How pancreatic cancer impacts carers in the UK: why do we know so little?

BACKGROUND: Pancreatic cancer is a disease with poor life expectancy and high symptom burden. The experiences of the spouses, family and friends who care for this group is poorly understood, especially during palliative care and within the UK. AIMS: To highlight the current gaps within research and provide some insight into the challenges faced by carers assisting those living with pancreatic cancer, and how community nurses can support this group. METHODS: A total of five research databases were searched using the terms 'pancreatic cancer', 'carer' and 'experience'. Cancer and palliative charity websites were also referenced for grey literature. FINDINGS: There is limited research exploring pancreatic cancer carers experiences in the UK healthcare system and community. Available information suggests that this group is likely to face significant psychological and physical challenges to caring. CONCLUSIONS: It is vital for community nurses to have an awareness of challenges this group face, to better recognise and support these vulnerable carers.

Congenital pleuropulmonary blastoma in a newborn with a variant of uncertain significance in DICER1 evaluated by RNA-sequencing.

BACKGROUND: Pleuropulmonary blastoma (PPB) is a rare mesenchymal malignancy of the lung and is the most common pulmonary malignancy in infants and children. Cystic PPB, the earliest form of PPB occurring from birth to approximately two years of age, is often mistaken for a congenital pulmonary airway malformation, as the two entities can be difficult to distinguish on imaging and pathology. Diagnosis of PPB should prompt workup for DICER1 syndrome, an autosomal dominant tumor predisposition syndrome. We report a newborn with a congenital PPB presenting with tachypnea and hypoxia, who was found to have variant of uncertain clinical significance (VUS) in DICER1. CASE PRESENTATION: A term female infant developed respiratory distress shortly after birth. Initial imaging was concerning for a congenital pulmonary airway malformation versus congenital diaphragmatic hernia, and she was transferred to a quaternary neonatal intensive care unit for management and workup. Chest CT angiography demonstrated a macrocytic multicystic lesion within the right lower lobe without systemic arterial supply. The pediatric surgery team was consulted, and the neonate underwent right lower lobectomy. Pathology revealed a type I PPB. Oncology and genetics consultants recommended observation without chemotherapy and single gene sequencing of DICER1, which identified a germline VUS in DICER1 predicted to alter splicing. RNA-sequencing from blood demonstrated that the variant resulted in an in-frame deletion of 29 amino acids in a majority of transcripts from the affected allele. Due to the patient's young age at presentation and high clinical suspicion for DICER1 syndrome, tumor surveillance was initiated. Renal and pelvic ultrasonography were unremarkable. CONCLUSION: We present the case of a term neonate with respiratory distress and cystic lung mass, found to have a type I PPB with a germline VUS in DICER1 that likely increased her risk of DICER1-related tumors. Nearly 70% of patients with PPB demonstrate germline mutations in DICER1. Review of RNA sequencing data demonstrates the difficulty in classifying splice variants such as this. Penetrance is low, and many patients with pathogenic DICER1 variants do not develop a malignancy. Best practice surgical and oncologic recommendations include an individualized approach and tumor board discussion. This case highlights the importance of a multidisciplinary team approach and the utility of international registries for patients with rare diagnoses.

Instruments for determining clinically relevant fatigue in breast cancer patients during radiotherapy.

BACKGROUND: This study aimed to determine radiotherapy (RT)-related changes in cancer-related fatigue (CRF), using Multidimensional Fatigue Inventory-20 (MFI-20), and fatigue-intensity rating (FIR) instruments at three different timepoints and to identify the optimal thresholds of MFI-20 scores which would correlate with moderate-to-severe fatigue warranting an intervention in breast cancer patients treated with RT. METHODS: Eighty-eight breast cancer patients treated with surgery followed by RT were included in the study. CRF was assessed with both FIR and MFI-20 tools at three different timepoints: within the week prior to RT (pre-RT), last week of RT, and 6 weeks after RT completion (post-RT). Changes in measurements, correlations between measurements and optimal cutpoints of MFI-20 scores were analyzed. RESULTS: While FIR scores significantly changed over time (η2: 0.179), changes in MFI-20 scores were relatively small (η2: 0.076). Comparisons of the last week of RT versus post-RT scores showed small-to-moderate decrease for MFI-20 and FIR. FIR and MFI-20 scores were correlated at all timepoints and most correlated during and after RT (r = 0.525 95%CI 0.346-0.667, r = 0.791 95%CI 0.692-0.860 and r = 0.716 95%CI 0.589-0.808, respectively). Furthermore, the most correlated MFI-20 subscale with FIR was general fatigue (r = 0.603 95%CI 0.442-0.725, r = 0.821 95%CI 0.734-0.881 and r = 0.754 95%CI 0.641-0.835, respectively). Optimal cutpoints of the MFI-20 total scores corresponding to FIR scores ≥ 4 was 43.5 for all timepoints and the MFI total scores corresponding to FIR score ≥ 7 were 53.5, 52.5 and 60.5, respectively. CONCLUSIONS: MFI-20 and FIR scores are highly correlated measures of CRF among breast cancer patients treated with RT. An MFI-20 score of ≥ 43.5 is suggested as a clinically significant score indicating moderate-to-severe fatigue, while an MFI score of ≥ 52.5 is indicative of severe fatigue.

Impact of Regional Nodal Irradiation and Hypofractionated Whole-Breast Radiation on Long-Term Breast Retraction and Poor Cosmetic Outcome in Breast Cancer Survivors.

PURPOSE: We performed a prospective longitudinal study to determine predictors of long-term breast asymmetry in breast cancer patients treated with breast-conserving surgery and whole-breast external-beam radiotherapy (XRT). PATIENTS AND METHODS: A total of 109 patients with stage 0 to III breast cancer treated with breast-conserving surgery followed by conventional (50 Gy plus boost) or hypofractionated (39.9 Gy with simultaneous integrated boost of 48 Gy) XRT were enrolled onto 2 studies of XRT-induced skin toxicity before (baseline), during, and 1 year after XRT. Using baseline and 1-year post-XRT photographs, breast asymmetry was objectively quantified by calculating the percentage breast retraction assessment (pBRA), with larger values indicating more asymmetry. Skin thickness ratio (STRA) values were calculated using ultrasound images. Univariate and multivariate analyses were conducted to determine the relationship among STRA-, patient-, tumor-, and treatment-related factors, and pBRA. RESULTS: Seventy-one patients (65%) had more breast asymmetry (positive change in pBRA) 1 year after XRT relative to baseline. Only pre-XRT STRA was associated with a higher pre-XRT baseline pBRA in multivariate analysis (P = .02). Larger breast volume, baseline pBRA, conventionally fractionated (vs. hypofractionated) XRT, supraclavicular nodal irradiation, and higher STRA at 1 year predicted for higher long-term pBRA in the multivariate model (all P < .05). Breast volume and supraclavicular nodal irradiation were associated with the largest changes in breast asymmetry (all P < .05). CONCLUSION: This prospective longitudinal study confirmed the known impact of breast volume, surgery, and XRT on breast asymmetry. We also found that supraclavicular nodal irradiation and conventionally fractionated XRT are associated with worse cosmetic outcome 1 year after XRT.

Full axillary lymph node dissection and increased breast epidermal thickness 1 year after radiation therapy for breast cancer.

BACKGROUND: We previously reported a prospective study showing axillary lymph node dissection (ALND) is associated with increased breast skin thickening during and 6 weeks post-radiation therapy (RT), and now report ALND's long-term impact at 1 year. METHODS: Among 66 women who received whole breast RT after lumpectomy, objective ultrasound measurements of epidermal thickness over four quadrants of the treated breast were measured at five time points: before RT, week 6 of RT, and 6 weeks, 6 months, and 1 year post-RT. Skin thickness ratio (STRA) was generated by normalizing for corresponding measurements of the contralateral breast. RESULTS: A total of 2,436 ultrasound images were obtained. Among 63 women with evaluable data at 1 year, mean STRA significantly increased at 6 months (absolute mean increase of 65%, SD 0.054), and remained elevated at 1 year post-RT (absolute mean increase of 44%, SD 0.048). In multivariable analysis, ALND compared to sentinel lymph node biopsy, longer interval between surgery and RT, increased baseline STRA, and Caucasian race predicted for more severe changes in STRA at 1 year compared to baseline (all P < .05). CONCLUSIONS: In the setting of whole breast RT, our findings suggest that ALND has long-term repercussions on breast skin thickening.

Tumor necrosis factor-α inhibitor-induced psoriasis: Systematic review of clinical features, histopathological findings, and management experience.

BACKGROUND: Tumor necrosis factor-α (TNF-α) inhibitors have been reported to induce new-onset psoriasis. OBJECTIVE: To better define the demographic, clinical features, and treatment approach of TNF-α inhibitor-induced psoriasis. METHODS: Systematic review of published cases of TNF-α inhibitor-induced psoriasis. RESULTS: We identified 88 articles with 216 cases of new-onset TNF-α inhibitor-induced psoriasis. The mean age at psoriasis onset was 38.5 years. The most common underlying diseases were Crohn disease (40.7%) and rheumatoid arthritis (37.0%). Patients underwent TNF-α therapy for an average of 14.0 months before psoriasis onset with 69.9% of patients experiencing onset within the first year. The majority of patients received skin-directed therapy, though patients who discontinued TNF therapy had the greatest resolution of symptoms (47.7%) compared with those who switched to a different TNF agent (36.7%) or continued therapy (32.9%). LIMITATIONS: Retrospective review that relies on case reports and series. CONCLUSION: While TNF-α inhibitor cessation may result in resolution of induced psoriasis, lesions may persist. Decisions regarding treatment should be weighed against the treatability of TNF-α inhibitor-induced psoriasis, the severity of the background rheumatologic or gastrointestinal disease, and possible loss of efficacy with cessation followed by retreatment. Skin-directed therapy is a reasonable initial strategy except in severe cases.

The dermatologic intimacy scale: quantitatively measuring the impact of skin disease on intimacy.

INTRODUCTION: Patient-reported outcome measures are increasingly utilized in dermatology to assess the impact of skin disease on quality of life. Despite recognition of the influence of skin disease on intimate relationships, an instrument to assess intimacy has not been developed. The objective of this study was to create the dermatologic intimacy scale (DIS) and administer the prototype to a patient population. METHODS: A group of healthcare providers at the University of California San Francisco created the DIS prototype. A total of 1676 psoriasis patients of an online community were invited to complete a cross-sectional survey including demographic information, DIS, body surface area (BSA) and anatomical involvement. RESULTS: A total of 1109 patients completed the survey in its entirety. Patients with moderate-to-severe psoriasis (BSA ≥3%) had a higher DIS score overall and for each individual question than patients with mild disease (BSA < 3%; p < .001). Patients with genitalia, nails, face, neck and scalp involvement had higher scores compared to patients without involvement (p < .001). CONCLUSIONS: Patients with more extensive disease and specific anatomical involvement experience a greater impact on intimacy. Interpretation is limited by patient response rate, as patients with or without intimacy issues may be more or less likely to respond. Further analysis is necessary for validation and interpretation.

Long-term spatiotemporal stability and dynamic changes in helminth infracommunities of bank voles (Myodes glareolus) in NE Poland.

Parasites are considered to be an important selective force in host evolution but ecological studies of host-parasite systems are usually short-term providing only snap-shots of what may be dynamic systems. We have conducted four surveys of helminths of bank voles at three ecologically similar woodland sites in NE Poland, spaced over a period of 11 years, to assess the relative importance of temporal and spatial effects on helminth infracommunities. Some measures of infracommunity structure maintained relative stability: the rank order of prevalence and abundance of Heligmosomum mixtum, Heligmosomoides glareoli and Mastophorus muris changed little between the four surveys. Other measures changed markedly: dynamic changes were evident in Syphacia petrusewiczi which declined to local extinction, while the capillariid Aonchotheca annulosa first appeared in 2002 and then increased in prevalence and abundance over the remaining three surveys. Some species are therefore dynamic and both introductions and extinctions can be expected in ecological time. At higher taxonomic levels and for derived measures, year and host-age effects and their interactions with site are important. Our surveys emphasize that the site of capture is the major determinant of the species contributing to helminth community structure, providing some predictability in these systems.

Clinical Utilization of Repeated Open Application Test Among American Contact Dermatitis Society Members.

BACKGROUND: The repeated open application test (ROAT) provides useful information regarding allergens in suspected cases of allergic contact dermatitis; however, standardized methodology has not been established. OBJECTIVE: The aim of this study was to assess how ROAT is used in clinical and research settings. METHODS: We distributed a survey regarding ROAT practice to the American Contact Dermatitis Society and conducted a literature review of ROAT utilization in research. RESULTS: A total of 67 American Contact Dermatitis Society members participated in the survey. Respondents most frequently recommend application of leave-on products twice daily (46.0%) and rinse-off products once daily (43.5%). The most commonly used anatomical sites include the forearm (38.7%) and antecubital fossa (32.3%). Most respondents continue ROAT for 1 (49.2%) or 2 weeks (31.7%). Literature review of 32 studies (26 leave-on, 6 rinse-off) revealed that application frequency is most common at twice daily for both leave-on (96.2%) and rinse-off (50.0%) products. The most common anatomical site is the forearm (62.5%), with an overall study duration of 3 to 4 weeks (65.6%). CONCLUSIONS: When comparing ROAT clinical and research practice, the majority trend was consistent for leave-on product application frequency and anatomical site, but not for rinse-off product application frequency, or overall duration. Further research is needed to determine best practice recommendations.

Psychodermatology.

Psychodermatology is an underappreciated field that studies psychocutaneous disorders, which are conditions that have both dermatologic and psychiatric characteristics. Underlying psychiatric comorbidity is estimated to occur in up to one-third of dermatologic patients, and psychiatric illness may either be the cause or the consequence of dermatologic disease. Psychodermatologic patients lack insight and often do not recognize a psychiatric etiology for their symptoms and therefore comprise some of the most challenging cases to treat. Herein, we discuss the background and clinical presentation of the most commonly encountered psychodermatologic conditions, including delusional infestation, neurotic excoriations, factitial dermatitis, trichotillomania and body dysmorphic disorder, followed by practical diagnostic and therapeutic recommendations.

Enhancing patient satisfaction in dermatology.

Patient satisfaction is an important component of dermatological care that reflects patients' perspectives on the care they receive. While physicians' expertise and judgment should always remain the foundation of providing appropriate and effective care, the patient experience can also be influenced by interpersonal relationships, expectations, and a sense of agency in the treatment patients receive. Dermatology providers can use practical techniques such as sitting rather than standing, reframing the concept of cure, and engaging patients in treatment decisions to improve the patient-provider experience and thereby optimize patient satisfaction.

Supraerythemogenic excimer laser in combination with clobetasol spray and calcitriol ointment for the treatment of generalized plaque psoriasis: Interim results of an open label pilot study.

BACKGROUND: The combination of phototherapy and topical therapy is one of the most widely used treatment modalities for moderate to severe psoriasis. The development of targeted phototherapy with excimer laser and new topical spray formulations has made these therapies both more convenient and more effective. In this open label pilot study, we aim to assess the efficacy of combination therapy using 308-nm excimer laser, clobetasol propionate spray and calcitriol ointment for the treatment of moderate to severe generalized psoriasis. METHODS: In this 12-week study, patients with moderate to severe psoriasis received twice weekly treatment with XTRAC® Velocity 308-nm excimer laser combined with clobetasol propionate twice daily followed by calitriol ointment twice daily. RESULTS: To date, 21 patients have completed the protocol. By week 12, 76% of the patients had a reduction in Psoriasis Area and Severity Index by at least 75% (PASI-75) and 52% had a Physicians Global Assessment of "clear" or "almost clear". CONCLUSIONS: Excimer laser therapy combined with an optimized topical regimen that includes clobetasol spray followed by calictriol ointment appears to be an effective treatment for moderate to severe generalized psoriasis that avoids the risk of serious internal side effects associated with many systemic agents.

Anti-IL-17 phase II data for psoriasis: A review.

UNLABELLED: Abstract Background: Studies investigating the molecular basis of psoriasis have established the central roles of TNFα, interleukin (IL)-12, IL-22 and IL-23 and there is increasing evidence that IL-17 plays a critical role in the complex pathophysiology. Preclinical studies suggest that IL-17 is a desirable therapeutic target for psoriasis treatment. METHODS: We reviewed the results of the phase II clinical trials for the anti-IL-17 agents secukinumab, ixekizumab and brodalumab in order to assess the efficacy and safety profile of each agent. RESULTS: By week 12, the proportion of patients reaching Psoriasis Area and Severity Index (PASI 75) was comparable among the most efficacious dosage between the different agents (secukinumab 82%, ixekizumab 83% and brodalumab 82%; p<0.001 compared to placebo for all agents). The safety profiles of the agents were similar with the most frequently reported adverse events of nasopharyngitis, upper respiratory infections and injection site reaction. A small percentage of patients experienced low-grade neutropenia that was predominantly transient and asymptomatic. CONCLUSION: The anti-IL-17 agents demonstrated a rapid and robust clinical improvement accompanied by a favorable short-term safety profile. The results of the phase II trials support the theory that the IL-17 pathway is an essential target in psoriasis treatment.

The role of IL-17 in psoriasis.

BACKGROUND: Psoriasis is a chronic skin condition traditionally believed to involve the Th1 pathway. Recently, the IL-23/Th17/IL-17 pathway has been highlighted in the pathogenesis of psoriasis and other autoimmune inflammatory conditions. From a clinician's perspective, we sought to review the basic science data relevant to IL-17's role in psoriasis pathogenesis. METHODS: We performed a Pubmed and Web of Knowledge search for English articles starting from 1990 that discussed the Th17 pathway. Search terms such as "IL-17" and "psoriasis" were utilized. RESULTS: The IL-17 pathway is regulated by IL-23, a cytokine that is vital for the expansion and maintenance of the Th17 cell population. Th17 derived cytokines (IL-17A, IL-17F, IL-17A/F and IL-22) were elevated in both psoriasis-like murine models and human psoriatic lesional biopsies. Ixekizumab (anti-IL-17A) treatment of psoriasis was found to normalize levels of IL-17 downstream gene products. CONCLUSION: Both preclinical and clinical studies support the central role of IL-17 in the pathogenesis of psoriasis.

How to optimally manage unhappy, anxious, and difficult patients.

Patient satisfaction has been and is of growing importance in healthcare. Recent healthcare initiatives aim to provide physicians with performance feedback reports based partially on patient completed surveys; thus, patient satisfaction will be an even more important determinant of high quality care. In the field of dermatology, patient satisfaction is particularly relevant and at times difficult to achieve, since many patients are plagued with chronic skin diseases often requiring intensive topical regimens or undesirable systemic immunosuppressants. The discussion of patient satisfaction is usually restricted to encounters with the general clinic population leaving encounters with difficult patients largely underreported; therefore, we provide examples of more common difficult patient encounters a dermatologist may face with specific recommendations on how to best optimize patient satisfaction.

Eruptive nodules of the head and neck: a case report of metastatic prostate cancer.

Cutaneous metastasis is an uncommon but well recognized phenomenon occurring as a result of internal malignancy. Cancers most often associated with cutaneous metastasis are melanoma and primary malignancies of the breast and head and neck. Cutaneous metastatic prostate cancer is rare, representing only 1% of cases. Herein we report a case of advanced prostate cancer with multiple cutaneous metastases and briefly review the literature highlighting the clinical and histopathological features as well as a management approach to the patient with metastatic prostate cancer involving the skin.

"Almost bleeding to death": the conundrum of acquired amegakaryocytic thrombocytopenia.

Acquired amegakaryocytic thrombocytopenia (AAT) is a rare hematological disorder causing severe thrombocytopenia and bleeding. Previous in vitro studies postulated both cell-mediated suppression of megakaryocytopoiesis in early megakaryocytic progenitor cells and humoral-mediated suppression by anti-thrombopoietin antibodies as possible etiologies of AAT. Patients with AAT usually present with severe bleeding and thrombocytopenia that is unresponsive to steroids and intravenous immunoglobulin (IVIG). Although standard guidelines have not been established for management of AAT, a few case reports have indicated a response to immunosuppressive treatment. The prompt recognition of this disease entity is essential in view of the substantial risk of morbidity and mortality from excessive bleeding. We report a case of AAT successfully treated with equine antithymocyte globulin (ATG) and cyclosporine (CSP).

Biologic fatigue in psoriasis.

BACKGROUND: Over the past 15 years, biologic medications have greatly advanced psoriasis therapy. However, these medications may lose their efficacy after long-term use, a concept known as biologic fatigue. We sought to review the available data on biologic fatigue in psoriasis and identify strategies to help clinicians optimally manage patients on biologic medications in order to minimize biologic fatigue. METHODS: We reviewed phase III clinical trials for the biologic medications used to treat psoriasis and performed a PubMed search for the literature that assessed the loss of response to biologic therapy. RESULTS: In phase III clinical trials of biologic therapies for the treatment of psoriasis, 20-32% of patients lost their PASI-75 response during 0.8-3.9 years of follow-up. A study using infliximab reported the highest percentage of patients who lost their response (32%) over the shortest time-period (0.8 years). Although not consistently reported across all studies, the presence of antidrug antibodies was associated with the loss of response to treatment with infliximab and adalimumab. CONCLUSION: Biologic fatigue may be most frequent in those patients using infliximab. Further studies are needed to identify risk factors associated with biologic fatigue and to develop meaningful antidrug antibody assays.

Successful use of the excimer laser for generalized psoriasis in an ustekinumab non-responder.

Effective treatments for moderate to severe psoriasis are phototherapy and biologics. These treatments are similar in that they both decrease cutaneous immune system hyperactivity yet do so via different mechanisms. Our patient, a 63 year old Asian male had a rapid response to treatment with the high dose excimer laser, having previously failed treatment with 28 weeks of ustekinumab therapy. A pre-treatment biopsy of a psoriatic plaque was found to contain relatively low levels of IFN-γ (Th1) and IL-17 (Th17) secreting T cells. Following treatment with the excimer laser, the patient had a quick improvement in PASI that was reflected by a 3-fold reduction in the number of live T cells found in the post-treatment biopsy. Although ustekinumab and the excimer laser both result in decreased levels of these cytokines, the excimer laser directly causes apoptosis of T cells and induces DNA damage in antigen presenting cells. Thus, the broader effects of phototherapy on immune cells compared to the targeted inhibition of IL-12 and IL-23 by ustekinumab likely account for the superior response observed.