Health-related quality of life in patients with solid tumors receiving implantable venous access ports for chemotherapy: A prospective randomized controlled trial.

PURPOSE: Implantable venous access ports are widely used in patients receiving chemotherapy, but there is still scarce evidence about any patient-reported outcome measures. This prospective randomized controlled trial examined the impact on patients' quality-of-life following the placement of an implantable port device for long-term chemotherapy treatment. METHOD: A total of 120 chemotherapy naïve adult outpatients scheduled to receive chemotherapy (duration ≥12 weeks) for solid tissue tumors in a single academic oncology unit were randomly allocated (n = 60 in each arm) between radiologically guided insertion of an implantable venous access port (PORT arm) or standard repeated peripheral venous access (Control arm). Health-related quality-of-life scores (HRQoL) were assessed with the EQ-5D-5L and the oncology-specific EORTC QLQ-C30 (version 3.0) questionnaires at baseline, 3- and 6-months post randomization. Non-parametric tests were applied and differences between medians (Δ) are reported because of skewed-left HRQoL data. RESULTS: Baseline clinical and demographic characteristics were well balanced between the two groups. There were no complications during insertion and no infection or device failure in the PORT subjects through the 6-month follow-up. The functional and symptom scales of the EORTC QLQ-C30 questionnaire were similar between both study arms at all time intervals. The EORTC QLQ-C30 global health status was significantly improved in the PORT subjects both at 3 months (Δ: 8.3 out of 100; P = 0.04) and 6 months follow-up (Δ: 16.7 out of 100; P = 0.003). Changes in EQ-5D-5L scores were significantly improved at 6 months in the PORT arm compared to control (Δ: 0.074 out of 1; P = 0.01). CONCLUSIONS: Implantable venous access ports may confer significantly improved patient-reported quality-of-life benefits in patients receiving chemotherapy for solid tissue tumors.

Prospective assessment of psychopathological symptoms and their relation to demographic factors in primary caregivers of cancer patients throughout chemotherapy.

PURPOSE: The present study aims to investigate the course of psychological symptoms through chemotherapy in a sample of primary caregivers of patients with cancer and to examine all possible correlations between psychological distress and demographic characteristics. METHODS: In this prospective study, 112 primary family caregivers of cancer patients were evaluated. Symptom checklist 90 revised (SCL-90-R) was administered to assess their pathological symptoms, the Hospital Anxiety and Depression Scale (HADS) to assess depression and anxiety. There was an evaluation at the beginning of chemotherapy and a second at the end of the patients' intravenous chemotherapy treatment (EOT). RESULTS: A total of 112 primary caregivers were initially enrolled in the study, and 99 (88.4%) completed it. Caregivers' psychopathology was low to moderate at both points of time (baseline and EOT). However, a considerable decrease in the Global Severity Index (GSI) emerged over time. CONCLUSIONS: At EOT, participants reported statistically significant decreases in five aspects of SCL 90, namely Depression, phobic anxiety, obsessive-compulsive symptoms, somatization, and psychoticism. A notable finding was that female caregivers were significantly more distressed, especially when providing care to a male recipient.

Gonadotropin-releasing hormone (GnRH) deficiency under treatment: psychological and sexual functioning impacts.

OBJECTIVE: GnRH (gonadotropin releasing hormone) is a crucial hormone for sexual development, puberty, and fertility, and its deficiency leads to hypogonadotropic hypogonadism (HH), which causes abnormal secondary sexual development and infertility. The combination of the lack of sense of smell, i.e., anosmia, and HH is a type of GnRH deficiency known as Kallmann syndrome, which affects both men and women. The impact of Kallmann syndrome can be very severe and causes a variety of psychological problems in patients. The aim of the present study was to investigate psychopathology, sexuality, and personality characteristics in patients with GnRH deficiency under hormonal replacement therapy. DESIGN: A total of 38 patients with GnRH deficiency aged 30.6 ± 10.44 years and 38 healthy matched for age individuals participated in the study and completed a series of questionnaires concerning sexual functioning, ego defense mechanisms, quality of life, personality characteristics, as well as anxiety and depression. RESULTS: After adjustment for anxiety and depression, no difference in sexuality parameters were reported between men with and without GnRH deficiency, while women with GnRH deficiency had significantly lower sexual desire compared to controls. Concerning quality of life, satisfaction with general health was significantly lower in patients compared to controls, even after adjusting for sex. Furthermore, patients with GnRH deficiency indicated markedly less anxiety and a trend for less depression compared to controls. Finally, defense styles, ego-strength, and hostility did not differ between GnRH deficiency patients and controls. CONCLUSIONS: Our study is the first to investigate psychological and sexual functioning impacts in patients with GnRH deficiency under hormonal replacement therapy. However, larger studies are needed so as to add further empirical evidence.

Impact of estrogen receptor α gene and oxytocin receptor gene polymorphisms on female sexuality.

Over the past decades, research attention has increasingly been paid to the neurobiological component of sexual behavior. The aim of the present study was to investigate the correlation of estrogen receptor α (ERA) gene polymorphism (rs2234693-PvuII) (T→C substitution) and oxytocin receptor gene polymorphism (rs53576) (G→A substitution) with sexuality parameters of young, healthy women. One hundred thirty-three Greek heterosexual women, students in higher education institutions, 20-25 years of age, sexually active, with normal menstrual cycles (28-35 days), were recruited in the study. Exclusion criteria were chronic and/or major psychiatric diseases, use of oral contraceptive pills (OCs), polycystic ovary syndrome (PCOS), thyroid diseases as well as drugs that are implicated in hypothalamus-pituitary-gonadal axis. T allele (wildtype) of rs2234693 (PvuII) polymorphism of ERA gene was correlated with increased levels of arousal and lubrication, whereas A allele (polymorphic) of rs53576 (OXTR) polymorphism was correlated with increased arousal levels. The simultaneous presence of both T allele of rs2234693 (PvuII) and A allele of rs53576 (OXTR) polymorphisms (T + A group) was correlated with increased arousal, orgasm levels as well as female sexual function index full score. To our knowledge, this is the first study to investigate the interaction between ERA and OXTR with regard to sexual function in women. Female sexuality is a complex behavioral trait that encompasses both biological and psychological components. It seems that variability in female sexual response stems from genetic variability that characterizes endocrine, neurotransmitter and central nervous system influences.

Iris Metastasis in a Patient With Small Cell Lung Cancer: A Case Report.

INTRODUCTION: Small cell carcinoma constitutes the most aggressive type of lung cancer, with the greatest propensity for early disseminated disease. Although commonly neglected due to its rarity and the presence of other comorbidities, cases of iris metastasis from small cell lung cancer have been reported in the literature. CASE PRESENTATION: We present the case of a 76-year-old female. Once diagnosed, the patient already had disseminated disease with metastatic foci found in the spleen, liver, and brain. The patient received six cycles of combination carboplatin/etoposide chemotherapy, followed by cranial irradiation. After an initial response, two months after the completion of cranial irradiation, the patient complained of visual impairment and was referred to an ophthalmologist. A diagnosis of secondary glaucoma was made, caused by metastasis to the left iris. CONCLUSIONS: Physicians should be aware of this rare site of metastasis. Early diagnosis is of paramount importance in order to effectively prevent the significant morbidity this condition can cause if left untreated.

Multiple primary malignancies: a report of two cases.

The diagnosis of multiple primary malignancies (MPMs) in a patient has been reported rather frequently during the past decade. Here we present two cases with three synchronous primary malignant tumors. The first patient is a 66-year-old male with synchronous colorectal cancer, renal cell carcinoma (RCC) and non-small cell lung cancer (NSCLC). The second patient is a 64-year-old female with breast cancer, transitional cell carcinoma of the ureter and endometrial cancer. MPMs seem to be diagnosed in a higher incidence than that predicted only by the influence of hazard and, whenever found, they raise questions regarding not only possible common etiologic factors or same pathogenetic mechanisms but also they cause a lot of troubles to both clinicians and patients because the therapeutic options usually become limited.

Assessment of sexual function in patients with cancer undergoing radiotherapy--a single centre prospective study.

AIM: The main objective was to delineate the rates and clinical course of sexual function and depression in cancer patients undergoing radiotherapy. PATIENTS AND METHODS: Forty-eight male and 90 female radiotherapy-naive outpatients with breast or pelvic cancer completed the International Index of Erectile Function (IIEF) or the Female Sexual Function Index (FSFI), and the Hamilton Depression Scale (HDS) prior to (phase 1), at the end of (phase 2) and 12 months after radiotherapy (phase 3). RESULTS: Overall, the majority of patients (93.8% of males and 80% of females) experienced intense sexual dysfunction. At presentation, males reported severe erectile dysfunction that was significantly associated with age. However, only in sexual desire was the difference between baseline and phase 3 significant. In females, an improvement was observed in all parameters of FSFI between phase 1 and 3. Females with stage III disease achieved lower scores in almost all parameters of FSFI than those with stage II. Finally, although a quarter of patients reported elevated depression scores, depression was not related to sexual function. CONCLUSION: A significant proportion of cancer patients experience intense levels of sexual dysfunction and depression throughout radiotherapy and the subsequent year. Pelvic radiotherapy affected sexual function to a higher degree than did breast radiotherapy.

Either called "chemobrain" or "chemofog," the long-term chemotherapy-induced cognitive decline in cancer survivors is real.

CONTEXT: In recent years, there is growing evidence in the medical literature to support an association between administration of commonly used chemotherapeutic agents and an increased risk for cognitive impairment. OBJECTIVES: We herein critically summarize data relating to the pathophysiological mechanisms by which chemotherapy may induce cognitive impairment in patients surviving from solid tumors. The clinical and epidemiological characteristics and the proposed management strategies to counter chemotherapy-induced cognitive impairment (CICI) also are presented. METHODS: References for this review were identified by searches of PubMed from 1995 until December 2009 with related terms. RESULTS: Both the pathogenetic mechanisms and the overall clinical nature of CICI remain vaguely defined. Findings indicate that CICI is a relatively common event that, in most of the cases, remains underdiagnosed, thereby adversely affecting the quality of life of patients with cancer. Effective pharmacological interventions toward the symptomatic or prophylactic management of CICI also are lacking. CONCLUSION: Either called "chemobrain" or "chemofog," the long-term CICI in cancer survivors is real. The need for multidisciplinary care interventions toward a timely diagnosis and management of CICI is clearly warranted.

Bariatric surgery is associated with reduced depressive symptoms and better sexual function in obese female patients: a one-year follow-up study.

Bariatric surgery is an effective treatment for obesity; few studies, however, have investigated its impact on patients' sexuality. We aimed to determine bariatric surgery's effect on female patients' body mass index (BMI), anxiety and depressive symptoms, and sexual function and delineate predictors of treatment outcomes. Fifty-nine obese female bariatric candidates were administered the Hospital Anxiety and Depression Scale and the Female Sexual Function Index 1 week before surgery (T1) and 1 year after (T2). Statistical analysis revealed significant reductions in BMI (p < 0.001), depression (p < 0.001), and sexual pain levels (p = 0.014) and significant improvements in sexual desire (p = 0.005), arousal (p = 0.001), lubrication (p = 0.003), satisfaction (p = 0.012), and total sexual function (p = 0.003) postoperatively. Postoperative total sexual function was independently predicted by baseline sexual function and low baseline BMI. Bariatric surgery is an effective way to reduce weight, manage depression, and improve sexual function in female obese patients.

Fatigue and depressive symptoms associated with chronic viral hepatitis patients. health-related quality of life (HRQOL).

BACKGROUND AND RATIONALE: It is well established that chronic viral hepatitis (CVH) negatively affects patients . health-related quality of life (HRQOL). The aim of the present study was to assess the extent to which fatigue and depressive symptoms are associated with CVH patients. HRQOL. METHODS: Eighty-four adult CVH outpatients [45 with hepatitis B virus (HBV) and 39 with hepatitis C virus (HCV) infection] participated in the study. The Short Form-36 Health Survey (SF-36), the Beck Depression Inventory-II (BDI-II) and the Fatigue subscale of the Functional Assessment of Cancer Therapy-Anemia Scale (FACT-F) were used to assess HRQOL, depression and fatigue, respectively. RESULTS: All aspects of HRQOL perceived by CVH patients were significantly impaired compared to the general population, as a comparison with Greek population-based normative data revealed. HBV patients presented similar HRQOL with HCV patients. Clinical parameters including infection activity, fibrosis stage or inflammation grade, as well as depressive symptoms and fatigue were found to be significantly associated with HRQOL. Multivariate analyses showed that older age (p <0.001) and higher fatigue scores (p <0.001) were the variables most closely associated with the physical HRQOL, whereas higher rates on depressive symptoms (p <0.0005) and fatigue (p <0.020) scales were the variables most closely associated with the mental HRQOL. CONCLUSIONS: In conclusion, CVH is associated with impaired HRQOL. Fatigue and impaired psychological functioning is associated with diminished HRQOL in CHV, independent of the disease etiology. Consequently, management of fatigue and depressive symptoms should be considered a priority, in order to improve HRQOL in CVH patients.

The upgraded role of HER3 and HER4 receptors in breast cancer.

The human epidermal growth factor receptor (HER) family comprises four homologous members. The activation of these receptors affects essential tumorigenic processes and plays a crucial role in the pathogenesis of breast cancer. Among HER family members, EGFR and HER2 are the most studied. However, accumulating data provide evidence for the significance of HER3 and HER4 alterations in breast carcinogenesis. The combination of HER2 and HER3 receptors may be critical in breast cancer growth and progression. Moreover, HER3 may provide a route for resistance to agents targeting EGFR or HER2. Although a number of studies have demonstrated that HER3 overexpression is associated with poor prognosis in patients with breast cancer, other studies have indicated that HER3 overexpression may be a positive prognostic factor. With respect to HER4 receptor, the existing evidence suggests that HER4 signalling promotes differentiation and growth inhibition of breast cancer cells. In addition, HER4 is more consistently related with a favourable prognosis in breast cancer. HER4 has multiple different activities in the breast, and many of these functions are mediated by a soluble HER4 intracellular domain. In addition, loss of HER4 expression may represent a marker for resistance to tamoxifen. Because of the functional interdependency among the HER receptors, it is possible that the effect on cell proliferation and tumor growth depends on receptor trans-signalling. Therefore, clarifying how and the extent to which these different signalling pathways interact in breast carcinogenesis, may lead to additional therapeutic opportunities. This review presents an update on the role of HER3 and HER4 receptors in breast cancer. Moreover, we provide current data relating to the prognostic significance of these receptors, as well as their impact on the activity of HER-targeting therapies in patients with breast cancer.

Treatment options for malignant gliomas, emphasizing towards new molecularly targeted therapies.

Malignant gliomas (MGs), including glioblastomas and anaplastic astrocytomas are the most common primary brain tumors. Despite treatment advances, the outcome of patients diagnosed with MGs is poor. The current standard treatment protocols for managing these tumors include maximally safe surgical resection, followed by fractioned radiation therapy of the tumor and surrounding brain parenchyma. Until recently, the use of systemic chemotherapy was restricted and ineffective, due to the fact that the blood brain barrier inhibits the adequate therapeutic concentrations of most chemotherapeutic agents into the tumor and peritumoral area. Genetic transformation, like the expression of the DNA repair enzyme methylguanine methyltransferase (MGMT) and specific characteristics of these neoplasms are also causal factors, accounting for the development of treatment resistance to standard chemotherapy options with alkylating compounds. Recent advances, mostly, in thorough understanding of the complex molecular pathogenesis of MGs have led to arousal of rational development of new molecularly targeted treatment options that simultaneously affect multiple signalling pathways. Currently, several molecularly targeted agents, like tyrosine kinase and growth factor inhibitors have been tested in clinical trials to establish future directions in the therapy of MGs. A number of novel targeted strategies, including among others radio-immuno and ligand-toxin conjugates and RNA-based therapies, are also under investigation. We herein review and discuss the standard treatment options and recent advances in the therapy of MGs, with emphasis on the current knowledge towards the molecular pathogenesis of MGs as well as molecularly targeted therapies. We also highlight areas of future research.

Religiosity and its relation to quality of life in Christian Orthodox cancer patients undergoing chemotherapy.

OBJECTIVES: The first objective of the current observational study was to assess the levels of religiosity in Greek Christian Orthodox cancer patients receiving chemotherapy. The second objective was to evaluate the associations between religiosity and quality of life (QoL), an endpoint of considerable importance in clinical cancer research and practice. METHOD: One hundred eighteen adult outpatients with solid tumors, who consented to participate, were administered the Systems of Belief Inventory (SBI-15R) and the European Organisation for Research and Treatment of Cancer (EORTC QLQ-C30) questionnaire. RESULTS: The analysis revealed high scores on religiosity, especially among female patients, who reported significantly higher levels of religious beliefs and practices as well as perceived social support provided by the religious community than did their male counterparts. Of all EORTC QOL-C30 subscales, only global QoL was found to be significantly associated with the SBI-15R religious beliefs subscale. The analysis revealed no significant correlations between the SBI-15R social support subscale and all QoL subscales. CONCLUSIONS: The current study reported high levels of religiosity among Greek Christian Orthodox cancer patients. However, levels of religiosity were only weakly associated with patients' QoL. The SBI-15R appeared to be a well-accepted and reliable tool, potentially useful for future research in Greek settings. Wide-scale studies from the same and diverse religious and cultural backgrounds are needed to clarify further the connections between religiosity, QoL, coping, and other health outcomes with the aim to devise appropriate multicomponent interventions to enhance patients' QoL.

Bortezomib-induced peripheral neuropathy in multiple myeloma: a comprehensive review of the literature.

Bortezomib has demonstrated significant activity in clinical trials, mainly against recurrent or newly diagnosed multiple myeloma (MM). Peripheral neuropathy is a significant toxicity of bortezomib, requiring dose modification and potential changes in the treatment plan when it occurs. The mechanism underlying bortezomib-induced peripheral neuropathy (BIPN) is unknown. Metabolic changes resulting from the accumulation of bortezomib in the dorsal root ganglia cells, mitochondrial-mediated disregulation of Ca(++) homeostasis, and disregulation of neurotrophins may contribute to the pathogenesis of BIPN. It is increasingly recognized that BIPN may be a proteasome inhibitor class effect, producing primarily a small fiber and painful, axonal, sensory distal neuropathy. Incidence of BIPN is mainly related to various risk factors, including cumulative dose and evidence of preexisting neuropathy. Assessment of BIPN is based primarily on neurologic clinical examination and neurophysiologic methods. To date, apart from the use of dose reduction and schedule change algorithm, there is no effective treatment with neuroprotective agents for BIPN. Analgesics, tricyclic antidepressants, anticonvulsants, and vitamin supplements have been used as symptomatic treatment against bortezomib-associated neuropathic pain with some success. This review looks critically at the pathogenesis, incidence, risk factors, diagnosis, characteristics, and management of BIPN, and highlights areas for future research.

A review on oxaliplatin-induced peripheral nerve damage.

Platinum compounds are a class of chemotherapy agents that posses a broad spectrum of activity against several solid malignancies. Oxaliplatin (OXL) is a third-generation organoplatinum compound with significant activity mainly against colorectal cancer (CRC). Peripheral neuropathy is a well recognized toxicity of OXL, usually resulting in dose modification. OXL induces two types of peripheral neuropathy; acute and chronic. The acute oxaliplatin-induced peripheral neuropathy (OXLIPN) may be linked to the rapid chelation of calcium by OXL-induced oxalate and OXL is capable of altering the voltage-gated sodium channels through a pathway involving calcium ions. On the other hand, decreased cellular metabolism and axoplasmatic transport resulting from the accumulation of OXL in the dorsal root ganglia cells is the most widely accepted mechanism of chronic oxaliplatin-induced peripheral neuropathy (OXLIPN). As a result, OXL produces a symmetric, axonal, sensory distal primary neuronopathy without motor involvement. The incidence of OXLIPN is usually related to various risk factors, including treatment schedule, dosage, cumulative dose and time of infusion. The assessment of OXLIPN is primarily based on neurologic clinical examination and quantitative methods, such as nerve conduction study. To date, several neuroprotective agents including thiols, neurotrophic factors, anticonvulsants and antioxidants have been tested for their ability to prevent OXLIPN. However, the clinical data are still controversial. We herein review and discuss the pathogenesis, incidence, risk factors, diagnosis, characteristics and management of OXLIPN. We also highlight areas of future research.

Incidence and characteristics of peripheral neuropathy during oxaliplatin-based chemotherapy for metastatic colon cancer.

AIM: The current prospective study sought to trace the incidence and severity of oxaliplatin-induced peripheral neuropathy (OXLIPN) and to determine its clinical and electrophysiological pattern. PATIENTS AND METHODS: Twenty-five adult patients scheduled to be treated with 12 courses of the oxaliplatin-based regimen, FOLFOX-4, for metastatic colon cancer participated in this study. Patients were clinically and electrophysiologically monitored at baseline and followed-up during chemotherapy. The severity of OXLIPN was summarized by means of a modified Total Neuropathy Score (TNS). RESULTS: Evidence of OXLIPN was disclosed in 16 of the 25 patients (64%). The mean TNS values for patients manifesting some grade of OXLIPN were 13.9 +/- 5.8 (range 7-28). All longitudinal comparisons concerning the motor conduction parameters failed to reach significance. By contrast, comparisons of the median changes at baseline and each of the follow-up studies revealed significant decrease in all sensory action potentials examined. CONCLUSION: Our results indicate that the majority of patients treated with the FOLFOX-4 regimen would manifest an axonal, predominately sensory peripheral neuropathy, of mild to moderate severity.

Assessing sexual function in obese women preparing for bariatric surgery.

BACKGROUND: Obesity has become a modern epidemic, increasingly affecting the general population worldwide. Obese people are vulnerable to a variety of co-morbidities, including cardiovascular and pulmonary disease, osteoarthritis, diabetes, cancer and psychiatric conditions, that not only diminish life expectancy but also impair quality of life. Research has shown that obesity is further linked to sexual dysfunction, although relevant studies are limited and further investigation is needed. METHODS: We assessed the sexual function of 60 obese women scheduled to undergo bariatric surgery and 50 healthy controls matched by age, education and marital status. All participants were administered the Female Sexual Function Index (FSFI). Additionally, participants completed the Hospital Anxiety and Depression Scale (HADS). RESULTS: Obese women reported significant impairment on most domains of sexual function, including sexual desire, arousal, lubrication, orgasm, and satisfaction, compared to healthy controls. The observed sexual impairment was associated with BMI but was not entirely attributed to the presence of anxiety or depression. CONCLUSION: Obese women complain of significant sexual impairment. Obesity-related sexual dysfunction appears to be a complex condition linked to a range of social, psychological and biological factors. Clinicians are encouraged to evaluate routinely sexual function in this patient population in order to detect those who are in need of intervention.

Preventing paclitaxel-induced peripheral neuropathy: a phase II trial of vitamin E supplementation.

A randomized, controlled trial was performed to assess the efficacy and safety of vitamin E supplementation for prophylaxis against paclitaxel-induced peripheral neuropathy (PIPN). Thirty-two patients undergoing six courses of paclitaxel-based chemotherapy were randomly assigned to receive either chemotherapy with vitamin E (300 mg twice a day, Group I) or chemotherapy without vitamin E supplementation (Group II). A detailed neurological examination and electrophysiological study was performed during and 3 months after chemotherapy. The severity of PIPN was summarized by means of a modified Peripheral Neuropathy (PNP) score. The incidence of neurotoxicity differed significantly between groups, occurring in 3/16 (18.7%) patients assigned to the vitamin E supplementation group and in 10/16 (62.5%) controls (P=0.03). The relative risk (RR) of developing PIPN was significantly higher in controls than in vitamin E group patients (RR=0.3, 95% confidence interval (CI)=0.1-0.9). Mean PNP scores were 2.25+/-5.1 (range 0-15) for patients in Group I and 11+/-11.63 (range 0-32) for those in Group II (P=0.01). Vitamin E supplementation was well tolerated and showed an excellent safety profile. This study shows that vitamin E effectively and safely protects patients with cancer from the occurrence of paclitaxel-induced peripheral nerve damage. A double-blind, placebo-controlled trial is needed to confirm these results.

A case of chondrosarcoma developing in a recurrent retroperitoneal mass after chemotherapy for testicular germ cell tumor.

Teratomas with malignant transformation occur in a small proportion of patients with metastatic germ cell tumors treated with platinum-based chemotherapy. Chondrosarcoma has rarely been reported as a component of the second non-germ cell malignancy. We report the case of a 37-year-old man who developed a chondrosarcoma in a recurrent retroperitoneal mass after chemotherapy for testicular germ cell tumor. Malignant transformation of the retroperitoneal teratomatous mass occurred in the absence of any symptoms or clinical signs, elevation in serum tumor markers, or the presence of atypical elements in previously resected specimens, suggesting the need for close radiographic follow-up of these patients.