Endorectal balloons in the post prostatectomy setting: Do gains in stability lead to more predictable dosimetry?

Purpose

To perform a comparative study assessing potential benefits of endorectal-balloons (ERB) in post-prostatectomy patients.

Method and materials

Ten retrospective post-prostatectomy patients treated without ERB and ten prospective patients treated with the ERB in situ were recruited. All patients received IMRT and IGRT using kilovoltage cone-beam computed tomography (kVCBCT). kVCBCT datasets were registered to the planning dataset, recontoured and the original plan recalculated on the kVCBCTs to recreate anatomical conditions during treatment. The imaging, structure and dose data were imported into in-house software for the assessment of geometric variation and cumulative equivalent uniform dose (EUD) in the two groups.

Results

The difference in location (ΔCOV) for the bladder between planning and each CBCT was similar for each group. The range of mean ΔCOV for the rectum was 0.15–0.58 cm and 0.15–0.59 cm for the non-ERB and ERB groups. For superior-CTV and inferior-CTV the difference between planned and delivered D_95% (mean ± SD) for the non-ERB group was 2.1 ± 6.0 Gy and −0.04 ± 0.20 Gy. While for the ERB group the difference in D_95% was 8.7 ± 12.6 Gy and 0.003 ± 0.104 Gy.

Conclusions

The use of ERBs in the post-prostatectomy setting did improve geometric reproducibility of the target and surrounding normal tissues, however no improvement in dosimetric stability was observed for the margins employed.     

What is the burden of axillary disease after neoadjuvant therapy in women with locally advanced breast cancer?

Background

The burden of axillary disease in patients with locally advanced breast cancer (labc) after neoadjuvant therapy (nat) has not been extensively described in a large modern cohort. Here, we describe the extent of nodal metastases after nat in patients with labc.

Methods

All patients with labc treated at a single institution during 2002–2007 were identified. Demographic, radiologic, and pathologic variables were extracted. To assess the extent of lymph node metastases after nat, patients were separated into two groups: those with and without clinical or radiologic evidence of lymph node metastases before nat. Axillary lymph nodes retrieved at surgery that had no evidence of metastases after hematoxylin and eosin (h&e) staining underwent further pathology evaluation.

Results

Of the 116 patients identified, 115 were female (median age: 48.5). Before nat, 26 patients were clinically and radiologically node-negative; of those 26, 14 were histologically negative on final pathology. After serial sectioning and immunohistochemistry, 9 of 26 (35%) were node-negative. Of the 90 patients who had clinical or radiologic evidence of lymph node metastases before nat, 23 (26%) had no evidence of lymph node metastases on h&e staining. After serial sectioning and immunohistochemistry, 19 (21%) had no further axillary lymph node metastases. Overall, 76% of patients had pathology evidence of lymph node metastases after nat.

Conclusions

Most patients with labc have axillary metastases after nat. Our findings support axillary lymph node dissection and locoregional radiation in most patients with labc after nat.     

Analysis of disease recurrence and survival for women with uterine malignancies undergoing robotic surgery

ObjectivesTo evaluate recurrence-free survival (RFS) and overall survival (OS) for patients who underwent robotic-assisted laparoscopic hysterectomy (RALH) for uterine malignancies.MethodsMedical records from 372 patients with uterine malignancies who underwent RALH from 3/06 to 3/09 at two institutions were reviewed for clinico-pathologic data, adjuvant therapies, disease recurrence, and survival. Median follow-up for survival analysis was 31 ± 14 months. Thirty (8.1%) patients were lost to follow-up before 12 months and censored from the recurrence analysis.ResultsMean age and BMI of 372 patients was 61.8 ± 9.8 years and 32.2 ± 8.4 kg/m² (range 19–70). Robotic procedures included RALH 16 (4.3%), RALH with pelvic lymphadenectomy (PL) 96 (25.8%), and RALH with pelvic-and-aortic lymphadenectomy (PAL) 252 (67.7%) cases. Histology included 319 (85.8%) endometrioid and 53 (12.6%) high-risk histologies. Mean pelvic and aortic lymph node counts were 16.8 ± 8.7 and 8.4 ± 4.5, respectively. Lymph node metastases were identified in 26 (7.3%) cases. Adjuvant therapies were prescribed for 108 (29.1%) of patients: 7.8% brachytherapy, 1.9% pelvic radiation + brachytherapy, 7.8% chemotherapy, 11.6% chemotherapy + radiation. Risk of recurrence for all patients was 8.3% and 17 (4.6%) patients died of disease. The estimated 3-year recurrence-free survival (RFS) for the entire study group was 89.3% and the estimated 5-year overall survival (OS) was 89.1%, compared to 92.5% and 93.4% for the endometrioid sub-set.ConclusionsPatients with endometrial cancer undergoing robotic hysterectomy with staging lymphadenectomies during our 3-years of robotic experience had low-risk for recurrence and excellent disease-specific survival at a median follow-up time of 31 months.     

Improved detection suggests all Merkel cell carcinomas harbor Merkel polyomavirus

A human polyomavirus was recently discovered in Merkel cell carcinoma (MCC) specimens. The Merkel cell polyomavirus (MCPyV) genome undergoes clonal integration into the host cell chromosomes of MCC tumors and expresses small T antigen and truncated large T antigen. Previous studies have consistently reported that MCPyV can be detected in approximately 80% of all MCC tumors. We sought to increase the sensitivity of detection of MCPyV in MCC by developing antibodies capable of detecting large T antigen by immunohistochemistry. In addition, we expanded the repertoire of quantitative PCR primers specific for MCPyV to improve the detection of viral DNA in MCC. Here we report that a novel monoclonal antibody detected MCPyV large T antigen expression in 56 of 58 (97%) unique MCC tumors. PCR analysis specifically detected viral DNA in all 60 unique MCC tumors tested. We also detected inactivating point substitution mutations of TP53 in the two MCC specimens that lacked large T antigen expression and in only 1 of 56 tumors positive for large T antigen. These results indicate that MCPyV is present in MCC tumors more frequently than previously reported and that mutations in TP53 tend to occur in MCC tumors that fail to express MCPyV large T antigen.     

Chemoradiation with adjuvant hysterectomy for stage IB-2 cervical cancer: a 10-year experience

To review outcomes of patients with stage IB-2 cervical carcinoma treated with chemoradiation therapy (CRT) followed by total abdominal hysterectomy (TAH), common iliac and para-aortic lymphadenectomy (PAL). A retrospective review of patients with stage IB-2 cervical cancer treated with CRT followed by TAH/PAL from 1999 to 2009 was performed. Brachytherapy was limited to 1,500–1,800?cGy. Sixty-nine patients were identified. The mean age was 46.7?years, tumor diameter 5.4?cm, and all patients had complete clinical response to CRT. The mean follow-up was 61.7?months. There were no central pelvic relapses and two pelvic sidewall failures (97% pelvic control). The mean time to progression was 31.6?months, and 5-year disease-specific survival was 81%. Three (4.3%) patients developed symptomatic vaginal stenosis. CRT plus adjuvant hysterectomy for stage IB-2 cervical cancer resulted in excellent pelvic control and 5-year survival. Vaginal stenosis was rare.     

Combating inappropriate use of medicines

Globally, it is possible that less than half of all patients are treated in compliance with guidelines and more than half of all patients fail to take their medicines as prescribed or dispensed. Such inappropriate use is wasteful of resources and causes patient harm in terms of lack of satisfactory outcome, serious adverse events and increased antimicrobial resistance. Combating inappropriate use of medicines involves four major steps: measuring the use of medicines; identifying the determinants of inappropriate use; developing, implementing and evaluating the impact of interventions to improve the use of medicines while taking into account the factors underlying inappropriate use; and working towards an enabling policy framework that encourages appropriate use. Global evidence on how to effectively combat inappropriate use of medicines is discussed herein, with reference to the aforementioned four steps. Most interventions undertaken to combat inappropriate use of medicines have been educational in nature, have had a relatively small impact and have not taken into account the determinants of behavior. A combination of interventions, involving managerial as well as educational components, appears to be more effective than a single intervention. Less than half of countries have a policy framework that actively encourages appropriate use of medicines. Since health systems are varied and complex, a nationally coordinated package of interventions and policies, contextualized to each country, will be needed to have any substantial impact on medicine use. There is now increasing global awareness of the need to strengthen health systems, to have national coordination to combat inappropriate use of medicines and to have coordination of international aid to developing countries in order to ensure it contributes to combating inappropriate use of medicines. The opportunities this presents for combating inappropriate use of medicines are discussed in this article.     

Being a qualitative researcher

This article, from a keynote address, is the result of some of the things which I learned about qualitative research during my many years of doing and teaching it. The main point I make is that qualitative researchers should present a good story which is based on evidence but focused on meaning rather than measurement. In qualitative inquiry, the researchers' selves are involved, their experiences become a resource. Researchers cannot distance themselves from the other participants, although they cannot fully present their meaning and experience. I also discuss voice, paradigm, and innovation as potentially problematic issues in qualitative research. These are terms often used but not always examined for their meaning in qualitative inquiry. If researchers are aware and sensitive, rather than overemotional or self-absorbed, qualitative research can be enlightening, person-centered, and humanistic.     

Effect of environmental contaminants on Beta cell function

There is an increasing concern that chemicals in the environment are contributing to the global rise in the prevalence of type 2 diabetes (T2D). However, there is limited evidence for direct effects of these chemicals on beta cell function. Therefore, the goals of this study were (1) to test the hypothesis that environmental contaminants can directly affect beta cell function and (2) examine mechanistic pathways by which these contaminants could affect beta cell function. Using mouse beta TC-6 cells, we examined the acute effects of 6 substances (benzo[a]pyrene, bisphenol A [BPA], propylparaben, methylparaben, perfluorooctanoic acid, and perfluorooctyl sulfone) on insulin secretion. Only BPA treatment directly affected insulin secretion. Furthermore, chronic exposure to BPA altered the expression of key proteins in the cellular and endoplasmic reticulum stress response. These data suggest that long-term BPA exposure may be detrimental to beta cell function and ultimately be an important contributor to the etiology of T2D.