Microenvironment shapes small-cell lung cancer neuroendocrine states and presents therapeutic opportunities.

Small-cell lung cancer (SCLC) is the most fatal form of lung cancer. Intratumoral heterogeneity, marked by neuroendocrine (NE) and non-neuroendocrine (non-NE) cell states, defines SCLC, but the cell-extrinsic drivers of SCLC plasticity are poorly understood. To map the landscape of SCLC tumor microenvironment (TME), we apply spatially resolved transcriptomics and quantitative mass spectrometry-based proteomics to metastatic SCLC tumors obtained via rapid autopsy. The phenotype and overall composition of non-malignant cells in the TME exhibit substantial variability, closely mirroring the tumor phenotype, suggesting TME-driven reprogramming of NE cell states. We identify cancer-associated fibroblasts (CAFs) as a crucial element of SCLC TME heterogeneity, contributing to immune exclusion, and predicting exceptionally poor prognosis. Our work provides a comprehensive map of SCLC tumor and TME ecosystems, emphasizing their pivotal role in SCLC's adaptable nature, opening possibilities for reprogramming the TME-tumor communications that shape SCLC tumor states.

DNA Released by Adeno-Associated Virus Strongly Alters Capsid Aggregation Kinetics in a Physiological Solution.

While adeno-associated virus is a leading vector for gene therapy, significant gaps remain in understanding AAV degradation and stability. In this work, we study the degradation of an engineered AAV serotype at physiological pH and ionic strength. Viral particles of varying fractions of encapsulated DNA were incubated between 30 and 60 °C, with changes in molecular weight measured by changes in total light scattering intensity at 90° over time. Mostly full vectors demonstrated a rapid decrease in molecular weight corresponding to the release of capsid DNA, followed by slow aggregation. In contrast, empty vectors demonstrated immediate, rapid colloid-type aggregation. Mixtures of full and empty capsids showed a pronounced decrease in initial aggregation that cannot be explained by a linear superposition of empty and full degradation scattering signatures, indicating interactions between capsids and ejected DNA that influenced aggregation mechanisms. This demonstrates key interactions between AAV capsids and their cargo that influence capsid degradation, aggregation, and DNA release mechanisms in a physiological solution.

Psychosocial outcomes and health service use after notifying women participating in population breast screening when they have dense breasts: a BreastScreen Queensland randomised controlled trial.

BACKGROUND: Robust evidence regarding the benefits and harms of notifying Australian women when routine breast screening identifies that they have dense breasts is needed for informing future mammography population screening practice and policy. OBJECTIVES: To assess the psychosocial and health services use effects of notifying women participating in population-based breast cancer screening that they have dense breasts; to examine whether the mode of communicating this information about its implications (print, online formats) influences these effects. METHODS AND ANALYSIS: The study population comprises women aged 40 years or older who attend BreastScreen Queensland Sunshine Coast services for mammographic screening and are found to have dense breasts (BI-RADS density C or D). The randomised controlled trial includes three arms (952 women each): standard BreastScreen care (no notification of breast density; control arm); notification of dense breasts in screening results letter and print health literacy-sensitive information (intervention arm 1) or a link or QR code to online video-based health literacy-sensitive information (intervention arm 2). Baseline demographic data will be obtained from BreastScreen Queensland. Outcomes data will be collected in questionnaires at baseline and eight weeks, twelve months, and 27 months after breast screening. Primary outcomes will be psychological outcomes and health service use; secondary outcomes will be supplemental screening outcomes, cancer worry, perceived breast cancer risk, knowledge about breast density, future mammographic screening intentions, and acceptability of notification about dense breasts. ETHICS APPROVAL: Gold Coast Hospital and Health Service Ethics Committee (HREC/2023/QGC/89770); Sunshine Coast Hospital and Health Service Research Governance and Development (SSA/2023/QSC/89770). DISSEMINATION OF FINDINGS: Findings will be reported in peer-reviewed journals and at national and international conferences. They will also be reported to BreastScreen Queensland, BreastScreen Australia, Cancer Australia, and other bodies involved in cancer care and screening, including patient and support organisations. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12623000001695p (prospective: 9 January 2023).

Optimized Production and Analysis of Recombinant Protein-Filled Vesicles from E. coli.

This innovative system, using a short peptide tag, that exports multiple recombinant proteins in membrane bound vesicles from E. coli, provides an effective solution to a range of problems associated with bacterial recombinant protein expression. These recombinant vesicles compartmentalise proteins within a micro-environment that facilitates the production of otherwise challenging, toxic, insoluble, or disulfide-bond containing proteins from bacteria. Protein yield is increased considerably when compared to typical bacterial expression in the absence of the vesicle-nucleating peptide tag. The release of vesicle-packaged proteins supports isolation from the culture medium and permits long-term active protein storage. This technology gives rise to increased yields of vesicle-packaged, functional proteins for simplified downstream processing for a diverse range of applications from applied biotechnology to discovery science and medicine. In the present article and the associated video, a detailed protocol of the method is provided, which highlights key steps in the methodology to maximize recombinant protein-filled vesicle production.

Minding the Bathwater: Fertility and Reproductive Toxicity in the Age of Immuno-Oncology.

Immune checkpoint inhibition has resulted in significant efficacy across many cancer types, including melanoma. Melanoma is the second most common cancer among those of reproductive age, yet the reproductive toxicities of adjuvant and first-line immunotherapy are largely unknown.The normal innate and adaptive immune systems play a vital role in reproductive organ homeostasis of men and women and are essential for implantation, fertility, and a successful pregnancy. The programmed cell death-1 receptor/programmed cell death receptor ligand-1 (PD-1/PD-L1) pathway is essential in several aspects of fertility and pregnancy. Recent studies have largely focused on the role of the PD-1/PD-L1 pathway in fetomaternal tolerance, highlighting the importance of intact immune regulation in promoting a successful pregnancy.In this review, we describe a case of a reproductive-aged female with stage IIIC melanoma who sought guidance on family planning after pembrolizumab therapy. We discuss the known fertility-related toxicities of immune checkpoint inhibitors, the potential targets for reproductive toxicity in males and nonpregnant females, and the implications of anti-PD-1 therapy in relation to fetomaternal tolerance. Informed decision making will benefit from data and consensus.

Male-specific late effects in adult hematopoietic cell transplantation recipients: a systematic review from the Late Effects and Quality of Life Working Committee of the Center for International Blood and Marrow Transplant Research and Transplant Complications Working Party of the European Society of Blood and Marrow Transplantation.

Male-specific late effects after hematopoietic cell transplantation (HCT) include genital chronic graft-versus-host disease (GvHD), hypogonadism, sexual dysfunction, infertility, and subsequent malignancies. They may be closely intertwined and cause prolonged morbidity and decreased quality of life after HCT. We provide a systematic review of male-specific late effects in a collaboration between transplant physicians, endocrinologists, urologists, dermatologists, and sexual health professionals through the Late Effects and Quality of Life Working Committee of the Center for International Blood and Marrow Transplant Research, and the Transplant Complications Working Party of the European Society of Blood and Marrow Transplantation. The systematic review summarizes incidence, risk factors, screening, prevention and treatment of these complications and provides consensus evidence-based recommendations for clinical practice and future research.

Male-Specific Late Effects in Adult Hematopoietic Cell Transplantation Recipients: A Systematic Review from the Late Effects and Quality of Life Working Committee of the Center for International Blood and Marrow Transplant Research and Transplant Complications Working Party of the European Society of Blood and Marrow Transplantation.

Male-specific late effects after hematopoietic cell transplantation (HCT) include genital chronic graft-versus-host disease (GVHD), hypogonadism, sexual dysfunction, infertility, and subsequent malignancies, such as prostate, penile, and testicular cancer. These effects may be closely intertwined and cause prolonged morbidity and decreased quality of life after HCT. Here we provide a systematic review of male-specific late effects in a collaboration among transplantation physicians, endocrinologists, urologists, dermatologists, and sexual health professionals through the Late Effects and Quality of Life Working Committee of the Center for International Blood and Marrow Transplant Research and the Transplant Complications Working Party of the European Society of Blood and Marrow Transplantation. We used a systematic review methodology to summarize incidence, risk factors, screening, prevention, and treatment of these complications and provide consensus evidence-based recommendations for clinical practice and future research. Most of the evidence regarding male GVHD is still based on limited data, precluding strong therapeutic recommendations. Therefore, we recommend systematic screening for male genital GVHD regularly and reporting of cases to large registries to allow for a better understanding. Future research also should address treatment, given the little published evidence currently available. Male-specific endocrine consequences of HCT include hypogonadism, which also may affect bone health. Given the scanty evidence, current recommendations for hormone substitution and/or bone health treatment are based on similar principles as for the general population. Following HCT, sexual health decreases, and this topic should be addressed at regular intervals. Future studies should focus on interventional strategies to address sexual dysfunction. Infertility remains prevalent in patients having undergone myeloablative conditioning, warranting the offer of sperm preservation for all HCT candidates. Most studies on fertility rely on descriptive registry analysis and surveys, underscoring the importance of reporting post-HCT conception data to large registries. Although the quality of evidence is low, the development of cancer in male genital organs does not seem more prevalent in HCT recipients compared with the general population; however, subsequent malignancies in general seem to be more prevalent in males than in females, and special attention should be given to skin and oral mucosa. Male-specific late effects, which likely are more underreported than female-specific complications, should be systematically considered during the regular follow-up visits of male survivors who have undergone HCT. Care of patients with male-specific late effects warrants close collaboration between transplantation physicians and specialists from other involved disciplines. Future research should be directed toward better data collection on male-specific late effects and on studies about the interrelationships among these late effects, to allow the development of evidence-based effective management practices.

Addressing Barriers to Fertility Preservation for Cancer Patients: The Role of Oncofertility Patient Navigation.

BACKGROUND: Infertility is a common late effect for cancer survivors. Whereas assisted reproductive technology has made it possible for survivors to take steps to preserve fertility before starting treatment, only a minority of patients proceed with preservation. Patient-, provider-, health system-, and societal-level barriers to fertility preservation (FP) exist. Oncofertility patient navigation is a valuable resource for addressing FP barriers. OBJECTIVES: To highlight the critical role of oncofertility patient navigation in addressing barriers to FP within an academic oncofertility program. METHODS: The role of the oncofertility patient navigator in reducing FP barriers, promoting informed decision-making, and ensuring program sustainability is described. Program metrics illustrating the impact of oncofertility patient navigation on referrals for FP counseling and access to FP in the last year also are provided. DISCUSSION: The oncofertility program at our academic adult and pediatric medical centers aims to facilitate rapid referral to fertility counseling and preservation services for postpubertal cancer patients. The patient navigator is integral to the success of the program. The navigator ensures that patients are: (1) well-informed about the potential impact of cancer on fertility and FP options, (2) aware of available resources (eg, financial) for pursuing FP, (3) able to access FP services if desired, and (4) well supported in making an informed FP decision. The inclusion of the patient navigator has led to an almost 2-fold increase in referrals for FP counseling in the past year over the historic annual average. CONCLUSIONS: Our institution's oncofertility program, with patient navigation at the core, provides a potential model for increasing patient access to oncofertility care and promoting program sustainability. Oncofertility patient navigation is a valuable resource for providing patients and families with education and support regarding FP decision-making, as well as addressing the multilevel barriers to FP.

Impact of surgical volume and resident involvement on patency rates after vasectomy reversal-A 14-year experience in an open access system.

OBJECTIVE: Evaluate the influence of fellowship training, resident participation, reconstruction type, and patient factors on outcomes after vasectomy reversals in a high volume, open access system. METHODS: Retrospective review of all vasectomy reversals performed at a single institution from January 1, 2002 to December 31, 2016 was conducted. Patient and spouse demographics, patient tobacco use and comorbidities, surgeon training and case volume, resident participation, reconstruction type, and postoperative patency were collected and analyzed. RESULTS: Five hundred and twenty-six vasectomy reversals were performed during the study period. Follow-up was available in 80.6% of the cohort and overall patency, regardless of reconstruction type was 88.7%. The mean time to reversal was 7.87 years (range of 0-34 years). The majority of cases included resident participation. Case volume was high with faculty and residents logging a mean of 37.0 and 38.7 (median 18 and 37) cases respectively. Bilateral vasovasostomy was the most common reconstruction type (83%) and demonstrated a significantly better patency rate (89%) than all other reconstructions (p=0.0008). Overall patency and patency by reconstruction type were not statistically different among faculty surgeons and were not impacted by fertility fellowship training, resident participation or post-graduate year. Multivariate analysis demonstrated that increased time to reversal and repeat reconstructions had a negative impact on patency (p=0.0023 and p=0.043, respectively). CONCLUSIONS: Surgeons with a high volume of vasectomy reversals have outcomes consistent with contemporary series regardless of fellowship training in fertility. Patency was better for bilateral vasovasostomies. Patency was not negatively impacted by tobacco use, comorbidities, resident participation, or post-graduate year.

High-Content Imaging of Unbiased Chemical Perturbations Reveals that the Phenotypic Plasticity of the Actin Cytoskeleton Is Constrained.

Although F-actin has a large number of binding partners and regulators, the number of phenotypic states available to the actin cytoskeleton is unknown. Here, we quantified 74 features defining filamentous actin (F-actin) and cellular morphology in >25 million cells after treatment with a library of 114,400 structurally diverse compounds. After reducing the dimensionality of these data, only ∼25 recurrent F-actin phenotypes emerged, each defined by distinct quantitative features that could be machine learned. We identified 2,003 unknown compounds as inducers of actin-related phenotypes, including two that directly bind the focal adhesion protein, talin. Moreover, we observed that compounds with distinct molecular mechanisms could induce equivalent phenotypes and that initially divergent cellular responses could converge over time. These findings suggest a conceptual parallel between the actin cytoskeleton and gene regulatory networks, where the theoretical plasticity of interactions is nearly infinite, yet phenotypes in vivo are constrained into a limited subset of practicable configurations.

A Noninvasive Blood-based Combinatorial Proteomic Biomarker Assay to Detect Breast Cancer in Women over age 50 with BI-RADS 3, 4, or 5 Assessment.

PURPOSE: With improvements in breast cancer imaging, there has been a corresponding increase in false-positives and avoidable biopsies. There is a need to better differentiate when a breast biopsy is warranted and determine appropriate follow-up. This study describes the design and clinical performance of a combinatorial proteomic biomarker assay (CPBA), Videssa Breast, in women over age 50 years. EXPERIMENTAL DESIGN: A BI-RADS 3, 4, or 5 assessment was required for clinical trial enrollment. Serum was collected prior to breast biopsy and subjects were followed for 6-12 months and clinically relevant outcomes were recorded. Samples were split into training (70%) and validation (30%) cohorts with an approximate 1:4 case:control ratio in both arms. RESULTS: A CPBA that combines biomarker data with patient clinical data was developed using a training cohort (469 women, cancer incidence: 18.5%), resulting in 94% sensitivity and 97% negative predictive value (NPV). Independent validation of the final algorithm in 194 subjects (breast cancer incidence: 19.6%) demonstrated a sensitivity of 95% and a NPV of 97%. When combined with previously published data for women under age 50, Videssa Breast achieves a comprehensive 93% sensitivity and 98% NPV in a population of women ages 25-75. Had Videssa Breast results been incorporated into the clinical workflow, approximately 45% of biopsies might have been avoided. CONCLUSIONS: Videssa Breast combines serum biomarkers with clinical patient characteristics to provide clinicians with additional information for patients with indeterminate breast imaging results, potentially reducing false-positive breast biopsies.

Could Nonenhanced Computer Tomography Suffice as the Imaging Study of Choice for the Screening of Asymptomatic Microscopic Hematuria?

OBJECTIVE: To compare the diagnostic accuracy of the noncontrast and contrast-enhanced phases of computed tomographic urography for detection of upper urinary tract findings in adults undergoing initial evaluation of newly diagnosed asymptomatic microscopic hematuria to determine if less-intensive noncontrast imaging has the potential to become a suitable imaging alternative in the work-up of this common condition. MATERIALS AND METHODS: Retrospective review from 2010-2015 for adults who underwent computed tomographic urography for initial evaluation of asymptomatic microscopic hematuria. Three nonblinded physicians independently categorized the upper urinary tract findings described in the computed tomography reports into one of three groups: normal, benign, or suspicious for malignancy. The noncontrast images of a randomized portion of the studies categorized as normal and all studies categorized as suspicious and benign were submitted to two blinded radiologists who independently classified each study into one of the aforementioned categories. RESULTS: The noncontrast images for 475 subjects were blindly reviewed. When compared to the computed tomographic urography reports, the negative predictive values of noncontrast images were 97.25% and 94.92% for radiologist 1 and radiologist 2, respectively, with an associated specificity of 88.6% and 97.95%. Of the 5 true upper tract malignancies, both blinded radiologists correctly identified 4 of the 5. CONCLUSION: Contrast imaging added little diagnostic value when compared with noncontrast imaging for most subjects undergoing initial evaluation for asymptomatic microscopic hematuria. Less-intensive imaging with nonenhanced computed tomography could reduce the nontrivial risks associated with multiphasic contrast imaging but further work is necessary to identify risk-stratifying criteria.

Nurses' Interest in Independently Initiating End-of-Life Conversations and Palliative Care Consultations in a Suburban, Community Hospital.

BACKGROUND: Patients who receive early palliative care consults have clinical courses and outcomes more consistent with their goals. Nurses have been shown to be advocates for early palliative care involvement and are able to lead advanced care planning discussions. OBJECTIVE: The purpose of this study was to assess whether after a brief educational session, nurses at a suburban, community hospital could demonstrate knowledge of palliative care principles, would want to independently initiate end-of-life conversations with patients and families, and would want to place specialty palliative care consults. DESIGN: Four 1 hour presentations were made at 4 nursing leadership council meetings from November through December 2015. Anonymous pre- and post-presentation surveys were distributed and collected in person. Setting/Participant: Nonprofit, suburban, community hospital in Maryland. Participants were full-time or part-time hospital employees participating in a nursing leadership council who attended the presentation. MEASUREMENTS: We compared responses from pre- and post-presentation surveys. RESULTS: Fifty nurses (19 departments) completed pre-presentation surveys (100% response rate) and 49 nurses completed post-presentation surveys (98% response rate). The average score on 7 index questions increased from 71% to 90%. After the presentations, 86% strongly agreed or agreed that nurses should be able to independently order a palliative care consult and 88% strongly agreed or agreed with feeling comfortable initiating an end-of-life conversation. CONCLUSION: Brief educational sessions can teach palliative care principles to nurses. Most participants of the study would want to be able to directly consult palliative care and would feel comfortable initiating end-of-life conversations after this educational session.

Reduction in Opioid Prescribing Using a Postoperative Pain Management Protocol following Scrotal and Subinguinal Surgery.

INTRODUCTION: Excess prescribing of opioid pain medication increases medical costs and the potential for abuse by patients and others. We sought to improve our understanding of postoperative pain and opioid use after scrotal and subinguinal urological surgery to develop a protocol for pain management. METHODS: We retrospectively analyzed opioid prescribing and usage in 20 patients undergoing scrotal or subinguinal surgery. Collected data were used to develop a standardized postoperative protocol. This protocol included enhanced pain management education and limiting outpatient opioid prescriptions. Outcomes analysis was then performed for 60 consecutive patients via questionnaire. Statistical analysis was performed using the Wilcoxon rank sum test and ANOVA. Linear regression was performed comparing age and narcotic use. RESULTS: Comparison of preprotocol and postprotocol implementation opioid prescriptions and consumption showed a statistically significant decrease in the number of tablets prescribed but no difference in opioid usage. Preprotocol and postprotocol opioid prescription usage was 20 and 10 tablets, respectively, while median usage was 3.5 and 3 tablets, respectively. CONCLUSIONS: Evaluation of postoperative pain management revealed excessive prescribing of opioid medications compared to actual usage. Our protocol resulted in a significant decrease in opioid prescribing without compromising management of postoperative pain. Adjunct treatments for pain, including scrotal support, ice packs, elevation and nonsteroidal anti-inflammatory drugs, may improve postoperative pain control without increasing opioid usage. The combination of enhanced patient education and reduced opioid prescribing may result in decreased opioid use, opioid abuse and medication costs.

Hexaminolevulinate Blue-Light Cystoscopy in a Patient with Metastatic Melanoma of the Bladder.

BACKGROUND: Although bladder cancer is one of the most frequently diagnosed tumors worldwide, metastatic melanoma of the bladder is a rare occurrence with only 29 cases reported in the literature. CASE PRESENTATION: We present the case of a 60-year-old male with a medical history significant for metastatic melanoma, who was referred to the urology department for gross hematuria. Transurethral resection of bladder tumor (TURBT) was performed with the assistance of hexaminolevulinate acid (HAL) with blue-light cystoscopy (BLC). Subsequent histopathologic analysis of the specimen confirmed a diagnosis of metastatic melanoma of the bladder. To our knowledge, this is the first reported case of metastatic bladder melanoma diagnosed with the assistance of HAL-BLC in a patient undergoing a TURBT. CONCLUSION: Although HAL-BLC is only indicated for use in the cystoscopic detection of papillary nonmuscle invasive bladder cancer, it may aid in the detection of nonconventional bladder pathologies, such as melanoma.

TOR complex 2 localises to the cytokinetic actomyosin ring and controls the fidelity of cytokinesis.

The timing of cell division is controlled by the coupled regulation of growth and division. The target of rapamycin (TOR) signalling network synchronises these processes with the environmental setting. Here, we describe a novel interaction of the fission yeast TOR complex 2 (TORC2) with the cytokinetic actomyosin ring (CAR), and a novel role for TORC2 in regulating the timing and fidelity of cytokinesis. Disruption of TORC2 or its localisation results in defects in CAR morphology and constriction. We provide evidence that the myosin II protein Myp2 and the myosin V protein Myo51 play roles in recruiting TORC2 to the CAR. We show that Myp2 and TORC2 are co-dependent upon each other for their normal localisation to the cytokinetic machinery. We go on to show that TORC2-dependent phosphorylation of actin-capping protein 1 (Acp1, a known regulator of cytokinesis) controls CAR stability, modulates Acp1-Acp2 (the equivalent of the mammalian CAPZA-CAPZB) heterodimer formation and is essential for survival upon stress. Thus, TORC2 localisation to the CAR, and TORC2-dependent Acp1 phosphorylation contributes to timely control and the fidelity of cytokinesis and cell division.

Increasing the Number of Outpatients Receiving Spiritual Assessment: A Pain and Palliative Care Service Quality Improvement Project.

BACKGROUND: Spirituality is a patient need that requires special attention from the Pain and Palliative Care Service team. This quality improvement project aimed to provide spiritual assessment for all new outpatients with serious life-altering illnesses. MEASURES: Percentage of new outpatients receiving spiritual assessment (Faith, Importance/Influence, Community, Address/Action in care, psychosocial evaluation, chaplain consults) at baseline and postinterventions. INTERVENTION: Interventions included encouraging clinicians to incorporate adequate spiritual assessment into patient care and implementing chaplain covisits for all initial outpatient visits. OUTCOMES: The quality improvement interventions increased spiritual assessment (baseline vs. postinterventions): chaplain covisits (25.5% vs. 50%), Faith, Importance/Influence, Community, Address/Action in care completion (49% vs. 72%), and psychosocial evaluation (89% vs. 94%). CONCLUSIONS/LESSONS LEARNED: Improved spiritual assessment in an outpatient palliative care clinic setting can occur with a multidisciplinary approach. This project also identifies data collection and documentation processes that can be targeted for improvement.

Qualitative inquiry: a method for validating patient perceptions of palliative care while enrolled on a cancer clinical trial.

BACKGROUND: Palliative care is a vital component of patient-centered care. It has increasingly become central to the management and care of seriously ill patients by integrating physical, psychosocial, and spiritual supportive services. Through qualitative inquiry, this paper examines cancer patients' perceptions of the process and outcomes of the pain and palliative care consultative services they received while enrolled in a clinical trial. METHODS: A qualitative analysis of open-ended questions was conducted from a sub-sample of patients (n = 34) with advanced cancers enrolled in a randomized controlled trial exploring the efficacy of a palliative care consult service. Two open-ended questions focused on patient perceptions of continued participation on their primary cancer clinical trials and their perceptions of interdisciplinary communication. RESULTS: THREE OVERARCHING THEMES EMERGED WHEN ASKED WHETHER RECEIVING PAIN AND PALLIATIVE CARE SERVICES MADE THEM MORE LIKELY TO REMAIN ENROLLED IN THEIR PRIMARY CANCER CLINICAL TRIAL: patients' past experiences with care, self-identified personal characteristics and reasons for participation, and the quality of the partnership. Four themes emerged related to interdisciplinary communication including: the importance of developing relationships, facilitating open communication, having quality communication, and uncertainty about communication between the cancer clinical trial and palliative care teams. CONCLUSIONS: Our findings suggest the importance of qualitative inquiry methods to explore patient perceptions regarding the efficacy of palliative care services for cancer patients enrolled in a cancer clinical trial. Validation of patient perceptions through qualitative inquiry regarding their pain and palliative care needs can provide insight into areas for future implementation research. TRIAL REGISTRATION: NIH Office of Human Subjects Research Protection OHSRP5443 and University of Pennsylvania 813365.

The nature of life-transforming changes among cancer survivors.

Some cancer survivors report positive subjective changes they describe as "life transforming." We used a grounded theory approach to identify the content, underlying process, and identifying characteristics of self-defined "life-transforming" changes (LTCs) reported by 9 cancer survivors. To actualize their hopes for improvement, participants used a self-guided process centered on pragmatic action: researching options, gaining experience, and frankly evaluating results. Many participants discovered unanticipated personal abilities and resources, and those became highly useful in coping with other challenges apart from cancer. This made the increased personal abilities and resources "life transforming" rather than being substantially limited to reducing cancer-related problems. The action-oriented features and processes of LTCs seemed to be more fully described by experiential learning theory than by posttraumatic growth and coping. Supportive intervention to facilitate positive change processes could decrease suffering and enhance positive psychosocial and spiritual outcomes for cancer survivors.

Obstructive azoospermia: reconstructive techniques and results.

Obstructive azoospermia is a common cause of male infertility and can result from infection, congenital anomalies, or iatrogenic injury. Microsurgical vasal reconstruction is a suitable treatment for many cases of obstructive azoospermia, although some couples will require sperm retrieval paired with in-vitro fertilization. The various causes of obstructive azoospermia and recommended treatments will be examined. Microsurgical vasovasostomy and vasoepididymostomy will be discussed in detail. The postoperative patency and pregnancy rates for surgical reconstruction of obstructive azoospermia and the impact of etiology, obstructive interval, sperm granuloma, age, and previous reconstruction on patency and pregnancy will be reviewed.