Patients' and Clinicians' Perceptions of the Clinical Utility of Predictive Risk Models for Chemotherapy-Related Symptom Management: Qualitative Exploration Using Focus Groups and Interviews.

BACKGROUND: Interest in the application of predictive risk models (PRMs) in health care to identify people most likely to experience disease and treatment-related complications is increasing. In cancer care, these techniques are focused primarily on the prediction of survival or life-threatening toxicities (eg, febrile neutropenia). Fewer studies focus on the use of PRMs for symptoms or supportive care needs. The application of PRMs to chemotherapy-related symptoms (CRS) would enable earlier identification and initiation of prompt, personalized, and tailored interventions. While some PRMs exist for CRS, few were translated into clinical practice, and human factors associated with their use were not reported. OBJECTIVE: We aim to explore patients' and clinicians' perspectives of the utility and real-world application of PRMs to improve the management of CRS. METHODS: Focus groups (N=10) and interviews (N=5) were conducted with patients (N=28) and clinicians (N=26) across 5 European countries. Interactions were audio-recorded, transcribed verbatim, and analyzed thematically. RESULTS: Both clinicians and patients recognized the value of having individualized risk predictions for CRS and appreciated how this type of information would facilitate the provision of tailored preventative treatments or supportive care interactions. However, cautious and skeptical attitudes toward the use of PRMs in clinical care were noted by both groups, particularly in relationship to the uncertainty regarding how the information would be generated. Visualization and presentation of PRM information in a usable and useful format for both patients and clinicians was identified as a challenge to their successful implementation in clinical care. CONCLUSIONS: Findings from this study provide information on clinicians' and patients' perspectives on the clinical use of PRMs for the management of CRS. These international perspectives are important because they provide insight into the risks and benefits of using PRMs to evaluate CRS. In addition, they highlight the need to find ways to more effectively present and use this information in clinical practice. Further research that explores the best ways to incorporate this type of information while maintaining the human side of care is warranted. TRIAL REGISTRATION: ClinicalTrials.gov NCT02356081; https://clinicaltrials.gov/study/NCT02356081.

Building research capacity and culture: Exploring nurses' experience of implementing a nurse-led clinical trial.

AIM: To explore the experiences of a nursing team who implemented an international nurse-led clinical trial in practice and understand the facilitators to their involvement. BACKGROUND: The role and responsibilities of the clinical nurse are advancing to encompass research activity to help inform evidence-based practice. However, several personal and organisational challenges can inhibit nurses' capacity to implement and undertake research within clinical practice. METHODS: Three focus groups were conducted with members of a nursing team (N = 18). Thematic analysis was employed, and themes were identified and agreed upon by the research team. RESULTS: Five themes were identified: 'Previous experience of and attitudes to participation in clinical research', 'Decision-making regarding participation in the clinical trial', 'Facilitators of participation in the clinical trial', 'Challenges of research in nursing practice' and 'Future orientation towards research'. CONCLUSION: Through their experiences of implementing a nurse-led clinical trial within practice, nurses recognized a number of facilitators and challenges to their participation. The perceived relevance of the clinical trial to the nurses' practice, potential to improve patient care and appreciation of the nurse leader's expertise and understanding of their context were key motivators. Reciprocal trust with the nurse leader who was encouraging, motivating, supportive and accessible resulted in the engagement and commitment of the nursing team. IMPLICATIONS FOR NURSING MANAGEMENT: This paper offers a perspective that can inform senior nursing management teams when implementing and conducting evidence-based research amongst nursing teams and in doing so meet the needs of developing research capacity amongst clinical nurses.

Enforced fucosylation of cord blood hematopoietic cells accelerates neutrophil and platelet engraftment after transplantation.

Delayed engraftment is a major limitation of cord blood transplantation (CBT), due in part to a defect in the cord blood (CB) cells' ability to home to the bone marrow. Because this defect appears related to low levels of fucosylation of cell surface molecules that are responsible for binding to P- and E-selectins constitutively expressed by the marrow microvasculature, and thus for marrow homing, we conducted a first-in-humans clinical trial to correct this deficiency. Patients with high-risk hematologic malignancies received myeloablative therapy followed by transplantation with 2 CB units, one of which was treated ex vivo for 30 minutes with the enzyme fucosyltransferase-VI and guanosine diphosphate fucose to enhance the interaction of CD34(+) stem and early progenitor cells with microvessels. The results of enforced fucosylation for 22 patients enrolled in the trial were then compared with those for 31 historical controls who had undergone double unmanipulated CBT. The median time to neutrophil engraftment was 17 days (range, 12-34 days) compared with 26 days (range, 11-48 days) for controls (P = .0023). Platelet engraftment was also improved: median was 35 days (range, 18-100 days) compared with 45 days (range, 27-120 days) for controls (P = .0520). These findings support ex vivo fucosylation of multipotent CD34(+) CB cells as a clinically feasible means to improve engraftment efficiency in the double CBT setting. The trial is registered to www.clinicaltrials.gov as #NCT01471067.

Radiofrequency Ablation of Hepatic Tumor: Subjective Assessment of the Perilesional Vascular Network on Contrast-Enhanced Computed Tomography Before and After Ablation Can Reliably Predict the Risk of Local Recurrence.

OBJECTIVE: To determine whether simple, subjective analysis of the perilesional vascular network can predict the risk of local recurrence after radiofrequency ablation (RFA) of liver malignancies on contrast-enhanced computed tomography (CECT). METHODS: Contrast-enhanced computed tomography's 103 patients (59 men and 44 women; mean age, 63 years (range, 31-84 years) with 134 lesions who underwent RFA between 2000 and 2010 were retrospectively analyzed. The primary tumors include colorectal carcinoma (58 patients), hepatocellular carcinoma (n = 13), breast carcinoma (n = 8), neuroendocrine tumor (n = 5), and others (n = 19). Three blinded radiologists independently reviewed the CECT (a triple phase liver protocol for hypervascular tumors and a single phase for the hypovascular tumors) before and 6 weeks after RFA and subjectively estimated the width of the ablative margin on a 3-point scale (optimal, 1; suboptimal, 2; and residual tumor, 3). Local recurrence was determined on follow-up CECT. RESULTS: The consensus score was 1 in 94, 2 in 28, and 3 in 12 lesions. κ among readers was 0.75. Local recurrence occurred in 3 lesions with a score of 1 and 12 lesions with a score of 2. The consensus score was a significant univariate predictor of local recurrence. CONCLUSIONS: Subjective estimation of the width of ablative margin can reliably predict the risk of local recurrence.

Long-Term Outcomes after Treatment with Clofarabine ± Fludarabine with Once-Daily Intravenous Busulfan as Pretransplant Conditioning Therapy for Advanced Myeloid Leukemia and Myelodysplastic Syndrome.

Pretransplant conditioning regimens critically determine outcomes in the setting of allogeneic stem cell transplantation (allo-SCT). The use of nucleoside analogs such as fludarabine (Flu) in combination with i.v. busulfan (Bu) has been shown to be highly effective as a pretransplant conditioning regimen in acute myeloid leukemia (AML), chronic myeloid leukemia (CML), and myelodysplastic syndrome (MDS). Because leukemia relapse remains the leading cause of death after allo-SCT, we studied whether clofarabine (Clo), a nucleoside analog with potent antileukemia activity, can be used to complement Flu. In a preliminary report, we previously showed the safety and efficacy of Clo ± Flu with i.v. Bu in 51 patients with high-risk AML, CML, and MDS. The study has now been completed, and we present long-term follow-up data on the entire 70-patient population, which included 49 (70%), 8 (11%), and 13 (19%) patients with AML, MDS, and CML, respectively. Thirteen patients (19%) were in complete remission, and 41 patients (59%) received matched unrelated donor grafts. Engraftment was achieved in all patients. Sixty-three patients (90%) achieved complete remission. There were no deaths reported at day +30, and the 100-day nonrelapse mortality rate was 4% (n = 3). Thirty-one percent of patients (n = 22) developed grades II to IV acute graft-versus-host disease, and the median overall survival and progression-free survival times were 2.4 years and .9 years, respectively. Our results confirm the safety and overall and progression-free survival advantage of the arms with higher Clo doses and lower Flu doses, which was most prominent in the AML/MDS group.

Microcalcifications in 1657 Patients with Pure Ductal Carcinoma in Situ of the Breast: Correlation with Clinical, Histopathologic, Biologic Features, and Local Recurrence.

PURPOSE: This study was designed to determine the relationship of microcalcification morphology and distribution with clinical, histopathologic, biologic features, and local recurrence (LR) in patients with pure ductal carcinoma in situ (DCIS) of the breast. METHODS: All patients with pure DCIS who underwent preoperative mammography at our institution from 1996 through 2009 were identified. Mammographic findings were classified according to the ACR BI-RADS lexicon. Associations between mammographic findings and clinical, histopathologic, biologic characteristics, and LR were analyzed. Statistical inference used multiple logistic regression and Cox proportional hazards regression adjusted for age and confounding due to bias from nonrandomized selection of radiation therapy. RESULTS: We identified 1657 patients with microcalcifications visualized on mammography. The mean age at diagnosis was 55 years (SD, 11). The mean follow-up was 7 years (range 1-16). Ipsilateral LR was 4 % in segmentectomy (987) and 1.5 % in mastectomy (670) patients. Increased LR risk was seen in patients with dense breast tissue (p < 0.05) and larger DCIS size (p < 0.01). Radiation therapy was associated with a 2.8-fold decrease in the LR risk. Fine linear (branching) microcalcifications were associated with 5.2-fold increase in LR. Extremely dense breast tissue was associated with positive/close margins (p = 0.04) and multicentricity (p < 0.01). Younger women were more likely to have extremely dense breast tissue (p < 0.0001), multicentric disease (p < 0.0004), and undergo mastectomy (p < 0.0001). CONCLUSIONS: Dense breast tissue, large DCIS size, and fine linear (branching) microcalcifications were associated with increased LR, yet overall LR rates remained low. Extremely dense breast tissue was a risk factor for multicentricity and positive margins in DCIS.

Atypical chronic myeloid leukemia is clinically distinct from unclassifiable myelodysplastic/myeloproliferative neoplasms.

Atypical chronic myeloid leukemia (aCML) is a rare subtype of myelodysplastic/myeloproliferative neoplasm (MDS/MPN) largely defined morphologically. It is, unclear, however, whether aCML-associated features are distinctive enough to allow its separation from unclassifiable MDS/MPN (MDS/MPN-U). To study these 2 rare entities, 134 patient archives were collected from 7 large medical centers, of which 65 (49%) cases were further classified as aCML and the remaining 69 (51%) as MDS/MPN-U. Distinctively, aCML was associated with many adverse features and an inferior overall survival (12.4 vs 21.8 months, P = .004) and AML-free survival (11.2 vs 18.9 months, P = .003). The aCML defining features of leukocytosis and circulating myeloid precursors, but not dysgranulopoiesis, were independent negative predictors. Other factors, such as lactate dehydrogenase, circulating myeloblasts, platelets, and cytogenetics could further stratify MDS/MPN-U but not aCML patient risks. aCML appeared to have more mutated RAS (7/20 [35%] vs 4/29 [14%]) and less JAK2p.V617F (3/42 [7%] vs 10/52 [19%]), but was not statistically significant. Somatic CSF3R T618I (0/54) and CALR (0/30) mutations were not detected either in aCML or MDS/MPN-U. In conclusion, within MDS/MPN, the World Health Organization 2008 criteria for aCML identify a subgroup of patients with features clearly distinct from MDS/MPN-U. The MDS/MPN-U category is heterogeneous, and patient risk can be further stratified by a number of clinicopathological parameters.

Imaging Factors That Influence Surgical Margins After Preoperative 125I Radioactive Seed Localization of Breast Lesions: Comparison With Wire Localization.

OBJECTIVE: The objective of this study was to compare the potential influence of imaging variables on surgical margins after preoperative radioactive seed localization (RSL) and wire localization (WL) techniques. MATERIALS AND METHODS: A total of 565 women with 660 breast lesions underwent RSL or WL between May 16, 2012, and May 30, 2013. Patient age, lesion type (mass, calcifications, mass with associated calcifications, other), lesion size, number of seeds or wires used, surgical margin status (close positive or negative margins), and reexcision and mastectomy rates were recorded. RESULTS: Of 660 lesions, 127 (19%) underwent RSL and 533 (81%) underwent WL preoperatively. Mean lesion size was 1.8 cm in the RSL group and 1.8 cm in the WL group (p = 0.35). No difference in lesion type was identified in the RSL and WL groups (p = 0.63). RSL with a single seed was used in 105 of 127 (83%) RSLs compared with WL with a single wire in 349 of 533 (65%) WLs (p = 0.0003). The number of cases with a close positive margin was similar for RSLs (26/127, 20%) and WLs (104/533, 20%) (p = 0.81). There was no difference between the RSL group and the WL group in close positive margin status (20% each, p = 0.81), reexcision rates (20% vs 16%, respectively; p = 0.36), or mastectomy rates (6% each, p = 0.96). Lesions containing calcifications were more likely to require more than one wire (odds ratio [OR], 4.44; 95% CI, 2.8-7.0) or more than one seed (OR, 7.03; 95% CI, 1.6-30.0) when compared with masses alone (p < 0.0001). Increasing lesion size and the presence of calcifications were significant predictors of positive margins, whereas the use of more than one wire or seed was not (OR, 0.9; 95% CI, 0.5-1.5) (p = 0.75). CONCLUSION: Close positive margin, reexcision, and mastectomy rates remained similar in the WL group and RSL group. The presence of calcifications and increasing lesion size increased the odds of a close positive margin in both the WL and RSL groups, whereas the use of one versus more than one seed or wire did not.

Prognostic Implication of Lymphovascular Invasion Detected by Double Immunostaining for D2-40 and MITF1 in Primary Cutaneous Melanoma.

BACKGROUND: Lymphovascular invasion (LVI) is associated with adverse outcomes in primary cutaneous melanoma (PCM). Detection of LVI by hematoxylin and eosin staining alone is 0%-6%, but targeting lymphovascular structures increases the detection rate. OBJECTIVE: To examine the prognostic significance of LVI detected by immunostaining for D2-40 and microphthalmia-associated transcription factor 1 (MITF1) in PCM. METHODS: The authors retrospectively analyzed 120 PCM samples. We compared the LVI detection rates of immunostaining for D2-40 only (22%), double staining for D2-40 and MITF1 (38%), and hematoxylin and eosin, and examined the association of LVI with clinicopathologic variables and clinical outcomes. RESULTS: Immunolabeling with both methods significantly increased the LVI detection rate. Double staining for D2-40 and MITF1 as well as D2-40-detected LVI was significantly associated with increased Breslow thickness, number of mitoses, and sentinel lymph node (SLN) metastasis. D2-40-detected LVI was also associated with ulceration. Although the difference was not significant, double staining for D2-40 and MITF1 allowed for easier detection of LVI than D2-40 alone. LIMITATIONS: This study was conducted in a tertiary referral institution; therefore, a referral bias cannot be excluded. CONCLUSIONS: Immunolabeling increased detection of LVI in PCM. Because LVI is a positive predictive marker for SLN metastasis, the authors propose using anti-D2-40 and anti-MITF1 in the evaluation of LVI in patients with PCM with a certain risk of SLN metastasis.

(18)F-FDG Uptake at the Surgical Margin after Hepatic Resection: Patterns of Uptake and Differential Diagnosis.

OBJECTIVE: To evaluate the patterns of (18)F-FDG uptake at the surgical margin after hepatectomy to identify features that may differentiate benign and malignant uptake. METHODS: Patients who had undergone a PET/CT after hepatectomy were identified. Delay between resection and PET/CT, presence of uptake at the surgical margin, pattern of uptake, and maximal standardized value were recorded. The PET/CT findings were correlated with contrast-enhanced CT or MRI. RESULTS: There were 26 patients with increased 18F-FDG uptake; uptake was diffuse in seven and focal in 19. Diffuse uptake was due to inflammation in all cases. Focal uptake was due to recurrence in 12 and inflammation in seven cases. Defining a focal pattern only as a positive for malignancy yielded 100 % sensitivity, 87 % specificity, 37 % false positive rate. As expected, SUVmax was significantly higher for recurrence than inflammation, but did overlap. Contrast-enhanced CT allowed differentiation between malignant and benign uptake in all cases. CONCLUSION: F-FDG uptake after hepatectomy does not equate to recurrence and yields a high false positive rate. Diffuse uptake did not require additional evaluation in our sample. Focal uptake, however, may be due to recurrence; differentiating benign and malignant nodular uptake relies on optimal contrast-enhanced CT or MRI. KEY POINTS: • Marginal uptake exposes patients to the risk of false positive diagnosis of recurrence. • Benign and malignant patterns of marginal uptake overlap. • Diffuse marginal uptake in our experience, has a high chance to be inflammatory. • Focal marginal uptake can be due to recurrent tumour or inflammation. • Contrast-enhanced CT or MR allows the differentiation between benign and malignant uptake.

Correlation between sonographic findings and clinicopathologic and biologic features of pure ductal carcinoma in situ in 691 patients.

OBJECTIVE: The objective of our study was to compare the sonographic features of pure ductal carcinoma in situ (DCIS) lesions with the initial clinical presentation and histopathologic findings. MATERIALS AND METHODS: The images and records of 691 patients with pure DCIS who underwent preoperative mammography and whole-breast sonography as part of staging workup in a single institution from January 1, 1996, through July 31, 2009, were reviewed. The BI-RADS sonography lexicon was used when reviewing the sonographic studies. Histopathologic features recorded included estrogen receptor (ER) status, nuclear grade, and presence or absence of comedonecrosis. Statistical comparisons were made using the Student t test, chi-square test, Fisher exact test, Kruskal-Wallis or Wilcoxon rank sum test, multiple logistic regression analysis, and Pearson correlation coefficient. RESULTS: A total of 304 (44%) tumors were visible on mammography and sonography; 315 (46%), on mammography only; 58 (8%), on sonography only; and 14 (2%), on neither mammography nor sonography. The most common sonographic appearance of DCIS was an irregular hypoechoic mass with indistinct margins and normal posterior features that was indistinguishable from invasive carcinoma. Patients with symptomatic high-nuclear-grade DCIS, dense breasts, and comedonecrosis were younger and had larger tumors on sonography than asymptomatic women with nondense breasts and low-nuclear-grade and noncomedo DCIS. Women with ER-negative DCIS were older and had larger tumors on sonography than women with ER-positive DCIS. ER-negative tumors were more frequently visible on sonography than ER-positive tumors (p=0.007). High-grade DCIS (p<0.0001) and comedo DCIS (p<0.0001) presented more frequently as microcalcifications, architectural distortion, and ductal changes on sonography than low-grade DCIS or noncomedo DCIS. CONCLUSION: Of the 691 pure DCIS lesions, 362 (52%) were visible on sonography and presented most commonly as a mass. Lesion visibility of DCIS on sonography was not related to nuclear grade or the presence of comedonecrosis.

Quantitative and Qualitative Comparison of Single-Source Dual-Energy Computed Tomography and 120-kVp Computed Tomography for the Assessment of Pancreatic Ductal Adenocarcinoma.

PURPOSE: The aim of this study was to compare contrast-to-noise ratio (CNR) and signal-to-noise ratio (SNR) between pancreatic-phase dual-energy computed tomography (DECT) and 120-kVp CT for pancreatic ductal adenocarcinoma (PDA). MATERIALS AND METHODS: Seventy-eight patients underwent multiphasic pancreatic imaging protocols for PDA (40, DECT; 38, 120-kVp CT [control]). Using pancreatic phase, CNR and SNR for PDA were obtained for DECT at monochromatic energies 50 through 80 keV, iodine material density images, and 120-kVp images. Using a 5-point scale (1, excellent; 5, markedly limited), images were qualitatively assessed by 2 radiologists in consensus for PDA detection, extension, vascular involvement, and noise. Wilcoxon signed rank and 2-sample tests were used to compare the qualitative measures, CNR and SNR, for DECT and 120-kVp images. Bonferroni correction was applied. RESULTS: Iodine material density image had significantly higher CNR and SNR for PDA than any monochromatic energy images (P < 0.0001) and the 120-kVp images. Qualitatively, 70-keV images were rated highest in the categories of tumor extension and vascular invasion and were similar to 120-kVp images. CONCLUSIONS: Our results indicate that DECT improves PDA lesion conspicuity compared with routine 120-kVp CT, which may allow for better detection of PDA.

Analysis of free-form radiology dictations for completeness and clarity for pancreatic cancer staging.

PURPOSE: To assess the completeness and clarity of current free-form radiology reports for pancreatic cancer staging by evaluating them against the elements of the RSNA CT oncology primary pancreas mass dictation template. METHODS: This retrospective study was approved by our Institutional Review Board (IRB). 295 free-form computed tomography (CT) reports for baseline staging of pancreatic cancer (PC) generated between August 2008 and December 2010 were evaluated by one of two radiologists with expertise in pancreatic cancer imaging. Reports which indicated that metastatic disease was present were excluded. The completeness and clarity of the reports were analyzed against the elements of the RSNA CT pancreas mass dictation template. Fisher's exact tests were used to analyze differences by year and type of radiologist. RESULTS: Primary lesion location, size, and effect on bile duct (BD) were provided in 93.9% (277/295), 69.8% (206/295), and 67.5% (199/295) of reports, respectively. Standard terms to describe vascular involvement were used in 47.5% (140/295) of reports. In 20.3% (60/295), the resectability status could not be defined based on the report alone. In 36.9% (109/295) of reports, review of CT images was necessary to understand vascular involvement. Radiologists expert in pancreatic oncology had a higher proportion of reports using standardized terminology and reports in which vascular involvement was understood without revisiting the images. CONCLUSIONS: Free-form reports were more likely to use ambiguous terminology and/or require review of the actual images for understanding resectability status. The use of a standardized reporting template may improve the usefulness of pancreatic cancer staging reports.

Multidetector CT detection of peritoneal metastases: evaluation of sensitivity between standard 2.5 mm axial imaging and maximum-intensity-projection (MIP) reconstructions.

OBJECTIVE: Our purpose was to evaluate the sensitivity of multidetector CT for the detection of peritoneal metastases between standard 2.5 mm axial imaging and maximum-intensity-projection (MIP) reconstructions. MATERIALS AND METHODS: The Institutional Review Board approved this retrospective study and waived the need to obtain patient consent. We retrospectively identified 36 patients with pancreatic adenocarcinoma and peritoneal metastatic disease who underwent a pancreatic protocol CT examination of the abdomen and pelvis between January 2012 and January 2014. Three independent radiologists reviewed a randomized combination of standard axial (2.5 mm reconstructed thickness, 2.5 mm interval) and axial MIP reconstructions (6, 3 mm interval) over two sessions. Each reader recorded metastasis location in PACS. Subsequent consensus review by two radiologists determined the final number and size of metastases. RESULTS: The reviewers found 328 peritoneal implants in 36 patients. After accounting for the size, location, and number of lesions as well as multiple readers, a generalized estimating equations model showed that the statistical combination of MIP with standard technique significantly increased the odds of correctly identifying a lesion (OR 2.16; 95% CI 1.86-2.51; p value < 0.0001) compared to standard technique alone. MIP reconstruction as a standalone technique was less sensitive compared to standard technique alone (OR 0.81; 95% CI 0.65-0.99; p value = 0.0468). When compared to standard axial imaging, evaluation via MIP reconstructions resulted in the identification of an additional 50 (15%), 45 (14%), and 55 (17%) lesions by Readers 1-3, respectively. CONCLUSION: The axial 6 mm MIP series is complimentary in the CT evaluation of peritoneal metastases. MIP reconstruction evaluation identified a significant number of additional lesions, but is not adequate as a standalone technique for peritoneal cavity assessment.

Impact of initial PET/CT staging in terms of clinical stage, management plan, and prognosis in 592 patients with non-small-cell lung cancer.

PURPOSE: Our objective was to determine the impact of initial (18)F-FDG PET/CT (PET/CT) staging on clinical stage and the management plan and the prognostic value of PET/CT in patients with non-small-cell lung cancer (NSCLC). METHODS: We retrospectively reviewed the records of 592 patients with NSCLC who were referred to The University of Texas MD Anderson Cancer Center during 2002/2011 and had both PET/CT and conventional CT for initial staging. Clinical stages and management plans were compared between PET/CT and CT. The impact of PET/CT on management plans was considered medium/high when PET/CT changed the planned treatment modality or treatment intent. PET/CT and CT stages were compared with all-cause mortality and survival rates. We also assessed potential prognostic factors for progression-free survival (PFS) and overall survival (OS). RESULTS: PET/CT changed the stage in 170 patients (28.7 %; 16.4 % upstaged, 12.3 % downstaged). PET/CT had a medium/high impact on the management plan in 220 patients (37.2 %). PFS and OS were significantly worse in patients with upstaged disease than in patients with no change in stage (median PFS 29.0 vs. 53.8 months, P < 0.001; median OS:64.7 vs. 115.9 months, P = 0.006). PFS and OS were significantly worse in patients with medium/high impact of PET/CT than in patients with no/low impact of PET/CT (median PFS 24.7 vs. 60.6 months, P < 0.001; median OS 64.7 vs. 115.9 months, P < 0.001). In multivariate analysis, a medium/high impact of PET/CT was an independent predictor of worse PFS (hazard ratio, HR, 1.73; 95 % CI 1.30 - 2.29; P = 0.0002) and OS (HR 1.84; 95 % CI 1.26 - 2.69; P = 0.002). CONCLUSION: Initial PET/CT staging not only impacts stage and management plan but also has prognostic value.

Stage IIIC ovarian/peritoneal serous carcinoma: a heterogeneous group of patients with different prognoses.

Primary ovarian serous carcinoma patients presenting with regional lymph node metastasis without extrapelvic peritoneal metastasis are considered International Federation of Gynecology and Obstetrics (FIGO) Stage IIIC. We studied their controversial survival compared with patients with extrapelvic peritoneal metastasis in same Stage IIIC. We included primary peritoneal carcinoma patients with lymph node metastasis to investigate whether primary site of tumor has a prognostic role. Charts of patients treated at the MD Anderson Cancer Center in Houston, TX; from 1992 to 2010 were reviewed. Primary ovarian serous carcinoma patients were grouped into patients with lymph node metastasis without extrapelvic involvement (Group 1, n=13) and patients with additional extrapelvic peritoneal involvement (Group 2, n=43). Group 3 patients (n=38) were selected using similar criteria as Group 2 but with negative lymph nodes. Group 4 patients were those with primary peritoneal serous carcinoma with lymph node metastasis (n=13). Group 1 patients had statistically significant better overall survival compared with the rest of the groups. Overall survival was significantly better in Groups 4 versus 2 and Groups 3 versus 2. Primary ovarian serous carcinoma patients with lymph node metastasis without extrapelvic peritoneal involvement have better survival than those with additional extrapelvic peritoneal involvement. Primary peritoneal serous carcinoma patients with lymph node metastasis have better survival than those with primary ovarian serous carcinoma with peritoneal and lymph node metastasis. Ovarian serous carcinoma patients with extrapelvic peritoneal involvement alone have better survival than those with extrapelvic peritoneal involvement and lymph node metastasis. These findings support the proposition to revise the FIGO staging system, especially for Stage IIIC patients, in order to reflect these prognostic differences.

Strain elastography of abnormal axillary nodes in breast cancer patients does not improve diagnostic accuracy compared with conventional ultrasound alone.

OBJECTIVE: The purpose of this study was to determine the diagnostic value of strain elastography (SE) alone and in combination with gray-scale ultrasound in the diagnosis of benign versus metastatic disease for abnormal axillary lymph nodes in breast cancer patients. SUBJECTS AND METHODS: Patients with breast cancer and axillary lymph nodes suspicious for metastatic disease on conventional ultrasound who underwent SE of the suspicious node before ultrasound-guided fine-needle aspiration biopsy (FNAB) were included in this study. On conventional ultrasound, the long- and short-axis diameters, long-axis-to-short-axis ratio, cortical echogenicity, thickness, and evenness were documented. The nodal vascularity was assessed on power Doppler imaging. Elastograms were evaluated for the percentage of black (hard) areas in the lymph node, and the SE-ultrasound size ratio was calculated. Two readers assessed the images independently and then in consensus in cases of disagreement. ROC AUCs were calculated for conventional ultrasound, SE, and both methods combined. Interreader reliability was assessed using kappa statistics. RESULTS: A total of 101 patients with 104 nodes were examined; 35 nodes were benign, and 69 had metastases. SE alone showed a significantly lower AUC (62%) than did conventional ultrasound (92%) (p<0.001). There was no difference between the AUC of conventional ultrasound and the AUC of the combination of conventional ultrasound and SE (93%) (p=0.16). Interreader reliability was moderate for all variables (κ≥0.60) except the SE-ultrasound size ratio (κ=0.35). CONCLUSION: Added SE does not improve the diagnostic ability of conventional ultrasound when evaluating abnormal axillary lymph nodes.

Speciation and reactivity of uranium products formed during in situ bioremediation in a shallow alluvial aquifer.

In this study, we report the results of in situ U(VI) bioreduction experiments at the Integrated Field Research Challenge site in Rifle, Colorado, USA. Columns filled with sediments were deployed into a groundwater well at the site and, after a period of conditioning with groundwater, were amended with a mixture of groundwater, soluble U(VI), and acetate to stimulate the growth of indigenous microorganisms. Individual reactors were collected as various redox regimes in the column sediments were achieved: (i) during iron reduction, (ii) just after the onset of sulfate reduction, and (iii) later into sulfate reduction. The speciation of U retained in the sediments was studied using X-ray absorption spectroscopy, electron microscopy, and chemical extractions. Circa 90% of the total uranium was reduced to U(IV) in each reactor. Noncrystalline U(IV) comprised about two-thirds of the U(IV) pool, across large changes in microbial community structure, redox regime, total uranium accumulation, and reaction time. A significant body of recent research has demonstrated that noncrystalline U(IV) species are more suceptible to remobilization and reoxidation than crystalline U(IV) phases such as uraninite. Our results highlight the importance of considering noncrystalline U(IV) formation across a wide range of aquifer parameters when designing in situ remediation plans.

Detection of mitotic figures and G2+ tumor nuclei with histone markers correlates with worse overall survival in patients with Merkel cell carcinoma.

BACKGROUND: High mitotic figure count (MFC) correlates with low survival rate in Merkel cell carcinoma (MCC). However, the prognostic impact of histone biomarkers as surrogates of MFC in MCC is unknown. We evaluated the prognostic significance of the immunodetection of mitotic figures and of G2+ tumor nuclei with histone-associated mitotic markers H3K79me3T80ph (H3KT) and phosphohistone H3 (PHH3) in MCC. METHODS: Immunohistochemical analyses of H3KT and PHH3 and proliferative marker Ki-67 were performed in a series of 21 cases of MCC. The significance of the pathologic data and immunoreactivity with these markers was evaluated with Pearson correlation and paired Student t-test. Univariate Cox proportional hazards regression models were performed to assess the relationships between these markers and survival. RESULTS: H3KT detected a higher number of mitotic figure (p<0.0001) and G2+ tumor nuclei (p<0.0052) than did PHH3. Furthermore, the MFC combined with G2+ tumor nuclei detected with H3KT compared to PHH3 and manual MFC was a significant predictor of impaired survival in patients with MCC (p=0.035; HR=1.0172), corresponding to a 1.72% increased risk of death for each unit increase in H3KT. CONCLUSIONS: Biomarker analysis of proliferative rates with histone markers may have relevance in stratifying risk in patients with MCC.

Immunohistochemical expression of hormone receptors in melanoma of pregnant women, nonpregnant women, and men.

The survival advantage of women over men with cutaneous melanoma and the reports of accelerated progression of melanoma during pregnancy have led to studies of the effect of hormones and hormone receptors on the development and progression of melanoma. However, the results are inconclusive. We therefore evaluated the expression of estrogen receptor α, estrogen receptor ß, and androgen receptor in melanomas of stage- and age-matched pregnant women, nonpregnant women, and men by immunohistochemical analysis of formalin-fixed, paraffin-embedded archival tissues. In addition, we also assessed the mitotic rate using the antiphosphohistone H3 antibody by immunohistochemistry. Our data showed a trend of more frequent expression of estrogen receptor ß in the melanomas of pregnant patients than in the melanomas of male patients, without a significant difference observed between pregnant and nonpregnant women. However, no association between the expression of estrogen receptor ß and survival was observed. The small cohort may have limited the statistical power of the study, and large-scale studies are needed to elucidate the potential role of estrogen receptor ß as a prognostic marker of melanoma.