Post-mastectomy and post-breast conservation surgery pain syndrome: a review of etiologies, risk prediction, and trends in management.

Postmastectomy pain syndrome (PMPS) or breast conservation surgery (BCS) pain syndrome could be long-term and lead to disability and impairment on body and social function. The pain syndromes are not uncommon in breast cancer patients. It can affect social, psychological, physical and behavioral aspects of a patient. Surgery, radiation, chemotherapy and psychological factors can all contribute to the development of pain syndromes. Axillary dissection is a strong predictor for pain development. Pain medications, ganglion blocks are typically given to the patient for management. Integrative medicine such as acupuncture and psychological management methods are promising modalities in the management arsenal. In this study, we summarized the up-to-date literature to elucidate the etiology, risk factors and management strategies for PMPS.

Daily Tracking of Glioblastoma Resection Cavity, Cerebral Edema, and Tumor Volume with MRI-Guided Radiation Therapy.

Radiation therapy (RT) plays a critical role in the treatment of glioblastoma. Studies of brain imaging during RT for glioblastoma have demonstrated changes in the brain during RT. However, frequent or daily utilization of standalone magnetic resonance imaging (MRI) scans during RT have limited feasibility. The recent release of the tri-cobalt-60 MRI-guided RT (MR-IGRT) device (ViewRay MRIdian, Cleveland, OH) allows for daily brain MRI for the RT setup. Daily MRI of three postoperative patients undergoing RT and temozolomide for glioblastoma over a six-week course allowed for the identification of changes to the cavity, edema, and visible tumor on a daily basis. The volumes and dimensions of the resection cavities, edema, and T2-hyperintense tumor were measured. A general trend of daily decreases in cavity measurements was observed in all patients. For the one patient with edema, a trend of daily increases followed by a trend of daily decreases were observed. These results suggest that daily MRI could be used for onboard resimulation and adaptive RT for future fluctuations in the sizes of brain tumors, cavities, or cystic components. This could improve tumor targeting and reduce RT of healthy brain tissue.

Magnetic Resonance-guided External Beam Radiation and Brachytherapy for a Patient with Intact Cervical Cancer.

Radiation treatment verification has improved significantly over the past decades. The field has moved from film X-rays and skin marks to fiducial tracking and daily cone beam computed tomography (CBCT) for tumor localization. We now have the ability to perform daily on-board magnetic resonance imaging (MRI), which provides superior soft tissue contrast compared to computed tomography (CT). In the management of cervical cancer, the brachytherapy literature has demonstrated that MRI allows for better delineation of the high-risk clinical target volume (HR-CTV) and the use of MRI-guided brachytherapy has translated into improved treatment outcomes. Consensus contouring guidelines for intensity modulated radiation therapy (IMRT) for cervical cancer advise including the whole uterus in the target volume and adding large planning target volume (PTV) margins to account for inter-fractional uterine motion and target motion resulting from variable rectal and bladder filling. MRI-guided radiation therapy (MRgRT) systems enable the possibility to precisely delineate the target volume on a daily basis and to perform truly adaptive delivery. This advancement in technology provides the opportunity to explore how external beam treatment volumes could be safely reduced for better sparing of pelvic organs for the benefit of our patients with cervical cancer. We describe the MR-guided definitive external beam radiation therapy and brachytherapy for a 32-year-old woman with intact cervical cancer. We contoured the uterus, bladder, rectum, and gross tumor volume (GTV) on each of her 25 set-up MRIs. We demonstrate a steady reduction in the GTV and increased displacement of the uterus and GTV as the GTV decreased in size. The findings presented suggest that cervical cancer could greatly benefit from an adaptive MRgRT approach.

Cost analysis of adjuvant management strategies in early stage (stage I) testicular seminoma.

BACKGROUND: Acceptable post-orchiectomy adjuvant therapy strategies for stage I seminoma patients include surveillance, para-aortic radiation therapy (RT), dog-leg RT, and a single cycle of carboplatin. The required follow-up recommendations were amended by the National Comprehensive Cancer Network (NCCN) in 2012. Given a cause-specific survival of nearly 100%, a closer analysis of the reimbursement for each treatment strategy is warranted. METHODS: NCCN guidelines were used to design treatment plans for each acceptable adjuvant treatment strategy. Follow-up charges were generated for 10 years based on 2012 (version 1.2012; unchanged in current version 1.2013) and 2011 NCCN (version 2.2011) surveillance recommendations. The 2012 Medicare reimbursement rates were used to calculate each treatment strategy and incremental cost-effectiveness ratios to compare the treatment options. RESULTS: Under the current NCCN follow-up recommendations, the total reimbursements generated over 10 years of surveillance, para-aortic RT, dog-leg RT, and carboplatin were $10,643, $11,678, $9,662, and $10,405, respectively. This is compared with the reimbursements as per the 2011 NCCN recommendations: $20,986, $11,517, $9,394, and $20,365 respectively. Factoring the rates of relapse into a salvage model, observation was found to be more costly and less effective ($-1,831, $-7,318, $-7,010) in the adjuvant management of stage I seminoma patients. CONCLUSION: Based on incremental cost-effectiveness ratios, para-aortic RT, dog-leg RT, and carboplatin are cost-effective options for the treatment of stage I seminoma when compared with observation; however, surveillance could potentially spare as many as 80%-85% of men diagnosed with stage I seminoma from additional therapy after radical inguinal orchiectomy. Such cost and reimbursement analyses are becoming increasingly relevant, but are not meant to usurp sound clinical judgment. Further studies are required to validate these findings.

Sulfur metabolism actively promotes initiation of cell division in yeast.

BACKGROUND: Sulfur metabolism is required for initiation of cell division, but whether or not it can actively promote cell division remains unknown. METHODOLOGY/PRINCIPAL FINDINGS: Here we show that yeast cells with more mtDNA have an expanded reductive phase of their metabolic cycle and an increased sulfur metabolic flux. We also show that in wild type cells manipulations of sulfur metabolic flux phenocopy the enhanced growth rate of cells with more mtDNA. Furthermore, introduction of a hyperactive cystathionine-beta-synthase (CBS) allele in wild type cells accelerates initiation of DNA replication. CONCLUSIONS/SIGNIFICANCE: Our results reveal a novel connection between a key sulfur metabolic enzyme, CBS, and the cell cycle. Since the analogous hyperactive CBS allele in human CBS suppresses other disease-causing CBS mutations, our findings may be relevant for human pathology. Taken together, our results demonstrate the importance of sulfur metabolism in actively promoting initiation of cell division.