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Introdução: A dor é equiparada a quinto sinal vital e deve ser avaliada de forma sistemática em todas as consultas de um paciente com cancro. Os fármacos utilizados na prática oncológica para tratar os doentes com dor crónica moderada a severa incluem analgésicos de ação periférica e central que têm sido abordados em múltiplas diretrizes nacionais e internacionais. No entanto, na prática clínica há que equacionar outros problemas e eventuais comorbilidades, que podem levantar dúvidas no momento da prescrição.Material e Métodos: Fez-se uma revisão da literatura, tentando refletir sobre algumas situações específicas na utilização de opióides, nomeadamente perda da via oral, insuficiência renal (hemodiálise), insuficiência hepática, interações medicamentosas e formulações de ação imediata.Resultados: Os opiáceos naturais (morfina e codeína) e os seus derivados sintéticos e semissintéticos (hidromorfona, oxicodona, fentanilo), o agonista parcial buprenorfina e finalmente o tramadol e tapentadol foram selecionados para esta análise. Os sistemas transdérmicos estão apenas disponíveis para a buprenorfina e o fentanilo. Na insuficiência hepática, o fentanilo foi considerado seguro, mascom exceção da codeína e do tramadol, podem todos ser usados com precaução. Na insuficiência renal, o fentanilo, a hidromorfona e o tapentadol foram considerados seguros. Deve evitar-se a morfina, e os restantes poderão ser usados com precaução. Em pacientes em hemodiálise pode usar-se buprenorfina, fentanilo, hidromorfona e tramadol (em doses até 200 mg/dia).Discussão: O não reconhecimento do impacto das várias situações descritas ao longo deste trabalho, nomeadamente a alteração da biodisponibilidade por perda de via oral, por alteração da farmacocinética e farmacodinâmica dos vários fármacos, quer no contexto da insuficiência de órgão responsável pelo metabolismo ou excreção, quer no contexto das interações farmacológicas, condiciona umnorme risco de subtratamento da dor e consequente impacto em termos de qualidade de vida.Conclusão: A prescrição de opióides é segura e efetiva, mesmo em situações de comorbilidades moderadas a graves como insuficiência renal e hepática e em doentes sem via oral disponível. Neste caso, como quando considerámos as interações farmacológicas, o plano terapêutico deve ser individualizado e o paciente deve ser avaliado regularmente. A seleção inadequada e/ou dose mal ajustada de um fármaco, o não reconhecimento do impacto dos efeitos adversos, frequentemente justificam o mau controlo da dor e a toxicidade excessiva.

The accomplishment of successful pain treatment requires evaluation, characterization and quantification. The present study characterized pain and survival in a cohort of patients with cancer with bone metastasis who were treated with intravenous bisphosphonates. A total of 84 patients self-completed the Brief Pain Inventory (BPI) and 36-Item Short Form Survey (SF-36), between November 2010 and March 2011 with a 5-year survival follow-up as a surrogate marker of cancer burden. The median age was 62 years old (34-85), 64% of patients were female and 58% of these females had breast cancer. In the population, self-reported pain was 91.6%, with 29 patients (34.5%) reporting severe pain (score 7-10). Among these patients, only 13 (44.8%) presented a similar report to that of their clinical files and 5 were undergoing treatment with strong opioids (17.2%). A total of 45 patients (46%) had not been prescribed analgesic drugs, of these patients, 32 were treated with a weak opioid, and 13 with a strong opioid. An association was observed between pain records and the prescribed analgesic (P=0.031). BPI maximum pain and overall survival data were analyzed, and a significant association was identified between male patients presenting severe pain and decreased survival (P=0.004). Male survival was associated with severe pain, which is consistent with other data. The results revealed a skeletal-related events (SRE)-free survival (time elapsed from diagnosis of the first bone metastasis to the first SRE) of 9 months (4.39-13.73, 95% CI) with a statistically significant difference between subgroups of time since diagnosis of bone metastasis (P=0.005). The added value of the present study is the suggestion that complete and accurate pain narratives are mandatory and may contribute to the optimization of analgesia, and may help to increase survival rates. Optimal pain management for patients with cancer remains an urgent requirement.

Background: Primary aldosteronism (PA) is the most common cause of endocrine hypertension (HT). PA subtypes include aldosterone-producing adenomas (APA) and bilateral adrenal hyperplasia. To date, few PA patients with bilateral adenomas have been reported, but only one case was well characterized by anatomopathological analysis and clinical outcome after adrenal sparing surgery (1). Clinical case: A 53-year-old woman was referred to investigate resistant HT and hypokalemia. (3.0 mEq/L). PA screening revealed aldosterone (A) of 37.9 ng/dL, renin (R) < 1.6 (4.4-46.1 mUI/L), A/R ratio of 24.8. Confirmatory testing confirmed PA diagnosis: seated saline infusion test (A= 83.3 ng/dL) and intravenous furosemide test (R= 3.1 mUI/L; positive test Conclusion: We herein described a very rare case of PA caused by bilateral-producing adenomas, confirmed by AVS and CYP11B2 staining after adrenal sparing surgery.

The prevalence of pain and skeletal complications of metastatic bone disease is high and an important factor, which contributes to decreased quality of life and low survival rate. Bone-targeted agents are well-established therapies to reduce the skeletal-related events in patients with bone metastasis. However, the analgesic effect of these medications is still controversial. The objective of this review is to summarize the existing evidence about the use of bone-targeted agents in the treatment of metastatic bone pain, trying to answer to the 10 most commonly asked questions in this matter. To achieve this goal, authors did a research of reviews published between January 2001 and January 2018, using the terms MeSH: "cancer pain" and bisphosphonates. The source used was the PubMed (NLM) database. The search yielded 36 reviews, but only 16 met the inclusion criteria. Even with the introduction of a new class of drugs, bisphosphonates and specially zoledronic acid are the most commonly used drugs in most oncology centers. Bisphosphonates and denosumab appear to be beneficial in preventing skeletal morbidity but their analgesic role and impact on quality of life and survival are not so well established.

Cancer patients with liver metastasis may be candidates for liver surgery and local interventional techniques as part of their treatment. Although rare in this setting, hepatopulmonary fistula has been described as a possible complication. The clinical picture may be atypical, and, without specific treatment, it usually has a dismal prognosis. As locoregional treatments (whether interventional or surgical techniques) in liver neoplasms are being more frequently used we need to include this entity as a possible differential diagnosis of local liver treatment complications.

Despite the various different candidate genetic polymorphisms of potential clinical relevance, there is not enough understanding of the inter-individual variability in analgesic administration. The cytochrome P450 2D6 (CYP2D6) genotype is thought to be one of the most studied. The aim of the present evidence-based review was to determine if there is now sufficient evidence to make clinical recommendations based on a specific genomic profile. The data sources utilized were as follows: PubMed (NLM) database, Evidence Based Medicine Guidelines and Google. Research on clinical guidance standards, systematic reviews, meta-analyses and clinical trials, published prior to January 2018, were evaluated in English, using the MeSH terms ‘cancer pain’, ‘polymorphism’, ‘genetic’ and ‘gene polymorphism’. To assess the level of evidence, the Strength of Recommendation Taxonomy of the American Family Physician was applied. From the initial search, 12 systematic reviews and/or meta-analyses, 5 clinical trials and 10 guidelines were selected. The results indicated that genetic variation of µ-opioid receptor 1 (OPRM1) may contribute to inter-individual differences in morphine consumption with recommendation grade A for OPRM A118G single nucleotide polymorphism (rs1799971). Polymorphisms associated with the metabolization process of morphine and other opioid drugs are very relevant in opioid titration and ethnic subgroup differences which have to be taken into account (particularly, for the recommendation grade A for the CYP2D6 polymorphism). In human studies, the catechol-O-methyl transferase (COMT) genotype affects the efficacy of opioids in acute and chronic pain under different settings, with recommendation grade B to the COMT single nucleotide polymorphism rs4680 (Val/Met). Finally, polymorphisms of the ATP-binding cassette family of efflux transporters were highlighted. Consistent data on pain polymorphisms is now widely available; however, these results have had very little impact on clinical guidelines and daily oncologist practice. Persisting pain, side effects of grade 3 (NCI-CTCAE v4.0) and breakthrough pain with more than 4 episodes/day should be considered the criteria for pain multidisciplinary team discussions and for polymorphism screening.

The primary tumor side is emerging as a prognostic factor for patients with liver metastatic colorectal cancer (mCRC). In a combined analysis of data from 2 randomized studies, the addition of selective internal radiation therapy to first-line chemotherapy in patients with mCRC was associated with statistically and clinically significant overall survival gains for patients with a right-sided primary tumor. Background: The primary tumor side is emerging as a major prognostic factor for patients with metastatic colorectal cancer (mCRC). We examined the survival data from 2 randomized studies to determine whether the outcomes differ between patients with mCRC with right-sided primary (RSP) tumors and those with left-sided primary (LSP) tumors after selective internal radiation therapy (SIRT) plus mFOLFOX6 (folinic acid [leucovorin], 5-fluorouracil, oxaliplatin) chemotherapy, versus chemotherapy alone. Patients and Methods: Separate and combined analyses were performed on the data from the SIRFLOX and FOXFIRE global trials, which compared chemotherapy plus SIRT with chemotherapy alone for patients with mCRC liver metastases. The primary tumor side data were prospectively collected. The principal outcome measure was overall survival (OS) stratified by treatment and primary tumor side. Results: In the combined analysis of all 739 patients enrolled, SIRT had no effect on OS (median OS, 24.3 vs. 24.6 months; hazard ratio [HR], 1.021; P = .810). For the 179 patients (24.2%) with a RSP tumor, OS was improved with the addition of SIRT (median, 22.0 vs. 17.1 months HR, 0.641; P = .008). The addition of SIRT was not associated with a significant difference in OS among the 540 patients with a LSP tumor (median, 24.6 vs. 26.6 months; HR, 1.120; P = .264). A test of treatment interaction by primary tumor side was statistically significant for RSP and SIRT (P = .002). Conclusion: The addition of SIRT for patients with RSP tumors, but not for those with LSP tumors, was associated with a statistically and clinically significant OS gain. (C) 2018 Elsevier Inc. All rights reserved.

PURPOSE:The purposes of this study were to estimate the incidence of chemotherapy-induced peripheral neuropathy (CIPN) and to identify its main determinants and impact in patient-reported outcomes. METHODS:We performed a prospective cohort study including 296 patients with incident breast cancer submitted to chemotherapy, followed for 1 year. Patients with incident CIPN were reevaluated 6 months after this diagnosis. Relative risks (RR) with 95 % confidence intervals (95 % CI) were computed to quantify the relation between different clinical characteristics and the occurrence of CIPN, using Poisson regression. The variation of patient-reported outcomes between baseline and 1-year follow-up assessments was compared between patients with and without CIPN. RESULTS:The cumulative incidence of CIPN in the first year after diagnosis was 28.7 % (95 % CI 23.8-34.1), and more than 80 % of the patients were still symptomatic after 6 months. Among the latter, there was a significant decrease in the median total neuropathy score, clinical version (7 versus 4) between the two periods. In multivariable analysis, the risk of CIPN was higher for treatment with docetaxel (cumulative doses ≤300 mg/m(2), RR = 6.96, 95 % CI 2.53-19.10; >300 mg/m(2), RR = 13.32; 95 % CI 4.11-43.14). Alcohol consumption and diabetes were not significantly associated with CIPN. There were no significant differences in the variation of patient-reported outcomes between the baseline and 1-year follow-up evaluations. CONCLUSIONS:CIPN was frequent in this contemporary cohort of early-stage breast cancer patients and was strongly associated with docetaxel-based regimens. Symptoms persisted for at least 6 months in most patients, but severity was low and CIPN had no impact on patient-reported outcomes.

Context: Neuropathic pain (NP) may be an important contributor to the morbidity burden of breast cancer. Objectives: We aimed to quantify the incidence of NP in the first year after diagnosis of breast cancer and to identify its main determinants. Methods: We performed a prospective cohort study including 506 patients with incident breast cancer, recruited at the Portuguese Institute of Oncology of Porto, and followed for one year; patients with incident NP were additionally evaluated when this condition was diagnosed and after six months, to identify chronic NP. Results: During the first year, 156 patients were diagnosed with NP (30.8%, 95% CI 27.0–35.0). Anxiety (relative risk [RR] 1.50; 95% CI 1.06–2.13), arm symptoms (RR 1.44; 95% CI 1.02–2.05), cancer Stage III/IV (RR 2.47; 95% CI 1.66–3.66), breast-conserving surgery with axillary lymph node dissection (RR 3.13; 95% CI 1.51–6.48), mastectomy with axillary lymph node dissection (RR 2.52; 95% CI 1.25–5.11), and damaging of the intercostobrachial nerve (RR 2.05; 95% CI 1.25–3.37) were predictors of a higher risk of NP. A total of 97 patients (62.2%, 95% CI 54.4–69.4) diagnosed with NP remained symptomatic after six months. Conclusion: NP and chronic NP were frequent in this population, being associated with anxiety and arm symptoms before breast cancer treatments and type of surgical management. These results highlight the need for monitoring the occurrence of this neurologic side effect of treatments and to develop strategies for reducing the morbidity burden of breast cancer. The work of F. F. was co-funded by “Fundação para a Ciência e a Tecnologia” (grant number SFRH/BD/92630/2013) and by the “Programa Operacional Capital Humano” (POCH/FSE). Data management activities were supported by the Chair on Pain Medicine of the Faculty of Medicine, University of Porto and by the Grünenthal Foundation—Portugal. The authors declare no conflicts of interests.

Objectives Neurological complications secondary to breast cancer treatment may be an important contributor to these patients morbidity. We aimed to quantify the incidence of neurological complications of breast cancer treatment during the first year after diagnosis. Materials and methods We performed a prospective cohort study with 506 patients recruited at the Portuguese Institute of Oncology of Porto, among those newly diagnosed. Participants underwent a neurological examination before treatment, after surgery, after chemotherapy (whenever applicable) and at one year after enrollment. The Montreal Cognitive Assessment was used to assess cognitive function, at baseline and at one year. We computed one-year cumulative incidence estimates and the corresponding 95% confidence intervals (95%CI) for each of the neurological complications. Results Just over half of women had breast cancer stage 0 or I. A total of 6.9% were submitted to neoadjuvant chemotherapy but most of them completed adjuvant treatment – endocrine therapy, radiotherapy or chemotherapy (83.9%, 73.0% and 52.5%, respectively). The cumulative incidence of at least one oncological-related neurological complication during the first year after diagnosis was 48.4% (95%CI: 44.1–52.8); the most frequent were neuropathic pain (30.8%, 95%CI: 27.0–35.0), chemotherapy-induced peripheral neuropathy (16.8%, 95%CI: 13.8–20.3), phantom breast pain/syndrome (16.6%, 95%CI: 13.6–20.1) and cognitive decline (8.1%, 95%CI: 5.8–11.1). Conclusions Neurological complications were a frequent side-effect of breast cancer management in the first year after diagnosis, especially neuropathic pain and chemotherapy-induced peripheral neuropathy. Accurate diagnosis and treatment of these complications are important to minimize the burden associated with breast cancer treatment in breast cancer survivors.

IntroductionThe improvement in breast cancer survival rates, along with the expected overdiagnosis and overtreatment associated with breast cancer screening, requires a comprehensive assessment of its burden. Neurological complications can have a devastating impact on these patients; neuropathic pain and chemotherapy-induced peripheral neuropathy are among the most frequently reported. This project aims to understand the burden of neurological complications of breast cancer treatment in Northern Portugal, and their role as mediator of the impact of the treatment in different dimensions of the patients’ quality of life.Methods and analysisA prospective cohort study was designed to include 500 patients with breast cancer, to be followed for 3 years. The patients were recruited at the Portuguese Oncology Institute of Porto and evaluations were planned at different stages: pretreatment, after surgery, after chemotherapy (whenever applicable) and at 1 and 3 years after enrolment. Patients diagnosed with neuropathic pain or chemotherapy-induced peripheral neuropathy (subcohorts), were also evaluated at the moment of confirmation of clinical diagnosis of the neurological complication and 6 months later. In each of the follow-up periods, a neurological examination has been performed by a neurologist. Data were collected on sociodemographic and clinical characteristics, quality of life, sleep quality, and anxiety and depression. Between January and December 2012, we recruited and conducted the baseline evaluation of 506 participants. The end of the follow-up period is scheduled for December 2015.Ethics and disseminationThe study protocol was approved by the Ethics Committee of the Portuguese Oncology Institute of Porto and all patients provided written informed consent. All study procedures were developed in order to assure data protection and confidentiality. Results from this project will be disseminated in international peer-reviewed journals and presented in relevant conferences.

The incidence of colorectal cancer cases in the Portuguese Institute of Oncology of Porto created the need of a telenursing program in the Gastro-Intestinal Cancer Unit. After staging, treatment may involve surgery radio and chemotherapy (either oral or IV). Patients with no treatment after surgery are scheduled for medical exams every 3 months in the first 2 years. Patients on chemotherapy need to be compliant and to have a close monitoring of adverse events. The GI Cancer Unit uses a telenursing information system to help assess colorectal cancer patients' follow-up after surgery, medical treatment compliance and adverse events. A mixed-methods evaluation was done to a) describe the target population, b) detect problems in the telenursing information system, and c) suggest changes to meet users' requirements. From 181 outbound phone calls, representing 67 patients (49 in treatment and 18 in follow-up), patients' main characteristics were extracted and system's problems were identified by the intervening nurses. Recommendations will be useful for a further development of the system.