Disease-related Causes Research Articles

Resultados preliminares de supervivencia global y libre de progresión a tres años en una cohorte de pacientes diagnosticados de cáncer de próstata (grupo GESCAP)

AimsTo describe the 3-year progression-free survival (PFS), overall survival (OS) and disease-specific mortality in the prospective prostate cancer GESCAP cohort, as well as the progression to castration resistance in patients on hormone therapy. Material and methodsProspective, observational, epidemiological, multicentre study. Of the 4087 patients recruited, 3843 were evaluable. The variables analysed were the risk group (localized, locally advanced, lymph involvement, metastatic), age, prostate-specific antigen (PSA) levels, Gleason score and initial treatment. Kaplan Meier survival analysis, the log-rank test and the Cox model were used to evaluate the survival data. ResultsThree-year PFS was 81.4% and OS was 92.4%. During the 3 years of follow-up, 303 patients died (7.9%), 110 of them (36.3%) due to disease-related causes. The probability of castration resistance for all patients on hormone therapy (n=715) was 14.2%: 5%, 9.9%, 26.1% and 44.4% in localized, locally advanced, lymph involvement and metastatic cancer, respectively (log-rank P<.0001). Patients with metastases had poorer outcomes with respect to PFS, OS, disease-specific mortality and castration resistance. In the multivariate analysis, the Gleason score, PSA and presence of metastases were associated with shorter OS and PFS. ConclusionsOur study showed stratification of risk, with a more unfavourable prognosis for patients with metastases. Patients with locally advanced disease differed with respect to those with localized disease due to their higher risk as regards disease-specific mortality. (Controlled-trials.com ISRCTN19893319).

Lactate clearance as a predictor of mortality among children admitted in pediatric intensive care unit with shock

Background : We conducted this prospective observational study to identify the various causes and contributory factors for children to be brought in dead (BID) state to tertiary care centre by carrying out a root cause analysis. These causes were forked out into biological and non-biological social/ system related determinants. By doing so it was intended to look beyond ‘disease and diagnosis’ into various hiatus in health care delivery system so as to identify and address potentially correctable variables. Methods : In this study, disease related causes of mortality were analysed retrospectively and socially modifiable factors were identified prospectively in all enrolled cases. The information required for study was collected by a) direct interview and b) field observation. Results : Of the enrolled cases, more than half (55%) were neonates among which 78% were LBW. Major symptoms with which child was referred were breathing difficulty (80%), fever (21%), refusal of feed (17%). The most common referral diagnosis among neonates were LBW (78%), RDS (38%), Birth asphyxia (34.5%) and among non neonates were pneumonia (24.4%), CHD (13%), AGE (13%). Moderate to severe malnutrition was an accompanying feature in more than two-third of cases. Of referred cases, 71% of referral notes were found to be insufficient. In over three-fourth cases ambulance was used as a means of transport but umpteen lacked accessories needed for pediatric usage. Paramedic who had accompanied the cases were found to be undertrained/ untrained in handling pediatric cases. Main reason for delay in transit was found to be heavy traffic (23%), poor road condition(15%) and unfamiliarity of route(7%). Rate of ROSC(2%) was poor in the study. Conclusion: A substantial number of deaths among the referred children/neonates are preventable. A proper adoption and implementation of integrated management of childhood and neonatal illness at first level of health care contact will help in curbing preventable deaths. Better outcome can be anticipated by ameliorating care at periphery by regular training of doctors and health workers/paramedics, making medicines and equipments available and strengthening support mechanism like effective pediatric transport system

Impact of bone disease and pain in thalassemia.

Conventional treatment of thalassemia, namely regular blood transfusion and iron chelation, improves perspectives and quality of life; however, successful treatment leads to more time in which long-term complications such as bone disease can develop. Thalassemia bone disease (TBD) is unique: all aspects, from bone anatomy and bone quality to mineral density, may be affected, with important morbidity including osteoporosis, fractures, spinal deformities, nerve compression, and pain. Clinical presentations include growth impairment, rickets-like features, back pain, spinal deformities, any sign of nerve compression, severe osteoporosis, and fragility fractures. Age, history, physical examination, and diagnostic tests support orientation on risk factors. These include bone marrow expansion, toxicity from iron overload and iron chelation, endocrine dysfunctions (hypogonadism, hypohyperparathyroidism, hypothyroidism, growth hormone deficiency, diabetes), and vitamin (D, C, K) and zinc deficiencies. Several of these may coexist in an individual for a long time and at different degrees, making clarification of the relative contribution and selection of the best therapeutic options a challenge. Milestones for prevention of TBD are early and full inhibition of bone marrow hyperplasia and iron toxicity. Empowering patients' positive resources is key for achieving long-term healthy habits with regard to diet, physical activity, sunlight exposure, and lifestyle. Pain, related or unrelated to bone disease, is frequent in thalassemia. The most important targets for the hematologist include having an expert orientation on disease-related causes of pain, driving differential diagnosis, providing effective pain relief and, where feasible, removing the cause.

A new measure for end of life planning, preparation, and preferences in Huntington disease: HDQLIFE end of life planning.

Huntington disease is a fatal inherited neurodegenerative disease. Because the end result of Huntington disease is death due to Huntington disease-related causes, there is a need for better understanding and caring for individuals at their end of life. The purpose of this study was to develop a new measure to evaluate end of life planning. We conducted qualitative focus groups, solicited expert input, and completed a literature review to develop a 16-item measure to evaluate important aspects of end of life planning for Huntington disease. Item response theory and differential item functioning analyses were utilized to examine the psychometric properties of items; exploratory factor analysis was used to establish meaningful subscales. Participants included 508 individuals with pre-manifest or manifest Huntington disease. Item response theory supported the retention of all 16 items on the huntington disease quality of life ("HDQLIFE") end of life planning measure. Exploratory factor analysis supported a four-factor structure: legal planning, financial planning, preferences for hospice care, and preferences for conditions (locations, surroundings, etc.) at the time of death. Although a handful of items exhibited some evidence of differential item functioning, these items were retained due to their relevant clinical content. The final 16-item scale includes an overall total score and four subscale scores that reflect the different end of life planning constructs. The 16-item HDQLIFE end of life planning measure demonstrates adequate psychometric properties; it may be a useful tool for clinicians to clarify patients' preferences about end of life care.

Persons with chronic widespread pain experience excess mortality: longitudinal results from UK Biobank and meta-analysis

ObjectiveIt is uncertain whether persons with chronic widespread pain (CWP) experience premature mortality. Using the largest study conducted, we determine whether such a relationship exists, estimate its magnitude and establish...

Video-assisted extirpation of cranial mediastinal masses in dogs: 18 cases (2009-2014).

OBJECTIVE To characterize clinical findings, surgical procedures, complications, and outcomes in dogs undergoing extirpation of masses from the cranial mediastinum via video-assisted thoracic surgery (VATS) and establish preliminary guidelines for case selection when considering VATS for thymectomy in dogs. DESIGN Retrospective case series. ANIMALS 18 client-owned dogs that underwent extirpation of a cranial mediastinal mass by means of VATS at 5 academic referral hospitals from 2009 through 2014. PROCEDURES Medical records were reviewed and data extracted regarding signalment, clinical signs, physical examination findings, diagnostic imaging results, surgical approach and duration, cytologic and histologic examination results, complications, outcome, and cause of death, when applicable. RESULTS 16 dogs had a thymoma, 1 had thymic anaplastic carcinoma, and 1 had hemangiosarcoma. Seven had both megaesophagus and myasthenia gravis. Median approximate tumor volume was 113.1 cm3 (interquartile range, 33.5 to 313.3 cm3). Median duration of VATS was 117.5 minutes (interquartile range, 91.5 to 136.3 minutes). Conversion to an open thoracic surgical procedure was required for 2 dogs, 1 of which died during surgery. Median survival time following VATS for dogs with thymoma and concurrent myasthenia gravis and megaesophagus was 20 days. Dogs with thymoma without paraneoplastic syndrome survived for ≥ 60 days, and none of these dogs died of disease-related causes. CONCLUSIONS AND CLINICAL RELEVANCE VATS appeared to be an acceptable approach for extirpation of masses from the cranial mediastinum in dogs under certain conditions. Dogs with myasthenia gravis and megaesophagus had a poor postoperative outcome.

Phase I study of lurbinectedin (PM11083) in patients with advanced AML and MDS.

e18521 Background: The FDA-approved drug trabectedin is a DNA minor groove binder (MGB) with activity against translocation-associated sarcomas. Lurbinectedin is a next-generation MGB, with activity against myeloid leukemia cells. A phase I clinical trial was initiated to determine recommended doses in MDS/AML. Further assessment of its safety, tolerability, and pharmacogenetics were studied. Methods: In total, 42 patients with relapsed/refractory MDS/AML received lurbinectedin, using a 3+3 study design. It was administered as a 1-hour IV infusion first at 3.5, 5, 6, and 7mg per dose on days 1 and 8. Subsequently, it was administered on days 1, 2, and 3, using 1, 1.5, 2, or 3mg per dose per patient. Results: Three patients had dose-limiting toxicities (DLTs), which were rhabdomyolysis (up to gr 4), hyperbilirubinemia (gr 3), and oral herpes (gr 3). All DLTs occurred in the 6 and 7mg cohorts. Adverse events included febrile neutropenia/infections (n = 3), GI (n = 6) and pulmonary (n = 2) toxicity, hyperhidrosis (n = 1), and QT prolongation (n = 1). Overall, 33 of 42 patients (79%) had reduction of blasts in peripheral blood (PB) or bone marrow (BM) at nadir, including 23 (55%) with &gt; 50% reduction in PB blasts alone (n = 18) or both BM and PB blasts (n = 5). One patient had PR, 2 patients had morphologic leukemia-free survival, and most (n = 30) were discontinued for progressive disease. Early deaths occurred from disease-related causes, not attributable to lurbinectedin. Thirty-two patients treated at MD Anderson were analyzed for clinical characteristics and responses. Notably, among patients with follow-up bone marrow biopsy, those with a cytogenetic abnormality at chromosome 11q21-23 had significantly greater bone marrow blast reduction than those without such abnormality (change in percentage blasts: -31±14% [n = 4] vs. 8±8% [n = 16], respectively; P= 0.04). Conclusions: Lurbinectedin is generally safe and tolerated at dose levels tested. While no sustained remissions &gt; 3 cycles were observed in these highest-risk patients, single-agent lurbinectedin was transiently leukemia suppressive for some patients, including some with abnormal chr11q or TP53 mutation. Rational combinations and situational uses of lurbinectedin are under consideration. Clinical trial information: NCT01314599.

Radiation therapy for biliary tract tumors: the joint experience of three centers.

This study presents the joint experience of three centers in the treatment of patients with biliary tract tumors with radiation therapy (RT). The records of 27 patients were retrospectively reviewed. All of the patients who had undergone surgical resection received postoperative adjuvant RT, whereas all of the patients who had not undergone a surgical resection received RT with palliative intent. Twenty patients with adequate performance status were treated with RT and chemotherapy, while the remaining seven patients were treated with RT alone. Follow-up ranged from 1 to 44 months. Local control was not achieved in 10 out of 11 patients who had received RT with palliative intent. Systemic failure was observed in eight patients at 5 to 16 months. Fifteen patients died due to disease-related causes at 1 to 22 months. At 2 years, overall survival was 33% and disease-free survival was 19%. A surgical resection with curative intent predicted improved local failure-free survival and improved disease-free survival. Since local recurrence is still the leading cause of failure following postoperative RT and the outcome following palliative RT is far from satisfactory, the indications, the target volume, and the doses for RT should be reconsidered.

Successes and Challenges of Pediatric AML: A Report on Survival, Salvage Therapy and Causes of Deaths in the AML-BFM Study Group from 1987 -2012

Background:Over the past 30 years, prospective randomized trials led to a markedly increased overall survival (OS) for pediatric patients with acute myeloid leukemia (AML). While hematopoietic stem cell transplantation (HSCT) was previously recommended to all patients with available matched sibling donor in first remission, recent protocols mainly restricted allogeneic HSCT to patients with very high relapse risk, refractory disease or after relapse. At the same time, the first-line treatment was heavily intensified, while supportive care was greatly improved. Also recent studies for relapsed patients demonstrated an improved, but still poor outcome (5yr-pOS: 24-38%). Thus, the factors that mainly contributed to the markedly increased OS in pediatric AML remain largely unknown. Here we present a retrospective analysis, which we performed to reveal those factors, but also to identify the obstacles that may hamper further improvement.Patients and Methods:From 1/1987 to 12/2012, a total of 1940 patients with de novo AML were enrolled in four consecutive trials of the AML-Berlin/Frankfurt/Muenster study group (AML-BFM-87, -93, -98, -04 and the following registry). Median follow-up was 10 years. Five year estimates of EFS and OS (pEFS, pOS), cumulative incidences (CI) of early death (ED), death in nonresponse (NR), death in complete remission (CR) or deaths of patients with one or more relapses were analyzed retrospectively over time in 3-year and 9-year periods and also according to study periods.Results:In this large population of 1940 patients with, we sought to systematically decipher the causes of death, incidences and survival after relapse or NR and the impact of HSCT in pediatric AML. As previously shown, the 5yr-pOS markedly increased from 52±4% (1987-1989) to 72±5% (2011-2012) (p<0.0001), but improvement of 5yr-pEFS was unsteady from 43±3% to 55±5%. This implies that factors after the first event are responsible for the better survival. Accordingly, the OS of patients with NR (n=48, OS 13±5% [AML-BFM 87], vs. n=65, OS 41±6% [AML-BFM 04]; p<0.001) and relapse (n=97, OS 19±4% [AML-BFM 87] vs. n=204, OS 42±4%, [AML-BFM 04]; p<0.001) improved remarkably (Figure 1). Treatment intensification resulted generally in less disease-related deaths in most subgroups, but in turn was associated with higher treatment-and procedure-related mortality over the last 25 years. Incidences of ED significantly decreased (p=0.002). More specifically, disease-related causes within this group decreased, whereas treatment-related deaths did not change (Figure 2). Patients with NR also showed less disease-related deaths in recent compared to the earlier cohorts (p=0.001), and no change in treatment-related lethality (p=0.43). In the recent cohort, we observed a trend of fewer deaths in CR. Treatment-related deaths decreased significantly (p=0.02). CI of death after relapse showed a remarkable decrease over time. This is mostly affecting disease-related deaths (p<0.011), while deaths due to HSCT increased (p=0.008). Deaths in patients with more than one relapse did not change, and the only significant change within this subgroup is a higher incidence of HSCT-related deaths. The increase of HSCT in first CR and after NR/relapse from 25% 1987 - 1995 to about 40% after 1995 translates into a higher incidence of procedure-treatment related deaths. Nevertheless OS of patients with HSCT after NR/relapse increased significantly (OS 35±5% [1987-1995], 37±4 [1996-2004] and 51±4% [2005-2012] (p=0.001)). The comparison within study periods showed no trend for a better pEFS and pOS in the second half of a study compared to the first so an improvement due to general measures like better supportive care cannot be proven. In a Cox regression analysis of OS there was a significant trend for better OS over the study periods (HR 0.88, 95% confidence interval 0.72-0.82) but not for better OS in the second half (HR 0.95, 0.82-1.09).Conclusion:In conclusion, efficacy of salvage therapy and better therapy strategy is one of the main reasons for improved outcome in pediatric AML within the last 3 decades. However, stable and in some subgroups decreased treatment-related mortality reflects better supportive care with respect to intensified therapy. Of note, procedure-related mortality increased, but nevertheless survival after HSCT improved. [Display omitted] [Display omitted] DisclosuresRasche:Jazz Pharma: Other: Travel accomodation. Reinhardt:Celgene: Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Jazz Pharma: Other: Travel Accomodation; Boehringer Ingelheim: Membership on an entity's Board of Directors or advisory committees.

Procedural and shunt‐related complications and mortality of the transjugular intrahepatic portosystemic shunt (TIPSS)

The implantation of a transjugular intrahepatic portosystemic shunt (TIPSS) is a complex angiographic procedure performed in patients with end-stage liver disease. Numerous case reports and narrative reviews have been published so far; however, studies systematically investigating procedural and shunt-related complications are lacking. To systematically investigate complications and mortality occurring during the index hospital stay and the early (4-week) period after TIPSS implantation. The study includes 389 patients who received a TIPSS implantation between 2004 and 2014. Data were obtained from the clinical records and technical reports of the TIPSS implantation. During the index hospital stay, procedure-related complications occurred in 42 patients (10.8%) with intraperitoneal bleeding in 8 patients (2.1%) and infections in 14 patients (3.6%). Shunt- and disease-related complications consisted of hepatic encephalopathy (1-year incidence 29%), non-procedural infections (8.7%) and acute hepatic decompensation (4.1%). Nine patients (2.3%) died during the index hospital stay from procedure-related (two patients, 0.5%), shunt-related (four patients, 1%) or disease-related causes (three patients, 0.8%). 23 patients (5.9%) died during 4 weeks after TIPSS implantation. The 1-year probability of survival was 67.7% and was negatively associated with severe hepatic encephalopathy and acute hepatic decompensation. Except hepatic encephalopathy, severe procedure- and shunt-related complications are rare and early mortality is low.

Cause of death in patients with chronic visceral and chronic neurovisceral acid sphingomyelinase deficiency (Niemann-Pick disease type B and B variant): Literature review and report of new cases

Acid sphingomyelinase deficiency (ASMD), [Niemann-Pick Disease Types A and B (NPD A and B)], is an inherited metabolic disorder resulting from deficiency of the lysosomal enzyme acid sphingomyelinase. Accumulation of sphingomyelin in hepatocytes, reticuloendothelial cells, and in some cases neurons, results in a progressive multisystem disease that encompasses a broad clinical spectrum of neurological and visceral involvement, including: infantile neurovisceral ASMD (NPD A) that is uniformly fatal by 3years of age; chronic neurovisceral ASMD (intermediate NPD A/B; NPD B variant) that has later symptom onset and slower neurological and visceral disease progression; and chronic visceral ASMD (NPD B) that lacks neurological symptoms but has significant disease-related morbidities in multiple organ systems. The purpose of this study was to characterize disease-related morbidities and causes of death in patients with the chronic visceral and chronic neurovisceral forms of ASMD. Data for 85 patients who had died or received liver transplant were collected by treating physicians (n=27), or abstracted from previously published case studies (n=58). Ages at symptom onset, diagnosis, and death; cause of death; organ involvement, and morbidity were analyzed. Common disease-related morbidities included splenomegaly (96.6%), hepatomegaly (91.4%), liver dysfunction (82.6%), and pulmonary disease (75.0%). The overall leading causes of death were respiratory failure and liver failure (27.7% each) irrespective of age. For patients with chronic neurovisceral ASMD (31.8%), progression of neurodegenerative disease was a leading cause of death along with respiratory disease (both 23.1%) and liver disease (19.2%). Patients with chronic neurovisceral disease died at younger ages than those with chronic visceral disease (median age at death 8 vs. 23.5years). The analysis emphasizes that treatment goals for patients with chronic visceral and chronic neurovisceral ASMD should include reducing splenomegaly and improving liver function and respiratory status, with the ultimate goal of decreasing serious morbidity and mortality.

Causes of death in 2877 patients with myelodysplastic syndromes.

Patients with myelodysplastic syndromes face a poor prognosis. The exact causes of death have not been described properly in the past. We performed a retrospective analysis of causes of death using data of 3792 patients in the Düsseldorf registry who have been followed up for a median time of 21months. Medical files as well as death certificates were screened and primary care physicians were contacted. Death after AML evolution, infection, and bleeding was considered to be clearly disease-related. Further categories of causes of death were heart failure, other possibly disease-related reasons, such as hemochromatosis, disease-independent reasons as well as cases with unclear causes of death. Median age at the time of diagnosis was 71years. At the time of analysis, 2877 patients (75.9%) had deceased. In 1212 cases (42.1%), the exact cause of death could not be ascertained. From 1665 patients with a clearly documented cause of death, 1388 patients (83.4%) succumbed directly disease-related (AML (46.6%), infection (27.0%), bleeding (9.8%)), whereas 277 patients (16.6%) died for reasons not directly related with myelodysplastic syndromes (MDS), including 132 patients with cardiac failure, 77 non-disease-related reasons, 23 patients with solid tumors, and 45 patients with possibly disease-related causes like hemochromatosis. Correlation with IPSS, IPSS-R, and WPSS categories showed a proportional increase of disease-related causes of death with increasing IPSS/IPSS-R/WPSS risk category. Likewise, therapy-related MDS were associated with a higher percentage of disease-related causes of death than primary MDS. This reflects the increasing influence of the underlying disease on the cause of death with increasing aggressiveness of the disease.

Hypertension artérielle maligne et décompensation cardiaque globale après consommation abusive de vasoconstricteur par voie nasale : à propos d’un cas et revue de la littérature

IntroductionVasoconstrictors, widely prescribed in the congestive states during acute rhinitis, are responsible for many cases of drug-related iatrogenic disease. Case reportWe report the case of a 40-year-old man, who presented with an episode of malignant hypertensive crisis associated with life-threatening congestive heart decompensation. The patient interview revealed consumption to supra-therapeutic dosage of an association of naphazoline and prednisolone nasal sprays. The diagnostic work-up allowed to rule out disease-related causes of secondary hypertension. The drug-related disease was thus retained. ConclusionThe results of the literature review showed many cases of vasoconstrictor poisoning responsible for central nervous system and cardiovascular involvement, especially in young children. This first case of heart failure related to nasal decongestant administration increases the scope of potentially serious risks of these drugs and demonstrates the outreach needs for health professionals and patients about their proper use.

Registry of the Spanish Network for Systemic Sclerosis: Survival, Prognostic Factors, and Causes of Death.

Systemic sclerosis (SSc) is a rare, multisystem disease showing a large individual variability in disease progression and prognosis. In the present study, we assess survival, causes of death, and risk factors of mortality in a large series of Spanish SSc patients. Consecutive SSc patients fulfilling criteria of the classification by LeRoy were recruited in the survey. Kaplan–Meier and Cox proportional-hazards models were used to analyze survival and to identify predictors of mortality. Among 879 consecutive patients, 138 (15.7%) deaths were registered. Seventy-six out of 138 (55%) deceased patients were due to causes attributed to SSc, and pulmonary hypertension (PH) was the leading cause in 23 (16.6%) patients. Survival rates were 96%, 93%, 83%, and 73% at 5, 10, 20, and 30 years after the first symptom, respectively. Survival rates for diffuse cutaneous SSc (dcSSc) and limited cutaneous SSc were 91%, 86%, 64%, and 39%; and 97%, 95%, 85%, and 81% at 5, 10, 20, and 30 years, respectively (log-rank: 67.63, P < 0.0001). The dcSSc subset, male sex, age at disease onset older than 65 years, digital ulcers, interstitial lung disease (ILD), PH, heart involvement, scleroderma renal crisis (SRC), presence of antitopoisomerase I and absence of anticentromere antibodies, and active capillaroscopic pattern showed reduced survival rate. In a multivariate analysis, older age at disease onset, dcSSc, ILD, PH, and SRC were independent risk factors for mortality. In the present study involving a large cohort of SSc patients, a high prevalence of disease-related causes of death was demonstrated. Older age at disease onset, dcSSc, ILD, PH, and SRC were identified as independent prognostic factors.

Autoimmune haemolytic anaemia in mantle cell lymphoma : an insidious complication associated with leukemic disease

Autoimmune haemolytic anaemia in mantle cell lymphoma : an insidious complication associated with leukemic disease

Causes of Death in Adults with Mitochondrial Disease.

Mitochondrial diseases are a clinically, biochemically and genetically heterogeneous group of disorders with a variable age of onset and rate of disease progression. It might therefore be expected that this variation be reflected in the age and cause of death. However, to date, little has been reported regarding the 'end-of-life' period and causes of death in mitochondrial disease patients. For some specific syndromes, the associated clinical problems might predict the cause of death, but for many patients, it remains difficult to provide an accurate prognosis. To describe a retrospective cohort of adult mitochondrial disease patients who had attended the NHS Highly Specialised Services for Rare Mitochondrial Diseases in Newcastle upon Tyne (UK), evaluate life expectancy and causes of death and assess the consequences for daily patient care. All deceased adult patients cared for at this centre over a period of 10 years were included in the study. Patient history, data on laboratory findings, biochemical investigations and genetic studies were analysed retrospectively. A total of 30 adult mitochondrial patients died within the time period of the study. The main mitochondrial disease-related causes of death in this patient cohort were respiratory failure, cardiac failure and acute cerebral incidents such as seizures and strokes. In almost half of the patients, the cause of death remained unknown. Based on our study, we present recommendations regarding the care of patients with mitochondrial disease.

Patterns and 14-year trends in mortality among illicit drug users in Finland: The HUUTI study

BackgroundAlthough mortality is a known complication of illicit drug use, robust epidemiological studies on drug-related mortality in Finland are scarce. We examined all deaths, specific causes of death, and trends in mortality among a large number of illicit drug users in Finland during a 14-year period. MethodsDetails of 4817 clients who sought treatment for drug use at Helsinki Deaconess Institute between 1997 and 2008 were linked to national cause of death register to identify all deaths and causes of death. Standardised mortality ratios (SMRs) were calculated to compare all-cause deaths in our study cohort with those in the general population. Trends in mortality rates were assessed using Poisson (log-linear) regression. ResultsA total of 496 deaths occurred during 41,567.5 person-years with crude mortality rate of 1193.2 per 100,000 person-years. Mean follow-up was 8.6 years and the mean age at death was 33.8 years. Most deaths (84.1%) occurred among male clients, 189 deaths occurred in the 25–34 age-group and all-cause SMR was 8.9 [95% confidence interval (CI)=8.1–9.7]. Two-thirds (64.9%) were deaths from external causes and 35.1% from disease-related causes. The four leading causes of death were accidental poisoning/overdose (n=165), suicide (n=108), mental and behavioural disorders (n=49) and circulatory system diseases (n=45). Younger clients died from acute effects of drug use while older clients died more from chronic health conditions. A decline in annual rates was noted for all-cause mortality (P=0.01), deaths from mental and behavioural disorders (P<0.001) and suicides (P<0.001). ConclusionThe four leading causes of death among illicit drug users are preventable. Overdose management training, drug education and other preventive measures could help reduce mortality.

Interpretation of suspect head and neck fixations seen on PET/CT in lung cancer

ObjectivesSmoking is the major risk factor for lung and head and neck cancer. The purpose of the present study was to determine the clinical impact of serendipitously revealed head and neck fixation on PET/CT in patients undergoing investigation for lung cancer. Material and methodsThe reports from PET/CT studies for patients with lung cancer from September 2005 and April 2012 were retrospectively reviewed. Head and neck incidentaloma was interpreted as suggestive of second primary malignancy. These incidental findings were compared with the final diagnosis obtained from clinical and histological investigation. ResultsFive hundred and ninety-two patients were investigated on PET/CT for lung cancer in the study period. PET/CT-positive head and neck lesions suggestive of second primary malignancy were found in 65 (11%) patients. Nasoendoscopy was performed in 23 patients and biopsy in 10. In 4 patients (17.4% of those explored), a second primary malignant lesion was proved on histology: 2 squamous cell carcinomas (larynx and oral cavity), 1 undifferentiated carcinoma (parotid), and 1 osteosarcoma (mandible). At a median 13months’ follow-up, 3 of the 4 patients with a second primary had died from disease-related causes and 1 was free of recurrence. Metastases from lung adenocarcinoma were found in 2 patients (0.34%). ConclusionsPET/CT detected incidental head and neck malignant tumors in at least 0.68% of lung cancer patients, but in 6.4% of those with suspect head and neck fixation.

Shedding light on adult medulloblastoma: current management and opportunities for advances.

Few evidence-based guidelines are available for the treatment of adult medulloblastoma, an extremely rare disease. Therapeutic regimens, typically modeled following pediatric protocols, consist of surgical resection followed by radiotherapy with or without adjuvant chemotherapy. Because of the rarity of this disease in adults, any treatment undertaken is based mainly on small and retrospective studies. Unlike pediatric patients, adults with medulloblastoma have been treated according to risk-adapted therapeutic strategies in only a few prospective studies. Overall, approximately 30% of patients experience recurrence and die of disease-related causes. Although the patients could respond to second-line treatments, the prognosis of patients with recurrence remains dismal. An important challenge for the future will be the biologic characterization of medulloblastoma in adults, with the identification of specific genetic patterns of patients with different prognosis and different response to targeted treatments.

P0191Radiation therapy for biliary tract tumours: Joint experience of three centres

Background This study presents the joint experience of three centres in the treatment of patients with biliary tract (BT) tumours with radiation therapy (RT). Methods Records of 27 patients, treated with RT from 2007 through 2013, were retrospectively reviewed. There were 14 males and 13 females aged 46–86 years. Findings Tumour location was the extrahepatic BT in 14 patients, the intrahepatic BT in four patients, and the perihilar region in nine patients. Nineteen patients were diagnosed with adenocarcinoma. A curative resection was performed in 16 patients, 11 of whom had microscopically involved surgical margins. All of these patients received postoperative RT. The remaining 11 patients received palliative RT. Median RT dose was 50.4 Gy. Twenty patients with adequate performance status were treated with RT and chemotherapy, and the remaining seven patients were treated with RT alone. Follow-up ranged from 1 month to 44 months (median 17 months). Local recurrence was observed in five out of the 16 patients who received postoperative RT at 4–23 months (median, 7 months). Eight patients developed distant metastases at 5–16 months (median 8 months). Fifteen patients died due to disease-related causes at 1–22 months (median 9 months). At 2 years, overall survival was 33% and local failure-free survival was 33%. A curative resection predicted improved survival and improved local failure-free survival on univariate analysis. Local control was not achieved in 10 of the 11 patients who received palliative RT. Interpretation In patients with inoperable BT tumours, outcomes after palliative RT were not satisfactory. For patients undergoing curative resection followed by postoperative RT, local recurrence was the leading cause of treatment failure. Therefore, indications, doses, and the target volume for postoperative RT should be reconsidered.