Meredith Mahan

Improved survival with HPV among African Americans with oropharyngeal cancer

Purpose: A major limitation of studies reporting a lower prevalence rate of human papilloma virus (HPV) in African American patients with oropharyngeal squamous cell cancer (OPSCC) than Caucasian Americans, with corresponding worse outcomes, was adequate representation of HPV-positive African American patients. This study examined survival outcomes in HPV-positive and HPV-negative African Americans with OPSCC. Experimental Design: The study cohort of 121 patients with primary OPSCC had 42% African Americans. Variables of interest included age, race, gender, HPV status, stage, marital status, smoking, treatment, and date of diagnosis. Results: Caucasian Americans are more likely to be HPV positive (OR = 3.28; P = 0.035), as are younger age (age < 50 OR = 7.14; P = 0.023 compared with age > 65) or being married (OR = 3.44; P = 0.016). HPV positivity and being unmarried were associated with being late stage (OR = 3.10; P = 0.047 and OR = 3.23; P = 0.038, respectively). HPV-negative patients had 2.7 times the risk of death as HPV-positive patients (P = 0.004). Overall, the HPV-race groups differed (log-rank P < 0.001), with significantly worse survival for HPV-negative African Americans versus (i) HPV-positive African Americans (HR = 3.44; P = 0.0012); (ii) HPV-positive Caucasian Americans (HR = 3.11; P = < 0.049); and (iii) HPV-negative Caucasian Americans (HR = 2.21; P = 0.049). Conclusions: HPV has a substantial impact on overall survival in African American patients with OPSCC. Among African American patients with OPSCC, HPV-positive patients had better survival than HPV negative. HPV-negative African Americans also did worse than both HPV-positive Caucasian Americans and HPV-negative Caucasian Americans. This study adds to the mounting evidence of HPV as a racially linked sexual behavior life style risk factor impacting survival outcomes for both African American and Caucasian American patients with OPSCC. Clin Cancer Res; 19(9); 2486–92. ©2013 AACR.

Continuous Bedside Pressure Mapping and Rates of Hospital-Associated Pressure Ulcers in a Medical Intensive Care Unit

BACKGROUNDnCritically ill patients are vulnerable to the development of hospital-associated pressure ulcers (HAPUs). Positioning of patients is an essential component of pressure ulcer prevention because it off-loads areas of high pressure. However, the effectiveness of such positioning is debatable. A continuous bedside pressure mapping (CBPM) device can provide real-time feedback of optimal body position though a pressure-sensing mat that displays pressure images at a patients bedside, allowing off-loading of high-pressure areas and possibly preventing HAPU formation.nnnMETHODSnA prospective controlled study was designed to determine if CBPM would reduce the number of HAPUs in patients treated in our medical intensive care unit. In 2 months, 422 patients were enrolled and assigned to beds equipped with or without a CBPM device. Patients skin was assessed daily and weekly to determine the presence and progress of HAPUs. All patients were turned every 2 hours. CBPM patients were repositioned to off-load high-pressure points during turning, according to a graphic display. The number of newly formed HAPUs was the primary outcome measured. A χ(2) test was then used to compare the occurrence of HAPUs between groups.nnnRESULTSnHAPUs developed in 2 of 213 patients in the CBPM group (0.9%; both stage II) compared with 10 of 209 in the control group (4.8%; all stage II; P = .02).nnnCONCLUSIONnSignificantly fewer HAPUs occurred in the CBPM group than the control group, indicating the effectiveness of real-time visual feedback in repositioning of patients to prevent the formation of new HAPUs.

Sentinel Lymph Node Pressure in Breast Cancer

BackgroundLeakiness of angiogenic tumor vessels results in elevated pressure in primary breast cancers and increased lymphatic flow to sentinel lymph node(s) (SLNs). We hypothesized that a similar pathophysiology in metastatic axillary SLNs would result in increased intranodal pressure (INP).MethodsSLNs were “hot” and “blue” after intramammary injection of dilute methylene blue and filtered Tc99 sulfur colloid. Intraoperative pressure was measured in SLNs by a noncoring needle and recording device in 114 breast cancer patients. Excised axillary SLNs were examined by standard pathological techniques and metastases measured, recorded, and compared with INP measurements for SLN #1 and sometimes #2.ResultsINP in 131 SLNs with no tumor (SLN #1, nxa0=xa093; SLN #2, nxa0=xa038) was 9.1xa0±xa06.2 (SD; range −2, 35) mmHg and 21.4xa0±xa015.4xa0mmHg (range 0–50) in 35 tumor-containing SLNs (SLN #1, nxa0=xa029; SLN #2, nxa0=xa06) (Pxa0=xa00.0066). Elevated INPs significantly correlated with SLN tumor metastasis sizes (Pxa0=xa00.0038; rxa0=xa00.4904). In two patients, tumor-laden SLNs with high INP were not blue or “hot” while a blue lymphatic bypassed these nodes and was traced to the next echelon tumor-free blue and “hot” nodes with low INP.ConclusionsBreast cancer metastasis in axillary SLNs was associated with significantly higher INP than in tumor-free lymph nodes. When “true” SLNs were replaced by tumor, and the INP levels were very high, lymph flow direction changed; lymphophilic particles (blue dye and radiocolloid) were redirected to the next echelon of nodes, where the pressures were much lower. Mechanical factors may increase the likelihood of metastasis to neighboring lymph nodes with lower INP.

Recurrence patterns and survival endpoints in women with stage II uterine endometrioid carcinoma: A multi-institution study

OBJECTIVEnThere is paucity of data in regard to prognostic factors and outcome of women with 2009 FIGO stage II disease. The objective of this study was to investigate prognostic factors, recurrence patterns and survival endpoints in this group of patients.nnnMETHODSnData from four academic institutions were analyzed. 130 women were identified with 2009 FIGO stage II. All patients underwent hysterectomy, oophorectomy and lymph node evaluation with or without pelvic and paraaortic lymph node dissections and peritoneal cytology. The Kaplan-Meier approach and Cox regression analysis were used to estimate recurrence-free (RFS), disease-specific (DSS) and overall survival (OS).nnnRESULTSnMedian follow-up was 44months. 120 patients (92%) underwent simple hysterectomy, 78% had lymph node dissection and 95% had peritoneal cytology examination. 99 patients (76%) received adjuvant radiation treatment (RT). 5-year RFS, DSS and OS were 77%, 90%, and 72%, respectively. On multivariate analysis of RFS, adjuvant RT, the presence of lymphovascular space invasion (LVSI) and high tumor grades were significant predictors. For DSS, LVSI and high tumor grades were significant predictors while older age and high tumor grade were the only predictors of OS.nnnCONCLUSIONSnIn this multi-institutional study, disease-specific survival for women with FIGO stage II uterine endometrioid carcinoma is excellent. High tumor grade, lymphovascular space invasion, adjuvant radiation treatment and old age are important prognostic factors. There was no significant difference in the outcome between patients who received vaginal cuff brachytherapy compared to those who received pelvic external beam radiation treatment.

Head and neck cancer in transplant recipients

The development of malignancy in organ transplant patients is a well‐known complication of long‐term immunosuppressive therapy. We sought to characterize our institutions 20‐year experience with head and neck cancer after solid organ transplantation.

Intraoperative clinical assessment and pressure measurements of sentinel lymph nodes in breast cancer.

AbstractBackgroundClinicians have long regarded firm enlarged axillary nodes as suspicious for metastasis, and this has been confirmed to represent increased pressure in sentinel lymph nodes (SLN) in vivo in breast cancer. We hypothesized that measuring intranodal pressure (INP) in the operating room would correlate with metastasis size and be more sensitive than clinical observation.nMethodsIntranodal pressure mmHg was measured in SLNs #1 and #2 (Nxa0=xa0134 and 32) in 122 patients with T1/2 cN0 and 6 controls (T0) (8 bilateral). Clinical “Level of Suspicion” (LOS) was: 0xa0=xa0benign; 1xa0=xa0slightly suspicious; 2xa0=xa0obvious metastasis. Statistical analysis was performed to compare INP, LOS, and SLN metastasis size mm.ResultsSentinel lymph nodes met size correlated with INP (rxa0=xa00.65; pxa0<xa00.001). INP was 22.0xa0±xa01.3xa0mmHg in 35 SLNs with metastases compared with 9.3xa0±xa00.7xa0mmHg in 132 without (pxa0<xa00.001). Six groups created by combining LOS 0, 1, and 2 with INP >17 or ≤17xa0mmHg showed a significant (pxa0<xa00.001) correlation with SLN histology; sensitivity and specificity for LOSxa0=xa02/INP >17xa0mmHgxa0=xa0100xa0% at predicting metastases; LOSxa0=xa00/INP ≤17xa0mmHg most often correct at predicting negative nodes (sensitivity 50xa0%, specificity 92.9xa0%, positive predictive value 55xa0%, negative predictive value 90.7xa0%). INP was better than LOS at predicting positive nodes in eight patients where INP was >17xa0mmHg. INP and LOS correlated significantly (pxa0<xa00.001).ConclusionsClinical suspicion of metastasis correlated well with INP particularly at predicting macrometastases. INP was slightly better at predicting micrometastases. Measurement of INP may be valuable adjunct when performing SLN biopsy when further axillary surgery is contemplated.

The impact of tumor grade on survival end points and patterns of recurrence of 949 patients with early-stage endometrioid carcinoma: a single institution study.

Objectives This study aimed to determine the impact of tumor grade on patterns of recurrence and survival end points in patients with endometrioid carcinoma 2009 International Federation of Gynecology and Obstetrics stages I-II. Methods We identified 949 patients who underwent hysterectomy between 1988 and 2011. Patients were divided into 3 groups based on tumor grade. Kaplan-Meier plots were generated for each group for recurrence-free survival (RFS), disease-specific survival (DSS), and overall survival (OS). Results Median follow-up was 52 months. Median age was 60 years. All patients underwent total abdominal hysterectomy and salpingo-oophorectomy. Eighty percent of patients underwent lymph node dissection, 83% had peritoneal cytology. There were 76 (8%) patients who developed tumor recurrence. Tumor recurrence rates were significantly higher in patients with grade 3 tumors compared to grade 1 (P = 0.006). Additionally, patients with grade 3 tumors developed significantly more frequent distant metastases compared to patients with grade 1 (P = 0.002). Five-year RFS for the patients with grade 1, 2, and 3 were 95%, 82%, and 68%, respectively (P = <0.001). Five-year DSS was 99%, 93%, and 79%, respectively (P = <0.001). Five-year OS was 89%, 84%, and 63%, respectively (P = <0.001). Lymphovascular space involvement and grade were significant independent predictors of RFS and DSS. For OS age, lymphovascular space involvement, grade, and body mass index were significant predictors. Conclusions International Federation of Gynecology and Obstetrics grade is a strong predictor of clinical survival end points in women with early-stage endometrioid carcinoma. The pattern of recurrence in patients with grade 3 tumors is mainly distant rather than locoregional. Further studies incorporating systemic therapy in the adjuvant settings in these patients are warranted.

Copeptin as a marker of relative arginine vasopressin deficiency after pediatric cardiac surgery

PurposeRelative arginine vasopressin (AVP) deficiency after pediatric cardiac surgery has recently been described. Copeptin, a more stable and easily measured product of pro-AVP processing, may be a means of identifying these patients. We aimed to determine if copeptin was correlated with AVP in these children and whether it can be a surrogate marker of relative AVP deficiency.MethodsPatients <6xa0years of age with basic Aristotle scores ≥7 requiring surgery with cardiopulmonary bypass were prospectively enrolled. Plasma AVP and copeptin concentrations were measured pre-cardiopulmonary bypass and 4 and 24xa0h post-cardiopulmonary bypass. Relative AVP deficiency was defined a priori based on our previous work as AVP <9.2xa0pg/ml at 4xa0h post-cardiopulmonary bypass.ResultsOf 41 children enrolled, relative AVP deficiency was present in 13 (32xa0%). AVP and copeptin concentrations were significantly lower in these 13 children at 4xa0h post-cardiopulmonary bypass as compared to the other 28 patients. A significant positive association between plasma AVP and copeptin concentrations over time was determined. Based on log-transformed analyses, a 1xa0% increase in plasma AVP led to a 0.19xa0% increase in copeptin. Further, copeptin <1.12xa0ng/ml at 4xa0h post-cardiopulmonary bypass had a sensitivity of 92xa0% and a negative predictive value of 95xa0% for relative AVP deficiency.ConclusionsPlasma AVP and copeptin are positively associated in children undergoing cardiac surgery. Copeptin may represent a useful means of identifying relative AVP deficiency in these patients.

Predictive Capacity of 3 Comorbidity Indices in Estimating Survival Endpoints in Women With Early-Stage Endometrial Carcinoma.

Objective The negative impact of comorbidity on survival in women with endometrial carcinoma (EC) is well-known. Few validated comorbidity indices are available for clinical use, such as the Charlson Comorbidity Index (CCI), the Age-Adjusted CCI (AACCI), and the Adult Comorbidity Evaluation-27 (ACE-27). The aim of the study is to determine which index best correlates with survival endpoints in women with EC. Materials and Methods We identified 1132 women with early-stage EC treated at an academic center. Three scores were calculated for each patient using CCI, AACCI, and ACE-27 at the time of hysterectomy. Univariate and multivariable modeling was used to determine predictors of survival. Results For each of the studied comorbidity indices, the highest scores were significantly correlated with poorer overall survival. The hazard ratio of death from any cause was 3.92 for AACCI, 2.25 for CCI, and 1.57 for ACE-27. All 3 indices were independent predictors of overall survival with a P value of less than 0.001 on multivariate analysis. In addition, lymphovascular space invasion, lower uterine segment involvement, and tumor grade were predictors of overall survival. Lymphovascular space invasion, grade (P < 0.001), and high AACCI score were the only significant predictors of recurrence-free survival (RFS). Lymphovascular space invasion and tumor grade were the only 2 predictors of disease-specific survival. Conclusions Although all 3 studied comorbidity indices were significant predictors of overall survival in women with early-stage EC, AACCI showed a stronger association. It should be considered for evaluating comorbidity in women with early-stage EC.

Stereotactic body radiotherapy for elderly patients with medically inoperable pancreatic cancer

Objectives: People over the age of 75 years account for approximately 40% of patients diagnosed with pancreatic cancer, many with comorbidities that may limit their treatment options. This study reports on the use of stereotactic body radiation therapy (SBRT) in this population. Materials and Methods: Twenty consecutively treated patients over the age of 75 with pathologically proven localized pancreatic cancer were included in this retrospective review. All had been evaluated by a multidisciplinary team as unable to tolerate surgery or combined chemoradiation therapy. Patient outcomes were analyzed to determine the safety and efficacy of SBRT in this elderly cohort. Results: The median age was 83.2 years (minimum 77 y, maximum 90 y). Eighteen patients were treated at time of initial diagnosis, and 2 for recurrence after surgery. Eleven (55%) of the patients had an Adult Comorbidity Evaluation-27 comorbidity index score of 3 (severe) and 6 (30%) had a score of 2 (moderate). Fourteen patients were treated with 35 Gy in 5 fractions, 5 with 30 Gy in 5 fractions, and 1 patient with 36 Gy in 3 fractions. Seven (35%) patients had common terminology criteria for adverse events (CTCAE) V4.0 toxicity grade of 1-2, and 3 patients had a CTCAE V4.0 toxicity grade of 3-4, 2 with dehydration, and 1 had episodes of gastrointestinal bleeding. Three patients recurred locally, 10 had distant metastases, 4 of whom were found on the first posttreatment scan. Median overall survival was 6.4 months (95% confidence interval, 3.5-10.8 mo). Median recurrence-free survival was 6.8 months (95% confidence interval, 1.3-23.5 mo). Two patients survived >23 months. Conclusion: SBRT for pancreatic cancer appears to be a safe and effective method for treatment of elderly patients, even in the setting of severe comorbidities.