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.

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.

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.

Platelet size has diagnostic predictive value for bone marrow metastasis in patients with solid tumors.

Though not very common, solid tumor involvement of the bone marrow (BM) may have serious consequences. Recent studies have shown that mean platelet volume (MPV) is a good indicator for BM disease in the differential diagnosis of thrombocytopenia. We investigated the significance of MPV in the diagnosis of BM metastasis in patients with solid tumors. Patients with histologically-verified solid tumors for whom BM biopsy specimens were available (n = 121) and healthy controls (n = 62) were included in this retrospective study. A total of 183 individuals were analyzed. Of the patients, 61 had a diagnosis of BM metastasis (Group A), 60 did not have BM metastasis (Group B). Group B and C (healthy controls) constituted the control group without BM metastasis (n = 122). The mean MPV was 7.0 +/- 0.8 fl in patients with BM metastasis and 8.4 fl in the control group (P < 0.001). A cut-off point of <7.4 fl was found to have significant predictive value according to receiver-operating characteristics curve analysis. This cut-off point had 85% positive predictive value and 90% negative predictive value in the diagnosis of BM metastasis (odds ratio: 53; 95% confidence interval: 20-135), and a sensitivity of 82.7% and specificity of 89.6%. MPV can be used as a reliable marker to guide the clinician as to the likely presence or absence of BM metastasis in patients with solid tumors.

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.

[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.

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.

Accelerated hepatitis C virus replication with rituximab treatment in a non-Hodgkin's lymphoma patient.

The treatment of patients with non-Hodgkin's lymphoma (NHL) may be complicated by concomitant chronic hepatitis C virus (HCV) infection. Recent data suggest that HCV may also be a contributing factor to the development of this disease. Although antiviral treatment has occasionally been reported to result in the regression of lymphoma in patients with HCV infection, the importance of the control of this infection on the prognosis of lymphoma needs to be defined. Here we report a patient with diffuse large B-cell lymphoma who presented with a mass in her left breast. She had had HCV-related liver cirrhosis for 6 years. She was given rituximab monotherapy for three consecutive weeks, but treatment had to be discontinued as a result of hematological toxicity. HCV viral load also increased, but then decreased gradually after rituximab was stopped. She could be given no further therapy. Six months later she presented with spinal involvement with infiltration of the cauda equina. Though cranial-spinal radiotherapy and steroids were started, she died shortly thereafter. Though rituximab is an invaluable drug in the treatment of B-cell lymphomas, we believe that the use of such agents with potentially long-lasting effects on B lymphocytes requires extended vigilance for accelerated replication of hepatitis B and C viruses.

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.

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.

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.

Intrathecal ropivacaine versus ropivacaine plus fentanyl for out-patient arthroscopic knee surgery.

We evaluated the effects of low-dose intrathecal ropivacaine with or without fentanyl for arthroscopic knee surgery. Fifty patients were randomized in equal groups to receive an intrathecal solution (3 ml) containing either 10 mg isobaric ropivacaine or 8 mg isobaric ropivacaine plus 25 pg fentanyl. Complete motor blockade occurred in 22 patients (88%) in both groups. The time taken to reach sensory blockade to T10 and total motor blockade was shorter in the ropivacaine-treated group, but differences were not statistically significant. The duration of sensory and motor blockade was shorter in the ropivacaine plus fentanyl-treated group. The cephalad spread of sensory blockade was higher with ropivacaine than with ropivacaine plus fentanyl. We conclude that although 25 microg fentanyl added to 8 mg ropivacaine provided shorter motor and sensory blockade durations than 10 mg ropivacaine alone, small doses of ropivacaine plus fentanyl can be used safely for arthroscopic knee surgery.

Comparison of two different techniques for brachial plexus block: infraclavicular versus axillary technique.

BACKGROUND: Brachial plexus block via the axillary approach is problematic in patients with limited arm mobility. In such cases, the infraclavicular approach may be a valuable alternative. The purpose of our study was to compare axillary and infraclavicular techniques for brachial plexus block in patients undergoing arm or forearm surgery. METHODS: After institutional approval and informed consent were obtained, 30 patients (ASA physical status I or II) scheduled for forearm and hand surgery under brachial plexus anesthesia were included in the study. Patients were randomly allocated into two groups. Brachial plexus block was performed via the axillary approach in the Group A patients and via the infraclavicular approach in the Group I patients using a peripheral nerve stimulator. All blocks were performed with a total dose of 40 ml 0.375% bupivacaine. RESULTS: In each nerve territory (radial, ulnar, median, and musculocutaneous), the mean values of the degree and the duration of the sensory block and motor block were not significantly different between the two groups (P > 0.05). Inadvertent vessel puncture was significantly more frequent in the axillary approach (P < 0.05). CONCLUSION: Brachial plexus block performed via the infraclavicular approach is as safe and effective as the axillary approach. Infraclavicular approach may be preferred to the axillary approach when the upper arm mobility is impaired or not desired.

Tamoxifen-induced tissue factor pathway inhibitor reduction: a clue for an acquired thrombophilic state?

BACKGROUND: Current understanding of hemostatic systems enables us to better explore the enigmatic pathobiology of tamoxifen (TAM)-induced thrombotic diathesis. We have therefore aimed to assess the hemostatic changes in breast cancer patients receiving TAM on an adjuvant basis. PATIENTS AND METHODS: The study population consisted of 43 female patients with hormone receptor-positive breast cancer who received TAM 20 mg/day as part of their adjuvant treatment. Mean age was 52+/-12 years (range 25-74). Twenty-one patients (49%) were premenopausal. Plasma samples were collected prior to and following 6 months of TAM therapy and were assayed for total tissue factor pathway inhibitor (TFPI), free TFPI, lipid-bound TFPI, thrombomodulin, D dimer, activated protein C resistance (APC res), factors VIIa, II, V, VII and X, and global fibrinolytic capacity (GFC). RESULTS: Median total TFPI decreased significantly from 48.5 ng/ml to 36.2 ng/ml (P=0.001), free TFPI from 10 to 7.6 ng/ml (P=0.001) and lipid-bound TFPI from 39.1 to 28.7 ng/ml (P=0.001). There were significant decreases in the levels of factor II (P=0.03), factor V (P=0.001), factor VII (P=0.06), thrombomodulin (P=0.01) and D dimer (P=0.001). However, APC res times were significantly prolonged (P=0.04). The remaining parameters that we have studied were not significantly affected. CONCLUSION: Our findings suggest that TAM tends to activate the coagulation pathway by counteracting major molecules involved in coagulation inhibition, namely TFPI and TM. As reflected by unchanged GFC, the drug appears to impair the expected compensatory activation of the fibrinolytic system, which removes fibrin polymers resulting from coagulation activation.