Vinod E. Nambudiri

Understanding Variation in Primary Prostate Cancer Treatment Within the Veterans Health Administration

OBJECTIVE To examine the variation in prostate cancer treatment in the Veterans Health Administration (VHA)--a national, integrated delivery system. We also compared the care for older men in the VHA with that in fee-for-service Medicare. METHODS We used data from the Veterans Affairs Central Cancer Registry linked with administrative data and Surveillance, Epidemiology, and End Results-Medicare data to identify men with local or regional prostate cancer diagnosed during 2001 to 2004. We used multinomial logistic and hierarchical regression models to examine the patient, tumor, and facility characteristics associated with treatment in the VHA and, among older patients, used propensity score methods to compare primary therapy between the VHA and fee-for-service Medicare. RESULTS The rates of radical prostatectomy and radiotherapy varied substantially across VHA facilities. Among the VHA patients, older age, black race/ethnicity, and greater comorbidity were associated with receiving neither radical prostatectomy nor radiotherapy. Facilities with more black patients with prostate cancer had lower rates of radical prostatectomy, and those with less availability of external beam radiotherapy had lower radiotherapy rates. The adjusted rates of radiotherapy (39.7% vs 52.0%) and radical prostatectomy (12.1% vs 15.8%) were lower and the rates of receiving neither treatment greater (48.2% vs 32.2%) in the VHA versus fee-for-service Medicare (P < .001). CONCLUSIONS In the VHA, the treatment rates varied substantially across facilities, and black men received less aggressive prostate cancer treatment than white men, suggesting factors other than patient preferences influence the treatment decisions. Also, primary prostate cancer therapy for older men is less aggressive in the VHA than in fee-for-service Medicare.

Nonmelanoma skin cancer in childhood after hematopoietic stem cell transplant: a report of 4 cases.

Although it is known that hematopoietic stem cell transplantation (HSCT) survivors are at risk of nonmelanoma skin cancer (NMSC), there is limited literature on the incidence of NMSC during childhood in this population. We present 4 HSCT patients ages 13 to 20 years diagnosed with NMSC in our clinic over a 1-year period. Each patient had multiple risk factors associated with NMSC including chronic graft-versus-host disease, prolonged immunosuppression, total-body irradiation, and voriconazole therapy. We conclude that the incidence of NMSC in children after HSCT may be underestimated and should be further investigated. Appropriate skin cancer screening, including annual skin examinations, are advised for pediatric patients with identifiable risk factors.

Clinicopathologic lessons in distinguishing cicatricial alopecia: 7 Cases of lichen planopilaris misdiagnosed as discoid lupus

the cause of the skin disease. In our patient, skin manifestations of mid-dermal elastolysis appeared at the same time of the immune restoration after HAART, thus suggesting that they may be etiologically related. Indeed, our case fulfills diagnostic criteria of IRIS, namely: temporal association between initiation of HAART and development of symptoms, evidence of immune restoration with virologic and immunologic response, and clinical symptoms consistent with an inflammatory process. The subsequent occurrence of Crohn’s disease may support the intriguing hypothesis of a multiorgan autoimmune IRIS phenomenon. In fact, IRIS-induced tissue inflammation may result in an increase in local inflammatory cytokines and recognition of viral and/or self-antigens by the infiltrating T cells. The inflammatory environment induced by IRIS and the loss of immune self-tolerance to tissue-associated antigens may lead to increased susceptibility to develop local and/or systemic pathological autoimmune conditions. This mechanism could support the hypothesis that mid-dermal elastolysis is an autoimmune process against elastic fibers.

Teledermatology Perception Differences Between Urban Primary Care Physicians and Dermatologists

Teledermatology Perception Differences Between Urban Primary Care Physicians and Dermatologists The implementation of the Patient Protection and Affordable Care Act has renewed interest in the appropriate use and delivery of specialty services.1 Teledermatology has been touted as a potential solution to improve access, particularly in the context of the impending dermatology workforce shortage.2 While studies have demonstrated that teledermatology may reduce disparities, enhance access in geographically isolated populations, and improve efficiency in integrated health systems, evidence for its use in urban underserved populations is limited.3 Urban underserved communities have a high prevalence of chronic dermatologic conditions yet have limited access to dermatologists secondary to insurance scarcity.4 Often, urban underserved patients are seen by academic medical center dermatologists and face lengthy wait times and access challenges.5 While teledermatology implementation has been studied in various settings, no studies, to our knowledge, have provided a description of the practical needs of primary care physicians (PCPs) in independent community health centers (CHCs) that serve urban underserved patients and of academic dermatologists in such communities. We evaluated perceived access to dermatologic care reported by urban CHC PCPs. Furthermore, we assessed PCPs’ and academic dermatologists’ receptiveness to incorporating teledermatology into their clinical practice to enhance dermatology access for urban underserved populations.

Update on the Diagnosis and Treatment of Cholangiocarcinoma.

Purpose of ReviewCholangiocarcinoma is a rare biliary adenocarcinoma associated with poor outcomes. Cholangiocarcinoma is subdivided into extrahepatic and intrahepatic variants. Intrahepatic cholangiocarcinoma is then further differentiated into (1) peripheral mass-forming tumors and (2) central periductal infiltrating tumors. We aimed to review the currently known risk factors, diagnostic tools, and treatment options, as well as highlight the need for further clinical trials and research to improve overall survival rates.Recent FindingsCholangiocarcinoma has seen significant increase in incidence rates over the last several decades. Most patients do not carry the documented risk factors, which include infections and inflammatory conditions, but cholangiocarcinoma typically forms in the setting of cholestasis and chronic inflammation. Management strategies include multispecialty treatments, with consideration of surgical resection, systemic chemotherapy, and targeted radiation therapy. Surgically resectable disease is the only curable treatment option, which may involve liver transplantation in certain selected cases. Referrals to centers of excellence, along with enrollment in novel clinical trials are recommended for patients with unresectable or recurrent disease.SummaryThis article provides an overview of cholangiocarcinoma and discusses the current diagnosis and treatment options. While incidence is increasing and more risk factors are being discovered, much more work remains to improve outcomes of this ominous disease.

Changes in Sex and Ethnic Diversity in Dermatology Residents Over Multiple Decades

Changes in Sex and Ethnic Diversity in Dermatology Residents Over Multiple Decades Increased ethnic diversity of physicians is associated with increased access to health care for underserved communities, better anticipation of patient needs, and acceleration of medical research.1 Similarly, sex concordance between physicians and patients can improve communication and patient satisfaction.2 Although sex and ethnic diversity of US physicians have both increased over the past several decades, not all clinical specialties have been impacted equally. To better characterize the dermatology field’s evolution during this time period, we analyzed sex and ethnicity trends among dermatology residents and compared them with other specialties and medical school graduates over multiple decades.

Milia en plaque of the Nose: Report of a Case and Successful Treatment With Topical Tretinoin

Milia are benign, superficial keratinaceous cysts that present as fine, small white papules. Milia en plaque is a rare, challenging-to-treat variant most often seen in the posterior auricular region. A total of 9 cases of milia en plaque have been reported in the pediatric literature to date. We report a case of milia en plaque of the nose in a 7-year-old boy, a novel site of involvement in the pediatric population, and successful treatment with the use of topical tretinoin. Topical retinoids offer an effective treatment option for the management of milia en plaque in the pediatric population.

Vitamin D deficiency is associated with a worse prognosis in metastatic melanoma

Vitamin D deficiency (≤20 ng/mL) is associated with an increased incidence and worse prognosis of various types of cancer including melanoma. A retrospective, single-center study of individuals diagnosed with melanoma from January 2007 through June 2013 who had a vitamin D (25(OH)D3) level measured within one year of diagnosis was performed to determine whether vitamin D deficiency and repletion are associated with melanoma outcome. A total of 409 individuals diagnosed with histopathology-confirmed melanoma who had an ever measured serum 25(OH)D3 level were identified. 252 individuals with a 25(OH)D3 level recorded within one year after diagnosis were included in the study and the individual and melanoma characteristics such as age, sex, Breslow thickness, ulceration, stage, mitotic rate, and LDH were obtained from the medical record. A worse melanoma prognosis was associated with vitamin D deficiency (P=0.012), higher stage (P<0.001), ulceration (P=0.001), and higher mitotic rate (P=0.001) (HR 1.93, 95% CI 1.15-3.22). In patients with stage IV metastatic melanoma, vitamin D deficiency was associated with significantly worse melanoma-specific mortality (adjusted HR 2.06, 95% CI 1.10-3.87). Patients with metastatic melanoma who were initially vitamin D deficient and subsequently had a decrease or ≤20 ng/mL increase in their 25(OH)D3 concentration had significantly worse outcomes (HR 4.68, 95% CI 1.05-20.88) compared to non-deficient patients who had a >20 ng/mL increase. Our results suggest that initial vitamin D deficiency and insufficient repletion is associated with a worse prognosis in patients with metastatic melanoma.

More Than Skin Deep—The Costs of Antibiotic Overuse: A Teachable Moment

4. Wells AW, Llewelyn CA, Casbard A, et al. The EASTR Study: indications for transfusion and estimates of transfusion recipient numbers in hospitals supplied by the National Blood Service. Transfus Med. 2009;19(6):315-328. 5. Youssef WI, Salazar F, Dasarathy S, Beddow T, Mullen KD. Role of fresh frozen plasma infusion in correction of coagulopathy of chronic liver disease: a dual phase study. Am J Gastroenterol. 2003;98 (6):1391-1394.

Small Interfering RNA

BacKGrOund: prOcesses OF rna inTerFerence Initially postulated by Francis Crick, the central dogma of molecular biology outlines the flow of genetic information through transcription of double-stranded DNA into singlestranded messenger RNA (mRNA), followed by translation into proteins, yielding the building blocks of life. The processes of transcription and translation are regulated by numerous molecular pathways, resulting in complex and sophisticated modifications to this linear process from gene to protein. However, in the late 1990s, researchers demonstrated the ability of certain RNA molecules to reduce the expression of particular genes through a process now collectively termed RNA interference (RNAi) (Fire et al., 1998). Since its initial discovery in the laboratory worm Caenorhabditis elegans, small interfering RNA (siRNA) has been used to impact gene expression in research laboratories around the world as an extraordinarily powerful genetic tool in biology and medicine for the elucidation of molecular pathways in organismal development and human disease. RNAi takes advantage of the fundamental principle of complementary base pairing between nucleic acids, such as in DNA–DNA and RNA–DNA double helices. In principle, RNAi is a natural process within cells, wherein double-stranded microRNA transcripts are expressed and participate in gene regulation. In addition, experimental cellular manipulation of double-stranded RNA serving as siRNAs of 20 to 30 base pairs in length (Meister and Tuschl, 2004) can be designed according to the complementarity principle to specifically target a particular gene’s mRNA transcript. Following the same mechanism as microRNA-mediated silencing, the experimentally introduced double-stranded RNAs are processed by a member of the Dicer enzyme family of RNA endonucleases, which trim the double-stranded RNAs into fragments of 21 to 23 base pairs in length. These double-stranded RNAs are then unwound into two short, single-stranded siRNAs (the leading and the lagging strands). The lagging strand is degraded intracellularly, whereas the leading strand binds the multicomponent protein complex termed the RNA-induced silencing complex (RISC) in the cellular cytoplasm. When the RNAi-loaded RISC complex comes into contact with the complementary target gene mRNA transcript, base pairing occurs. This base pairing activates the cleavage mechanism of the RISC complex and is catalyzed by a member of the Argonaute protein family. The target mRNA transcript is cleaved, rendering it untranslatable, and, hence, synthesis of the particular protein synthesis is prevented. Given its genetic mechanism of action, siRNA is considered a powerful technique for posttranscriptional gene silencing. The regulation of siRNA-mediated RNAi is an area of ongoing research.