Efficacy Of Various Treatment Options Research Articles

Variability in Diagnosis and Management of Hypoglycemia in Neonatal Intensive Care Unit.

Hypoglycemia, the most common metabolic derangement in the newborn period remains a contentious issue, not only due to various numerical definitions, but also due to limited therapeutical options which either lack evidence to support their efficacy or are increasingly recognized to lead to adverse reactions in this population. This study aimed to investigate neonatologists' current attitudes in diagnosing and managing transient and persistent hypoglycemia in newborns admitted to the Neonatal Intensive Care Unit (NICU). A web-based electronic survey which included 34 questions and a clinical vignette was sent to U.S. neonatologists. There were 246 survey responses with most respondents using local protocols to manage this condition. The median glucose value used as the numerical definition of hypoglycemia in first 48 hours of life (HOL) for symptomatic and asymptomatic term infants and preterm infants was 45 mg/dL (2.5 mmol/L; 25-60 mg/dL; 1.4-3.3 mmol/L), while after 48 HOL the median value was 50 mg/dL (2.8 mmol/L; 30-70 mg/dL; 1.7-3.9 mmol/L). There were various approaches used to manage transient and persistent hypoglycemia that included dextrose gel, increasing caloric content of the feeds using milk fortifiers, using continuous feedings, formula or complex carbohydrates, and use of various medications such as diazoxide, glucocorticoids, and glucagon. There is still large variability in current practices related to hypoglycemia. Further research is needed not only to provide evidence to support the values used as a numerical definition for hypoglycemia, but also on the efficacy of current strategies used to manage this condition. · Numerical definition of glucose remains variable.. · Strategies managing transient and persistent hypoglycemia are diverse.. · There is a need for further research to investigate efficacy of various treatment options..

Septic Tibial Nonunions on Proximal and Distal Metaphysis-A Systematic Narrative Review.

Infected nonunion of the tibia represents a challenging complication for orthopedic surgeons and poses a major financial burden to healthcare systems. The situation is even more compounded when the nonunion involves the metaphyseal region of long bones, a rare yet demanding complication due to the poor healing potential of infected cancellous bone; this is in addition to the increased likelihood of contamination of adjacent joints. The purpose of this study was to determine the extent and level of evidence in relation to (1) available treatment options for the management of septic tibial metaphyseal nonunions; (2) success rates and bone healing following treatment application; and (3) functional results after intervention. We searched the MEDLINE, Embase, and CENTRAL databases for prospective and retrospective studies through to 25 January 2021. Human-only studies exploring the efficacy of various treatment options and their results in the setting of septic, quiescent, and metaphyseal (distal or proximal) tibia nonunions in the adult population were included. For infection diagnosis, we accepted definitions provided by the authors of source studies. Of note, clinical heterogeneity rendered data pooling inappropriate. In terms of the species implicated in septic tibial nonunions, staphylococcus aureus was found to be the most commonly isolated microorganism. Many authors implemented the Ilizarov external fixation device with a mean duration of treatment greater than one year. Exceptional or good bone and functional results were recorded in over 80% of patients, although the literature is scarce and possible losses of the follow-up were not recorded. A demanding orthopedic condition that is scarcely studied is infected metaphyseal tibial nonunion. External fixation seems promising, but further research is needed. PROSPERO No. CRD42020205781.

Potential treatments of COVID-19: Drug repurposing and therapeutic interventions

The coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The infection is caused when Spike-protein (S-protein) present on the surface of SARS-CoV-2 interacts with human cell surface receptor, Angiotensin-converting enzyme 2 (ACE2). This binding facilitates SARS-CoV-2 genome entry into the human cells, which in turn causes infection. Since the beginning of the pandemic, many different therapies have been developed to combat COVID-19, including treatment and prevention. This review is focused on the currently adapted and certain other potential therapies for COVID-19 treatment, which include drug repurposing, vaccines and drug-free therapies. The efficacy of various treatment options is constantly being tested through clinical trials and in vivo studies before they are made medically available to the public.

Treatment options for external inflammatory root resorption

Was to compare the efficacy of various treatment options for external inflammatory root resorption according to literature data. Literature was searched in electronic databases «eLibrary» and «PubMed» for key words «external inflammatory resorption treatment», «external inflammatory resorption management». Inclusion criteria comprised publications in Russian or English, clinical and experimental studies, full description of treatment protocol and obtained results. Studies with no full text, describing root resorption of orthodontic origin, clinical cases and clinical case series were excluded from the study. The problem of external inflammatory root resorption is poorly described in the Russian scientific literature. There are no registered protocols for its prevention and treatment or therapeutic agents with proved efficacy available in Russia. The only accessible approach for external inflammatory root resorption remains timely pulp extirpation after dental trauma which importance is underlined by all authors involved in the field of dental trauma studies. MTA and calcium hydroxide being popular as intracanal medications still have significant inconveniences as they potentially provoke root dentine fractures or replacement resorption. There is a need for elaboration and implementation of new prevention and treatment options for external inflammatory root resorption after dental trauma.

Diagnosis, Treatment and Prognosis of Primary Pulmonary NUT Carcinoma: A Literature Review.

NUT carcinoma is a rare, highly lethal cancer characterized with the rearrangement of the nuclear protein in testis (NUT) gene on chromosome 15q14, which primarily occurs in the midline organs. Primary pulmonary NUT carcinoma (NC) lacks characteristic clinical manifestations, which leads to the high rate of misdiagnose and nonstandard treatment. To date, fewer than one hundred cases have been reported worldwide. Here, a comprehensive literature search involving a total of 35 articles with 55 patients was conducted in this paper. We reviewed and analyzed the associated clinical and pathological characteristics, the efficacy of various treatment options and the prognosis. Pulmonary NC mainly occurred in middle young-aged men (median age, 36) with no smoking history (2:1) and would present with symptoms of cough (63.6%), dyspnea (29.5%), chest pain (18.2%) and hemoptysis (18.2%). The initial imaging frequently revealed large and irregular lesions in the lower lobe (46.5%) of the left or right lungs; lymph node metastasis was also prevalent (91.9%). A focal squamous differentiation with abrupt keratinization often occurred in the undifferentiated or poorly differentiated (93.75%) tumor cells, with abundant necrosis and numerous neutrophils infiltrated. The mean overall survival (OS) in patients of this malignant disease was 6.21 months, and the median OS was 4.4 months. According to our results, this disease is sensitive to radiotherapy, and chemoradiotherapy (either concurrent chemoradiotherapy or sequential chemoradiotherapy) was the most efficient therapeutic regimen to prolong the OS of patients with pulmonary NC.

Comparative effectiveness of interventional therapeutic modalities for unresectable hepatocellular carcinoma: A systematic review and network meta-analysis.

It is unclear whether hepatic artery infusion chemotherapy (HAIC) or transcatheter arterial chemoembolization (TACE) is more efficient in the combination therapy of hepatocellular carcinoma (HCC). Head-to-head comparisons among HAIC-related therapies are lacking. For this network meta-analysis, PubMed, EMBASE and Cochrane Library databases were searched up to April 1, 2022. Randomized controlled trials (RCTs) were eligible if they evaluated the use or prolongation of TACE or HAIC in patients with advanced HCC and reported or collected survival data. A network meta-analysis was performed to synthesize data and make direct and indirect comparisons between treatments. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated to explore the efficacy of various treatment options on overall survival (OS), odds ratios (ORs) with 95% CI were used for overall response rate (ORR), whereas risk ratios (RRs) with 95% CI were used for serious adverse events (SAEs). The analysis of 7 trials including a total of 1,073 patients found that sorafenib with HAIC-oxaliplatin improved survival (HR=0.33, 95% CI: 0.25-0.44); the ORR was also improved in patients treated with sorafenib plus HAIC-oxaliplatin and sorafenib plus PF-HAIC (OR=22.18, 95% CI: 10.69-52.56; and OR=2.72, 95% CI: 1.43-5.36, respectively). The incidence of liver injury was elevated in patients treated with sorafenib plus TACE (OR=5.93, 95% CI: 2.70-15.41). However, no differences in the incidences of other SAEs were identified among the treatment groups. The present meta-analysis provides preliminary evidence for the comparative safety and efficacy of HAIC and TACE combined with sorafenib, and indicates the dominance of HAIC-oxaliplatin in HCC interventional therapy. However, high-quality RCTs are required to further confirm the efficacy of HAIC-oxaliplatin. The present study has been registered with PROSPERO (registration no. CRD42021288497).

Survival benefits from neoadjuvant treatment in gastric cancer: a systematic review and meta-analysis

BackgroundSurgery is the main treatment option for patients with local gastric cancer. However, surgery alone is usually not sufficient for stomach cancer patients, and combined therapies are recommended for these patients. In recent studies, some preoperative treatments have shown benefits. However, the treatment selection is still uncertain because previous studies failed to obtain a statistically significant difference between preoperative chemotherapy and preoperative chemoradiotherapy. Therefore, we plan to perform a systematic review and meta-analysis to compare the benefits among these preoperative treatments.Methods/designThis review includes randomized controlled trials with or without blinding as well as published studies, high-quality unpublished studies, full articles and meeting abstracts with an English context if sufficient results were provided for analysis. Data sources include the Cochrane Central Register of Controlled Trials, Embase, MEDLINE, major relevant international conferences and manual screening of references. Patients with a diagnosis of resectable primary gastric or EGJ adenocarcinoma (stage II or higher) who underwent surgery alone or preoperative treatment followed by surgery and who were pathologically confirmed as proposed by the AJCC 2017 guidelines without age, sex, race, subtypes of adenocarcinoma and molecular pathology limitations will be included. The following three interventions will be included: surgery alone, neoadjuvant chemistry followed by surgery and neoadjuvant chemoradiotherapy followed by surgery. All-cause mortality, overall survival (OS, the time interval from diagnosis to death) and/or progression-free survival (PFS, the time interval from diagnosis to disease progression or death from any cause) will be defined as major results of concern. The clinical and pathological response rate (according to RECIST and tumour regression score), R0 resection rate, quality of life and grade 3 or above adverse events (according to the National Cancer Institute Common Terminology Criteria for Adverse Events, NCI-CTCAE) will be defined as the secondary outcomes.DiscussionThe aim of this systematic review is to compare the benefits of different preoperative treatments for patients with locoregional stomach cancer. This systematic review will improve the understanding of the relative efficacy of these treatment options by providing the latest evidence on the efficacy of various treatment options in the management of gastric cancer patients and may guide clinical practice.Systematic review registrationPROSPERO CRD4202123718

Analyzing the efficacy of various treatment options for patients with oral mucosal hyperkeratosis

Diseases of the oral mucosa (COR), characterized by a violation of its cornea, constitute a vast group among the variety of diseases of COR, of particular interest is a separate group called hyperkeratosis of the oral mucosa. Current treatment protocols include a variety of therapeutic and surgical methodologies and principles, with surgical excision of the lesion being the primary treatment measure. However, surgical treatments are often associated with increased risks of pain, swelling, bleeding and, recurrence of malignancy.
 The aim of this review was to identify the optimal treatment option for oral mucosal leukoplakia. The current review included all studies focusing on the treatment of oral mucosal leukoplakia and published between 2016 and 2021.
 The findings of this study showed that laser surgical treatment of oral mucosal verrucous leukoplakia resulted in statistically significant advantages in the intra- and postoperative periods.

Post-acne erythema treatment: A systematic review of the literature.

Post-acne erythema (PAE) is a common sequela of acne inflammation, and it refers to telangiectasia and erythematous lesions remaining after the acne treatment. Although some PAE lesions may improve over time, persisting PAE might be esthetically undesirable for patients. The efficacy of various treatment options for PAE has been investigated in many studies but there exists no gold standard treatment modality. In this study, we aimed to give a systematic literature review on various treatment options for PAE, the advantage of each modality, and compare their efficacy, safety, and feasibility. By using the selected keywords, we carried out a systematic search for articles published from the inception to 28 April 2021 in PubMed/Medline and Embase databases. Of the 5796 initially retrieved articles, 18 of them were fully eligible to be enrolled in our study. In this study, we found that light and laser-based devices were the most frequently used treatments for PAE. Generally, pulsed-dye lasers were the most commonly used laser devices for PAE. Neodymium:yttrium aluminum-garnet lasers were the second most commonly used modalities in treating PAE. Topical treatments such as oxymetazoline, tranexamic acid, and brimonidine tartrate are promising treatments in reducing PAE lesions. In our study, no severe side effects were found. In conclusion, both laser devices and topical agents seem to be effective for PAE lesions; however, further randomized clinical trials are needed in this field.

Long-term efficacy assessment of current treatment options for epistaxis in HHT

PurposeHereditary hemorrhagic telangiectasia (HHT) is a vascular disorder that presents with recurrent, intractable epistaxis. The aim of this study was to retrospectively analyze the efficacy of various treatment options for epistaxis in patients with HHT, over a period of 18 years, and to correlate these findings with available evidence in the literature.MethodsRecords of patients with HHT, treated for epistaxis between 2000 and 2018 were analyzed. Treatment procedures carried out and their efficacy were extracted and analyzed.ResultsForty-three records were evaluated. All patients were given nasal humidifying ointments, 93% required acute treatment with bipolar electrocautery, and 60% underwent atraumatic nasal packing. Recurrent cases were treated medically with tranexamic acid (26%), oestrogen (19%), and bevacizumab (2%). Laser photocoagulation was done in selected cases (40%) and if unsuccessful, septal dermoplasty was performed (2.3%). Endovascular embolization was reserved for life-threatening emergencies (7%).ConclusionEpistaxis in HHT is not curable, but can be managed by employing a comprehensive stepwise approach. An algorithm for effective and comprehensive management has been presented.

American Society of Retina Specialists Clinical Practice Guidelines on the Management of Nonproliferative and Proliferative Diabetic Retinopathy without Diabetic Macular Edema.

Nonproliferative (NPDR) and proliferative diabetic retinopathy (PDR) without diabetic macular edema (DME) affect millions of individuals living with diabetes throughout the world. There is increasing data on various management strategies for such patients, but there is limited consensus on how the data should be adopted into clinical practice. This literature review and editorial presents and synthesizes the current evidence for various management paradigms for NPDR and PDR without DME. Retina specialists are an integral member of the diabetes management team, and should encourage patients on the importance of glycemic and cardiovascular optimization for both systemic and retinopathy risk factor reduction. The diabetic retinopathy severity scale (DRSS) is now an approvable endpoint for clinical trials in the United States, therefore becoming more clinically relevant. For PDR without DME, the Diabetic Retinopathy Study (DRS) and the Early Treatment Diabetic Retinopathy Study (ETDRS) established the standard of care with panretinal photocoagulation (PRP). Laser parameters have since evolved to include less intense and earlier intervention. Studies have recently demonstrated that anti-vascular endothelial growth factor (VEGF) treatment of PDR is effective at regressing neovascularization and improving DRSS levels in many patients. Further evidence is required to determine optimal treatment frequency, duration, and retreatment criteria, in the real world. There are concerns for adverse events in patients being lost to follow up during anti-VEGF treatment. For NPDR without DME, the standard of care has been a wait-and-watch approach. Data within the DRS and the ETDRS suggest that PRP for severe NPDR can be an option for select patients as well. Multiple clinical trials have now demonstrated that anti-VEGF treatment can improve the DRSS score in NPDR. Further studies are required to assess whether this positively affects long-term visual outcomes, and whether the benefits outweigh the risks in the real world for routine use. There is cumulative evidence demonstrating the efficacy of various treatment options for NPDR and PDR without DME. Currently, patients would most likely benefit from thoughtful management strategies that are tailored to the individual patient.

Determining the role of adjuvant radiotherapy in the management of meningioma: a Surveillance, Epidemiology, and End Results analysis.

OBJECTIVEThe aim of this study was to illustrate the demographic characteristics of meningioma patients and observe the effect of adjuvant radiation therapy on survival by using the Surveillance, Epidemiology, and End Results (SEER) database. More specifically, the authors aimed to answer the question of whether adjuvant radiotherapy following resection of atypical meningioma confers a cause-specific survival benefit. Additionally, they attempted to add to previous characterizations of the epidemiology of primary meningiomas and assess the effectiveness of the standard of care for benign and anaplastic meningiomas. They also sought to characterize the efficacy of various treatment options in atypical and anaplastic meningiomas separately since nearly all other analyses have grouped these two together despite varying treatment regimens for these behavior categories.METHODSSEER data from 1973 to 2015 were queried using appropriate ICD-O-3 codes for benign, atypical, and anaplastic meningiomas. Patient demographics, tumor characteristics, and treatment choices were analyzed. The effects of treatment were examined using a multivariate Cox proportional hazards model and Kaplan-Meier survival analysis.RESULTSA total of 57,998 patients were included in the analysis of demographic, meningioma, and treatment characteristics. Among this population, cases of unspecified WHO tumor grade were excluded in the multivariate analysis, leaving a total of 12,931 patients to examine outcomes among treatment paradigms. In benign meningiomas, gross-total resection (HR 0.289, p = 0.013) imparted a significant cause-specific survival benefit over no treatment. In anaplastic meningioma cases, adjuvant radiotherapy imparted a significant survival benefit following both subtotal (HR 0.089, p = 0.018) and gross-total (HR 0.162, p = 0.002) resection as compared to gross-total resection alone. In atypical tumors, gross-total resection plus radiotherapy did not significantly change the hazard risk (HR 1.353, p = 0.628) compared to gross-total resection alone. Similarly, it was found that adjuvant radiation did not significantly benefit survival after a subtotal resection (HR 1.440, p = 0.644).CONCLUSIONSThe results of this study demonstrate that the role of adjuvant radiotherapy, especially after the resection of atypical meningioma, remains somewhat unclear. Thus, given these results, prospective randomized clinical studies are warranted to provide clear information on the effects of adjuvant radiation in meningioma treatment.

Itching at night: A review on reducing nocturnal pruritus in children.

The most common causes of chronic nocturnal itching in children are atopic dermatitis and psoriasis, with lichen simplex chronicus and prurigo nodularis contributing to lesser degrees. Despite the prevalence of nocturnal itching, its pathophysiology remains poorly understood. The most troubling consequence of itching at night is poor quality of sleep. Poor sleep quality in children with nocturnal itching has been linked to adverse neurocognitive, behavioral, and physiologic outcomes, including poor performance in school, attention deficit hyperactivity disorder, short stature, hypertension, obesity, and impaired immune function. There is no consensus on the best management of nocturnal itching in children. We conducted a review of the literature evaluating the efficacy of various treatment options for children with chronic nocturnal pruritus. Our review found three recently conducted randomized controlled trials and one case report demonstrating the efficacy of topical corticosteroids, oral melatonin, and clonidine in reducing nocturnal itching or improving sleep quality in children with nocturnal pruritus. Future research is needed to elucidate the pathophysiology of nocturnal itching to best develop targeted, effective treatment strategies.

Daptomycin and vancomycin heteroresistance revealed among CC5-SCCmecII MRSA clone and in vitro evaluation of treatment alternatives.

Methicillin-resistant Staphylococcus aureus (MRSA) is a threat to the success of clinical treatment. Besides high antimicrobial resistance rates, the presence of heterogeneous vancomycin-intermediate S. aureus (hVISA) and heterogeneous daptomycin-non-susceptible S. aureus (hDNSSA) in the hospital environment is underestimated and is associated with treatment failure. The aim of this study was to investigate MRSA dissemination in a Brazilian hospital and to evaluate the efficacy of various treatment options in vitro. MRSA strains were typed by MLST, PFGE and SCCmec typing. Minimum inhibitory concentrations (MICs) to daptomycin, linezolid, quinupristin/dalfopristin, teicoplanin, tetracycline, tigecycline, vancomycin and tedizolid were determined by broth microdilution. The presence of a heterogeneous population was detected by population analysis profile (PAP). Regarding hVISA and hDNSSA strains, the sequences and expression levels of genes involved in resistance to daptomycin and vancomycin were determined as well as cell wall thickness and autolysis. ST5/ST105-SCCmecII lineage was prevalent amongst 27 clinical MRSA characterised in this study. Two hDNSSA strains (one also hVISA) were detected and were confirmed by PAP. Isolate SCMSC29 (hVISA and hDNSSA) showed increased expression of genes involved in cell wall metabolism, slight cell wall thickening, reduction of autolysis, and single nucleotide polymorphisms (SNPs) in the rpoB and mprF genes compared with the susceptible strain SCMSC31. SCMSC35 (hDNSSA) presented SNPs in the rpoB and mprF genes as well as a thickened cell wall. Despite this worrying and hard to detect phenotype, treatment alternatives such as teicoplanin, linezolid, tetracycline, tigecycline, quinupristin/dalfopristin and tedizolid were all active against these isolates.

Management of radiotherapy-induced salivary hypofunction and consequent xerostomia in patients with oral or head and neck cancer: meta-analysis and literature review

To analyze the efficacy of various treatment options for radiation-induced hyposalivation in patients with head and neck cancer. A literature review and meta-analysis was performed on all appropriate literature identified via MEDLINE/PubMed. Fourteen articles were identified that met inclusion criteria for review, and 8 articles qualified for inclusion in the meta-analysis. The available literature addressed both objective and subjective responses of hyposalivation, xerostomia, or both to cholinergic agonists (such as pilocarpine and cevimeline), salivary substitutes, hyperbaric oxygen, and acupuncture. This analysis indicated that cholinergic agonists were more effective in treating radiation-induced hyposalivation compared with salivary substitutes, hyperbaric oxygen, and acupuncture. However, other treatment modalities, such as salivary substitutes and hyperbaric oxygen, were also found to subjectively improve patients' perception of xerostomia.

Treatment of sternoclavicular joint osteomyelitis with debridement and delayed resection with muscle flap coverage improves outcomes.

The objective of this study was to evaluate the efficacy of various treatment options for sternoclavicular joint osteomyelitis. We evaluated patients with a diagnosis of sternoclavicular joint osteomyelitis, treated at our hospital from 2002 to 2012. Four treatment options were compared. Three out of twelve patients were successfully cured with antibiotics alone (25%). Debridement with or without negative pressure therapy was successful for one of three patients (33%). Simultaneous debridement, bone resection, and muscle flap coverage of the acquired defect successfully treated one of two patients (50%). Debridement with delayed bone resection and muscle flap coverage was successful in five of five patients (100%). Osteomyelitis of the sternoclavicular joint is a rare disease that has become more prevalent in recent years and can be associated with increasing use of long-term indwelling catheters. Initial debridement with delayed bone resection and pectoralis major muscle flap coverage can effectively treat sternoclavicular joint osteomyelitis.

Mounting Evidence Against Complex Decongestive Therapy As a First-Line Treatment for Early Lymphedema

Arm lymphedema is a feared and presently incurable complication of breast cancer surgery and radiation treatment (RT). Lymphedema results from excess interstitial fluid accumulation, which leads to limb swelling and eventual tissue fibrosis that can cause lifelong impairment of arm use. Lymphedema concerns take center stage at many, if not the majority, of preoperative and postoperative consultations with patients who are undergoing breast cancer surgery, given that this complication can permanently harm quality of life, from both a physical/functional perspective as well as a psychosocial one. Findings from a 2013 systematic review and meta-analysis of 72 studies revealed an estimated 17% risk of arm lymphedema among patients with breast cancer, with risk increasing up to 2 years after surgery. The risk was four times higher in women who had a complete axillary lymph node dissection (ALND; 20%) versus those who had sentinel lymph node biopsy alone (5.6%). Among women who receive adjuvant RT after ALND, lymphedema risk is significantly higher. In a 2001 systematic review, the rate of lymphedema among women who underwent surgery plus axillary RT was an alarming 41%. Aside from treatment-related risk factors, a number of patient or disease-related risk factors exist for the development of lymphedema. Postoperative infection or delayed wound healing is associated with heightened lymphedema risk. A much more prevalent risk factor is obesity (body mass index 30 kg/m), which portends a nearly three-fold increase in risk for lymphedema. According to 2009/2010 Centers for Disease Control and Prevention statistics, 36% of all women and 42% of women age 60 years or older are obese in the United States. In the current era, with widening adoption of the findings of the American College of Surgeons Oncology Group (ACOSOG) Z0011 trial, incidence of lymphedema should decline, given that we see decreasing rates of completion ALND among a subset of women undergoing breast-conserving therapy. However, there remains a large population of patients with node-positive disease for whom ALND is still indicated, including those with clinically positive nodes, locally advanced disease, those receiving neoadjuvant chemotherapy, and those undergoing mastectomy. Hence, research into the treatment of this chronic condition remains an important public health issue. Because many lymphedema risk factors are not modifiable, attention has largely been directed at treatment. To this aim, a number of studies have compared efficacy of various treatment options for lymphedema. Treatment options include, alone or in combination, exercise, skin care, compression bandaging, compression garments, manual therapy (massage), laser therapy, and pneumatic pumps. Complex decongestive therapy (CDT) incorporates manual lymphatic drainage, daily bandaging, exercise, and skin care. A systematic review of these therapies was published in 2006 and found that, in general, more intensive treatment by health professionals, such as CDT or manual lymphatic drainage, produced larger volume reductions than therapies undertaken by the patient, such as compression bandaging, exercise, or skin care. Studies of CDT showed an estimated 43% reduction in arm volume compared with only 11% with compression alone. However, excitement over CDT has been tempered by subsequent randomized trials that have thus far failed to demonstrate a significant benefit of CDT over standard compression therapy. In one trial by McNeely et al, 50 women were randomly assigned to 4 weeks of CDT or compression alone. Arm volume decreased significantly with both treatments, but no difference was observed between groups (46% CDT v 39% compression alone; P .22). This study was limited in follow-up to 1 month and did not assess quality-of-life parameters associated with treatment of lymphedema. Another trial by Andersen et al randomly assigned 42 women with lymphedema to CDT versus compression, and observed patients for 12 months. They also found no significant difference in arm volume reduction over the 12-month period between CDT and compression groups (48% v 60%, respectively; P .66). Armed with these data, one might question why yet another randomized controlled trial was necessary to examine this question. Limitations of the above trials included their small size, singleinstitution setting (and sometimes, even single CDT provider), and lack of long-term follow-up. In the article that accompanies this editorial, Dayes et al address all of these limitations in their eloquently designed, randomized, multicenter trial of CDT versus compression bandaging alone for patients with lymphedema. Dayes et al randomly assigned 103 women from six Canadian cancer centers to either CDT or compression bandaging between 2003 and 2009. Type and duration of CDT were standardized across groups, as were arm measurement techniques. Diary logs were JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 31 NUMBER 30 OCTOBER 2

Endocrine Therapy for Postmenopausal Women with Hormone Receptor–Positive her2–Negative Advanced Breast Cancer after Progression or Recurrence on Nonsteroidal Aromatase Inhibitor Therapy: A Canadian Consensus Statement

Approximately 22,700 Canadian women were expected to be diagnosed with breast cancer in 2012. Despite improvements in screening and adjuvant treatment options, a substantial number of postmenopausal women with hormone receptor positive (hr+) breast cancer will continue to develop metastatic disease during or after adjuvant endocrine therapy. Guidance on the selection of endocrine therapy for patients with hr+ disease that is negative for the human epidermal growth factor receptor 2 (her2-) and that has relapsed or progressed on earlier nonsteroidal aromatase inhibitor (nsai) therapy is of increasing clinical importance. Exemestane, fulvestrant, and tamoxifen are approved therapeutic options in this context. Four phase iii trials involving 2876 patients-efect, sofea, confirm, and bolero-2-have assessed the efficacy of various treatment options in this clinical setting. Data from those trials suggest that standard-dose fulvestrant (250 mg monthly) and exemestane are of comparable efficacy, that doubling the dose of fulvestrant from 250 mg to 500 mg monthly results in a 15% reduction in the risk of progression, and that adding everolimus to exemestane (compared with exemestane alone) results in a 57% reduction in the risk of progression, albeit with increased toxicity. Multiple treatment options are now available to women with hr+ her2- advanced breast cancer recurring or progressing on earlier nsai therapy, although current clinical trial data suggest more robust clinical efficacy with everolimus plus exemestane. Consideration should be given to the patient's age, functional status, and comorbidities during selection of an endocrine therapy, and use of a proactive everolimus safety management strategy is encouraged.

Pulmonary histiocytosis

Introduction. Langerhans cell histiocytosis encompasses a group of disorders of unknown origin with different clinical presentations and outcomes. It is characterized by infiltration of the involved tissues by large numbers of Langerhans cells, often organized into granulomas. The accumulation of these cells causes the classic lytic bone lesions, skin rashes, lymphadenopathy, splenomegaly, and dysfunction of organ such as the pituitary gland, lungs, liver, and bone marrow. Pulmonary histiocytosis. Adult pulmonary Langerhans cell histiocytosis is a rare disorder of unknown etiology. It occurs predominantly in male smokers, with an incidence peak between 20 and 40 years of age. High-resolution computed tomography of the chest can show nodules, cavitated nodules, and thickand thin-walled cysts. The definite diagnosis of pulmonary Langerhans cell histiocytosis requires identification of Langerhans? cell granulomas infiltrating and destroying distal bronchioles, which is usually achieved by lung biopsy at a site selected by chest high-resolution computed tomography. Treatment. Treatment options for adults have never been clarified by a clinical trial. The published literature provides minimal data on the comparative efficacy of various treatment options which include surgery/curettage, steroids, radiation, and various chemotherapy regimens. The improved understanding of the mechanisms involved in the pathogenesis of pulmonary Langerhans cell histiocytosis should help in the development of specific therapeutic strategies and effective treatment.

Optimal Prophylactic and Definitive Therapy for Bicalutamide-Induced Gynecomastia: Results of a Meta-analysis

Bicalutamide is approved as an adjuvant to primary treatments (radical prostatectomy or radiotherapy) or as monotherapy in men with locally advanced, nonmetastatic prostate cancer (pca). However, this treatment induces gynecomastia in most patients, which often results in treatment discontinuation. Optimal therapy for these breast events is not known so far. We undertook a meta-analysis to assess the efficacy of various treatment options for bicalutamide-induced gynecomastia. The medline, cancerlit, and Cochrane library databases were searched and the Google search engine was used to identify prospective and retrospective controlled studies published in English from January 2000 to December 2010 comparing prophylactic or curative treatment options with a control group (no treatment) for pca patients who developed bicalutamide-induced gynecomastia. Radiotherapy-induced cardiotoxicity was also evaluated. The search identified nine controlled trials with a total patient population of 1573. Pooled results from prophylactic trials showed a significant reduction of gynecomastia in pca patients treated with prophylactic tamoxifen 20 mg daily (odds ratio: 0.06; 95% confidence interval: 0.05 to 0.09; p = 0.09), and pooled results from treatment trials showed a significant response of gynecomastia to definitive radiotherapy (odds ratio: 0.06; 95% confidence interval: 0.01 to 0.24; p < 0.0001). Aromatase inhibitors and weekly tamoxifen were not found to be effective as prophylactic and curative options. For the radiotherapy, skin-to-heart distance was found to be an important risk factor for cardiotoxicity (p = 0.006). A funnel plot of the meta-analysis showed significant heterogeneity (Egger test p < 0.00001) because of low sample size. Our meta-analysis suggests using prophylactic tamoxifen 20 mg daily as the first-line preventive measure and radiotherapy as the first-line treatment option for bicalutamide-induced gynecomastia. Aromatase inhibitors and weekly tamoxifen are not recommended.