Indicators of cure for women living after uterine and ovarian cancers: a population-based study.

This study aims to estimate long-term survival, cancer prevalence, and several cure indicators for Italian women with gynaecological cancers. Thirty-one cancer registries, representing 47% of the Italian female population, were included. Mixture cure models were used to estimate Net Survival (NS), Cure Fraction, Time To Cure (5-year conditional NS>95%), Cure Prevalence (women who will not die of cancer), and Already Cured (living longer than Time to Cure). In 2018, 0.4% (121,704) of Italian women were alive after corpus uteri cancer, 0.2% (52,551) after cervical, and 0.2% (52,153) after ovarian cancer. More than 90% of patients with uterine cancers and 83% with ovarian cancer will not die from their neoplasm (Cure Prevalence). Women with gynaecological cancers have a residual excess risk of death <5% after 5 years since diagnosis. The Cure Fraction was 69% for corpus uteri, 32% for ovarian, and 58% for cervical cancer patients. Time To Cure was ≤10 years for women with gynaecological cancers aged <55 years. 74% of patients with cervical cancer, 63% with corpus uteri cancer, and 55% with ovarian cancer were Already Cured. These results will contribute to improving follow-up programs for women with gynaecological cancers and supporting efforts against discrimination of already cured ones.

Cure indicators and prevalence by stage at diagnosis for breast and colorectal cancer patients: A population-based study in Italy.

People alive many years after breast (BC) or colorectal cancer (CRC) diagnoses are increasing. This paper aimed to estimate the indicators of cancer cure and complete prevalence for Italian patients with BC and CRC by stage and age. A total of 31 Italian Cancer Registries (47% of the population) data until 2017 were included. Mixture cure models allowed estimation of net survival (NS); cure fraction (CF); time to cure (TTC, 5-year conditional NS >95%); cure prevalence (who will not die of cancer); and already cured (prevalent patients living longer than TTC). 2.6% of all Italian women (806,410) were alive in 2018 after BC and 88% will not die of BC. For those diagnosed in 2010, CF was 73%, 99% when diagnosed at stage I, 81% at stage II, and 36% at stages III-IV. For all stages combined, TTC was >10 years under 45 and over 65 years and for women with advanced stages, but ≤1 year for all BC patients at stage I. The proportion of already cured prevalent BC women was 75% (94% at stage I). Prevalent CRC cases were 422,407 (0.7% of the Italian population), 90% will not die of CRC. For CRC patients, CF was 56%, 92% at stage I, 71% at stage II, and 35% at stages III-IV. TTC was ≤10 years for all age groups and stages. Already cured were 59% of all prevalent CRC patients (93% at stage I). Cancer cure indicators by stage may contribute to appropriate follow-up in the years after diagnosis, thus avoiding patients' discrimination.

Cancer and Pregnancy: Estimates in Italy from Record-Linkage Procedures between Cancer Registries and the Hospital Discharge Database.

The aim of this study is to describe the frequency and trend of pregnancy-associated cancer (PAC) in Italy, an increasingly relevant phenomenon due to postponing age at childbirth. To this purpose, a population-based retrospective longitudinal study design based on cohorts of women aged 15-49 diagnosed with cancer and concomitant pregnancy is proposed. The study uses 19 population-based Cancer Registries, covering about 22% of Italy, and linked at an individual level with Hospital Discharge Records. A total of 2,861,437 pregnancies and 3559 PAC are identified from 74,165 women of the cohort with a rate of 1.24 PAC per 1000 pregnancies. The most frequent cancer site is breast (24.3%), followed by thyroid (23.9%) and melanoma (14.3%). The most frequent outcome is delivery (53.1%), followed by voluntary termination of pregnancy and spontaneous abortion (both 12.0%). The trend of PAC increased from 2003 to 2015, especially when the outcome is delivery, thus confirming a new attitude of clinicians to manage cancer throughout pregnancy. This represents the first attempt in Italy to describe PAC from Cancer Registries data; the methodology is applicable to other areas with the same data availability. Evidence from this study is addressed to clinicians for improving clinical management of women with PAC.

Projecting cancer prevalence by phase of care: a methodological approach for health service planning.

Background: In most developed countries, the number of cancer survivors is expected to increase in the coming decades because of rising incidence and survival rates and an aging population. These patients are heterogeneous in terms of health service demands: from recently diagnosed patients requiring first-course therapy to patients with extensive care needs and severe disabilities to long-term survivors who only need minimal care. Therefore, in terms of providing healthcare planners and policymakers with useful indicators for addressing policies according to health service demands, it is worth supplying updated measures of prevalence for groups of patients based on the level of care they require. The aim of this paper is to illustrate a new method for estimating short-term projections of cancer prevalence by phase of care that applies to areas covered by cancer registration. Methods: The proposed method combines linear regression models to project limited duration prevalence derived from cancer registry data and a session of the freely available software COMPREV to estimate the projected complete prevalence into three distinct clinically relevant phases of care: initial, continuing, and final. The method is illustrated and validated using data from the Veneto region in Italy for breast, colorectal, and lung cancers. Results: Prevalence is expected to increase in 2015-2026 for all considered cancer sites and sexes, with average annual variations spanning from 2.6% for women with lung cancer to 0.5% for men with colorectal cancer. The only exception is lung cancer prevalence in men, which shows an average annual decrease of 1.9%. The majority of patients are in the continuing phase of care, followed by the initial and final phases, except for lung cancer, where the final phase of care prevails over the initial one. Discussion: The paper proposes a method for estimating (short-term) future cancer healthcare needs that is based on user-friendly and freely available software and linear regression models. Validation results confirm the applicability of our method to the most frequent cancer types, provided that cancer registry data with at least 15 years of registration are available. Evidence from this method is addressed to policymakers for planning future cancer care, thus improving the cancer survivorship experience for patients and caregivers.

Complete prevalence and indicators of cancer cure: enhanced methods and validation in Italian population-based cancer registries.

Objectives: To describe the procedures to derive complete prevalence and several indicators of cancer cure from population-based cancer registries. Materials and methods: Cancer registry data (47% of the Italian population) were used to calculate limited duration prevalence for 62 cancer types by sex and registry. The incidence and survival models, needed to calculate the completeness index (R) and complete prevalence, were evaluated by likelihood ratio tests and by visual comparison. A sensitivity analysis was conducted to explore the effect on the complete prevalence of using different R indexes. Mixture cure models were used to estimate net survival (NS); life expectancy of fatal (LEF) cases; cure fraction (CF); time to cure (TTC); cure prevalence, prevalent patients who were not at risk of dying as a result of cancer; and already cured patients, those living longer than TTC at a specific point in time. CF was also compared with long-term NS since, for patients diagnosed after a certain age, CF (representing asymptotical values of NS) is reached far beyond the patient's life expectancy. Results: For the most frequent cancer types, the Weibull survival model stratified by sex and age showed a very good fit with observed survival. For men diagnosed with any cancer type at age 65-74 years, CF was 41%, while the NS was 49% until age 100 and 50% until age 90. In women, similar differences emerged for patients with any cancer type or with breast cancer. Among patients alive in 2018 with colorectal cancer at age 55-64 years, 48% were already cured (had reached their specific TTC), while the cure prevalence (lifelong probability to be cured from cancer) was 89%. Cure prevalence became 97.5% (2.5% will die because of their neoplasm) for patients alive >5 years after diagnosis. Conclusions: This study represents an addition to the current knowledge on the topic providing a detailed description of available indicators of prevalence and cancer cure, highlighting the links among them, and illustrating their interpretation. Indicators may be relevant for patients and clinical practice; they are unambiguously defined, measurable, and reproducible in different countries where population-based cancer registries are active.

Trends in radioactive iodine treatment after total thyroidectomy in Italy, 2001-2018.

Objective: A decrease in the use of radioactive iodine (RAI) treatment for thyroid cancer has been described in the last decade in the US following subsequent updates of the American Thyroid Association guidelines. By contrast, population-based data from European countries are lacking. The study aims to assess the frequency and long-term trends in the use of RAI in Italy. Methods: From the Italian national hospital discharge database, the proportion of RAI treatment after total thyroidectomy with thyroid cancer diagnosis has been assessed by sex and age class during 2001-2018. Results: Throughout the whole study period, RAI was performed after 58% of 149,419 total thyroidectomies. The use of RAI was higher for men and younger patients; it peaked in 2007 (64% in women and 68% in men) and declined thereafter (2018: 46% in women and 53% in men), with a similar pattern observed across all ages and areas. Conclusion: National data show that in Italy trends in RAI treatment paraleled those observed in the US. Further monitoring of the use of RAI is warranted in Italy, as elsewhere, to assess the impact of international guidelines on real-life clinical management of thyroid cancer.

Cancer treatment data available in European cancer registries: Where are we and where are we going?

Population-based cancer registries are responsible for collecting incidence and survival data on all reportable neoplasms within a defined geographical area. During the last decades, the role of cancer registries has evolved beyond monitoring epidemiological indicators, as they are expanding their activities to studies on cancer aetiology, prevention, and quality of care. This expansion relies also on the collection of additional clinical data, such as stage at diagnosis and cancer treatment. While the collection of data on stage, according to international reference classification, is consolidated almost everywhere, data collection on treatment is still very heterogeneous in Europe. This article combines data from a literature review and conference proceedings together with data from 125 European cancer registries contributing to the 2015 ENCR-JRC data call to provide an overview of the status of using and reporting treatment data in population-based cancer registries. The literature review shows that there is an increase in published data on cancer treatment by population-based cancer registries over the years. In addition, the review indicates that treatment data are most often collected for breast cancer, the most frequent cancer in women in Europe, followed by colorectal, prostate and lung cancers, which are also more common. Treatment data are increasingly being reported by cancer registries, though further improvements are required to ensure their complete and harmonised collection. Sufficient financial and human resources are needed to collect and analyse treatment data. Clear registration guidelines are to be made available to increase the availability of real-world treatment data in a harmonised way across Europe.

Cancer cost profiles: The Epicost estimation approach.

Sustainability of cancer burden is becoming increasingly central in the policy makers' debate, and poses a challenge for the welfare systems, due to trends towards greater intensity of healthcare service use, which imply increasing costs of cancer care. Measuring and projecting the economic burden associated with cancer and identifying effective policies for minimising its impact are important issues for healthcare systems. Scope of this paper is to illustrate a novel comprehensive approach (called Epicost) to the estimation of the economic burden of cancer, based on micro-data collected from multiple data sources. It consists of a model of cost analysis to estimate the amount of reimbursement payed by the National Health Service to health service providers (hospitals, ambulatories, pharmacies) for the expenses incurred in the diagnoses and treatments of a cohort of cancer patients; these cancer costs are estimated in various phases of the disease reflecting patients' patterns of care: initial, monitoring and final phase. The main methodological features are illustrated using a cohort of colon cancer cases from a Cancer Registry in Italy. This approach has been successfully implemented in Italy and it has been adapted to other European countries, such as Belgium, Norway and Poland in the framework of the Innovative Partnership for Action Against Cancer (iPAAC) Joint Action, sponsored by the European Commission. It is replicable in countries/regions where population-based cancer registry data is available and linkable at individual level with administrative data on costs of care.

Thyroidectomies in Italy: A Population-Based National Analysis from 2001 to 2018.

Background: The incidence of thyroid disease is generally increasing, and it is subject to major geographic variability, between and within countries. Moreover, the incidence rates and the proportion of overdiagnosis for thyroid cancer in Italy are among the highest worldwide. This study aimed to estimate population-based frequency and trends of thyroidectomies in Italy by type of surgical procedure (total/partial), indication (tumors/other conditions), sex, age, and geographical region. Materials and Methods: Age-standardized rates (ASRs) of thyroidectomies were estimated from 2001 to 2018 using the national hospital discharges database. Results: In Italy, ASRs of thyroidectomies were nearly 100 per 100,000 women in 2002-2004 and decreased to 71 per 100,000 women in 2018. No corresponding variation was shown in men (ASR 27 per 100,000 men) in the overall period. A more than twofold difference between Italian regions emerged in both sexes. The proportion of total thyroidectomies (on the sum of total and partial thyroidectomies) in the examined period increased from 78% to 86% in women and from 72% to 81% in men. Thyroidectomies for goiter and nonmalignant conditions decreased consistently throughout the period (from 81 per 100,000 women in 2002 to 49 in 2018 and from 22 to 16 per 100,000 men), while thyroidectomies for tumors increased until 2013-2014 up to 24 per 100,000 women (9 per 100,000 men) and remained essentially stable thereafter. Conclusions: The decrease in thyroidectomies for nonmalignant diseases since early 2000s in Italy may derive from the decrease of goiter prevalence, possibly as a consequence of the reduction of iodine deficiency and the adoption of conservative treatments. In a context of overdiagnosis of thyroid cancer, recent trends have suggested a decline in the diagnostic pressure with a decrease in geographic difference. Our results showed the need and also the possibility to implement more conservative surgical approaches to thyroid diseases, as recommended by international guidelines.

A direct method for the identification of patterns of care using administrative databases: the case of breast cancer.

OBJECTIVES: To identify and provide lists of procedures and drugs related to diagnosis and treatment of breast cancer. These lists can be used for the estimation of the cost of illness. METHODS: The method consists of identifying lists of procedures/interventions/drugs related to the tumour of interest, drawn by a panel of expert clinicians and oncologists on the basis of clinical guidelines and current practice. The lists are applied to data referring to breast cancer female patients, collected by population-based Cancer Registries and linked at individual level with information on health care treatments. A comparison with lists obtained via the matched control method is implemented. RESULTS: The distribution of administered procedures and drug prescriptions is coherent with the patient clinical pathway: surgery is the main cause of hospitalization in the first year since diagnosis, diagnostic and monitoring interventions are more frequent in the following years (recurrences detection), and at end-of-life (palliative care). Most outpatient services are due to diagnosis and monitoring, one third of services in the first year since diagnosis is radiotherapy and chemotherapy. Drugs prescribed to patients and sold in pharmacy include hormonal drugs as first course treatment and analgesics as palliative care. CONCLUSIONS: This direct method represents a valid alternative to the matched control method in describing patterns of care and costs related to the entire disease pathway. It is particularly suitable in case of cancer sites with complex patterns of care, such as breast cancer. The lists of codes developed here are based on international classification systems and can be easily applicable to other countries.

The Economic Impact of Rectal Cancer: A Population-Based Study in Italy

Costs of cancer care are increasing worldwide, and sustainability of cancer burden is critical. In this study, the economic impact of rectal cancer on the Italian healthcare system, measured as public healthcare expenditure related to investigation and treatment of rectal cancer patients is estimated. A cross-sectional cohort of 9358 rectal cancer patients is linked, on an individual basis, to claims associated to rectal cancer diagnosis and treatments. Costs refer mainly to years 2010-2011 and are estimated by phase of care, as healthcare needs vary along the care pathway: diagnostic procedures are mainly provided in the first year, surveillance procedures are addressed to chronically ill patients, and end-of-life procedures are given in the terminal status. Clinical approaches and corresponding costs are specific by cancer type and vary by phase of care, stage at diagnosis, and age. Surgery is undertaken by the great majority of patients. Thus, hospitalization is the main cost driver. The evidence produced can be used to improve planning and allocation of healthcare resources. In particular, early diagnosis of rectal cancer is a gain in healthcare budget. Policies raising spreading of and adherence to screening plans, above all when addressed to people living in Southern Italy, should be strongly encouraged.

Cancer prevalence by phase of care: an indicator for assessing health service needs.

INTRODUCTION: Cancer prevalence (people alive on a certain date in a population who previously had a cancer diagnosis) is expected to increase in the United States and Europe due to improvements in survival and population aging. Examination of prevalence by phase of care allows us to identify subgroups of patients according to their care trajectories, thus allowing us to improve health care planning, resource allocation, and calculation of costs. METHODS: A new method to estimate prevalence by phase of care using grouped data is illustrated. Prevalence is divided into 3 mutually exclusive phases: initial, continuing, and end-of-life. An application to US and Italian data is applied to prevalent cases diagnosed with colon-rectum, stomach, lung, or breast cancer. RESULTS: The distribution of phase of care prevalence estimated by cancer type and sex and results from the two datasets are very similar. Most survivors are in the continuing phase; the end-of-life phase is larger for cancers with worse prognosis. All phases prevalence is generally higher in the Italian than in the US dataset, except for lung cancer in women, where prevalence proportion in the Italian dataset is 30% lower than in the United States. DISCUSSION: Incidence, survival, and population age structure are the main determinants of prevalence and they can affect differences in all phases of prevalence, as well as in discrete phases. Incidence is the most influential determinant. Ours is the first study that compares prevalence by phase of care between two populations in Italy and the United States. Despite great differences in health care management in the two countries, we found extremely similar distribution of survivors by phase of care for most cancer sites under study.

Cancer cure for 32 cancer types: results from the EUROCARE-5 study.

BACKGROUND: Few studies have estimated the probability of being cured for cancer patients. This study aims to estimate population-based indicators of cancer cure in Europe by type, sex, age and period. METHODS: 7.2 million cancer patients (42 population-based cancer registries in 17 European countries) diagnosed at ages 15-74 years in 1990-2007 with follow-up to 2008 were selected from the EUROCARE-5 dataset. Mixture-cure models were used to estimate: (i) life expectancy of fatal cases (LEF); (ii) cure fraction (CF) as proportion of patients with same death rates as the general population; (iii) time to cure (TTC) as time to reach 5-year conditional relative survival (CRS) >95%. RESULTS: LEF ranged from 10 years for chronic lymphocytic leukaemia patients to <6 months for those with liver, pancreas, brain, gallbladder and lung cancers. It was 7.7 years for patients with prostate cancer at age 65-74 years and >5 years for women with breast cancer. The CF was 94% for testis, 87% for thyroid cancer in women and 70% in men, 86% for skin melanoma in women and 76% in men, 66% for breast, 63% for prostate and <10% for liver, lung and pancreatic cancers. TTC was <5 years for testis and thyroid cancer patients diagnosed below age 55 years, and <10 years for stomach, colorectal, corpus uteri and melanoma patients of all ages. For breast and prostate cancers, a small excess (CRS < 95%) remained for at least 15 years. CONCLUSIONS: Estimates from this analysis should help to reduce unneeded medicalization and costs. They represent an opportunity to improve patients' quality of life.

Patterns of care and cost profiles of women with breast cancer in Italy: EPICOST study based on real world data.

OBJECTIVES: To estimate total direct health care costs associated to diagnosis and treatment of women with breast cancer in Italy, and to investigate their distribution by service type according to the disease pathway and patient characteristics. METHODS: Data on patients provided by population-based Cancer Registries are linked at individual level with data on health-care services and corresponding claims from administrative databases. A combination of cross-sectional approach and a threephase of care decomposition model with initial, continuing and final phases-of-care defined according to time occurred since diagnosis and disease outcome is adopted. Direct estimation of cancer-related costs is obtained. RESULTS: Study cohort included 49,272 patients, 15.2% were in the initial phase absorbing 42% of resources, 79.7% in the continuing phase absorbing 44% of resources and 5.1% in the final phase absorbing 14% of resources. Hospitalization was the most important cost driver, accounting for over 55% of the total costs. CONCLUSIONS: This paper represents the first attempt in Italy to estimate the economic burden of cancer at population level taking into account the entire disease pathway and using multiple current health care databases. The evidence produced by the study can be used to better plan resources allocation. The model proposed is replicable to countries with individual health care information on services and claims.

Prognosis and cure of long-term cancer survivors: A population-based estimation.

BACKGROUND: Increasing evidence of cure for some neoplasms has emerged in recent years. The study aimed to estimate population-based indicators of cancer cure. METHODS: Information on more than half a million cancer patients aged 15-74 years collected by population-based Italian cancer registries and mixture cure models were used to estimate the life expectancy of fatal tumors (LEFT), proportions of patients with similar death rates of the general population (cure fraction), and time to reach 5-year conditional relative survival (CRS) >90% or 95% (time to cure). RESULTS: Between 1990 and 2000, the median LEFT increased >1 year for breast (from 8.1 to 9.4 years) and prostate cancers (from 5.2 to 7.4 years). Median LEFT in 1990 was >5 years for testicular cancers (5.8) and Hodgkin lymphoma (6.3) below 45 years of age. In both sexes, it was ≤0.5 years for pancreatic cancers and NHL in 1990 and in 2000. The cure fraction showed a 10% increase between 1990 and 2000. It was 95% for thyroid cancer in women, 94% for testis, 75% for prostate, 67% for breast cancers, and <20% for liver, lung, and pancreatic cancers. Time to 5-year CRS >95% was <10 years for testis, thyroid, colon cancers, and melanoma. For breast and prostate cancers, the 5-year CRS >90% was reached in <10 years but a small excess remained for >15 years. CONCLUSIONS: The study findings confirmed that several cancer types are curable. Became aware of the possibility of cancer cure has relevant clinical and social impacts.

Trends of colorectal cancer incidence and mortality rates from 2003 to 2014 in Italy.

OBJECTIVE: To evaluate the trends of colorectal cancer (CRC) incidence and mortality rates from 2003 to 2014 in Italy by age groups and regions. METHODS: We used the data of 48 cancer registries from 17 Italian regions to estimate standardized incidence and mortality rates overall and by sex, age groups (<50, 50-69, 70+ years), and geographic area (northwest, northeast, center, south, and islands). Time trends were expressed as annual percent change in rates (APC) with 95% confidence intervals (95% CI). RESULTS: Incidence rates decreased from 104.3 (2003) to 89.9 × 100,000 (2014) in men and from 64.3 to 58.4 × 100,000 in women. Among men, incidence decreased during 2007-2010 (APC -4.0, 95% CI -6.0 to -1.9) and 2010-2014 (APC -0.7, 95% CI -1.4 to 0.0), while in women it linearly decreased during the whole period (APC -1.1, 95% CI -1.4 to -0.8). Mortality rates showed a linear reduction both in men (APC -0.7, 95% CI -1.0 to -0.3) and women (APC -0.9, 95% CI -1.2 to -0.6) and decreased respectively from 41.1 to 39.2 × 100,000 and from 24.6 to 23.1 × 100,000. In the 50- to 69-year-old range (screening target age), incidence showed a prescreening increase, followed by a peak after screening started, and a decline thereafter. Incidence and mortality rates significantly decreased in all areas but in the south and islands, where incidence increased and mortality remained stable. CONCLUSIONS: A renewed commitment by all regional health systems to invest in primary (i.e., lifestyle) and secondary (i.e., screening programs) prevention is of utmost importance.

Cancer incidence and mortality trends from 2003 to 2014 in Italy.

OBJECTIVE: To evaluate short-term (2003-2014) cancer incidence and mortality trends in Italy. METHODS: Italian Cancer Registries data, available in the AIRTUM database, from 17 out of 20 regions were used. The number of incident cases and deaths were estimated for those registries and those years with incomplete information. Age-standardized rates, overall and stratified by geographic area, region, sex, cancer site, and major age group, were computed. Time trends were expressed as annual percent change of rates. RESULTS: In Italy, among males, incidence rates for all cancers showed during 2003-2014, a significant decrease (-0.9%/year), with stronger reductions in the northwest (-1.3%/year) and northeast (-2.0%/year since 2006) than in central (-0.7%/year) and southern (-0.4%/year) areas. Among females, a weak but significant overall reduction was detected (-0.1%/year), with a stronger decrease in the northwest (-0.5%/year). Incidence increased among women in the south (0.3%/year) of Italy. Mortality decreased in both sexes (-1.0%/year among males and -0.5%/year among females), but not in the south, where rates had a stable tendency. CONCLUSIONS: Incidence among males decreased, supported by trends for prostate, lung, colorectal, and urinary bladder cancers; among females the. The overall cancer incidence trend was stable, or even decreasing, in the northern and central areas and increasing in the southern areas, due to lung, thyroid, and melanoma rising trends. Study results provided information on the outcomes, in terms of cancer incidence and mortality, of primary and secondary prevention measures employed by regional health systems.

Gcn5 histone acetyltransferase is present in the mitoplasts.

In Saccharomyces cerevisiae the Lysine-acetyltransferase Gcn5 (KAT2) is part of the SAGA complex and is responsible for histone acetylation widely or at specific lysines. In this paper we report that G CN5 deletion differently affects the growth of two strains. The defective mitochondrial phenotype is related to a marked decrease in mtDNA content, which also involves the deletion of specific regions of the molecule. We also show that in wild-type mitochondria the Gcn5 protein is present in the mitoplasts, suggesting a new mitochondrial function independent from the SAGA complex and possibly a new function for this protein connecting epigenetics and metabolism.

Ubiquitin protease Ubp8 is necessary for S. cerevisiae respiration.

Healthy mitochondria are required in cell metabolism and deregulation of underlying mechanisms is often involved in human diseases and neurological disorders. Post-translational modifications of mitochondrial proteins regulate their function and activity, accordingly, impairment of ubiquitin proteasome system affects mitochondria homeostasis and organelle dynamics. In the present study we have investigated the role of the ubiquitin protease Ubp8 in S. cerevisiae respiration. We show that Ubp8 is necessary for respiration and its expression is upregulated in glycerol respiratory medium. In addition, we show that the respiratory defects in absence of Ubp8 are efficiently rescued by disruption of the E3 Ub-ligase Psh1, suggesting their epistatic link. Interestingly, we found also that Ubp8 is localized into mitochondria as single protein independently of SAGA complex assembly, thus suggesting an independent function from the nuclear one. We also show evidences on the importance of HAT Gcn5 in sustaining Ubp8 expression and affecting the amount of protein in mitochondria. Collectively, our results have investigated the role of Ubp8 in respiratory metabolism and highlight the role of ubiquitin related pathways in the mitochondrial functions of S. cerevisiae.