Browsing by Subject "CANCER-PATIENTS"

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  • Havunen, Riikka; Santos, Joao M.; Sorsa, Suvi; Rantapero, Tommi; Lumen, Dave; Siurala, Mikko; Airaksinen, Anu J.; Cervera-Carrascon, Victor; Tähtinen, Siri; Kanerva, Anna; Hemminki, Akseli (2018)
    Cancer treatment with local administration of armed oncolytic viruses could potentially induce systemic antitumor effects, or the abscopal effect, as they self-amplify in tumors, induce danger signaling, and promote tumor-associated antigen presentation. In this study, oncolytic adenovirus coding for human tumor necrosis factor alpha (TNF-alpha) and interleukin-2 (IL-2) Ad5/3-E2F-d24-hTNF-alpha-IRES-hIL-2 (also known as [a.k.a.] TILT-123) provoked antitumor efficacy in tumors that were injected with Ad5/3-E2F-d24-hTNF-alpha-IRES-hIL-2 and those that were left non-injected in the same animal. Importantly, the virus was able to travel to distant tumors. To dissect the effects of oncolysis and cytokines, we studied replication-incompetent viruses in mice. Systemic antitumor effects were similar in both models, highlighting the importance of the arming device. The cytokines induced positive changes in immune cell infiltrates and induced the expression of several immune-reaction-related genes in tumors. In addition, Ad5/3-E2F-d24-hTNF-alpha-IRES-hIL-2 was able to increase homing of adoptively transferred tumor-infiltrating lymphocytes into both injected and non-injected tumors, possibly mediated through chemokine expression. In summary, local treatment with Ad5/3-E2F-d24-hTNF-alpha-IRES-hIL-2 resulted in systemic antitumor efficacy by inducing immune cell infiltration and trafficking into both treated and untreated tumors. Moreover, the oncolytic adenovirus platform had superior systemic effects over replication-deficient vector through spreading into distant tumors.
  • Efraim Investigators Nine; Mokart, Djamel; Darmon, Michael; Schellongowski, Peter; Valkonen, Miia; Azoulay, Elie (2020)
    Background The impact of neutropenia in critically ill immunocompromised patients admitted in a context of acute respiratory failure (ARF) remains uncertain. The primary objective was to assess the prognostic impact of neutropenia on outcomes of these patients. Secondary objective was to assess etiology of ARF according to neutropenia. Methods We performed a post hoc analysis of a prospective multicenter multinational study from 23 ICUs belonging to the Nine-I network. Between November 2015 and July 2016, all adult immunocompromised patients with ARF admitted to the ICU were included in the study. Adjusted analyses included: (1) a hierarchical model with center as random effect; (2) propensity score (PS) matched cohort; and (3) adjusted analysis in the matched cohort. Results Overall, 1481 patients were included in this study of which 165 had neutropenia at ICU admission (11%). ARF etiologies distribution was significantly different between neutropenic and non-neutropenic patients, main etiologies being bacterial pneumonia (48% vs 27% in neutropenic and non-neutropenic patients, respectively). Initial oxygenation strategy was standard supplemental oxygen in 755 patients (51%), high-flow nasal oxygen in 165 (11%), non-invasive ventilation in 202 (14%) and invasive mechanical ventilation in 359 (24%). Before adjustment, hospital mortality was significantly higher in neutropenic patients (54% vs 42%;p = 0.006). After adjustment for confounder and center effect, neutropenia was no longer associated with outcome (OR 1.40, 95% CI 0.93-2.11). Similar results were observed after matching (52% vs 46%, respectively;p = 0.35) and after adjustment in the matched cohort (OR 1.04; 95% CI 0.63-1.72). Conclusion Neutropenia at ICU admission is not associated with hospital mortality in this cohort of critically ill immunocompromised patients admitted for ARF. In neutropenic patients, main ARF etiologies are bacterial and fungal infections.
  • Zafar, Sadia; Quixabeira, Dafne Carolina Alves; Kudling, Tatiana Viktorovna; Cervera-Carrascon, Victor; Santos, Joao Manuel; Grönberg-Vähä-Koskela, Susanna; Zhao, Fang; Aronen, Pasi; Heiniö, Camilla; Havunen, Riikka; Sorsa, Suvi; Kanerva, Anna; Hemminki, Akseli (2021)
    Oncolytic adenoviruses are promising cancer therapeutic agents. Clinical data have shown adenoviruses' ability to transduce tumors after systemic delivery in human cancer patients, despite antibodies. In the present work, we have focused on the interaction of a chimeric adenovirus Ad5/3 with human lymphocytes and human erythrocytes. Ad5/3 binding with human lymphocytes and erythrocytes was observed to occur in a reversible manner, which allowed viral transduction of tumors, and oncolytic potency of Ad5/3 in vitro and in vivo,with or without neutralizing antibodies. Immunodeficient mice bearing xenograft tumors showed enhanced tumor transduction following systemic administration, when Ad5/3 virus was bound to lymphocytes or erythrocytes (P <0.05). In conclusion, our findings reveal that chimeric Ad5/3 adenovirus reaches non-injected tumors in the presence of neutralizing antibodies: it occurs through reversible binding to lymphocytes and erythrocytes.
  • Liu, Xingzhi; Zhang, Hongbo; Cheng, Ruoyu; Gu, Yanzheng; Yin, Yin; Sun, Zhiyong; Pan, Guoqing; Deng, Zhongbin; Yang, Huilin; Deng, Lianfu; Cui, Wenguo; Almeida Santos, Helder; Shi, Qin (2018)
    Antibody-based cancer immune therapy has attracted lots of research interest in recent years; however, it is greatly limited by the easy distribution and burst release of antibodies. In addition, after the clearance of the tissue, healthy tissue regeneration is another challenge for cancer treatment. Herein, we have developed a specific immunological tissue engineering scaffold using the agonistic mouse anti-human CD40 antibody (CD40mAb) incorporated into poly(l-lactide) (PLLA) electrospun fibers through the dopamine (PDA) motif (PLLA-PDA-CD40mAb). CD40mAb is successfully incorporated onto the surface of the electrospun fibrous scaffold, which is proved by immunofluorescence staining, and the PLLA-PDA-CD40mAb scaffold has an anti-tumor effect by locally releasing CD40mAb. Therefore, this immunological electrospun scaffold has very good potential to be developed as a powerful tool for localized tumor treatment, and this is the first to be reported in this area.
  • Trabulo, Carolina; Lopes, Joana; Dias, David da Silva; Gramaca, Joao; Fernandes, Isabel; Gameiro, Rita; Pina, Idilia; Mäkitie, Antti; Ottery, Faith; Ravasco, Paula (2022)
    BackgroundNutritional status in patients with cancer has a determining role in the evolution of the disease and tolerance to treatments. Severity of undernutrition impacts morbidity and mortality in cancer patients and can limit patient response to the optimal therapies if nutritional issues are not appropriately addressed and managed. Despite the importance of malnutrition for the clinical evolution of oncology patients, there is not yet a universally accepted standard method for evaluating malnutrition in such patients. The aim of this study was to stratify the nutritional status of inpatients at an Oncology Department. MethodsThis is an observational study with 561 cancer patients, assessed at admission to a Medical Oncology Department from November 2016 to February 2020. All patients were considered eligible. Non-compliant and/or comatose patients were excluded. Nutritional status was assessed using the PG-SGA, BMI classified with the WHO criteria, and calculation of the percentage of weight loss in the previous 3-6 months. ResultsA total of 561 patients (303 F: 258 M; mean age 65 +/- 13 years) were included. One-third of the patients, n=191/561 (34%), lost 6% of their weight in the month prior to admission and 297/561 (53%) patients lost 10.2% of weight in the previous 6 months. Mean BMI was 24.1 +/- 5.8 kg/m(2); N = 280/561 (50%) patients had regular BMI according to the WHO criteria. N = 331/561 (59%) patients reported eating less in the month prior to admission. N = 303/561 (54%) had moderate/severe deficits of muscle and adipose compartments. The PG-SGA identified 499/561 (89%) patients as moderately/severely malnourished, of which 466/561 (83%) patients scored >= 9 points, meeting criteria for a critical need for nutritional support. Fifteen percent of patients scored >4 points, indicating a need for directed therapy for symptom control and only 1% scored
  • Hosio, Mayu; Urpilainen, Elina; Hautakoski, Ari; Marttila, Mikko; Arffman, Martti; Sund, Reijo; Ahtikoski, Anne; Puistola, Ulla; Läärä, Esa; Karihtala, Peeter; Jukkola, Arja (2021)
    We investigated the survival of female patients with pre-existing type 2 diabetes (T2D) diagnosed with invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) of breast, in relation to the use of metformin, other antidiabetic medication (ADM) and statins. The study cohort consisted of 3,165 women (2,604 with IDC and 561 with ILC). The cumulative mortality from breast cancer (BC) and from other causes was calculated using the Aalen-Johansen estimator. The cause-specific mortality rates were analysed by Cox models, and adjusted hazard ratios (HRs) were estimated for the use of different medications. No evidence of an association of metformin use with BC mortality was observed in either IDC (HR 0.92, 95% confidence interval [CI] 0.64-1.31) or ILC (HR 0.68, 95% CI 0.32-1.46) patients, when compared to other oral ADMs. The mortality from other causes was found to be lower amongst the IDC patients using metformin (HR 0.64, 95% CI 0.45-0.89), but amongst ILC patients the evidence was inconclusive (HR 1.22, 95% CI 0.64-2.32). Statin use was consistently associated with reduced mortality from BC in IDC patients (HR 0.77, 95% CI 0.62-0.96) and ILC patients (HR 0.59, 95% CI 0.37-0.96), and also mortality from other causes in IDC patients (HR 0.81, 95% CI 0.67-0.96) and in ILC patients (HR 0.66, 95% CI 0.43-1.01). We found no sufficient evidence for the possible effects of metformin and statins on the prognosis of BC being different in the two histological subtypes.
  • Koski, Anniina; Bramante, Simona; Kipar, Anja; Oksanen, Minna; Juhila, Juuso; Vassilev, Lotta; Joensuu, Timo; Kanerva, Anna; Hemminki, Akseli (2015)
    In clinical trials with oncolytic adenoviruses, there has been no mortality associated with treatment vectors. Likewise, in the Advanced Therapy Access Program (ATAP), where 290 patients were treated with 10 different viruses, no vector-related mortality was observed. However, as the patient population who received adenovirus treatments in ATAP represented heavily pretreated patients, often with very advanced disease, some patients died relatively soon after receiving their virus treatment mandating autopsy to investigate cause of death. Eleven such autopsies were performed and confirmed disease progression as the cause of death in each case. The regulatory requirement for investigating the safety of advanced therapy medical products presented a unique opportunity to study tissue samples collected as a routine part of the autopsies. Oncolytic adenoviral DNA was recovered in a wide range of tissues, including injected and noninjected tumors and various normal tissues, demonstrating the ability of the vector to disseminate through the vascular route. Furthermore, we recovered and cultured viable virus from samples of noninjected brain metastases of an intravenously treated patient, confirming that oncolytic adenovirus can reach tumors through the intravascular route. Data presented here give mechanistic insight into mode of action and biodistribution of oncolytic adenoviruses in cancer patients.
  • Kohtamaki, Laura M.; Hernberg, Micaela; Jaakkola, Marjut; Makela, Siru (2021)
    Although new compounds have improved the treatment landscape of metastatic melanoma, very limited data exist on the efficacy and safety of treating older patients with novel agents. Here, we provide results of BRAF (BRAFi) +/- MEK (MEKi) inhibitor treatment in patients over 75 years (oldest-old patients) with metastatic melanoma. Between 2011 and 2020, 34 consecutive patients with metastatic melanoma over 75 years of age (range 75-89) were treated with BRAFi +/- MEKi at the Comprehensive Cancer Center of Helsinki University Hospital. Data on clinical and histopathological features, toxicity, response rate (RR), progression-free survival (PFS) and overall survival (OS) were collected. Patients were treated with BRAFi (n = 22) or BRAFi in combination with MEK inhibitor (MEKi) (n = 12). Grade 1-2 adverse events occurred in 68% of the patients, 32% had grade 3 adverse effects, dose reductions were made for 41% of patients and 29% terminated treatment due to toxicity. Overall, the RR was 62%. Complete responses were achieved in 27% of the patients, and 35% had partial responses. The median PFS was 8 months (range 0-57), and the median OS was 15 months (range 0-71). Tailored BRAFi +/- MEKi treatment for older patients is feasible. Adverse effects occur frequently but are manageable by dose adjustment. The occurrence of toxicity of monotherapy was similar to that of combination therapy. The RR and median OS from our retrospective study are comparable with those reported in clinical trials and combination therapy produced somewhat more and longer-lasting responses. Hence, it seems that older patients may benefit from BRAFi treatment.
  • Kanerva, Anna; Koski, Anniina; Liikanen, Ilkka; Oksanen, Minna; Joensuu, Timo; Hemminki, Otto; Palmgren, Juni; Hemminki, Kari; Hemminki, Akseli (2015)
  • Zafar, Sadia; Sorsa, Suvi; Siurala, Mikko; Hemminki, Otto; Havunen, Riikka; Cervera-Carrascon, Victor; Santos, Joao Manuel; Wang, Hongjie; Lieber, Andre; De Gruijl, Tanja; Kanerva, Anna; Hemminki, Akseli (2018)
    Dendritic cells (DCs) are crucial players in promoting immune responses. Logically, adoptive DC therapy is a promising approach in cancer immunotherapy. One of the major obstacles in cancer immunotherapy in general is the immunosuppressive tumor microenvironment, which hampers the maturation and activation of DCs. Therefore, human clinical outcomes with DC therapy alone have been disappointing. In this study, we use fully serotype 3 oncolytic adenovirus Ad3-hTERT-CMV-hCD40L, expressing human CD40L, to modulate the tumor microenvironment with subsequently improved function of DCs. We evaluated the synergistic effects of Ad3-hTERT-CMV-hCD40L and DCs in the presence of human peripheral blood mononuclear cells ex vivo and in vivo. Tumors treated with Ad3-hTERT-CMV-hCD40L and DCs featured greater antitumor effect compared with unarmed virus or either treatment alone. 100% of humanized mice survived to the end of the experiment, while mice in all other groups died by day 88. Moreover, adenovirally-delivered CD40L induced activation of DCs, leading to induction of Th1 immune responses. These results support clinical trials with Ad3-hTERT-CMV-hCD40L in patients receiving DC therapy.
  • Knaster, Peter; Estlander, Ann-Mari; Karlsson, Hasse; Kaprio, Jaakko; Kalso, Eija (2016)
    Background Diagnosing depression in chronic pain is challenging due to overlapping somatic symptoms. In questionnaires, such as the Beck Depression Inventory (BDI), responses may be influenced more by pain than by the severity of depression. In addition, previous studies have suggested that symptoms of negative self-image, a key element in depression, are uncommon in chronic pain-related depression. The object of this study is to assess the relationship of the somatic and cognitive-emotional items of BDI with the diagnosis of depression, pain intensity, and disability. Methods One hundred consecutive chronic pain patients completed the Structured Clinical Interview for DSM Disorders (SCID) for the diagnosis of major depressive disorder (MDD) according to DSM-IV. Two subscales of BDI (negative view of self and somatic-physical function) were created according to the factor model presented by Morley. Results In the regression analysis, the somatic-physical function factor associated with MDD, while the negative view of self factor did not. Patients with MDD had higher scores in several of the BDI items when analysed separately. Insomnia and weight loss were not dependent on the depression diagnosis. Limitations The relatively small sample size and the selected patient sample limit the generalisability of the results. Conclusions Somatic symptoms of depression are also common in chronic pain and should not be excluded when diagnosing depression in pain patients. Regardless of the assessment method, diagnosing depression in chronic pain remains a challenge and requires careful interpretation of symptoms.
  • Nobre, Nuno; Pereira, Marco; Roine, Risto P.; Sutinen, Jussi; Sintonen, Harri (2018)
    We examined how HIV-related self-stigma was associated with different domains of quality of life (QoL), as measured by the World Health Organization Quality of Life in HIV-infected persons instrument (WHOQOL-HIV-Bref), and health-related quality of life (HRQoL) as measured by the generic 15D (15-dimensional measure of HRQoL), to identify the factors associated with self-stigma of people living with HIV (PLWH). The study sample included 440 patients living with HIV followed at the Infectious Disease Clinic of Helsinki University Hospital. Participants with more severe self-stigma reported significantly lower QoL and HRQoL. Male gender, cohabiting with a partner, and disclosure of HIV status were associated with less self-stigma; high education level and financial difficulties were associated with greater self-stigma. Having lived longer with HIV, being unemployed, and living alone were also predictors of self-stigma via financial difficulties. The findings suggest that self-stigma is a complex and multidimensional phenomenon that impacts the HRQoL of PLWH. Psychosocial interventions to enhance the well-being of PLWH are increasingly needed. Copyright (C) 2017 Association of Nurses in AIDS Care
  • Duivenvoorden, Wilhelmina C. M.; Daneshmand, Siamak; Canter, Daniel; Lotan, Yair; Black, Peter C.; Abdi, Hamidreza; van Rhijn, Bas W. G.; van de Putte, Elisabeth E. Fransen; Zareba, Piotr; Koskinen, Ilmari; Kassouf, Wassim; Traboulsi, Samer L.; Kukreja, Janet E.; Bostrom, Peter J.; Shayegan, Bobby; Pinthus, Jehonathan H. (2016)
    Purpose: Neoadjuvant chemotherapy and pelvic surgery are significant risk factors for thromboembolic events. Our study objectives were to investigate the timing, incidence and characteristics of thromboembolic events during and after neoadjuvant chemotherapy and subsequent radical cystectomy in patients with muscle invasive bladder cancer. Materials and Methods: We performed a multi-institutional retrospective analysis of 761 patients who underwent neoadjuvant chemotherapy and radical cystectomy for muscle invasive bladder cancer from 2002 to 2014. Median followup from diagnosis was 21.4 months (range 3 to 272). Patient characteristics included the Khorana score, and the incidence and timing of thromboembolic events (before vs after radical cystectomy). Survival was calculated using the Kaplan-Meier method. The log rank test and multivariable Cox proportional hazards regression were used to compare survival between patients with vs without thromboembolic events. Results: The Khorana score indicated an intermediate thromboembolic event risk in 88% of patients. The overall incidence of thromboembolic events in patients undergoing neoadjuvant chemotherapy was 14% with a wide variation of 5% to 32% among institutions. Patients with thromboembolic events were older (67.6 vs 64.6 years, p = 0.02) and received a longer neoadjuvant chemotherapy course (10.9 vs 9.7 weeks, p = 0.01) compared to patients without a thromboembolic event. Of the thromboembolic events 58% developed preoperatively and 72% were symptomatic. On multivariable regression analysis the development of a thromboembolic event was not significantly associated with decreased overall survival. However, pathological stage and a high Khorana score were adverse risk factors for overall survival. Conclusions: Thromboembolic events are common in patients with muscle invasive bladder cancer who undergo neoadjuvant chemotherapy before and after radical cystectomy. Our results suggest that a prospective trial of thromboembolic event prophylaxis during neoadjuvant chemotherapy is warranted.
  • Christiansson, Lisa; Soderlund, Stina; Svensson, Emma; Mustjoki, Satu; Bengtsson, Mats; Simonsson, Bengt; Olsson-Stromberg, Ulla; Loskog, Angelica S. I. (2013)
  • Mroueh, R.; Haapaniemi, A.; Saarto, T.; Grönholm, L.; Grénman, R.; Salo, T.; Mäkitie, A. A. (2019)
    PurposeLate-stage OTSCC is associated with poor overall survival (OS). Non-curative treatment approach aims to improve quality of life and prolong survival of patients deemed incurable. The purpose of this study was to investigate the used non-curative treatment modalities for OTSSC and patient survival.MethodsAll patients diagnosed with OTSCC and treated with non-curative intent at the HUS Helsinki University Hospital (Helsinki, Finland) during the 12-year period of 2005-2016 were included. Survival analysis after the non-curative treatment decision was conducted using the Kaplan-Meier method in this population-based study.ResultsEighty-two patients were identified. A non-curative treatment decision was made at presentation without any previous treatment in 26 patients (7% of all patients diagnosed with OTSCC during the study period). Palliative radiotherapy was administered to 24% of all patients. The average survival time after the non-curative treatment decision was 3.7months (median 2 and range 0-26).ConclusionsDue to the short mean survival time after decision for treatment with non-curative intent, and the notable symptom burden in this patient population, a prompt initiation of all non-curative measures is warranted.
  • Kuosmanen, Lotta; Hupli, Maija; Ahtiluoto, Satu; Haavisto, Elina (2021)
    Background Shared decision-making is a process where the decisions regarding patients' care are done in collaboration with the patient, the patient's family and a healthcare professional or an interdisciplinary team. Shared decision-making is considered to be a part of patient centred care, and it enables patient autonomy which is a cornerstone of palliative care. In the past, research on the experiences of palliative care patients' participation in shared decision-making involving a nurse has been limited as the focus has mainly been on specific medical interventions, rather than holistic palliative care. Objectives To synthesise research findings on patient participation in shared decision-making in palliative care. Research design An integrative literature review. Methods The literature search was conducted by searching computerised databases (CINAHL, PubMed, PsychINFO and COCHRANE). The search resulted in 12 articles. The quality of the included articles was evaluated with JBI checklist, and the data analysis was done using inductive content analysis. Reporting was done according to a PRISMA checklist. Findings Patients do participate in shared decision-making and desire to participate in everyday nursing care decisions, treatment-related medical decisions and end-of-life decisions. The prerequisites for patient participation in shared decision-making are interdisciplinary teamwork, open communication, good patient-healthcare professional relationship, a favourable environment and mutual information. Conclusion Palliative care patients do participate and desire to participate in decisions that cover a much broader range of topics than just medical interventions and this should be addressed in future research and in practise. The main responsibility for successful patient participation in shared decision-making lies with the healthcare professionals and the organisations providing palliative care. There is a need to conduct more research from the patient's perspective and explore the meaning of participating in shared decision-making from the patient's point of view.
  • Gomes-Silva, Wagner; Prado-Ribeiro, Ana Carolina; Brandao, Thais Bianca; Morais-Faria, Karina; de Castro Junior, Gilberto; Mak, Milena Perez; Lopes, Marcio Ajudarte; Rocha, Marcelo Marques; Salo, Tuula; Tjaderhane, Leo; de Goes, Mario Fernando; Santos-Silva, Alan Roger (2017)
    Recent evidence suggests that head-and-neck radiotherapy (HNRT) increases active forms of matrix metalloproteinase-20 (MMP-20) in human tooth crowns, degrading the dentin-enamel junction (DEJ) and leading to enamel delamination, which is a pivotal step in the formation of radiation-related caries (RRC). Additional participation of enzymatic degradation of organic matrix components in caries progression was attributed to MMP-20 in dentin. Therefore, the current study tested the hypothesis that MMP-20 is overexpressed in the DEJ, dentin-pulp complex components, and carious dentin of post-HNRT patients, leading to detectable micromorphological changes to the enamel and dentin. Thirty-six teeth were studied, including 19 post-HNRT specimens and 17 nonirradiated controls. Optical light microscopy was used to investigate the micromorphological components of the DEJ, dentin-pulp complex components, and carious dentin. The samples were divided into 2 subgroups: nondemineralized ground sections (n = 20) and demineralized histological sections (n = 16). In addition, immunohistochemical analysis using the immunoperoxidase technique was conducted to semiquantitatively assess MMP-20 expression in the DEJ, dentin-pulp complex components, and carious dentin. No apparent damage to the DEJ microstructure or other dentin-pulp complex components was observed and no statistically significant differences were detected in MMP-20 expression (p > 0.05) between the irradiated and control groups. This study rejected the hypothesis that MMP-20 is overexpressed in the DEJ, dentin-pulp complex components, and carious dentin of post-HNRT patients, leading to detectable micromorphological changes. Hence, direct effects of radiation may not be regarded as an independent factor to explain aggressive clinical patterns of RRC. (C) 2017 S. Karger AG, Basel
  • Wendt, Frank R.; Sajantila, Antti; Budowle, Bruce (2018)
    The pharmacogene, CYP2D6, is commonly used to infer metabolizer phenotype of many marketed drugs and endogenous toxins in ante- and post-mortem patients but only represents the efficiency of phase 1 metabolism. Downstream metabolic enzymes encoded by UGT2B7, ABCB1, OPRM1, and COMT also have been implicated in variable individual response to drugs due to their activity at different stages of the tramadol ADME (absorption, distribution, metabolism, and excretion) process. While commonly studied as single genes using targeted genotyping approaches, a more comprehensive tramadol metabolism profile has not been evaluated. 1000 Genomes Project data for UGT2B7, ABCB1, OPRM1, and COMT were used to characterize full-gene haplotypes and their effect on protein function using in-house excel-based workbooks, PopART, and TreeView. Population genetic summary statistics and intergenic analyses associated these haplotypes with full-gene CYP2D6-inferred metabolizer phenotype. The findings suggest that UGT2B7, ABCB1, OPRM1, and COMT may contribute to predicted metabolizer phenotype as opposed to relying solely on CYP2D6.
  • Mattila, Nora; Seppänen, Hanna; Mustonen, Harri; Przybyla, Beata; Haglund, Caj; Lassila, Riitta (2018)
    Pancreatic ductal adenocarcinoma (PDAC) is a deadly cancer often diagnosed late. Earlier detection is urgently needed. Pancreatic ductal adenocarcinoma is known to associate with increased coagulation activity. We studied whether preoperative coagulation biomarkers are useful in distinguishing PDAC from a benign tumor, intraductal papillary mucinous neoplasm (IPMN) in this observational study. We analyzed standard clinical and coagulation variables in patients operated during 2010 and 2015 at Helsinki University Hospital. Pancreatic ductal adenocarcinoma with preoperative coagulation variables available and no neoadjuvant treatment or other active cancer was observed in 80 patients (stage I-III in 67 and IV in 13) and IPMN in 18 patients. Fibrinogen, factor VIII (FVIII), carbohydrate antigen (CA) 19-9, albumin, alkaline phosphatase, and conjugated bilirubin were higher in both stages I to III and IV PDAC compared to IPMN (P <.05). Factor VIII was highest in stage IV (P <.05). Combining these variables in a panel increased sensitivity and specificity for PDAC. In receiver operating characteristic analysis, the area under the curve (95% confidence interval) was 0.95 (0.90-1.00) for the panel, compared to 0.80 (0.71-0.88) for CA 19-9 alone (P <.01). In conclusion, PDAC was associated with increased fibrinogen and FVIII. Combining these coagulation biomarkers with CA 19-9, albumin, and alkaline phosphatase improves diagnostic accuracy.
  • Ruohoalho, Johanna; Aro, Katri; Makitie, Antti A.; Atula, Timo; Haapaniemi, Aaro; Keski-Santti, Harri; Kylanpaa, Leena; Takala, Annika; Back, Leif J. (2017)
    Percutaneous endoscopic gastrostomy (PEG) is often the treatment of choice in head and neck cancer (HNC) patients needing long-term nutritional support. Prospective studies on PEG tube placement in an otorhinolaryngologist service are lacking. At our hospital, otolaryngologist-head and neck (ORL-HN) surgeons-have performed PEG insertions for HNC patients since 2008. We prospectively analyzed 127 consecutive HNC patients who received their PEG tubes at the Department of Otorhinolaryngology-head and neck surgery, and evaluated the outcome of PEG tube insertions performed by ORL-HN surgeons. To compare time delays before and after, PEG placement service was transferred from gastrointestinal surgeons to ORL-HN surgeons, and we retrospectively analyzed a separate group of 110 HNC patients who had earlier received PEG tubes at the Department of Gastrointestinal Surgery. ORL-HN surgeons' success rate in PEG insertion was 97.6%, leading to a final prospective study group of 124 patients. Major complications occurred in four (3.2%): two buried bumper syndromes, one subcutaneous hemorrhage leading to an abscess in the abdominal wall, and one metastasis at the PEG site. The most common minor complication was peristomal granulomatous tissue affecting 23 (18.5%) patients. After the change in practice, median time delay before PEG insertion decreased from 13 to 10 days (P <0.005). The proportion of early PEG placements within 0-3 days increased from 3.6 to 14.6% (P <0.005). PEG tube insertion seems to be a safe procedure in the hands of an ORL-HN surgeon. Independence from gastrointestinal surgeons' services reduced the time delay and improved the availability of urgent PEG insertions.