Increasing performance of a hospital-based cancer registry: Hacettepe University hospitals experience.

PURPOSE: High-quality hospital-based cancer registry systems are the key elements of a healthy population-based cancer data. The purpose of this study was to present a recent history of establishing a valuable and reliable hospital- based cancer registry in a university hospital in Turkey, and the data gathered by this system in the last 9 years. METHODS: This study included the cancer registry records of Hacettepe University Hospitals between 1-Jan-2003, and 31-Dec-2011. The study cohort included data of 39351 cancer patients and the cancer registry system was based on active data acquisition method. RESULTS: Most frequent departments of reference were Medical Oncology, Radiation Oncology, General Surgery, Urology, and Pediatrics. The annual number of records gradually increased from 2675 in 2003 to 5152 in 2011. The 5 cancer types most frequency seen in adults were lung (15.5%), prostate (13.5%), stomach (6.6%), bladder (6.2%), and colon (5.8%) in men; and breast (32.7%), ovary (6.4%), uterine corpus (6.2%), uterine cervix (5.6%), and thyroid (5.0%) in women. Childhood cancers were classified according to the International Classification of Childhood Cancers, 3rd Edition (ICCC-3), and the most frequent 5 cancer types in children were tumors of the central nervous system (20.1%), lymphomas (14.6%), leukemia (14.1%), retinoblastoma (9.4%), and tumors of the sympathetic nervous system (7.7%). CONCLUSION: Active data acquisition from departments that deal with oncologic patients in a hospital is the precise method for establishing a high-quality cancer registry system that is able to resemble the general population. Hospital- based cancer registry systems also provide highly critical information for planning, monitoring, and measuring the cancer-related services, research, and education.

Frequency of comorbid illnesses in cancer patients in Turkey.

PURPOSE: Comorbidities in cancer patients can adversely affect the management and outcome of their primary illnesses at all levels from diagnosis to therapy. We sought to examine comorbid conditions of cancer patients, treated at 4 university hospitals, each representing a different geographic location in Turkey. METHODS: A total of 769 consecutive cancer patients presenting to outpatient clinics were recruited between November 2007 and May 2008. The patients filled in a questionnaire on comorbidities. Based on the questionnaire, Charlson Comorbidity Index (CCI( was calculated. RESULTS: The patient median age was 55 years (range 21-87) and 456 (59.3%) were female. Breast (36.5%), colorectal (21.4%) and lung cancers (13.9%) were the 3 most frequent malignancies. Of the patients, 59.3% had at least one comorbid disease and 46.3% were using at least one medication daily. The most frequent comorbidities were hypertension (25.3%), diabetes mellitus (13.1%) and peptic ulcer (7.7%). Increasing age positively correlated with the extent of comorbidities (r=0.30, p<0.001), number of medications (r=0.32, p<0.001) and the CCI (r=0.20, p<0.001). CONCLUSION: It is crucial to remember that comorbid illnesses are not rare and many patients are treated for conditions unrelated to their cancer, which potentially may affect various stages of their clinical management.

PILE: a candidate prognostic score in cancer patients treated with immunotherapy.

BACKGROUND: Although the immune checkpoint inhibitors (ICIs) became a vital part of cancer care, many patients do not respond to treatment, indicating need for biomarkers. The Pan-Immune-Inflammation Value (PIV) is a recently developed peripheral blood count-based biomarker. Herein, we evaluated a PIV-based candidate scoring system as a prognostic biomarker in ICI-treated patients. METHODS: A total of 120 advanced cancer patients treated with anti-PD-1 or anti-PD-L1 inhibitors for any cancer type were included in this study. The PILE scoring system incorporating the PIV (< median vs. ≥ median), lactate dehydrogenase levels (normal vs. > normal) and Eastern Cooperative Oncology Group performance status (0 vs. ≥ 1) was constructed from the multivariate analyses and used for stratification. The association between overall survival (OS), progression-free survival and PILE risk category was evaluated with multivariate analysis. RESULTS: The median follow-up was 9.62 months and the median OS of all cohort were 12.42 ± 2.75 months. Patients with higher PIV had significantly decreased OS (7.75 ± 1.64 vs. 18.63 ± 4.26 months, p = 0.037). The patients in the PILE high-risk group (PILE score 2-3) had decreased OS (18.63 ± 4.02 vs. 5.09 ± 1.23 months, HR: 2.317, 95% CI: 1.450-3.700, p < 0.001) and PFS (7.69 ± 1.30 vs. 2.69 ± 0.65 months, HR: 1.931, 95% CI: 1.263-2.954, p = 0.002) compared to PILE low-risk group (PILE score 0-1). The Harrell C-Index values were 0.65 and 0.61 for OS and PFS prediction, respectively. CONCLUSION: In this study, we demonstrated a decreased overall survival in ICI-treated patients with a higher PILE score. If prospective studies validate our results, PILE score could be a biomarker for immunotherapy.

Conformations of prostaglandin F 2alpha and recognition of prostaglandins by their receptors.

The conformation of prostaglandin F 2alpha (PGF 2alpha) has been determined by x-ray diffraction techniques. Two independent conformers of PGF 2alpha, studied as the tris(hydroxymethyl)methylamine salt, are observed to adopt the familiar "hairpin" conformation with the alpha and omega chains aligned roughly parallel. The conformers differ in ring conformation and at the C(17)-C(18) bond, one adopting a C(9) envelope ring conformation and a trans geometry at the C(17)-C(18) bond, while the other adopts a C(8) envelope ring conformation and a novel gauche geometry about C(17)-C(18). Comparison of the conformation of PGF 2alpha with that of prostaglandin E2 suggests a recognition mechanism which would permit PGF 2alpha and prostaglandin E receptors to distinguish between the two potent prostaglandins. The recognition model explains much of the binding data for the PGF 2alpha receptor in the corpus luteum and predicts the existence of an interesting PGF 2alpha analog.

In Vitro Fertilization After Renal Transplantation: A Single-Center Experience.

INTRODUCTION: Although kidney transplantation often increases the chances of fertility, the rate of infertile patients is still high. In vitro fertilization promises successful results for infertile renal transplantation patients. The purpose of this study was to analyze the experience of a single center. METHODS: Patients were invited to complete a survey for their obstetric history. Documentation review included demographic and clinical characteristics of patients, like procedure records, follow-up complications, immunosuppression maintenance protocols, and pregnancy outcomes. RESULTS: Thirteen patients were reached to complete the survey. The mean age of patients was 33 ± 4 years at in vitro fertilization (IVF). The median duration of infertility was 2 years. Twenty-four IVF sessions were applied to these 13 women with renal transplantation. The procedure failed in 13 of these sessions; and 8 women achieved 11 clinical pregnancies. There were 3 miscarriages and 2 stillbirths. Six women had live births with no neonatal deaths. One patient had a graft rejection after the IVF procedure. Serum creatinine level increased more than 30% in 3 patients after the IVF procedure, while 9 patients had a minimal or no change. DISCUSSION: In our study, we evaluated the records of 13 patients with renal transplantation who had IVF procedures. Fortunately, more than half of these patients had live births with no neonatal deaths. In our opinion, our findings show that IVF procedures can be accepted as a promising method in patients with renal transplantation and need a therapy for fertility. Moreover, a 25% live-birth rate per procedure is also a satisfactory result.

Fertility Outcome After Renal Transplantation: A Single-Center Experience.

BACKGROUND: Women suffering from kidney disease are more prone to fertility problems, due to uremia. Fortunately, their fertility rate increases dramatically after renal transplantation. This study analyzes the predictors/risk factors of successful pregnancy with live birth outcome while presenting an overview of the 7-year experience of a single center. METHODS: This retrospective cohort study includes 239 women of reproductive age (18-40 years) who underwent renal transplantation in a tertiary Turkish clinic between October 1, 2011, and August 24, 2017. The subjects were invited to take part in a survey questioning their obstetric characteristics and they were assessed in 2 groups: fertile and infertile. Multivariable linear regression analysis was conducted to determine the predictors of a successful pregnancy. RESULTS: Thirty-five 35 patients wished to become pregnant: 12 got pregnant spontaneously, while 21 failed to become pregnant (spontaneously). The mean age of the patients at the survey was 34 ± 7. Regular menstrual cycles after renal transplantation, tacrolimus-mycophenolate mofetil maintenance protocol, and age at transplantation were found to be predictors of spontaneous pregnancy. The duration of peritoneal dialysis was significantly longer in the infertile group (48 vs 12 months). CONCLUSION: End-stage renal disease's negative impacts, including menstrual abnormality and fertility problems, can be overcome by successful kidney transplantation with appropriate immunosuppression. Minimizing the duration of peritoneal dialysis, particularly in patients who desire future fertility, may be accepted as a logical management strategy.

A decision-analytic model for early stage breast cancer: lumpectomy vs mastectomy.

The purpose was to construct a decision model that incorporated patient preferences over differing health state prospects and to analyze the decision context of early stage breast cancer patients in relation to two main surgical treatment options. A Markov chain was constructed to project the clinical history of breast carcinoma following surgery. A Multi Attribute Utility Model was developed for outcome evaluation. Transition probabilities were obtained by using subjective probability assessment. This study was performed on the sample population of female university students and utilities were elicited from these healthy volunteers. The results were validated by using Standard Gamble technique. Finally, Monte Carlo Simulation was utilized in Treeage-Pro 2006-Suit software program in order to calculate expected utility generated by each treatment option. The results showed that, if the subject had mastectomy, mean value for the quality adjusted life years gained was 6.42; on the other hand, if the preference was lumpectomy, it was 7.00 out of a possible 10 years. Sensitivity analysis on transition probabilities to local recurrence and salvaged states was performed and two threshold values were observed. Additionally, sensitivity analysis on utilities showed that the model was more sensitive to no evidence of disease state; however, was not sensitive to utilities of local recurrence and salvaged states. The decision model was developed with reasonable success for early stage breast cancer patients, and tested by using general public data. The results obtained from these data showed that lumpectomy was more favourable for these participants.

The effects of opioids, local anesthetics and adjuvants on isolated pregnant rat uterine muscles.

Local anaesthetics, opioids and adjuvants are often used for managing labor pain. Some others of these agents are reported to cause alterations on uterine contractility during labor. However, there are controversies and the effects of some others are unknown. In the present study, we aimed to elucidate the effects of opioids such as alfentanyl, meperidine, remifentanyl; local anesthetics such as mepivacaine, ropivacaine, bupivacaine; and adjuvants such as clonidine and midazolam on isolated pregnant rat uterine muscle. Strips of longitudinal uterine smooth muscle obtained from rats pregnant for 18-21 days were suspended in 20 ml organ baths. Isometric tension was continuously measured with an isometric force transducer connected to a computer-based data acquisition system. The effects of cumulative concentrations of alfentanyl, meperidine, remifentanyl, mepivacaine, ropivacaine, bupivacaine, clonidine and midazolam (10(-8) - 10(-4) M, for all) on contractions induced by oxytocin (1 mU/ml) were studied. Alfentanyl (10(-5) M), meperidine (10(-5) M), remifentanyl (10(-4) M), bupivacaine (10(-4) M), ropivacaine (10(-4) M) and midazolam (3 x 10(-5) M) caused significant decreases in contractile responses of uterine strips to oxytocin. Contrastingly, mepivacaine increased (33.1% +/- 7.2%) oxytocin-induced contractions of uterine strips while clonidine exerted no significant effect. The sensitivity of myometrial preparations to tested local anesthetics or opioids did not differ significantly. The findings of the present study demonstrated that some local anesthetics, opioids and adjuvants caused significant and agent-specific alterations on contractility of the pregnant rat myometrium. Therefore, they seemed to have a potential to influence uterine contractility during clinical management of pain during labor. However, further research is needed to extrapolate these finding to clinical practice.

In vitro effects of opioids on pregnant uterine muscle.

Opioids are often used for obstetric analgesia. Ideal obstetric analgesia is attained with optimal pain relief and minimal risk for the parturient. Therefore, investigators in the present study explored the effects of different opioids on the myometrium of pregnant rats. Myometrial strips were exposed to increased concentrations of fentanyl (10(-8) M to 10(-6) M), alfentanil (10(-8) M to 10(-4) M), remifentanil (10(-8) M to 10(-4) M), and meperidine (10(-8) M to 10(-4) M). Decreased contractile activity was observed in myometrial strips isolated from pregnant rats at cumulative concentrations of fentanyl, alfentanil, remifentanil, and meperidine. The amplitude of contractions was reduced with increasing concentrations of opioids; this effect was statistically significant at a concentration of 10(-4) M. When administered at higher concentrations, opioids may decrease contractions in pregnant rat myometrium.

[Specific features of a course of chronic glomerulonephritis with onset in childhood].

AIM: Analysis of the course and rate of progression of morphologically confirmed forms of chronic glonerulonephritis (CGN) with onset in childhood and adolescence (1950 to 2005). MATERIAL AND METHODS: The course of the disease was examined in 110 patients with morphologically verified form of CGN with onset in childhood. Maximal history of CGN was 42 years. RESULTS: CGN was morphologically mesangio-proliferative in 50.9% patients, while nephritis with minimal alterations occurred only in 10% patients. Most of the patients (71; 64.6%) had secondary hypertension, chronic renal failure (39; 35.5%). Programmed hemodialysis was conducted in 14 (12.7%) patients, 10 (9.1%) patients died. Stable dysability developed in 41 (37.3%) patients. The most severe course of the diseases was observed in patients with family history of CGN. CONCLUSION: Recently, CGN with debut in childhood shows a trend to an unfavourable course, had severe manifestations at a disease debut, and progresses rapidly.

Recombinant human erythropoietin in comparison to amifostine against cisplatin-induced peripheral sensorial neurotoxicity in rats.

Cisplatin (CDDP) can cause dose-limiting neurotoxicity. We have investigated the role of recombinant human erythropoietin (rHuEPO) in the prevention of CDDP-induced peripheral sensory neurotoxicity. Wistar-albino rats were randomly assigned to three groups: Group A received only CDDP, Group B received CDDP plus amifostine and Group C received CDDP plus rHuEPO. At 7 weeks, Group C was divided into two subgroups; C1 received maintenance rHuEPO for 3 additional weeks, C2 received no treatment. Somatosensory evoked potentials (SEPs) were carried out at baseline, and at 7 and 10 weeks. At baseline, all groups were comparable in terms of area, amplitude and spinal potential normalized velocity (SPNV). The comparison of area, amplitude and SPNV data as well as their percent changes between 7 and 10 weeks showed no difference between Groups A, B, C1 and C2. We conclude that at the given dose and schedule, rHuEPO appears to have neuroprotective activity; however, maintenance rHuEPO treatment does not seem to provide further benefit.

Mechanism of inhibition of 3 alpha, 20 beta-hydroxysteroid dehydrogenase by a licorice-derived steroidal inhibitor.

BACKGROUND: Bacterial 3 alpha, 20 beta-hydroxysteroid dehydrogenase (3 alpha, 20 beta-HSD) reversibly oxidizes the 3 alpha and 20 beta hydroxyl groups of androstanes and pregnanes and uses nicotinamide adenine dinucleotide as a cofactor. 3 alpha, 20 beta-HSD belongs to a family of short-chain dehydrogenases that has a highly conserved Tyr-X-X-X-Lys sequence. The family includes mammalian enzymes involved in hypertension, digestion, fertility and spermatogenesis. Several members of the enzyme family, including 3 alpha, 20 beta-HSD, are competitively inhibited by glycyrrhizic acid, a steroidal compound found in licorice, and its derivative, carbenoxolone, an anti-inflammatory glucocorticoid. RESULTS: The three-dimensional structure of the enzyme-carbenoxolone complex has been determined and refined at 2.2 A resolution to a crystallographic R-factor of 19.4%. The hemisuccinate side chain of carbenoxolone makes a hydrogen bond with the hydroxyl group of the conserved residue Tyr152 and occupies the position of the nicotinamide ring of the cofactor. The occupancies of the inhibitor in four independent catalytic sites refine to 100%, 95%, 54% and 36%. CONCLUSIONS: The steroid binds at the catalytic site in a mode much like the previously proposed mode of binding of the substrate cortisone. No bound cofactor molecules were found. The varying occupancy of steroid molecules observed in the four catalytic sites is either due to packing differences or indicates a cooperative effect among the four sites. The observed binding accounts for the inhibition of 3 alpha, 20 beta-HSD.

The refined three-dimensional structure of 3 alpha,20 beta-hydroxysteroid dehydrogenase and possible roles of the residues conserved in short-chain dehydrogenases.

BACKGROUND: Bacterial 3 alpha,20 beta-hydroxysteroid dehydrogenase reversibly oxidizes the 3 alpha and 20 beta hydroxyl groups of steroids derived from androstanes and pregnanes. It was the first short-chain dehydrogenase to be studied by X-ray crystallography. The previous description of the structure of this enzyme, at 2.6 A resolution, did not permit unambiguous assignment of several important groups. We have further refined the structure of the complex of the enzyme with its cofactor, nicotinamide adenine dinucleotide (NAD), and solvent molecules, at the same resolution. RESULTS: The asymmetric unit of the crystal contains four monomers, each with 253 amino acid residues, 38 water molecules, and 176 cofactor atoms belonging to four NAD molecules--one for each subunit. The positioning of the cofactor molecule has been modified from our previous model and is deeper in the catalytic cavity as observed for other members of both the long-chain and short-chain dehydrogenase families. The nicotinamide-ribose end of the cofactor has several possible conformations or is dynamically disordered. CONCLUSIONS: The catalytic site contains residues Tyr152 and Lys156. These two amino acids are strictly conserved in the short-chain dehydrogenase superfamily. Modeling studies with a cortisone molecule in the catalytic site suggest that the Tyr152, Lys156 and Ser139 side chains promote electrophilic attack on the (C20-O) carbonyl oxygen atom, thus enabling the carbon atom to accept a hydride from the reduced cofactor.

Structure of uncomplexed and linoleate-bound Candida cylindracea cholesterol esterase.

BACKGROUND: Candida cylindracea cholesterol esterase (CE) reversibly hydrolyzes cholesteryl linoleate and oleate. CE belongs to the same alpha/beta hydrolase superfamily as triacylglycerol acyl hydrolases and cholinesterases. Other members of the family that have been studied by X-ray crystallography include Torpedo californica acetylcholinesterase, Geotrichum candidum lipase and Candida rugosa lipase. CE is homologous to C. rugosa lipase 1, a triacylglycerol acyl hydrolase, with which it shares 89% sequence identity. The present study explores the details of dimer formation of CE and the basis for its substrate specificity. RESULTS: The structures of uncomplexed and linoleate-bound CE determined at 1.9 A and 2.0 A resolution, respectively, reveal a dimeric association of monomers in which two active-site gorges face each other, shielding hydrophobic surfaces from the aqueous environment. The fatty-acid chain is buried in a deep hydrophobic pocket near the active site. The positioning of the cholesteryl moiety of the substrate is equivocal, but could be modeled in the hydrophobic core of the dimer interface. CONCLUSIONS: The monomer structure is the same in both the complexed and uncomplexed crystal forms. The dimers differ in the relative positions of the two monomers at the dimer interface. Of the 55 residues that are different in CE from those in C. rugosa lipase 1, 23 are located in the active site and at the dimer interface. The altered substrate specificity is a direct consequence of these substitutions.

Comparison of epidural and combined spinal-epidural analgesia in the management of labour without pain.

The effects of combined spinal-epidural analgesia (CSEA) and epidural analgesia (EA) were studied in 50 healthy parturients randomly allocated to receive bupivacaine plus fentanyl either epidurally, or intrathecally and epidurally. Significant differences from baseline values were seen in systolic blood pressure at all time-points except for 4 h in the EA group and at 3 and 4 h in the CSEA group. Significant differences from baseline values were seen in diastolic blood pressure at 1, 2, 3 and 4 h in the EA group, whereas no significant differences from baseline were seen in the CSEA group. Pain scores in both groups were significantly decreased compared with baseline and all scores, except at 2h, were significantly lower in the CSEA group compared with the EA group. The duration of labour and total amount of drugs used were significantly decreased and cervical dilatation was faster with CSEA compared with EA. In conclusion, CSEA was associated with more rapid onset of analgesia and faster progress in cervical dilatation compared with EA, and can be used safely for labour analgesia.

Posterior leukoencephalopathy after combination chemotherapy in a patient with lymphoma.

Posterior leukoencephalopathy syndrome is a recently described syndrome involving mainly parieto-occipital gray/white matter of the brain. It occurs secondary to various clinical entities, like hypertension and immunosuppressive therapy. Few cases after combination chemotherapy have been reported. This study describes a 36-year-old woman with primary refractory T-cell lymphoma, who developed central nervous system toxicity due to treatment with intrathecal methotrexate and intravenous ifosfamide, idarubicine and etoposide given as a salvage regimen. Both clinical features as well as magnetic resonance imaging findings were typical for posterior leukoencephalopathy syndrome. The patient died despite anti-hypertensive therapy and haemodialysis. Central nervous system toxicity related to chemotherapeutics and posterior leukoencephalopathy syndrome are discussed briefly.

Polysomnographic findings in recently drug-free and clinically remitted depressed patients.

Thirteen patients were examined by sleep polysomnograph (PSG) and the dexamethasone suppression test when clinically depressed and later when clinically remitted for six months and no longer receiving antidepressant medication for two to five weeks. None of the PSG variables (rapid eye movement [REM] latency, total sleep time, stage 1 through 4 times, REM time, and REM densities in periods 1 through 3) was significantly changed between symptomatic depression and symptom remission. While symptomatic, 11 of 13 patients exhibited a reduced REM latency (65 minutes or less). After clinical remission, eight of the 11 continued to exhibit reduced REM latencies, whereas the dexamethasone suppression test tended to show nonsuppression only during clinical depression. These data represent either longer-term (ie, slow to normalize) biologic consequences of a depressive episode or biologic antecedents of clinical depression that may herald a return of the depression in individuals vulnerable to recurrence. Whether PSG abnormalities identify clinically remitted patients who are prone to develop another depressive episode requires longitudinal follow-up studies.

Alprazolam vs amitriptyline in depressions with reduced REM latencies.

This study was designed to compare the antidepressant effects of alprazolam, a triazolobenzodiazepine, with amitriptyline hydrochloride in a group of patients with nonpsychotic, major depressions diagnosed by Research Diagnostic Criteria. A mean rapid eye movement latency of less than 65 minutes was required to enter this study. Dexamethasone suppression tests were conducted before treatment. By strictly applied Research Diagnostic Criteria, 83.6% of the subjects were endogenous, and 34.7% were inpatients. A significantly greater percentage of alprazolam-treated patients responded within the first seven days of treatment. By the end of this six-week trial, alprazolam was associated with significant reductions in Hamilton, Beck, Covi, Raskin, and Carroll Rating scores (pretreatment to posttreatment). However, by the end of treatment the effects of amitriptyline exceeded those of alprazolam on both the Hamilton and Beck scales. These data indicate that alprazolam is not as effective as amitriptyline in major depressions with a shortened rapid eye movement latency.