CLINICAL COURSE OF THE DISEASE AND TREATMENT OUTCOME IN PATIENTS WITH MALIGNANT LARYNGEAL TUMOR: RETROSPECTIVE FIVE-YEAR ANALYSIS.

The aim was to investigate clinical course of disease in patients with malignant laryngeal tumors with emphasis on various forms of disease recurrence (local recurrence, metastasis to regional lymph nodes, occurrence of second primary tumor). A retrospective research including 78 patients with histopathologically confirmed diagnosis of squamous cell laryngeal carcinoma was conducted. Information on cancer stage, histologic grade, type of treatment and disease recurrence was obtained from medical history. Tissue samples of the patients were submitted to immunohistochemical analysis and assessment of Ki-67 proliferation index expression. The occurrence of second primary tumor was found to be related to the significantly higher Ki-67 proliferation index. The number of patients having not undergone oncologic therapy and remained free from disease recurrence was significantly higher than expected. Treatment outcome depends on patient age, histologic grade, radiotherapy applied, and clinical course of disease. It is necessary to define the predictive factors of various forms of disease recurrence more precisely in order to identify better treatment options for patients with malignant tumors of the larynx.

Should we treat pain in the elderly palliative care cancer patients differently?

Opioids are considered the cornerstone of pain management in palliative care. Available data suggest that older patients use different analgesics and lower opioid doses compared to younger patients. However, it has not been elucidated yet whether such dosing is associated with worse pain levels or shorter survival in the palliative care setting. We evaluated the relationship among pain scores, quality of life, opioid dose, and survival in palliative care cancer patients in a hospice setting. A total of 137 palliative care cancer patients were analyzed prospectively. We divided patients into two groups using the age of 65 as a cut-off value. Younger patients exhibited significantly higher pain ratings (5.14 vs. 3.59, p=0.01), although older patients used almost 20 mg less oral morphine equivalent (OME) on arrival (p=0.36) and 55 mg OME/day less during the last week (p=0.03). There were no differences in survival between the two groups (17.36 vs. 17.58 days). The elderly patients also used nonsteroidal analgesics less often and paracetamol more often. Hence, using lower opioid doses in older palliative care cancer patients does not result in worse pain rating, and could be a plausible approach for pain management in this patient group.

Mystery Story about Erythropoietin (Epo) and Erythropoietin Receptor (EpoR) are Disguised?

In this review we would like to focus our attention upon very controversial reports on Erythropoietin (Epo) and Erythropoietin Receptor (EpoR) expression in cancer patients. The effects of Epo on cancerous tissues are poorly understood. Hypoxia results in an increase in the level of the production of both Epo and EpoR via activation of the hypoxia-inducible factor 1 (HIF-1) pathway. HIF-1α, promotes the expression of vascular endothelial growth factor (VEGF). The signaling through VEGF in both a paracrine and an autocrine manner is required for the homeostasis of adult vessels. Macrophages stimulate vessel sprouting via a soluble factor other than VEGF, rather than through direct contact with endothelial cells. The intriguing questions are set about many researches to link Epo/EpoR expression and function in order to establish one of the mechanisms of tumor growth, disease progression of cancer patient. However, it is uncertain role in tumour angiogenesis as promoter and stimulator of tumour growth which should need to be furtherly validated.

Circulating cancer cells are potential weapon for future generations.

As metastatic "seeds," CTCs are believed to be responsible for dissemination from a primary tumor to anatomically distant organs. For the most epithelial tumors the presence of CTCs is associated with tumor progression, increased risk of local and regional recurrence as well as the development of distant metastases. CTCs could be used as a strong prognostic and predictive marker for patient's clinical outcome and survival. A considerable number of promising CTC-detection techniques based on molecular and immunologic methods have been developed in recent years. Most of them need an enrichment step to improve sensibility and/or specificity.

Real-World Data with CDK4/6 Inhibitors-A Single Center Experience from Croatia.

BACKGROUND: There are limited real-world data (RWD) regarding the use of cyclin-dependent kinase (CDK) 4/6 inhibitors in western Balkan. The aim of our study was thus to analyze factors influencing progression-free survival (PFS) and overall survival (OS), along with the differences in adverse effects of CDK 4/6 therapy in a tertiary healthcare center in Croatia. METHODS: We evaluated medical and demographic data for 163 consecutive patients with metastatic breast cancer treated with CDK4/6 inhibitors for at least one month, from October 2018, after the drug became available in Croatia. Eligible patients in our study were those patients who were treated with palbociclib, ribociclib, or abemaciclib. RESULTS: The median PFS of CDK4/6 inhibitors treatment was 2.2 years (95% CI 1.8-3.3), with the longest ongoing treatment for 5.4 years. Treatment with CDK4/6 inhibitors in the first line was associated with a longer PFS compared to the second line or beyond (HR 0.50, 95% CI 0.3-0.9), and patients without liver metastasis exhibited longer survival compared to patients with liver metastasis (HR 0.46, 95% CI 0.2-0.8) (both p < 0.05). Regarding the choice of CDK4/6 inhibitors, ribociclib exhibited longer PFS compared to palbociclib (HR 0.49, 95% CI 0.29-0.82) (p = 0.0032), although the effect was not statistically significant when separating patients who were treated with CDK4/6 inhibitors in the first-line (HR 0.59, 95% CI 0.29-1.2), or second- or later-line therapy (0.49, 95% CI 0.15-1.55); the trend was present in both lines, however. The presence of liver metastasis (p = 0.04), initial luminal A grade (p = 0.039), and time to metastasis up to 5 years from the initial cancer (p = 0.002) were the only factors that remained statistically significant for PFS in multivariate analysis. Median OS since the diagnosis of metastatic disease was 4.5 years (95% CI 3.9-6.3), median OS since the start of CDK4/6 inhibitors treatment was 3.7 years (95% CI 3.4-4.4), while median OS from initial cancer diagnosis was 15.8 years (95% CI 13.8-18.3). There was no difference in OS based on the choice of CDK4/6 inhibitor (p = 0.44) or the adjuvant hormonal therapy (p = 0.12), although a nonsignificant trend for better OS with ribociclib was present for both regardless of whether it was in first- or second/later-line therapies (p > 0.05). In a multivariate analysis, only the presence of liver metastasis (p = 0.0003) and time to metastasis under 5 years from primary breast cancer (p = 0.03) were associated with a worse OS. CONCLUSIONS: Our study provides the RWD with the use of CDK4/6 inhibitors in the treatment of metastatic HR+/HER2- breast cancer. To our best knowledge, there are limited RWD regarding CDK 4/6 inhibitors use in western Balkan; thus, our study provides valuable data from everyday clinical practice for this region of Europe, bridging the gap between randomized clinical trials and clinical reality in western Balkan.

Effectiveness and Safety of Immune Checkpoint Inhibitors in Older Cancer Patients.

BACKGROUND: The development of immunotherapy checkpoint inhibitors (ICIs) has revolutionized cancer care. However, old patients are underrepresented in most clinical trials, although they represent a significant proportion of real-world patients. We aimed to evaluate the effectiveness and safety of ICIs in patients older than the age of 70. METHODS: We performed a retrospective chart review of 145 patients aged 70 or older treated with ICIs for metastatic or unresectable cancer. RESULTS: Median progression-free survival (PFS) was 10.4 months (95% CI 8.6-13.7), with no differences between octogenarians and septuagenarians (p = 0.41). Female gender (p = 0.04) and first-line treatment setting (p < 0.0001) were associated with a longer median PFS. Median overall survival (OS) was 20.7 months (95% CI 13.5-35.0 months), with no difference based on performance status, cancer site, gender, or between septuagenarians and octogenarians (all p > 0.005). Patients treated with ICIs in the first-line setting reported longer OS compared to treatment in the second-line setting (p < 0.001). Discontinuation of ICIs due to adverse effects was associated with both shorter PFS (p = 0.0005) and OS (p < 0.0001). CONCLUSION: The effectiveness of ICIs in older cancer patients primarily depends on the line of treatment and treatment discontinuation. Octogenarians experienced similar treatment responses, PFS, OS, and adverse effects compared to septuagenarians.

Nutritional support in patients with colorectal cancer during chemotherapy: does it work?

BACKGROUND/AIMS: Early intervention with nutritional supplementation has been shown to halt malnutrition and may improve outcome in some patients with colorectal cancer. The aim of this study was to investigate whether dietary counseling, oral nutrition and megestrol acetate during chemotherapy affected nutritional status and survival in patients with advanced disease. METHODOLOGY: Six hundred and twenty-eight patients with colorectal advanced disease were included in the study from January 2000 through December 2009 and divided into one of two groups. Group I consisted of 315 patients who were monitored prospectively and were given nutritional support. Group II included 313 patients without nutritional counseling and support. After the completion of chemotherapy all patients were evaluated (BMI, NST, Appetite Loss Scale and ECOG). RESULTS: After the completion of chemotherapy, there were lower proportions of patients in Group I with a BMI<20, NST>=5, loss of appetite and decreased weight gain. Nutritional counseling and supplemental feeding temporarily halted weight loss and improved appetite. This improvement may have implications for patient survival. Patients with early nutritional support lived 19.1 months while patients in the control group had a survival of 12.4 months (p=0.022). CONCLUSIONS: This study demonstrated that concurrent individualized dietary counseling and nutritional support are effective in improving nutritional status thereby lessening chemotherapy-induced morbidity.

The approaches in the care for terminal cancer patients in radiotherapy and oncology clinic, Rijeka University Hospital Center.

We sought to determine the proportion of our admitted patients in terminal phase of ilness who recieved some kind of active oncological therapy. We conducted a pilot study on the records of patients who died in the University Hospital. We assessed the percentage of mortality, a therapeutic approach in terms of treating the underlying disease, and access to palliative treatment. Of 2097 patients hospitalized in the UHC Rijeka Department of Radiation Therapy and Oncology during 2010 and 2011, 44 pts died which accounts for 2.1%. The most common primary sites of cancer in patients who died in our Department were the lungs and then the breast. Ten (22.7%) patients were admitted exclusively to receive palliative care, while others (34-77.3%) were admitted for planned active chemo- and/or radiotherapy administration. Within three months before death, 18 (40.9%) patients underwent chemotherapy treatment. The number of patients hospitalized due to providing palliative care is extremely low, which could indicate a good supply of out-patient treatment of cancer patients in the terminal stage of the disease. However, concerned about the high percentage of patients who tried to provide oncology treatments in the three months before his death. The percentages referred to in their daily work is still guided by the principles of healing "to the end" and thus we plunge into the realm disthanasia.

Predictive value of endoscopic ultrasound in diagnosis and staging of primary gastric lymphoma.

The aim of the paper is to investigate significance of the endoscopic ultrasound (EUS) in diagnostic and staging of gastric lymphoma. Retrospective clinical study was conducted at the Clinic for Hematology and Clinic for Gastroenterology of the University Clinical Center of Sarajevo in the period of years 2002 to 2009. Patients (N = 40) with diagnosis of gastric lymphoma confirmed by pathohistological diagnosis were included in the study. Stage of the disease was determined based on EUS, proximal endoscopy, CT and ultrasound of abdomen, and classified according to the Ann Arbor classification. 39 patients had various types of non Hodgkin lymphoma and one patient had Hodgkin lymphoma. Based on morphological characteristics of gastric tumor visualized with EUS in 16 patients a gastric cancer was suspected. In 40% patients EUS finding was not confirmed by pathohistological finding. Compared both to CT and ultrasound of abdomen, EUS showed statistically significant higher frequency of establishing existence of infiltration (p < 0.001). In patients with primary gastric lymphoma EUS has more significant role in determination of stage of disease spread than for the diagnosis itself. Therefore EUS should be included into algorithm of patient diagnostic protocol when suspected to the malignant gastric disease.

Analysis of the Gut Microbiome and Dietary Habits in Metastatic Melanoma Patients with a Complete and Sustained Response to Immunotherapy.

Immunotherapy has improved the prognosis of metastatic melanoma patients, although most patients do not achieve a complete response. While specific gut microbiome and dietary habits might influence treatment success, there is a lack of concordance between the studies, potentially due to dichotomizing patients only into responders and non-responders. The aim of this study was to elucidate whether metastatic melanoma patients with complete and sustained response to immunotherapy exhibit differences in gut microbiome composition among themselves, and whether those differences were associated with specific dietary habits. Shotgun metagenomic sequencing revealed that patients who exhibited a complete response after more than 9 months of treatment (late responders) exhibited a significantly higher beta-diversity (p = 0.02), with a higher abundance of Coprococcus comes (LDA 3.548, p = 0.010), Bifidobacterium pseudocatenulatum (LDA 3.392, p = 0.024), and lower abundance of Prevotellaceae (p = 0.04) compared to early responders. Furthermore, late responders exhibited a different diet profile, with a significantly lower intake of proteins and sweets and a higher intake of flavones (p < 0.05). The research showed that metastatic melanoma patients with a complete and sustained response to immunotherapy were a heterogeneous group. Patients with a late complete response exhibited microbiome and dietary habits which were previously associated with an improved response to immunotherapy.

Etiology and oncogenesis of pancreatic carcinoma.

Pancreatic cancer is the fourth leading cause of cancer death overall. The factors that favor the development of pancreatic cancer can be divided into hereditary and acquired. Cancerogenesis is best explained by a "multi-hit" hypothesis, charcterized with the developmental sequence of cellular mutatitions, forcing mutant cell to inappropriate proliferation and preventing its repair and programmed cell death (apoptosis). The most common mutations involve K-ras gene, epidermal growth factor (EGF-R) and HER2 gene. Continuous stimulation and secretion of vascular endothelial growth factor (VEGF) enhances the permeability of blood vessels provides nutrient supply to tumor site through newly formed vascular channels. This phenomena is known as vasculogenic mimicry. Loss of function of tumor-suppressor genes has been documented in pancreatic cancer, especially in CDKN2a, p53, DPC4 and BRCA2 genes. SDKN2A gene inactivation occurs in 95% of pancreatic adenocarcinoma. As regards acquired factors, smoking is only confirmed risk factor that increases the risk of pancreatic cancer. Diabetes, alcohol consumption, central obesity in men, infection with Helicobacter pylori and chronic pancreatitis are suspected, but not proven risk factors. Consumption of fruits and vegetables does not protect, while the consumption of meat processed at high temperatures increases the risk of pancreatic cancer. According to some studies, lykopene and folate levels are reduced in pancreatic carcinoma patients, reduced folate intake increases the risk of pancreatic carcinoma (48%), and this risk can be diminished by introducing folate-rich foods to diet, not by using pharmaceutical products. Occupational exposure to chlorinated hydrocarbons, vinyl chloride, nickel, chromium, insecticides and acrylic amide minimally increases the risk for pancreatic cancer. Exposure to cadmium (metal industry) associated with smoking result in the accumulation of cadmium in pancreatic tissue and the possible impact on carcinogenesis.

Gastric cancer detection using the serum pepsinogen test method.

BACKGROUND: Gastric cancer (GC) is the eighth most common cause of cancer deaths in Croatia and one of the most common causes of cancer deaths worldwide. A reliable diagnostic tool for the early detection of GC is essential. OBJECTIVE: We previously suggested a pepsinogen test method to reduce the mortality from GC by allowing early detection. Here, we report an updated analysis from a prospective single-center clinical study to evaluate the sensitivity and specificity of the pepsinogen test method and to determine whether this test can be used as a part of routine laboratory assessment of high-risk patients. METHODS: We present mature data of the pepsinogen test method in the Croatian population after a median follow-up of 36 months. Statistical analyses were performed using a Mann-Whitney U test, multiple logistic regression, and receiver operating characteristics (ROC) to evaluate the predictive power of the assayed biomarkers. RESULTS: Of the 116 patients, 25 patients had GC and 91 demonstrated a nonmalignant pathology based on tissue biopsy. Cutoff values were pepsinogen I ⩽70 and pepsinogen I/II ratio ⩽3.0. Using ROC curve analysis, the accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were determined to be 87.22%, 78.12%, 90.10%, 71.43%, and 92.86%, respectively, for the diagnosis of GC. The area under the curve was 0.700 (95% confidence interval 0.57-0.83). CONCLUSION: Pepsinogen tests are valuable for screening a population in need of further diagnosis and could help to avoid unnecessary invasive endoscopic procedures.

Placebo in the treatment of pain.

Placebo is the use of the substance or procedure without specific activity for the condition that is trying to be healed. In medicine, benefits of placebo effect are used since 1985 and 1978 placebo effect was first scientifically confirmed. It was found that placebo induced analgesia depends on the release of endogenous opiates in the brain and that the placebo effect can be undone using the opiates antagonist naloxone. Functional magnetic resonance imaging of the brain showed that placebo analgesia was obtained regarding the activation and increased functional relationship between ant. cingulate, prefrontal, orbitofrontal, and insular cortex, nucleus accumlens, amygdala, periaqueduktalne gray matter and spinal cord. Placebo also facilitates descending inhibition of nociceptive reflexes through periacvaeductal gray substance. Placebo effect can be achieved in several ways: by using pharmacological preparations or simulation of operating or other procedures. This phenomenon is associated with perception and expectation of the patient. To achieve the effect of placebo it is essential degree of the suggestions of the person who prescribe a placebo, and the degree of belief of the person receiving the placebo. Expected effect of placebo is to achieve the same effect as the right remedy. Achieved placebo effect depends on the way of presentation. If a substance is presented as harmful, it may cause harmful effects, called 'nocebo" effect. Placebo effect is not equal in all patients, same as the real effect of the drug is not always equal in all patients. Application of placebo in terms of analgesia will cause a positive response in 35% of patients. Almost the same percentage (36%) of patients will respond to treatment with morphine in medium doses (6-8 mg). Therefore, one should remember that response to placebo does not mean that a person simulates the pain and then it is unethical to withhold the correct treatment especially in light of findings that the prefrontal cortex is activated expecting liberation of pain and how this action reduce activities in brain regions responsible for sensation of pain (thalamus, somatosensory cortex and other parts of the cortex). However, the use of placebos is ethically, legally and morally very dubious. The basis for the placebo effect is deception. It undermines honest relationship and trust between doctor and patient which is extremely important for successful treatment. Consciously giving placebos to patients for a condition that can be adequately treated, with prejudice the right of patients to the best care possible, opens up many bioethical issues. Despite all the current knowledge level, placebo effect remains still a scientific mystery.

Aggressive multifocal form of epithelioid hemangioendothelioma--case report.

Epithelioid hemangioendothelioma (EHE) is a rare tumor of the vascular origin. It was first described in its pulmonary form by Dail and Leibow in 1975 and named "intravascular bronchioalveolar tumor" (IVBAT). Since then, reports of occurrences of the tumor have been made for number of locations, but most often tumor can be found in soft tissues, liver, lungs, bone and skin. It is considered to be a low or borderline malignant tumor with, usually, slow progression, but aggressive forms have been described. We here report a case of a 46-year old female patient with multifocal malignant tumor spreading to lungs, liver, spleen and with synchronous involvement of lumbal vertebrae, illiac bones and central nervous system dissemination. To the best of the authors knowledge, no case of malignant EHE with multiorgan involvement of this proportions and synchronous central nervous system and bone involvement in one patient has been reported to this date in English-speaking literature.

New insights into erythropoietin and erythropoietin receptor in laryngeal cancer tissue.

ABSTRACT: To investigate whether laryngeal cancer cells express erythropoietin (Epo) and erythropoietin receptor (EpoR) and what is their possible relationship with clinical and pathological features of the tumor.We performed immunohistochemical analysis of Epo and EpoR expression on 78 tissue samples of invasive and in situ squamous cell laryngeal carcinoma.The statistical analysis showed a weak positive and statistically significant correlation of EpoHS and EpoR HS expression levels. Epo HS and EpoR HS levels did not correlate with patient sex or age, type of diagnosis, cancer stage, histological tumor grade, presence or absence of disease recurrence, type of oncologic cancer therapy provided, or results of selected laboratory blood work. The results show a statistically significant difference in Epo expression with respect to survival.We confirmed the presence of Epo an EpoR in malignant laryngeal tumors and demonstrated the correlation between Epo expression and survival. Further studies are needed to more precisely define the role of Epo and EpoR in treatment of patients with laryngeal cancer.

Smoking Cessation after a Cancer Diagnosis: A Cross-Sectional Analysis in the Setting of a Developing Country.

Since smoking accounts for around 30% of all cancer deaths, public health campaigns often focus on smoking cessation as a means of primary prevention. However, smoking after cancer diagnosis is also associated with a higher symptom burden and lower survival rate. As data regarding smoking cessation vary dramatically between different populations, we aimed to analyze smoking prevalence in cancer patients, smoking cessation after cancer diagnosis, and the factors associated with smoking cessation in the setting of a developing country. We performed a cross-sectional survey on 695 patients in two clinical hospital centers. After cancer diagnosis, 15.6% of cancer patients stopped smoking. Male gender, younger age, and smoking-related cancer were the main factors associated with greater smoking cessation (p < 0.05). A total of 96% of breast cancer patients continued to smoke after cancer diagnosis and, compared to lung and colorectal cancer patients, exhibited a lower reduction in the number of cigarettes smoked (p = 0.023). An alarming rate of smoking prevalence was recorded in younger patients (45.6% at the time of cancer diagnosis) suggesting a future rise in smoking-related cancers and complications. These results should guide anti-smoking public health campaigns in transitional countries with a critical focus on younger and breast cancer patients.

Nutritional and pharmacologic support in patients with pancreatic cancer.

UNLABELLED: The aim of our study was to assess whether the influence of nutritional support, consisting of counseling, enteral liquids support and pharmacologic support, can slow down weight loss and whether the change in weight has the impact on the performance status in our patients. In our study 44 patients with pancreatic cancer were included--26 males (mean age 69 years +/- 2.4 years) and 18 females (mean age 63 +/- 3.2 years). Metastatic disease was found in 21 patients, 15 patients had liver metastasis. Locally advanced disease was found in 24 patients and metastatic and locally advanced disease in 17 patients. Surgery was performed in 34 patients. Forty four (100%) patients underwent nutritional counseling, 33 of them (75%) took supplemental enteral feeding and 44 (100%) took megestrol acetate 400 mg per a day. The patients were followed up during 8 weeks during 5 visits. At first visit we took initial nutritional status of patients. Appetite loss, weight gain and Karnofsky performance status were monitored at every visit. All patients were treated with gemcitabin for a 7 week period. RESULTS: NTS score at initial visit in 44 patients (100%) was > or = 5. Using nutritional counseling, enteral food substitution and pharmacological support, weight gain was observed in 61.1% patients and appetite improved. Average KPS mostly improved after first month of therapy while after two months was again at the basal level. With nutritional counseling, supplemental feeding and pharmacologic support weight loss in our patients slowed down and appetite improved. Despite of that, Karnofsky Performance Status didn't change significantly, reflecting the impact of the disease itself and chemotherapy procedures to the patient's condition. We can conclude that nutritional and pharmacological support can temporarily stop weight loss and improve appetite, social life and quality of life in those groups of patients but have no implications on patients KPS and course of their disease.

Correlation of anaemia and cognitive functions measured by the complex reactiometer Drenovac.

Cognitive impairment impinges significantly on the quality of life. Previous research revealed that anaemia can have a major influence on cognitive functioningt. The article is a correlational study examining the relationship between anaemia levels and cognitive functioning in adult patients. Sixty-one patients (both inpatients and outpatients), among them 30 anemic and 31 non-anaemic, 33 female and 28 male, aged 32-60 (median 43) treated at the Dept. of Hematology, Clinical Hospital Center Rijeka, Croatia were analysed according to hemoglobin (Hb) level and cognitive ability. Assessment of cognition (convergent inductive thinking) was performed by the Complex reactiometer Drenovac (CRD). The results showed that anaemia significantly undermines cognitive functions in adult patients (p < 0.01). Even in non-anaemic patients (Hb higher than 120 g/L), Hb level is related to better cognitive ability.

The Impact of Combined Use of Opioids, Antipsychotics, and Anxiolytics on Survival in the Hospice Setting.

CONTEXT: Opioids and sedatives are the cornerstone of symptom management in the end-of-life patients, but undertreatment is a common problem. Although several studies explored the individual effect of opioids, anxiolytics, and antipsychotics on survival, not much is known regarding their combined use. As these drugs share similar and potentially fatal side effects, primarily respiratory depression which occurs more often during night-hours, it is crucial to explore whether their interaction poses a danger for fragile hospice patients. OBJECTIVES: To analyze the relationship of a combination of opioids, anxiolytics, and antipsychotics on survival and the change of night-time death percentage. METHODS: A retrospective study of 765 consecutive patients admitted to hospice in Croatia over the period of four years (2013-2017). The main outcome was the total length of survival of hospice patients regarding different drug combination, along with night-time death percentage. RESULTS: Different combinations of opioids, anxiolytics, and antipsychotics were associated with longer survival in hospice compared with patients using no such drugs. When we included different parameters which affected overall survival into a multivariate analysis, only the patients who had the combination of both opioids, anxiolytics, and antipsychotics in their regular therapy were associated with longer survival in hospice (11 vs. five days, hazard ratio 0.54, P < 0.001). No combination of opioids, anxiolytics, and antipsychotics significantly changed the night-time death percentage. CONCLUSION: This research supports the safety of opioids, anxiolytics, and antipsychotics in the hospice setting when used both individually as well as in combination.

Differences between Transdermal Fentanyl and Buprenorphine in the Elderly Hospice Patients.

INTRODUCTION: Opioids are the most important drugs in treating pain in palliative care patients. Transdermal formulations are especially useful due to their noninvasive nature and minimal interference in daily life. However, studies have shown a controversial relationship of opioids to survival and a rise in deaths associated with the use of transdermal opioids. Although applying precise doses is paramount, we have no clear recommendations for the exact equianalgesic ratio for buprenorphine patch and no recommendation for the type of transdermal opioid to use in hospice. METHODS: We analyzed the differences between the transdermal fentanyl and buprenorphine group by analyzing patient characteristics and evaluating the differences in survival in hospice patients over the age of 65, from 2013 to 2017. RESULTS: A total of 292 patients (75.8%) used fentanyl patch and 93 (24.1%) were on buprenorphine patch. Patients had virtually the same characteristics in both groups. However, when using a 1:100 buprenorphine equianalgesic ratio, there were significant differences in initial and final doses, and it seems that a 1:80 conversion rate is more accurate for elderly hospice patients. Finally, there was no difference in survival between the two groups using transdermal opioids, with or without adjuvant analgesics. DISCUSSION: There were no differences in survival between the group using transdermal fentanyl and the group using buprenorphine in the elderly hospice population. Although adjuvant NSAIDs could be useful in the treatment of pain in terminal cancer, they do not affect survival or reduce the opioid doses, while a 1:80 equianalgesic ratio of buprenorphine might be the most appropriate in this population.