Prostate cancer: the influence of stigma on quality of life and relationship satisfaction for survivors and their partners

Objectives: Prostate cancer (PCa) stigma and its relationship to quality of life (QoL) is a relatively new finding. As the experiences of couples facing PCa are shared, the study examined the relationship between of PCa stigma, QoL, and relationship satisfaction of PCa survivors and their spouses.

Design: A correlational design with dyadic data was used.

Sample: Participants (N?=?80 dyads) were PCa survivors and their spouses sampled from an oncology center and PCa support groups.

Methods: Structural equation modeling was used to assess how stigma related to the QoL and relationship satisfaction of participants.

Findings: Stigma had a negative association with QoL, but not relationship satisfaction. There were no significant demographic differences in regards to stigma.

Conclusion: Overall, stigma has a relationship with the experience of couples, but not with every aspect of their experience.

Implications for psychosocial providers: Implications for clinicians in regards to addressing PCa stigma with clients and areas for future research are discussed.     

Benefits,challenges, and needs of people living with cancer and their companion dogs: An exploratory study

Purpose/Objectives: The study examined whether the bond with a companion dog is associated with well-being among people with cancer, and described the perceived benefits, challenges, and needs accompanying the relationship with the dog.

Design: The design was cross-sectional.

Sample: Participants were 140 people recently diagnosed with cancer with at least one dog in their household.

Methods: The online survey included measures of the human–pet bond, depressive symptoms, positive affect, and health-related quality of life, as well as open-ended questions about the experience of having a dog since being diagnosed with cancer.

Findings: Although the bond with a companion dog was not directly linked with well-being, the association between the human–pet bond and depressive symptoms depended in part on treatment status.

Conclusions: Companion dogs may play an important role in the lives of people recently diagnosed with cancer.

Implications for psychosocial providers: Health care providers can help to support the bond with a companion dog.     

Goal disturbance in early-stage breast cancer survivors

Purpose: Cancer-related goal disturbance can influence long-term outcomes in cancer patients and survivors; however, few studies have examined the factors that contribute to goal disturbance in early survivorship.

Design: The current study examined the relationships between demographic variables, cancer- and treatment-related factors, and behavioral and psychological symptoms (i.e., fatigue, pain, cognitive complaints, depressive symptoms, and anxiety) and goal disturbance in breast cancer survivors 1?year after treatment completion.

Methods: Women diagnosed with early-stage breast cancer (n?=?171) completed assessments following primary treatment (i.e., surgery, radiation, and chemotherapy) and again 6?months and 1?year later. We focused on the 1-year post-treatment assessment when participants were asked if they had experienced a cancer-related goal disturbance.

Findings: Approximately, 27% of women reported a cancer-related goal disturbance. Analyses indicated that both receipt of chemotherapy and behavioral and psychological symptoms—analyzed as a composite score and individually—were associated with a higher probability of reporting a goal disturbance.

Conclusions: Chemotherapy and behavioral and psychological symptoms were unique correlates of goal disturbance, suggesting that the impact of chemotherapy extends beyond its influence on persistent symptoms.

Implications: Elucidating factors that inhibit the pursuit of meaningful activities in early survivorship is critically important to understanding the long-term psychosocial impacts of cancer diagnosis and treatment.     

Microwave ablation of hyperplastic parathyroid glands is a treatment option for end-stage renal disease patients ineligible for surgical resection

Background: Secondary hyperparathyroidism (SHPT) is a frequently encountered problem in patients with end-stage renal disease (ESRD). Some patients with severe SHPT could not be managed by medical treatment and are ineligible for surgical resection.

Purpose: Our objective was to evaluate the efficacy, safety of microwave ablation (MWA) on these patients.

Materials and Methods: Between 1 April 2015 and 28 February 2017, 35 patients (M/F 19/16, age 49.8?±?12.9?years) were enrolled. All patients were treated with MWA. Levels of intact parathyroid hormone (iPTH) and of serum calcium and phosphorus were compared pre- and post-ablation. Repeated-measures ANOVA was used to compare treatment outcomes pre- and post-ablation.

Results: Complete ablation was achieved in all 63 glands in the 35 patients with SHPT. The mean follow-up time was 15.9?±?2.2?months. The maximum gland diameter was 6–31?mm (mean, 14.9?±?5.5?mm). The trends of the changes in iPTH and calcium levels showed a curve: the level of iPTH and calcium at 6?months post-ablation were lower than those pre-ablation (both p?<?.0001); after then iPTH remained relatively stable and the end of follow up, with no rebound (p?<?.0001), while instead of calcium at the end of follow up was not significantly lower than pre-ablation (p?=?.462). The trend in the change in phosphate levels showed a straight line; the level of phosphate at 6?months post-ablation and at the end of follow up both were significantly lower than pre-MWA (p?<?.001). There was no major complication.

Conclusions: In this series, MWA was used successfully to treat SHPT patients who are ineligible for surgical resection.     

Percutaneous renal mass biopsy: historical perspective,current status,and future considerations

Introduction: Percutaneous renal mass biopsy has evolved over the last decade with improvements on previous pitfalls including low tissue yield, high non-diagnostic rates, and complications. As understanding of tumor biology and natural history of renal cortical neoplasms has improved, percutaneous renal mass biopsy is poised to have an expanding role in an area characterized by individualized management and refined risk stratification.

Areas covered: This review summarizes the evolution of renal mass biopsy to its current state with respect to outcomes, indications, and clinical guidelines.

Expert opinion: With improved understanding of differential biological potential of renal cortical neoplasms combined with technical improvements in diagnostic yield and accuracy, utilization of renal mass biopsy is becoming an important adjunct to patient care in a broad range of clinical scenarios, including active surveillance, thermal ablation, and use of primary systemic therapy in localized and advanced settings.     

The self-reported perceptions of the repercussions of the disease and its treatments on daily life for young women with breast cancer and their partners

Purpose: This study aimed to compare the self-reported perceptions of the repercussions of the disease and its treatments and emotional distress in young women with breast cancer and their partners.

Design: Cross-sectional study using self-reported questionnaires.

Sample: 491 couples in which women were aged <45?years when diagnosed with non-metastatic breast cancer in four different groups of treatment: during chemotherapy with or without Trastuzumab; under Trastuzumab with or without hormone therapy; during hormone therapy; and during the follow-up period.

Methods: Patients and partners completed a questionnaire assessing their self-reported perceptions of the disease and treatments (Patient YW-BCI and Partner YW-BCI for the partners) and their emotional distress (CESD; STAI).

Findings: Patients reported more difficulties than partners in the management of child(ren) and everyday life, body image and sexuality, negative affectivity about the disease and apprehension about the future, career management, and finances. While the difficulties were generally more marked in the chemotherapy and Trastuzumab groups than in the hormone therapy and follow-up groups, the negative affectivity about the disease and apprehension about the future was high in all four groups, especially in patients. The partners reported more difficulties in sharing with close relatives, and even more in those groups reflecting the latest treatment phases. No difference appeared between patients and partners in couple cohesion and deterioration of relationships with relatives. Partners were less anxious than patients but as depressed as them.

Conclusions: Difficulties of patients and partners seem particularly severe in the early care pathway, maybe reflecting better adjustment in women under surveillance and their partners. A longitudinal study will substantiate this finding and enable a better identification of some explanatory processes of these differences and similarities in the daily self-reported repercussions of the disease throughout the cancer care pathway.

Implications for psychosocial oncology: It seems important to support young women with breast cancer and their partners, as our results evidence distress in both and differences according to the type of treatment the woman is currently receiving. Healthcare providers need consistent methods to identify and respond to couples’ distress and reduce significant disparities in support.     

Prevalence of psychosocial distress in cancer patients across 55 North American cancer centers

Routine distress screening in United States oncology clinics has been mandatory since 2015.

Objective: This study was the first to assess distress in a geographically diverse sample of cancer patients following mandated distress screening implementation by oncology social workers.

Methods: Sites were self-selected via social workers who applied to participate in the Association of Oncology Social Work’s Project to Assure Quality Cancer Care, advertised through their social media outlets and conference. Electronic screening records were collected from 55 cancer treatment centers in the United States and Canada. Cases required cancer diagnoses and Distress Thermometer (DT) scores to be included. Distress rates and rates by age, sex, cancer type, and ethnicity were examined.

Results: Of 4664 cases, 46% (2157) experienced significant distress (DT score?≥?4). Being female, age 40-59, and having diagnoses of pancreatic or lung cancer was associated with increased likelihood of distress. Half of cases experience clinically-significant distress, though this need was not evenly distributed across patient or cancer types.

Conclusion: Identifying those at risk for distress may help inform optimal resource allocation. Methods to address needs of distressed patients in cases of limited resources are discussed.     

Ixazomib promotes CHOP-dependent DR5 induction and apoptosis in colorectal cancer cells

Background: Ixazomib (Ninlaro), a novel proteasome inhibitor, has been developed for the treatment of many cancers and has demonstrated anti-tumor efficacy against various malignancies. However, the mechanism of the anti-tumor effect of ixazomib in colorectal cancer (CRC) cells remains unclear.

Methods: MTS and flow cytometry were performed to determine the effect of ixazomib on CRC cells. Western blotting and real-time RT-PCR were performed to detect ixazomib-induced DR5 upregulation. ChIP was performed to detect CHOP binding to DR5 promoter. Finally, xenograft experiments were carried out to measure the antitumor effect of ixazomib in vivo.

Results: In this study, we revealed the mechanism by which ixazomib inhibits the growth of CRC cells. Our findings indicated that ixazomib treatment induces CHOP-dependent DR5 induction, irrespective of p53 status. Furthermore, DR5 is necessary for ixazomib-mediated apoptosis. Ixazomib also synergized with TRAIL to induce marked apoptosis via DR5 in CRC cells.

Conclusions: Our findings further suggested that ixazomib sensitizes TRAIL/death receptor signaling pathway-targeted CRC and suggested that DR5 induction could be a valuable indicator of ixazomib sensitivity.     

Family dynamics in young adult cancer caregiving: “It should be teamwork”

Purpose/Objectives: Young adult cancer patients undergo stress at a time when their primary source of psychosocial support may be changing. Our goal was to provide insight into the expectations young adult patients and their family caregivers for types of psychosocial support.

Research Approach: Semi-structured interviews.

Participants: Fifteen patients, 9 caregivers recruited from an AYA clinic.

Methodological Approach: Thematic content analysis using the constant comparison method.

Findings: Two themes were identified. First, families described coordinating support around strengths to determine who would take on caregiving roles/tasks. Second, families described the importance of patient-caregiver relationship status/history in determining trust and expectations.

Interpretation: Family strengths and existing relationships can impact caregiving roles and expectations for families of young adult cancer patients.

Implications for Psychosocial Providers: Cancer clinics may need to involve members of the psychosocial provider team to better understand the family dynamics of their patients and how these relate to support.     

Proteomic and bioinformatic analysis of condyloma acuminata: mild hyperthermia treatment reveals compromised HPV infectivity of keratinocytes via regulation of metabolism,differentiation and anti-viral responses

Background: Hyperthermia has proved successful in treating cutaneous human papillomavirus infectious diseases such as plantar wart and condyloma acuminata (CA). Moreover, this treatment provides improved therapeutic efficacy in these conditions as compared with conventional therapies.

Objectives: To investigate the global proteome changes in CA in response to hyperthermia and achieve a better understanding of the mechanisms of hyperthermia therapy against HPV-infectious diseases.

Methods: CA tissue was obtained from patients undergoing pathological examinations. Diagnosis was verified as based on results of both HE staining and HPV-DNA PCR assay. Hyperthermia was achieved with a 44?°C water bath. Differentially expressed proteins (DEPs) were identified by iTRAQ labeling, SCX chromatography and LC-MS/MS assay. Validation of proteomic results was performed using real-time qPCR and western blot, while bioinformatic analysis of DEPs was accomplished by R 3.4.1, STRING and Cytoscape softwares.

Results: In response to hyperthermia, a total of 102 DEPs were identified with 37 being upregulated and 65 downregulated. Among these DEPs, hyperthermia induced proteins involved with anti-viral processes such as OAS1, MX1, BANF1, CANX and AP1S1, whereas it inhibited proteins that participated in cellular metabolism, such as GALT, H6PD, EXOSC4 and EXOSC6; protein translation, such as RPS4Y1; as well as keratinocyte differentiation, such as KRT5, KRT27, KRT75, KRT76 and H2AFY2.

Conclusions: Hyperthermia inhibited enzymes and molecules responsible for metabolism modulation and keratinocyte differentiation in CA tissue, whereas it promoted factors involved in anti-viral responses. Such effects may, in part, contribute to the efficacy of local hyperthermia therapy against HPV infection.     

The use of cytoreductive nephrectomy in patients with renal cell carcinoma

Introduction: The systemic options for managing metastatic renal cell carcinoma (mRCC) have expanded considerably over the past decade. Initially limited to cytokines, clinicians may now choose from several classes of targeted therapies and, most recently, immune checkpoint inhibitors.

Areas covered: In this review, we discuss the role and timing of cytoreductive nephrectomy (CN) and its evolution starting with cytokines, and then alongside the emergence of targeted therapy and novel immunotherapy with immune checkpoint inhibitors. Patient selection remains the most critical determinant in offering CN, and the anticipated survival benefits of CN must be weighed against the surgical morbidity and potential delay to receipt of systemic therapies.

Expert opinion: Proper patient selection is key for decision-making in mRCC. Prospective data is urgently needed to define the role of CN in the contemporary immunotherapy era, with greater personalization of prognostic models.     

Starvation in cancer cells: circulating arginine is good for cancer but bad for patients

Introduction: Currently, basic understanding of heterogeneity and complexity of tumors is depicted at molecular, cellular, genetic, epigenetic and metabolic adaptations levels.

Areas covered: There are appreciable numbers of views to pinpoint signaling axis that support metabolic adaptations of cancer cells in response to environmental pressures including nutritional factors and drug treatments. Specifically, nutritional deprivation and autophagy in certain types of cancer are linked to the abilities of cancer cells to use arginine in an auxotrophic or prototrophic manner.

Expert opinion: Hence, this paper highlights the current scope of arginine- and autophagy-centered metabolic adaptations across tumor types and possible avenues to bring tumors towards cytotoxic or cytostatic death.     

Ultrasound-guided percutaneous microwave ablation versus surgical resection for recurrent intrahepatic cholangiocarcinoma: intermediate-term results

Objective: The aims of this study were to compare the clinical outcomes between ultrasound-guided percutaneous microwave ablation (US-PMWA) and surgical resection (SR) in patients with recurrent intrahepatic cholangiocarcinoma (ICC) and to identify the prognostic factors associated with the two treatment methods.

Methods: This retrospective study was institutional review board approved. A total of 121 patients (102 men and 19 women) with 136 ICCs after hepatectomy from April 2011 to January 2017 were reviewed. Fifty-six patients underwent US-PMWA and 65 patients underwent SR. Survival, recurrence and liver function were compared between the two groups. Effect of changes in key parameters [i.e., overall survival (OS) and recurrence-free survival (RFS)] was statistically analyzed with the log-rank test. Univariate and multivariate analysis were performed on clinicopathological variables to identify factors affecting long-term outcome.

Results: The OS and RFS after MWA were comparable to that of SR (p?=?.405, and p?=?.589, respectively). Estimated 5-year OS rates were 23.7% after MWA and 21.8% after SR; for RFS, estimated 3-year RFS rates were 33.1% after MWA and 30.6% after SR. Major complication rates in SR group were higher than that in MWA (p?<?.001) (SR, 13.8% vs. MWA, 5.3%). Multivariate analysis showed tumor number (p?=?.012), ALBI grade (p?=?.007), and metastasis (p?=?.016), may become OS rate predictors.

Conclusions: US-PMWA had comparable oncologic outcomes with SR and could be a safe and effective treatment for recurrent ICC after hepatectomy.     

Factors influencing MR changes associated with sacral injury after high-intensity focused ultrasound ablation of uterine fibroids

Purpose: We investigated the risk factors influencing MR changes associated with sacral injury from ultrasound-guided high-intensity focused ultrasound (USgHIFU) ablation for uterine fibroids.

Methods: We retrospectively analyzed a total of 346 patients with symptomatic uterine fibroids who received USgHIFU ablation. All of the patients underwent contrast-enhanced magnetic resonance imaging (CE-MRI) before and after treatment. Injury to the sacrum was set as the dependent variable, while fibroid features and the treatment parameters were set as independent variables. These variables were used to assess respectively their correlation with sacral injury by using univariate and multivariate analyses.

Results: The results of univariate analysis revealed that the volume, distance from the fibroid to the skin, maximal diameter, distance from the fibroid to the sacrum, fibroid types, degree of enhancement, therapeutic dosimetry (TD), energy efficiency factor (EEF) and non-perfused volume (NPV) ratio manifested significant correlations with the sacral injury (p?<?.05). Multivariate analysis showed that the degree of enhancement, TD and EEF were independent risk factors for sacral injury (p?<?.05), while the distance from fibroid to sacrum and intramural or subserosal types were protective factors (p?<?.05). The incidence of sacral tail pain and leg pain showed a significant positive correlation with sacral injury (p?<?.05).

Conclusion: As important affecting factors, the degree of enhancement, distance from fibroid to sacrum and fibroid types all possess significant correlations with MR changes associated with sacral injury.     

Precoagulation with microwave ablation for hepatic parenchymal transection during liver partial resection

Purpose: To evaluate the feasibility of precoagulation with microwave ablation (MWA) for hepatic parenchymal transection during liver partial resection.

Methods: A total of 66 eligible patients were enrolled in this double-blind, randomized, controlled study. Patients were randomized to receive either the traditional clamp-crushing method (Control group) or the MWA precoagulation method (MWA group) for hepatic parenchymal transection during liver partial resection. The operative time, hepatic portal occlusion time, intraoperative blood loss and transfusion, postoperative complications and recovery outcomes were compared.

Results: Compared to the Control group, the MWA group had significantly less intraoperative blood loss. Fewer red blood cell transfusions were observed in the MWA group but without statistical significance. The MWA group showed significantly higher serum alanine aminotransferase and aspartate aminotransferase levels at day 1 postoperatively, but no differences between the MWA and Control groups were found at days 3 and 7. There were no significant differences in terms of operative time, hepatic portal occlusion time, postoperative total bilirubin levels, human albumin solution consumption or length of hospital stay. Postoperative complications such as impaired renal function, pyrexia, admission to ICU, abscess, biliary leakage, intrahepatic and distant tumor recurrence and in-hospital mortality were comparable between the two groups.

Conclusion: Precoagulation with MWA reduced intraoperative blood loss with similar postoperative complications, providing a safe, effective, novel alternative for hepatic parenchymal transection during liver partial resection. Additional results from larger series are recommended to confirm these findings.     

The impact of epidermal growth factor receptor mutations on the efficacy of definitive chemoradiotherapy in patients with locally advanced unresectable stage III non-small cell lung cancer: a systematic review and meta-analysis

Objectives: To investigate the impact of EGFR mutations on the efficacy of definitive chemoradiotherapy (CRT) in patients with locally advanced unresectable stage III NSCLC.

Methods: PubMed and EMBASE were searched for eligible studies. Efficacy outcomes included objective response rate (ORR), overall disease progression, local-regional recurrence (LRR), distant progression (DP), brain metastasis, progression-free survival (PFS) and overall survival (OS). Meta-analysis was performed when relevant data were available.

Results: The authors identified seven eligible studies including 695 patients. No significant difference was detected in ORR (Risk Ratio [RR] 1.13, 95% confidence interval [CI] 0.91–1.39, P = 0.28) and overall disease progression (RR 1.06, 95% CI 0.95–1.19, P = 0.29) between EGFR-mutant and EGFR-wild-type groups. EGFR-mutant group had significantly lower LRR (RR 0.49, 95% CI 0.33–0.72, P < 0.01), higher DP (RR 1.36, 95% CI 1.18–1.55, P < 0.01) and higher brain metastasis (RR 2.48, 95% CI 1.46–4.20, P < 0.01) than the EGFR-wild-type group. No sufficient data were available to perform pooled analysis regarding PFS and OS.

Conclusion: For patients with locally advanced unresectable stage III NSCLC treated with definitive CRT, the presence of EGFR mutations may be indicative of lower locoregional recurrence and higher distant progression, especially brain metastasis.     

Reactivation of heat-inactivated Ku proteins by heat shock cognate protein HSC73

Purpose: Mouse double-stranded DNA-dependent protein kinase (DNA-PK) activity is heat sensitive. Recovery of heat-inactivated DNA repair activity is a problem after combination therapy with radiation and heat. We investigated the mechanism of recovery of heat-inactivated DNA-PK activity.

Methods: Hybrid cells containing a fragment of human chromosome 8 in scid cells (RD13B2) were used. DNA-PK activity was measured by an in vitro assay. Immunoprecipitation of the nuclear extract was performed with an anti-Ku80 antibody. Proteins co-precipitated with Ku80 were separated by sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis and detected by Western blotting using anti-heat shock protein (HSP)72 and anti-heat shock cognate protein (HSC)73 antibodies. HSC73 was overexpressed with the pcDNA3.1 vector. Short hairpin (sh)RNA was used to downregulate HSC73 and HSP72.

Results: The activity of heat-inactivated DNA-PK recovered to about 50% of control during an additional incubation at 37?°C after heat treatment at 44?°C for 15?min in the presence of cycloheximide (which inhibits de novo protein synthesis). Maximal recovery was observed within 3?h of incubation at 37?°C after heat treatment. Constitutively expressed HSC73, which folds newly synthesized proteins, reached maximal levels 3?h after heat treatment using a co-immunoprecipitation assay with the Ku80 protein. Inhibiting HSC73, but not HSP72, expression with shRNA decreased the recovery of DNA-PK activity after heat treatment.

Conclusions: These results suggest that de novo protein synthesis is unnecessary for recovery of some heat-inactivated DNA-PK. Rather, it might be reactivated by the molecular chaperone activity of HSC73, but not HSP72.     

Unique genomic profiles obtained from cerebrospinal fluid cell-free DNA of non-small cell lung cancer patients with leptomeningeal metastases

Background: Leptomeningeal metastases (LM), associated with poor prognosis, are frequent complications of advanced non-small cell lung cancer (NSCLC) patients, especially in patients with epidermal growth factor receptor (EGFR) mutations. Due to limited access to leptomeningeal lesions, the mutational landscape of LM has not been comprehensively investigated in large cohorts and the underlining biology of LM remains elusive. Some studies have explored the potential of cerebrospinal fluid (CSF) in reflecting the molecular profile of LM but with limited number of patients enrolled.

Methods: In this study, we performed capture-based targeted sequencing using a panel consisting of 168 lung cancer-related genes on matched CSF and plasma samples from 72 advanced NSCLC patients with confirmed LM to interrogate the potential of CSF as a source of liquid biopsy.

Results: We revealed a rate of detection of 81.5% and 62.5% for CSF and plasma, respectively (p = 0.008). The maximum allelic fraction (MaxAF) was also significantly higher in CSF (43.6% vs. 4.6%) (p < 0.001). CSF, harboring a unique genomic profile by having a significant number of CSF-specific mutations, primarily copy number variations, is superior to plasma in reflecting the mutational profile of LM. Further pathway enrichment analysis revealed that most of CSF-specific mutations participated in pathways relevant to the tumorigenesis and the development of metastases. Moreover, our data also revealed that TP53 loss of heterozygosity (LOH) predominantly existed in CSF (p < 0.001).

Conclusions: Collectively, we demonstrated that CSF provides a more comprehensive profile of LM than plasma in a large cohort, thus can be used as an alternative source of liquid biopsy for LM patients.