> 80%), < -1), , 0.05). 63.6% 13.7% 7.2% ( (95% CI)

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1 GANDER REVIEW Mid- to Long-term Results of Total Disc Replacement: A Prospective Analysis with 5- to 10-Year Follow-Up The Spine Journal Volume 14m Number 8 Christopher J. Siepe, Franziska Heider, Karsten Wiechert, Wolfgang Hitzl, Basem Ishak, Michael H. Mayer This prospective single center study of a single total disc replacement (TDR ProDisc II, Synthes) for refractory degenerative disc disease (DDD) with intractable low back pain (LBP, > 80%), evaluated the results of 181 of 201 patients initially operated upon, with 5 to 10 year post-operative follow-up. The authors were not potentially conflicted by any financial or commercial interests with the disc replacement reviewed. Data from this article represents the largest series of TDR patients with follow-up greater than five years. Patients were excluded with: osteopenia (T score < -1), prior discectomy and radicular pain or significant intra-canal scarring, facet disease on MRI as evidenced by facet trophism, or provocation of pain with facet or SI joint injection challenge. Patients were evaluated after the initial year on an annual basis. Visual analog scale (VAS), Oswestry Disability Index (ODI), patient satisfaction rates (three scale rating), and professional/employment activity was evaluated. Surgery was performed via an anterior retroperitoneal approach. Average follow-up was 7.4 years. Patients generally experienced significant improvements from preoperative levels for VAS and ODI scores, there was a slight but significant decline in VAS scores from 48 months onward (VAS from 2.6 to 3.3, p< 0.05). Patient satisfaction remained stable, with 63.6% of the patients reporting a highly satisfactory outcome and 13.7% reporting unsatisfactory outcomes. The incidence for revision surgery was 7.2% (13 of the 181 patients available for follow-up). Complication rates were significantly higher and statistically significant (95% CI) in two level replacement procedures (27.6%) versus single level TDR (11.9%). The authors point out that the most critical series published to date, not surprisingly, has the longest follow-up. Careful preoperative selection was deemed critical.

2 Proton Beam Therapy for Localized Prostate Cancer 101: Basics, Controversies and Facts Reviews in Urology Volume 16, Number 2, 2014 Eric S. Wisenbaugh, Paul E. Andrews, Robert G. Ferrigni, Steven E. Schild, Sameer R. Keole, William W. Wong, Sujay A. Vora Proton beam therapy (PBT) has become a source of controversy in the urologic community. It is not uncommon to hear mixed messages regarding the issue, from zealous advocates to cost-conscious skeptics, leaving many urologists unsure what to tell their patients with prostate cancer. This article examines the differences between conventional external beam radiation therapy (EBRT) and PBT, with respect to cost, safety, and effectiveness, based upon a review of published peer review literature. The most common beam used for EBRT is composed of photons or radiation. The peak dose occurs within a few centimeters from the entrance surface, and then the dose slowly attenuates as lower-energy photons are absorbed or scattered. The shallow depth of maximum dose portends that the largest dose is deposited at a superficial level. One way to compensate for the depth dose characteristics of photons is to use multiple beams that converge at the target from different directions, thus delivering the maximal dose within the target, while spreading a moderate dose bath over the surrounding normal tissues. There has been an evolution in EBRT processing from two-dimensional radiation to three-dimensional conformal radiation therapy (3DCRT), and, intensity-modulated radiation therapy (IMRT). IMRT employs computer algorithms that through dose distribution, allow better sparing of the surrounding normal organs. Protons with their heavy mass are accelerated into tissue with their maximum effect occurring at a specific depth of tissue penetration with lesser effect superficial structures and none deeper. This peak of energy delivery is commonly referred to as the Bragg peak. The Bragg peak is very narrow and must be spread out using multiple proton energies to

3 Proton Beam Therapy for Localized Prostate Cancer 101: Basics, Controversies and Facts Page 2 ensure that the peak encompasses the entire target. This spread-out Bragg peak (SOBP) is applied to the prostate to maximize the radiation damage to the cancerous organ while still delivering less radiation to surrounding tissues. There is no widely used method for confirming the proton range or that the SOBP is encompassing the prostate in vivo. The pencil beam is swept in a raster pattern back and forth across a target guided out of the nozzle by magnets. This allows the delivery of intensity-modulated proton beam therapy (IMPT). The incremental cost effectiveness ratio for PBT over IMRT was calculated to be $63,578 per quality adjusted life year (QALY) for a 70- year-old man and $55,726 per QALY for a 60-year-old man. However, adding to the uncertainty of this study is the fact that 91.8 Gy has not been used clinically. Using the commonly accepted, although arbitrary standard of $50,000 per QALY, PBT did not appear to be cost effective. Loma Linda University Medical Center (Loma Linda, CA) was the first center to open a hospital based proton facility in 1990, and reported the first large single-arm experience.13 The authors analyzed 1255 patients, 731 of whom received 3D-CRT plus a boost with PBT and 524 of whom received PBT only. Included were patients with low-, intermediate-, and high-risk prostate cancer. Using American Society for Therapeutic Radiology Oncology consensus criteria, the 5- and 8-year biochemical failure free (BCFF) survival was 75% and 73%, respectively. More importantly, there were very low rates of Radiation Therapy Oncology Group grade 3 or higher morbidity: 1% genitourinary (GU) and 0.2% GI. To put these numbers in perspective, patients treated with IMRT at a university affiliated institution might have a 6% GU and 1% GI grade 3 or higher Morbidity. In contrast to the dose escalation studies performed with 3D-CRT, this PBT dose escalation was achieved without an increase in significant late urinary or rectal morbidity. Unfortunately, there are no randomized trials completed that directly compare 3D-CRT or IMRT with PBT.

4 Endometrial Cancer: Molecular and Cellular Basis of Tumor Development, Novel Biomarkers and Therapeutic Agents, and Innovative Research Approaches Obstetrics and Gynecology International Volume 2014 Donghai Dai, Andrew P. Bradford, and Eric R. Prossnitz Carcinoma of the endometrium is the most common cancer of the female reproductive tract with over 40,000 new cases diagnosed per year and over 7,000 deaths per year in the United States alone. Although a majority of endometrial tumors present with welldifferentiated low grade endometrioid histology (Type 1), expressing high levels of estrogen and progesterone receptors (ER/PR) as well as epidermal growth factor receptor (EGFR), about one-quarter present as more advanced and aggressive tumors (Type 2), that are unlikely to be ER/PR-positive and have a much poorer prognosis. Although histology, genetic aberrations, and epidemiological profiles overlap between the two tumor types, they appear to represent distinct carcinogenic processes with distinct molecular characteristics. Whereas type 1 tumors are typically preceded by endometrial hyperplasia and are associated with a loss of PTEN expression as well as abnormalities in catenin, Kras, and DNA mismatch repair genes, type 2 tumors represent a heterogeneous group of tumors including high grade (undifferentiated) endometrioid carcinomas, uterine papillary serous carcinomas, clear cell carcinomas, and carcinosarcomas. Whereas, uterine papillary serous carcinomas are typically associated with p53 mutations and often Her-2/neu mutations, with PTEN mutations being rare, carcinosarcomas, characterized by both malignant epithelial and mesenchymal components, are associated with many of the epidemiological risk factors linked to endometrioid carcinomas including obesity and tamoxifen therapy, which suggests that dysregulated estrogen signaling may have a role in its pathogenesis and may represent a therapeutic target.

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