Neoadjuvant chemotherapy prior to radical hysterectomy in locally advanced cervical cancer: a systematic review and meta-analysis.

OBJECTIVE: The objective of this systematic review was to evaluate the effect of different types of neoadjuvant chemotherapy regimens, in terms of optimal pathological response and oncological outcomes, in patients with locally advanced cervical cancer. METHODS: A systematic search of the literature was performed. MEDLINE through PubMed and Embase databases were searched from inception to June 2023. The study was registered in PROSPERO (ID number CRD42023389806). All women with a pathological diagnosis of locally advanced cervical cancer (International Federation of Gynecology and Obstetrics (FIGO) 2009 classification stages IB2-IVA), any age or histology, who underwent intravenous neoadjuvant chemotherapy before radical surgery, and articles only in English language, were included. We conducted a meta-analysis for optimal pathological response after surgery and survival outcomes. The risk of bias was assessed using the Newcastle-Ottawa scale and the Risk of Bias 2 (RoB) tools. The review methods and results were reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: 25 studies with a total number of 1984 patients fulfilled the eligibility criteria of our review and were included for data extraction and efficacy analysis. When compared with a two-drug regimen, the three-drug combination including cisplatin, paclitaxel, and ifosfamide or anthracyclines showed superior efficacy in terms of optimal pathological response with an odds ratio of 0.38 (95% CI 0.24 to 0.61, p<0.0001), with no difference in disease-free survival (hazard ratio (HR) 0.72, 95% CI 0.50 to 1.03, I2=0%, p=0.07) and higher overall survival (HR 0.63, 95% CI 0.41 to 0.97, I2=0%, p=0.03). CONCLUSIONS: The three-drug combination of cisplatin, paclitaxel, and ifosfamide or anthracyclines showed a higher rate of complete or optimal partial response, with the triple regimens having an advantage over the platinum-based schedules in terms of overall survival. Neoadjuvant chemotherapy followed by radical surgery should not be considered a standard of care in locally advanced cervical cancer.

Living systematic review to assess the analgesic undertreatment in cancer patients.

BACKGROUND AND AIMS: This living and systematic review aimed to provide an updated summary of the available evidence on pain undertreatment prevalence in patients with cancer; correlations with some potential determinants and confounders were also carried out. MATERIALS AND METHODS: We updated a systematic review published on 2014, including observational and experimental studies reporting the use of the pain management index (PMI) in adults with cancer and pain, from 2014 to 2020. We conducted searches in PubMed/MEDLINE, Embase, and Google Scholar. We performed univariate and multivariable regression analyses to describe the relationship between PMI and a list of potential explanatory variables. RESULTS: Twenty new papers were identified, yielding a total sample size of 66 studies. The proportion of patients classified as undertreated according to the year of study publication shows a higher decrease from 1994 to 2013 (-13% as relative change) than the most recent years 2014-2020 (-11%). The quality of the included studies has increased over the years (from 80% to 93%). At the multivariable analysis, a statistically significant relationship was confirmed between undertreatment and the year of the publication of the study and with a low-medium economic level of the countries, where the studies were conducted. DISCUSSION: Despite the improvement when compared to the period 1994-2000, still about 40% of the cases identified received an analgesic treatment inadequate to the intensity of pain, according to the PMI. Despite its intrinsic limitations, PMI continues to be widely used, and it could allow a continuous monitoring of pain management across a different mix of studies and patients.

Sleep disturbances, fatigue and psychological health in women with endometriosis: a matched pair case-control study.

RESEARCH QUESTION: What are the associations between endometriosis, pelvic pain symptoms, fatigue and sleep? Psychological health and quality of life in endometriosis patients with good versus bad quality of sleep were also examined. DESIGN: This matched pair case-control study included 123 consecutive endometriosis patients and 123 women without a history of endometriosis (matched to patients for age and body mass index). Endometriosis-related pelvic pain severity was rated on a 0-10 numerical rating scale. Fatigue was measured on a 1-5 Likert scale. Women also completed a set of self-report questionnaires for assessing sleep disturbances (Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, Insomnia Severity Index), psychological health (Hospital Anxiety and Depression Scale) and quality of life (Short Form-12). RESULTS: Painful endometriosis had an impact on fatigue (P = 0.006; η2p = 0.041) and sleep (P < 0.001; η2p = 0.051). Women with painful endometriosis reported significantly greater fatigue, poorer quality of sleep, higher daytime sleepiness and more severe insomnia than women without significant pain symptoms and controls. Poorer quality of sleep among endometriosis patients was associated with greater fatigue (P < 0.001; η2p = 0.130), poorer psychological health (P < 0.001; η2p = 0.135), and lower quality of life (P < 0.001; η2p = 0.240). CONCLUSIONS: Pelvic pain (rather than endometriosis in itself) is associated with fatigue and sleep disturbances, with poor sleep having a detrimental impact on women's psychological health and quality of life.

["Donnainformata-mammografia": a decision aid developed and validated in the Italian setting]. / Donnainformata-mammografia: un decision aid costruito e validato nel setting italiano.

The decision aid "Donnainformata-mammografia" (https://www.donnainformata-mammografia.it/en/) has been developed with the aim of providing clear information on the benefits and harms of breast cancer screening, and the controversies on the relationship between mortality reduction and overdiagnosis. It was evaluated in a randomized clinical trial showing it increases informed choice and does not decrease participation in screening.This article describes the framework, the guiding principles, and the operational phases of the tool development.The project was developed within the national screening programme. The promoters decided to state their placement, to start from the information needs of women and what is already known, and to balance spontaneous navigation with "nudging" to key contents. Three focus groups with 18 women and 4 interviews were organized. Participants expressed a favourable attitude towards screening, and no knowledge of the debate on screening efficacy and overdiagnosis. A literature review and a comparison of decision aids were conducted. The online tool included the results of these steps. The home page presents key information with links to relevant topics, so that the person can decide to stop there having an overview or to continue. The «ready to decide¼ button, which leads to the section of decision support, can be clicked on every page. Here, the person can evaluate a list of key points on the basis of her values, in order to decide to participate in screening or not.

A dynamic web-based decision aid to improve informed choice in organised breast cancer screening. A pragmatic randomised trial in Italy.

BACKGROUND: Improving the quality of information and communication is a priority in organised breast cancer screening and an ethical duty. Programmes must offer the information each woman is looking for, promoting informed decision-making. This study aimed to develop and evaluate a web-based dynamic decision aid (DA). METHODS: A pragmatic randomised trial carried out in six regional organised screening programmes recruited women at the first invitation receiving DA or a web-based standard brochure (SB). The primary outcome was informed choice measured on knowledge, attitudes, and intentions. Follow-up period: 7-10 days. Secondary outcomes included participation rate, satisfaction, decisional conflict, and acceptability of DA. RESULTS: Two thousand one hundred and nineteen women were randomised and 1001 completed the study. Respectively, 43.9% and 36.9% in the DA and SB reached the informed choice. The DA gave a 13-point higher proportion of women aware about overdiagnosis compared to SB (38.3% versus 25.2%, p < 0.0001). The percentage of women attending screening was the same: 84% versus 83%. Decisional conflict was significantly lower in the DA group (14.4%) than in the SB group (19.3%). CONCLUSION: DA increases informed choice. Complete information including the pros, cons, controversies, and overdiagnosis-overtreatment issues boost a woman's knowledge without reducing the rate of actual screening participation. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov number NCT03097653.

Choosing Wisely Italy: online survey on opinions and behaviors of 1006 people and 355 volunteers of healthcare advocacy associations.

BACKGROUND: In the framework of 'Doing more does not mean doing better - Choosing Wisely Italy' health professionals, general population and healthcare advocacy associations are widely involved. PartecipaSalute-Mario Negri IRCCS and Altronconsumo organized a survey in order to assess the opinions and behaviors of people toward unnecessary tests and drugs. METHODS: An online survey was distributed by Altroconsumo to a voluntary panel of 6304 Italian citizens covering the whole of the country and by PartecipaSalute-Mario Negri IRCCS through the PartecipaSalute website, e-mail lists, website articles, lay journals and Facebook. RESULTS: In all 1006 people reached by Altroconsumo, and 355 volunteers of healthcare advocacy associations reached by PartecipaSalute responded. Respondents usually decides on their treatment together with the physician, respectively 50% for general population and 64% for volunteers of healthcare advocacy associations. The respondents are aware of the question of over-use of drugs and tests (80%), more often among the volunteers of healthcare advocacy associations (86%). Over-use is considered a problem mostly for economic reasons among the general population, while in the advocacy associations the risks for patients' health is considered more important. CONCLUSION: These findings suggest that patients do not always ask for more, especially if they receive an answer to their questions and clarifications about unnecessary treatments. There is a need for further understanding of the factors influencing decision-making aimed at achieving good care. Engaging the public and patients at all levels of healthcare is essential for a valuable use of health resources.

Prognostic Value of Hormonal Abnormalities in Heart Failure Patients.

The model used to explain the pathophysiologic substrate and progressive worsening in chronic heart failure (CHF) is based on the hyperactivity of renin-angiotensin-aldosterone system and adrenergic pathway. Although the neurohormonal medical approach has many advantages, it has several pitfalls, as demonstrated by high rates of CHF mortality and hospitalization. A growing body of evidence has led to the hypothesis that CHF is a multiple hormone deficiency syndrome, characterized by a reduced anabolic drive that has relevant functional and prognostic implications. The aim of this review is to summarize the evidence of reduced drive of main anabolic axes in CHF.

HIV priorities by Italian AIDS advocacy groups: information on prevention (still) comes first. An on-line survey.

OBJECTIVES: to define a list of priorities for activities and research projects based on the consultation of Italian AIDS advocacy groups through an online survey. DESIGN: a multidisciplinary advisory board was set up to define the survey and discuss the findings. Five areas - and related items - were listed: prevention, continuity of care, discrimination, research, key populations. Fifty-eight AIDS advocacy groups were identified and invited through e-mail to the survey, which lasted two months. Responders were asked to select a priority area and vote two items. Then, as second choice, they had to choose up to three items across the other areas. The final step of the prioritization process was the discussion of the survey findings with the advisory board. SETTING AND PARTICIPANTS: Italian HIV advocacy groups. RESULTS: thirty-seven groups responded (64%). The priority selected by most was prevention (around 80%), particularly preventive information addressed to teenagers and the general population. For the second choice, the most chosen items referred to discrimination and the continuity of care. The advisory board members underlined the need for a planned, organized, monitored, and evidence-based approach for HIV prevention information in different settings. CONCLUSIONS: different strategies to provide HIV prevention information should be proposed and monitored according to different targets, following an evidence-based approach. The stigma and discrimination against people with HIV and AIDS must be cleaned up to foster safe sex behaviours, providing education interventions at school. Wider structural issues have to be addressed, such as the availability and affordability of health services, contraceptive choices and condoms, poverty, and cultural gender norms.

Oral prolonged-release Oxycodone-Naloxone: analgesic response, safety profile, and factors influencing the response in advanced cancer patients.

BACKGROUND: Oxycodone-Naloxone (OXN) aims to reduce opioid-related constipation while being successfully analgesic. METHODS: We evaluated the analgesic response, prevalence, and severity of side effects in 176 cancer patients with moderate to severe pain and treated with OXN. Patients were followed for 28 days and evaluated every seven. Pain intensity, changes of therapy, and adverse drug reactions were recorded at each visit. The primary efficacy endpoint was the proportion of responders (≥30% reduction of pain intensity from baseline to final) and final average pain score ≤4 on a 0-10 scale. RESULTS: Average and worst pain intensity, and breakthrough pain (BTP) prevalence decreased over time and 81.3% of patients were responders. The starting daily dose of OXN was raised from 25.1±13.0 mg to 44.1±29.9 mg, and dose escalation >5%/day was observed in 19.4% of patients; 40.8-46.2% and 11.0-17.0% experienced any and severe grade of constipation during the follow-up visit, respectively. Digestive system tumor, thyroid endocrinopathies, psychological irritability, and BTP increased the risk of analgesic non-response. CONCLUSIONS: OXN had strong analgesic effect in moderate to severe cancer pain patients: the safety profile is in line with the common adverse effects of opioids and severe constipation was uncommon. This article is protected by copyright. All rights reserved.

Medical treatment or surgery for colorectal endometriosis? Results of a shared decision-making approach.

STUDY QUESTION: What is the degree of patient satisfaction in women with symptomatic colorectal endometriosis who choose medical or surgical treatment after a shared decision-making (SDM) process? SUMMARY ANSWER: The degree of satisfaction with treatment was high both in women who chose medical treatment with a low-dose oral contraceptive (OCP) or a progestin, and in those who chose to undergo surgical resection of bowel endometriosis. WHAT IS KNOWN ALREADY: Hormonal therapies and surgery for colorectal endometriosis have been investigated in non-comparative studies with inconsistent results. STUDY DESIGN, SIZE, DURATION: Parallel cohort study conducted on 87 women referring to our centre with an indication to surgery for colorectal endometriosis. A standardised SDM process was adopted, allowing women to choose their preferred treatment. Median follow-up was 40 [18-60] months in the medical therapy group and 45 [30-67] in the surgery group. PARTICIPANTS/MATERIALS, SETTING, METHODS: Patients with endometriosis infiltrating the proximal rectum, the rectosigmoid junction, and the sigmoid, not causing severe sub-occlusive symptoms were enroled. A total of 50 patients chose treatment with an OCP (n = 12) or a progestin (n = 38), whereas 37 women confirmed their previous indication to surgery. Patient satisfaction was graded according to a 5-category scale. Variations in bowel and pain symptoms were measured by means of a 0-10 numeric rating scale. Constipation was assessed with the Knowles-Eccersley-Scott Symptom Questionnaire (KESS), health-related quality of life with the Short Form-12 questionnaire (SF-12), psychological status with the Hospital Anxiety and Depression scale (HADS) and sexual functioning with the Female Sexual Function Index (FSFI). MAIN RESULTS AND THE ROLE OF CHANCE: Six women in the medical therapy group requested surgery because of drug inefficacy (n = 3) or intolerance (n = 3). Seven major complications were observed in the surgery group (19%). At 12-month follow-up, 39 (78%) women in the medical therapy group were satisfied with their treatment, compared with 28 (76%) in the surgery group (adjusted odds ratio (OR), 1.37; 95% confidence interval (CI), 0.45-4.15; intention-to-treat analysis). Corresponding figures at final follow-up assessment were 72% in the former group and 65% in the latter one (adjusted OR, 1.74; 95% CI, 0.62-4.85). The 60-month cumulative proportion of dissatisfaction-free participants was 71% in the medical therapy group compared with 61% in the surgery group (P = 0.61); the Hazard incidence rate ratio was 1.21 (95% CI, 0.57-2.62). Intestinal complaints were ameliorated by both treatments. Significant between-group differences in favour of medical treatment were observed at 12-month follow-up in diarrhoea, dysmenorrhoea, non-menstrual pelvic pain and SF-12 physical component scores. The total HADS score improved significantly in both groups, whereas the total FSFI score improved only in women who chose medical therapy. LIMITATIONS REASONS FOR CAUTION: As treatments were not randomly assigned, selection bias and confounding are likely. The small sample size exposes to the risk of type II errors. WIDER IMPLICATIONS OF THE FINDINGS: When adequately informed and empowered through a SDM process, most patients with non-occlusive colorectal endometriosis who had already received a surgical indication, preferred medical therapy. The possibility of choosing the preferred treatment may allow maximisation of the potential effect of the interventions. STUDY FUNDING/COMPETING INTEREST(S): This study was financed by Italian fiscal contribution '5 × 1000'-Ministero dell'Istruzione, dell'Università e della Ricerca-devolved to Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy. P.V., M.P.F., R.R., D.D., A.R., P.M., O.D.G. and M.C. declare that they have no conflicts of interest. E.S. received grants from Ferring and Serono.

Deciding on cystic fibrosis carrier screening: three citizens' juries and an online survey.

Background: Health technology assessment and ethical issues have to be dealt with in deciding on national carrier screening for cystic fibrosis (CF)-the most frequent severe autosomal recessive disease in Caucasian populations and several stakeholders need to be involved. A citizens' jury is one way to ask citizens to deliberate on controversial topics in the interests of a society. The aims of this project were to gather opinions about CF carrier screening through citizens' jury deliberations and to match them with the findings of a large online consultation survey open to the general population, people with CF and families and health professionals. Methods: Three citizens' juries and an online survey were asked: 'Should the Health Service organize screening of the population with the aim of identifying healthy people who may have children with CF?' The jurors had no medical background and no personal or family CF history. The survey was open to people with CF, families, and healthcare professionals. Results: Jurors and survey respondents were in favour of CF carrier screening, mainly considering the severity of CF, the value of informed reproductive choices and the equality of the screening. All the citizens' juries felt positively about the health service actively offer CF carrier screening to provide women and couples of reproductive age equal access and standardized information on the pros and cons. Conclusion: Considering the favourable attitude towards CF screening, the feasibility of CF screening, in terms of best setting, target age and healthcare professionals providing it, should be tested in a clinical trial.

Shifting from Oral Contraceptives to Norethisterone Acetate, or Vice Versa, because of Drug Intolerance: Does the Change Benefit Women with Endometriosis?

BACKGROUND/AIMS: Oral contraceptives (OC) and norethisterone acetate (NETA) are among first-line medical therapies for symptomatic endometriosis, but their use is sometimes associated with intolerable side effects. We investigated whether shifting from low-dose OC to NETA (2.5 mg/day), or vice versa, improved tolerability. METHODS: Sixty-seven women willing to discontinue their treatment because of intolerable side effects despite good pain relief, were enrolled in a self-controlled study, and shifted from OC to NETA (n = 35) or from NETA to OC (n = 32). The main study outcome was satisfaction with treatment 12 months after the change. Tolerability, pain symptoms, health-related quality of life, psychological status, and sexual functioning were also evaluated. RESULTS: After treatment change, good tolerability was reported by 37% of participants who shifted to NETA, and by 52% of those who shifted to OC. At 12-month assessment, 51% of women intolerant to OC were satisfied with NETA, and 65% of those intolerant to NETA were satisfied with OC (intention-to-treat analysis). Other study variables did not vary substantially. CONCLUSIONS: In selected endometriosis patients, shifting from OC to NETA, or vice versa, because of side effects, improved tolerability. Better results were observed when substituting NETA with OC rather than the other way round.

Nonresponsiveness and Susceptibility of Opioid Side Effects Related to Cancer Patients' Clinical Characteristics: A Post-Hoc Analysis.

BACKGROUND: The response to opioids is not always positive in cancer patients. A considerable proportion of patients do not respond (nonresponders [NRs]) or experience severe toxicity. The aim of this analysis was to assess the role of demographic characteristics, pain features, comorbidities, and ongoing therapy on the lack of efficacy and on the occurrence of severe adverse drug reactions (ADRs). METHODS: This is a post-hoc analysis of a randomized controlled trial that involved 520 patients and aimed to evaluate the efficacy and safety of 4 strong opioids. Patients who presented with unchanged or worsened pain compared to the first visit were considered to be NRs. As for toxicity, severe ADRs with an incidence of greater than 10% were evaluated. Univariate and multivariate logistic models were used. RESULTS: 498 patients were analyzed. Liver metastases and breakthrough pain (BTP) were found to increase the risk for nonresponse. Conversely, a high basal pain intensity significantly decreased the same risk. Constipation risk was worsened by previous weak opioid therapy but decreased with aging and with the use of transdermal opioids. Risk for drowsiness was aggravated by bone metastases and concomitant treatment with anticoagulant, antidiabetic, and central nervous system drugs. Risk for confusion increased with antidiabetics, antibiotics, and previous weak opioid therapy but decreased when fentanyl was used. Occurrence of nausea increased in patients with a high rating on the Karnofsky Performance Status Index. Risk for xerostomia was higher in women and in patients treated with antidiabetic or long-term opioids. CONCLUSIONS: Several clinical variables are correlated with opioid response in cancer patients. In particular, the presence of BTP is associated with nonresponse. Additionally, patients who receive polypharmacological therapy are more likely to experience opioid adverse events.

Personalised informed choice on evidence and controversy on mammography screening: study protocol for a randomized controlled trial.

BACKGROUND: In Italy women aged 50-69 are invited for a population-based breast cancer (BC) screening. Physicians, policy makers and patients associations agree on the need to inform women about the benefits and harms in order to permit an informed decision. Decision aids (DA) are an effective way to support people in their decisions about health. This trial aims to assess women's informed choices, according to their health literacy and values, on participating or not in BC screening for the first time. Benefits, harms and controversies are presented. METHODS/DESIGN: The impact of the DA will be evaluated in a randomized controlled trial with a two-week follow-up. Women will be randomized via web to DA or a standard brochure. We will invite 8160 women, to obtain a final sample of 816 women. The primary outcome will be informed choice, measured on the basis of knowledge, attitudes and intentions on BC screening. Secondary outcomes are participation rate, satisfaction on information and decisional conflict. DISCUSSION: The web DA will be open-source and implemented on BC screenings and its efficacy for increasing informed choice will be tested. This model could be applied to other healthcare settings, cancer screenings, and public health programs. TRIAL REGISTRATION: The protocol for this trial was registered with the Clinicaltrials.gov registry on March 16, 2017: NCT03097653 .

Knowledge and attitudes towards clinical trials among women with ovarian cancer: results of the ACTO study.

BACKGROUND: Despite several initiatives by research groups, regulatory authorities, and scientific associations to engage citizens/patients in clinical research, there are still obstacles to participation. Among the main discouraging aspects are incomplete understanding of the concepts related to a clinical trial, and the scant, sometimes confused, explanations given. This observational, cross-sectional multicenter study investigated knowledge, attitudes and trust in clinical research. We conducted a survey among women with ovarian cancer at their first follow-up visit or first therapy session, treated in centers belonging to the Mario Negri Gynecologic Oncology (MaNGO) and Multicenter Italian Trials in Ovarian Cancer (MITO) groups. A questionnaire on knowledge, attitudes and experience was assembled ad hoc after a literature review and a validation process involving patients of the Alliance against Ovarian Cancer (ACTO). RESULTS: From 25 centers 348 questionnaire were collected; 73.5% of responders were 56 years or older, 54.8% had a high level of education, more than 80% had no experience of trial participation. Among participants 59% knew what clinical trials were and 71% what informed consent was. However, more than half did not know the meaning of the term randomization. More than half (56%) were in favor of participating in a clinical trial, but 35% were not certain. Almost all responders acknowledged the doctor's importance in decision-making. Patients' associations were recognized as having a powerful role in the design and planning of clinical trials. CONCLUSIONS: This study helps depict the knowledge and attitudes of women with ovarian cancer in relation to clinical trials, suggesting measures aimed at improving trial "culture", literacy and compliance, and fresh ways of communication between doctors and patients.

Learning discloses abnormal structural and functional plasticity at hippocampal synapses in the APP23 mouse model of Alzheimer's disease.

B6-Tg/Thy1APP23Sdz (APP23) mutant mice exhibit neurohistological hallmarks of Alzheimer's disease but show intact basal hippocampal neurotransmission and synaptic plasticity. Here, we examine whether spatial learning differently modifies the structural and electrophysiological properties of hippocampal synapses in APP23 and wild-type mice. While no genotypic difference was found in the pseudotrained mice, training elicited a stronger increase in spine density and a more rapid decay of long-term potentiation (LTP) in APP23 mutants. Thus, learning discloses mutation-related abnormalities regarding dendritic spine formation and LTP persistence, thereby suggesting that although unaltered in naïve synapses, plasticity becomes defective at the time it comes into play.

Surgical removal of an exceedingly rare papillary fibroelastoma of the aortic wall causing unstable angina.

Difficult diagnosis is due to rarity of the case. TT or TE echocardiography is sufficient to make a correct diagnosis. The risk of embolism or coronary ostia occlusion should guide the decision for surgery.

Identification of genetic polymorphisms modulating nausea and vomiting in two series of opioid-treated cancer patients.

Nausea and vomiting are often associated with opioid analgesia in cancer patients; however, only a subset of patients develop such side effects. Here, we tested the hypothesis that the occurrence of nausea and vomiting is modulated by the genetic background of the patients. Whole exome sequencing of DNA pools from patients with either low (n = 937) or high (n = 557) nausea and vomiting intensity, recruited in the European Pharmacogenetic Opioid Study, revealed a preliminary association of 53 polymorphisms. PCR-based genotyping of 45 of these polymorphisms in the individual patients of the same series confirmed the association for six SNPs in AIM1L, CLCC1, MUC16, PDE3A, POM121L2, and ZNF165 genes. Genotyping of the same 45 polymorphisms in 264 patients of the Italian CERP study, also treated with opioids for cancer pain, instead confirmed the association for two SNPs in ZNF568 and PDE3A genes. Only one SNP, rs12305038 in PDE3A, was confirmed in both series, although with opposite effects of the minor allele on the investigated phenotype. Overall, our findings suggest that genetic factors are indeed associated with nausea and vomiting in opioid-treated cancer patients, but the role of individual polymorphisms may be weak.