that inpatient status was a strong and statistically significant factor for indeterminates, however, nurse collected specimens and indeterminate results had no statistically significant association in non-cancer patients. The lack of data denoting the specific nurse performing specimen collection excluded the QFTNurse surrogate in our analysis. ^ Findings suggests training of staff personnel in specimen procedures may have little effect on the number of indeterminates while inpatient status and thus possibly illness severity may be the most important factor for indeterminate results in this population. The lack of congruence between our surrogate measures may imply that our inpatient surrogate gauged illness severity rather than collection procedures as intended. ^ Despite the lack of clear findings, our analysis indicated that more than half of indeterminates were found in specimens drawn by nurses and as such staff training may be explored. Future studies may explore methods in measuring modifiable variables during pre-analytical QFT-GIT procedures that can be discerned and controlled. Identification of such measures may provide insight into ways to lowering indeterminate QFT-GIT rates in children.^