Understanding changes in pulmonary function and functional status in breast cancer patients after systemic chemotherapy and radiotherapy: a prospective study.

BACKGROUND: Respiratory complications in breast cancer (BC) patients after chemotherapy (CT) and radiotherapy (RT) have been well acquainted and these complications should be investigated to prevent secondary problems and/or improve BC patients' clinical outcomes. Therefore, this study aimed to assess the potential acute effect of systemic chemotherapy and radiotherapy on respiratory function and functional status of patients with breast cancer. METHODS: A total of 25 BC patients who were candidates for systemic chemotherapy and radiotherapy were recruited after oncological examination and included in this study. Respiratory function and functional status were assessed with the Pulmonary Function Test (PFT) and the Six-Minute Walk Test (6MWT), respectively. Patients were assessed before CT (c0), after CT (c1), and after RT (r1). RESULTS: 25 BC patients were assessed in c0 and c1 while only 15 out of 25 patients (60%) were assessed in r1. The actual values of Forced vital capacity (FVC) (t = 2.338, p =.028), Forced expiratory volume in 1s (FEV1 (t = 2.708, p =.012), and the forced expiratory flow of between 25% and 75% of vital capacity (FEF25-75%) (t = 2.200, p =.038) were found significantly different after systemic CT. Inspiratory (MIP) and expiratory (MEP) muscle strength also did not show a significant change from c0 to c1. A significant effect of the type of surgery was found (Wilks' lambda, F [1, 19] = 6.561, p =.019, ηp2 = 0.25) between c0 and c1 in actual FVC value. The main effect of time was found significant in FVC (F [2, 28] = 4.840, p =.016, ηp2 = 0.25) from c0 to r1. Pairwise comparisons with Bonferroni correction showed that there was a significant difference between c0 and r1 (p =.037). DISCUSSION: The present study showed decreased FVC and FEV1 actual values and percent predicted rates from baseline to the completion of treatment. Since the interactional effect of the type of surgery was significant, we suggest that clinical and demographic factors such as age should be considered when interpreting the early changes in PFT. In addition, the significant linear trend of decreasing in some specific outcomes in respiratory function also highlighted the need for continuous monitoring of potential respiratory problems in patients with BC from baseline to the completion of chemotherapy and radiotherapy.

Assessment of sensorimotor and strength related function of breast cancer patients during systemic drug therapy: a prospective observational study.

BACKGROUND: Chemotherapy is a well-known risk factor for sensorial and motor disturbances. Chemotherapy induced peripheral neuropathy (CIPN) which predominantly affects sensory nerves might cause a diminished fine motor function. This prospective observational study aimed to assess the sensorimotor functions of breast cancer patients before, during, and after chemotherapy. METHODS: A total of 56 breast cancer patients were evaluated at three different times as follows: T1 (before chemotherapy), T2 (middle chemotherapy), and T3 (completion of chemotherapy). Motor function was assessed with handgrip strength (HGS), peripheral muscle strength (PMS), and the Minnesota Manual Dexterity Test (MMDT). Semmes Weinstein Monofilament Test (SWMT) was performed to assess the sensory function. Fatigue was evaluated with the European Organization for Research and Treatment of Cancer Quality of Life Module Cancer Related Fatigue (EORTC-QLQ-FA12), respectively. RESULTS: HGS and MMDT were found significant (χ2: 11.279, p = 0.004 and χ2: 9.893, p = 0.007, respectively) whereas PMS was not found significant (F (2,110) = 1.914, p = 0.152). Pairwise comparisons with Bonferroni adjustments revealed that HGS was found significant between T1 and T3, while significant results were obtained between T1 and T2 as well as T2 and T3 in MMDT (p = 0.01 and p = 0.042). There were significant results in some reference points of SWMT, though they were not found after pairwise comparisons with Bonferroni adjustment (p > 0.05). Fatigue was found significantly increased from T1 through T3 (Median: 19.44 vs 27.77, z: -2.347, p = 0.019, Wilcoxon test). CONCLUSION: Our study showed that decreased handgrip strength and fine motor function, as well as increased fatigue, are evident during the chemotherapy. SWMT can be an optional assessment in the context of tracking changes in cutaneous sensation during chemotherapy due to its non-invasive, cheap, and easily repeatable features among cancer patients. To preserve functional capacity as well as independence in daily living, precautions and follow up assessments during the systemic therapy process should be integrated as early as possible to prevent future deteriorations in daily life for patients who undergo chemotherapy. TRIAL REGISTRATION: NCT04799080.

Comparison of Alectinib/Crizotinib Data in First-Line Therapy in Patients with Anaplastic LymphomakinasePositive Nonsmall Cell Lung Carcinoma with Poor Prognostic Features for Alectinib.

OBJECTIVE: Alectinib has a much better central nervous system transmission than crizotinib in patients diagnosed with anaplastic lymphoma kinase mutation-positive nonsmall cell lung carcinoma. We aimed to investigate alectinib's efficacy in the treatment and its place in the first-line treatment and report our real-life data. MATERIAL AND METHODS: The data of 38 patients who were diagnosed with anaplastic lymphoma kinase-positive nonsmall cell lung carcinoma in our clinic between 2016 and 2021, who did not receive any treatment before were retrospectively analyzed. RESULTS: Of the 19 patients who received alectinib, 14 had multiple, and 6 had pretreatment brain metastases. No newly emerging brain metastases were detected during the treatment period. The progression-free survival of patients was 23.5 ± 4.2 months, and overall survival was 24.6 ± 4.1 months. Progression was observed in 10 (52.6%) patients. Of the 19 patients who received crizotinib, 7 had multiple metastases, and brain metastases were detected in 1 patient before treatment and 6 patients during the treatment period. Progression-free survival of crizotinib patients was 17.1 ± 4.8 months and their overall survival was 26.5 ± 6.1 months. Progression was observed in 17 (89.5%) patients. The second line of alectinib could be given to 8 of these patients. Overall survival after second-line treatment of alectinib was 18.2 ± 7.0 months. Overall survival of the patients who could not receive second-line treatment of alectinib was 4.0 ± 2.0 months. CONCLUSION: The progression rate was lower in alectinib than the crizotinib patients, although there were more patients with multiple metastases and brain metastases in the alectinib arm.

Effect of Postoperative Adjuvant Radiotherapy on Quality of Life, Anxiety, and Depression in Adult Female Breast Cancer Patients.

AIM: This study aims to identify anxiety and depression caused by adjuvant radiotherapy in breast cancer cases to determine the deterioration in the quality of life and investigate the effect of early treatment. MATERIALS AND METHODS: In this study, the Beck Depression Inventory, Beck Anxiety Inventory, and European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-30 (EORTC QLQ-C30) Turkish 3.0 forms were evaluated in 63 breast cancer patients before the start of radiotherapy treatment (T1) and at six weeks after the end of radiotherapy treatment (T2). RESULTS: A high level of anxiety was detected in 77.8% of patients, and depression was found in 25.4% of patients in T1. When depressive cases were evaluated with EORTC QLQ-C30 scores, the general health status (p = 0.043), role function (p = 0.027), emotional (p < 0.002), cognitive (p < 0.001), and social (p < 0.0001) scales were statistically lower in T1, whereas pain (p = 0.045) and insomnia (p < 0.0001) symptoms were higher in T1. Anxiety and EORTC QLQ-C30 scores in terms of emotional function (p = 0.015), social function (p < 0.003), and symptoms of insomnia (p = 0.027) were found to be statistically higher in T1 anxious cases. However, anxiety was detected in only 3% of T2 cases, and no depression was found in any of the cases. Anxiety and EORTC QLQ-C30 scores and symptom scales were evaluated in terms of role function (p < 0.0001), emotional (p = 0.041) and social scales (p = 0.014), fatigue (p = 0.028), pain (p = 0.033), insomnia (p = 0.011), and constipation (p < 0.0001); these were found to be statistically significant in T2. CONCLUSION: This study revealed that early diagnosis and treatment of anxiety before initiating adjuvant radiotherapy reduces the development of long-term anxiety-related depression in the future. Therefore, it is recommended that patients be evaluated for anxiety and depression before starting adjuvant radiotherapy.

Assessment of the cardiorespiratory fitness and the quality of life of patients with breast cancer undergoing chemotherapy: a prospective study.

BACKGROUND: Diminished cardiorespiratory fitness is a well-known side effect of chemotherapy as well as a risk factor for potential cardiovascular diseases among cancer patients. This study aimed to assess the potential effects of systemic adjuvant (ACT) or neoadjuvant (NACT) chemotherapy on cardiorespiratory fitness and quality of life (QoL) among breast cancer (BC) patients. METHODS: Demographic data, cardiorespiratory fitness, health-related QoL domains were assessed with simple data form, six-minute walk test (6MWT), European Organization for Research and Treatment of Cancer quality of life module (EORTC-C30), and Functional Assessment of Cancer Therapy (FACT-B+), respectively. Time1 (T1, prior to chemotherapy), Time2 (T2; interim assessment), and Time3 (T3, final assessment) were set as assessment points. RESULTS: A total of 42 patients (32 ACT vs 10 ACT) completed all assessments. There were no significant differences of main effect of time and time*group interaction on total walked distance (TWD) after controlling for age and BMI (F(2,28) = 1.309, p = 0.286; F(2,28) = 1.444, p = 0.253). EORTC symptoms subscale was found to be correlated with EORTC and FACT-B+ physical function (PF) subscales (r = - 861, p < 0.001; r = - 0.877, p < 0.001) in T3. The EORTC PF subscale was found to be correlated with the TWD in the baseline (r = 0.411, p = 0.024). CONCLUSIONS: This study showed that the effect of chemotherapy on diminished PF and remarkably increased symptom burden among BC patients. Yet, the type of chemotherapy had no effect on TWD regarding cardiorespiratory fitness. Monitoring potential functional decline regarding cardiorespiratory fitness can be performed via simple field tests such as 6MWT.

The effect of adjuvant radiotherapy on skin biophysical properties in patients with breast cancer at risk for breast lymphedema: A prospective study.

Breast cancer (BC) is the most common type of cancer among women. Radiotherapy (RT) is one of the main and primary treatment options for BC, especially in breast-conserving surgery (BCS). BC patients who underwent RT experience a wide range of symptoms, in which breast oedema and irritation of the skin take the lion's share. Breast oedema/lymphedema, which is also a prominent side effect after RT should be well determined in earlier settings due to the chronicity of lymphedema. Therefore, this study aimed to analyze the biophysical parameters of skin on the ipsilateral (IL) and contralateral (CL) sites via Tissue dielectric constant (TDC) and Transepidermal water loss (TEWL) methods in terms of oedema and skin barrier function (SBF). The following reference points before and after the RT were measured: (R1: Pectoralis muscle, R2: Upper breast, R3: Lower breast, R4: Lateral site of the thorax). A total of 24 BC patients (mean age and BMI: 52.78 ± 9.85 years and 28.42 ± 5.64 kg/m2 ) were evaluated. In the IL site, the SBF was not found significant in R1-R3, whereas significantly lower SBF was observed in R4 after RT (t = -3.361, p = 0.003). A significant increase in TDC was observed in R2 at the 5.0 mm depth (t = -2.500, p = 0.02). We suggest that a longer period of follow-up should be carefully carried out to track changes in terms of SBF and oedema in the irradiated breast. The increased need for early detection of changes associated with breast lymphedema can be achievable via noninvasive, safe, cheap, and easily repeatable devices.

Real-life comparison of afatinib and erlotinib in non-small cell lung cancer with rare EGFR exon 18 and exon 20 mutations: a Turkish Oncology Group (TOG) study.

OBJECTIVES: To compare the survival of first- and second-generation tyrosine kinase inhibitors (TKIs) in patients with rare EGFR exon 18 and exon 20 mutation-positive non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: We retrospectively evaluated survival characteristics of 125 patients with EGFR exon 18 and exon 20 mutated NSCLC who received erlotinib or afatinib as first line treatment between 2012 and 2021 from 34 oncology centres. Since exon 20 insertion is associated with TKI resistance, these 18 patients were excluded from the study. RESULTS: EGFR exon 18 mutations were seen in 60%, exon 20 mutations in 16%, and complex mutations in 24% of the patients with NSCLC who were evaluated for the study. There were 75 patients in erlotinib treated arm and 50 patients in afatinib arm. Patients treated with erlotinib had progression-free survival time (PFS) of 8.0 months and PFS was 7.0 months in the afatinib arm (p = 0.869), while overall survival time (OS) was 20.0 vs 24.8 months, respectively (p = 0.190). PFS of exon 18 mutated arm was 7.0 months, exon 20 mutated arm was 4.3 months, and complex mutation positive group was 17.3 months, and this was statistically significant (p = 0.036). The longest OS was 32.5 months, seen in the complex mutations group, which was not statistically different than exon 18 and in exon 20 mutated groups (21.0 and 21.2 months, respectively) (p = 0.323). CONCLUSION: In this patient group, especially patients with complex mutations are as sensitive to EGFR TKI treatment similar to classical mutations, and in patients with rare exon 18 and exon 20 EGFR mutation both first- and second-generation EGFR-TKIs should be considered, especially as first- and second-line options.

The prognostic relationship of 18F-FDG PET/CT metabolic and volumetric parameters in metastatic ALK + NSCLC.

OBJECTIVE: The aim of this study is to determine the role of metabolic and volumetric parameters obtained from 18Fluorine-Fluorodeoxyglucose PET/computed tomography (18F-FDG PET/CT) imaging on progression-free survival (PFS) and overall survival (OS) in patients with advanced nonsquamous cell lung carcinoma (NSCLC) with anaplastic lymphoma kinase (ALK) rearrangement. METHODS: Pre and post-treatment PET/CT images of the ALK + NSCLC patients between January 2015 and July 2020 were evaluated. The highest standardized uptake value (SUVmax), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) values were obtained from pre-tyrosine kinase inhibitor (TKI) basal PET/CT (PETpre) and post-TKI PET/CT (PETpost) images. Total MTV (tMTV) and total TLG (tTLG) values were calculated by summing MTV and TLG values in all tumor foci. The change (Δ) in pSUVmax, pMTV, pTLG, tMTV and tTLG before and after treatment was calculated.The relationship of these parameters with OS and PFS was analyzed. RESULTS: tTLGpre, tMTVpre, pTLGpre, pMTVpre, ∆SUVmax, ∆tMTV and ∆tTLG values were found to be associated with OS; ∆tMTV, ∆tTLG, tTLGpre, tMTVpre, pTLGpre and pMTVpre were associated with PFS. The cutoff values in both predicting OS and PFS were calculated as -31.6 and 391.1 for ∆tMTV and tTLGpre, respectively. In Cox regression analysis, ∆tMTV and stage for OS and ∆tMTV and tTLGpre for PFS were obtained as prognostic factors. CONCLUSIONS: Metabolic and volumetric parameters, especially TLG values in the whole body before treatment and change in whole body MTV value, obtained from PET/CT may be useful in predicting prognosis and determining treatment strategies for patients with advanced ALK + NSCLC.

The Characteristics of Pain Tolerance in Patients Who Underwent Unilateral Breast Cancer Surgery: The Effect of Handedness and Surgical Site to Assess the Potential Musculoskeletal Symptoms and Function.

BACKGROUND: Breast cancer survivors (BCS) usually experience musculoskeletal pain and strength imbalance between surgical and nonsurgical sites. MATERIAL AND METHODS: This study aimed to assess the effect of handedness and surgical site on pain tolerance and upper extremity strength in BCS. A total of 96 female BCS (Mean age and BMI: 51.06 ± 9.36 years and 27.77 ± 3.75 kg/m2) were included in this study. BCS were categorized as "DoS" or "NoS" whether they had surgery on their dominant or nondominant site, respectively. Socio-demographic data, upper extremity strength, pain tolerance, and pain-related function measurements were performed by simple form, manual muscle tester, pain algometer, and Disabilities of Arm, Shoulder, and Hand's (DASH) pain subscale, respectively. RESULTS: Pain tolerances were significantly lower in upper trapezius muscle region in the surgical site (t = -4,263, P < .001 and t = -2138, P = 0.037) while in the deltoid tuberosity, pain tolerance was significantly higher in surgical site (t = 2633, P = 0.011). Mean differences in strength in shoulder flexion and abduction were significantly lower in the DoS group compared to the NoS group (z = -3.166, P = .002 and z = -2.131, P = .033, respectively), whereas the pain subscale was significantly higher in the DoS (P = .013). CONCLUSION: Pain tolerance decreased in the upper trapezius muscle region on the surgical site irrespective of the handedness. However, in deltoid tuberosity, the effect of handedness was remarkable. Exercise programs should focus to establish a strength balance in nondominant surgery BCS since strength imbalance might be more prominent to affect them to take part in activities in daily living.

IMPORTANCE of PRETREATMENT 18F-FDG PET/CT TEXTURE ANALYSIS in PREDICTING EGFR and ALK MUTATION in PATIENTS with NON-SMALL CELL LUNG CANCER.

OBJECTIVE: Identification of anaplastic lymphoma kinase (ALK) and epidermal growth factor receptor (EGFR) mutation types is of great importance before treatment with tyrosine kinase inhibitors (TKIs). Radiomics is a new strategy for noninvasively predicting the genetic status of cancer. We aimed to evaluate the predictive power of 18F-FDG PET/CT-based radiomic features for mutational status before treatment in non-small cell lung cancer (NSCLC) and to develop a predictive model based on radiomic features. METHODS: Images of patients who underwent 18F-FDG PET/CT for initial staging with the diagnosis of NSCLC between January 2015 and July 2020 were evaluated using LIFEx software. The region of interest (ROI) of the primary tumor was established and volumetric and textural features were obtained. Clinical data and radiomic data were evaluated with machine learning (ML) algorithms to create a model. RESULTS: For EGFR mutation prediction, the most successful machine learning algorithm obtained with GLZLM_GLNU and clinical data was Naive Bayes (AUC: 0.751, MCC: 0.347, acc: 71.4%). For ALK rearrangement prediction, the most successful machine learning algorithm obtained with GLCM_correlation, GLZLM_LZHGE and clinical data was evaluated as Naive Bayes (AUC: 0.682, MCC: 0.221, acc: 77.4%). CONCLUSIONS: In our study, we created prediction models based on radiomic analysis of 18F-FDG PET/CT images. Tissue analysis with ML algorithms are non-invasive methods for predicting ALK rearrangement and EGFR mutation status in NSCLC, which may be useful for targeted therapy selection in a clinical setting.

The Prognostic Value of 18F-FDG PET/CT Metabolic Parameters in Predicting Treatment Response Before EGFR TKI Treatment in Patients with Advanced Lung Adenocarcinoma.

Objectives: This study makes a retrospective examination of exploring the prognostic value of 18fluorine-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) related metabolic-volumetric variables, nutritional status, and immune and inflammatory markers on progression-free survival (PFS) and overall survival (OS) in advanced adenocarcinoma patients with positive epidermal growth factor receptor (EGFR) mutations undergoing EGFR tyrosine kinase inhibitor (TKI) therapy. Methods: A retrospective examination was made of patients diagnosed with lung adenocarcinoma who underwent 18F-FDG PET/CT imaging for staging maximum four weeks before starting treatment, between January 2015 and July 2020. Included in the study were 68 patients identified histopathologically to have locally advanced/metastatic EGFR mutation-positive adenocarcinoma, and who underwent EGFR TKI therapy. The laboratory data of the patients, obtained 15 days before imaging performed for PET/CT staging, were evaluated. Results: Metabolic tumor volume, modified Glasgow prognostic score and locally advanced disease were identified as independent prognostic parameters for PFS (p=0.004, p=0.029, p=0.016, respectively). A univariate Cox regression analysis revealed albumin/alkaline phosphatase and tumor size to be significant parameters for prognosis (p=0.033, p=0.043, respectively). A multivariate Cox regression analysis revealed that none of the parameters were predictive or OS. Conclusion: The parameters of 18F-FDG PET/CT, especially the volumetric parameters, were found to be strong prognostic factors with statistical significance for predicting PFS. We believe that these parameters are important prognostic markers that should be evaluated together in the management and follow-up of patients with EGFR mutation-positive adenocarcinoma.

An analysis of adjuvant treatment strategies in operated pancreatic cancer patients: An Izmir oncology group study.

BACKGROUND: Adjuvant treatment is necessary in pancreatic cancer patients, but the optimal approach is not clear yet. Our aim was to explore the effectiveness of adjuvant treatment modalities in patients with operated pancreatic cancer. METHODS: There were five groups of patients operated for primary pancreas adenocarcinoma. The first two groups included patients who were treated with only adjuvant chemotherapy or radiotherapy. The patients in third group had received combination chemotherapy and radiotherapy either sequentially or concomitantly. The fourth group was composed of patients who were treated with adjuvant chemotherapy after concurrent chemoradiotherapy, whereas the patients in the fifth group were only observed after surgery without any adjuvant treatment. RESULTS: There were 83 operated pancreatic cancer patients available for analysis. Median age of the patients was 63 years (range, 40-82 years). There were 55 patients who had local disease recurrence (n = 14) or metastasis (n = 41) during or after adjuvant treatment. The median overall survival for all patients was 14 months. When we compared the median survival of patients who had any adjuvant treatment with the patients treated without any adjuvant therapy, we found a significant statistical difference between the groups (32.4 vs 6.5 months; P = 0.000). In addition, survival of each treatment group was also compared with each other but we did not find any significant statistical difference. CONCLUSIONS: Our result suggests that any adjuvant therapy in the treatment of pancreatic cancer patients is important. However, we could not find any superiority between adjuvant treatment modalities.

Cold Pulsatile Machine Perfusion Versus Static Cold Storage for Kidneys Donated After Circulatory Death: A Multicenter Randomized Controlled Trial.

BACKGROUND: The benefits of cold pulsatile machine perfusion (MP) for the storage and transportation of kidneys donated after circulatory death are disputed. We conducted a UK-based multicenter, randomized controlled trial to compare outcomes of kidneys stored with MP versus static cold storage (CS). METHODS: Fifty-one pairs of kidneys donated after circulatory death were randomly allocated to receive static CS or cold pulsatile MP. The primary endpoint, delayed graft function, was analyzed by "intention-to-treat" evaluation. RESULTS: There was no difference in the incidence of delayed graft function between CS and MP (32/51 (62.8%) and 30/51 (58.8%) P = 0.69, respectively), although the trial stopped early due to difficulty with recruitment. There was no difference in the incidence of acute rejection, or in graft or patient survival between the CS and MP groups. Median estimated glomerular filtration rate at 3 months following transplantation was significantly lower in the CS group compared with MP (CS 34 mL/min IQR 26-44 vs MP 45 mL/min IQR 36-60, P = 0.006), although there was no significant difference in estimated glomerular filtration rate between CS and MP at 12 months posttransplant. CONCLUSIONS: This study is underpowered, which limits definitive conclusions about the use of MP, as an alternative to static CS. It did not demonstrate that the use of MP reduces the incidence of delayed graft function in donation after circulatory death kidney transplantation.

Spinal Cord Ischemia in Pancreas Transplantation: The UK Experience.

BACKGROUND: Spinal cord ischemia (SCI) is a rare but devastating condition that can occur in the perioperative period resulting in paraplegia. Although diabetes mellitus is a risk factor for SCI in other types of major surgery, SCI is not widely recognized in transplantation. The aim of this study was to quantify the risk of SCI in pancreatic transplantation. METHODS: All UK pancreas transplant units were surveyed between 2017 and 2018. The risk of SCI in pancreas transplantation was estimated using the number of radiologically confirmed cases relative to the number of pancreatic transplants from UK registry data during the same time period. RESULTS: There have been 6 cases of SCI during pancreas transplantation since 2002. No aortic clamping occurred in any recipient. During or after surgery, all patients experienced episodes of hypotension (systolic blood pressure ≤ 90 mm Hg) before the onset of neurological symptoms. Epoprostenol, epidural anesthesia, and postoperative hemodialysis may have contributed to systemic hypotension. The mainstay of early treatment for SCI for all cases was blood pressure control. CONCLUSIONS: Based on these findings, there is approximately a 1:440 risk of SCI in pancreas transplantation. Hypotension appears to be a prominent risk factor. Strategies for mitigating the risk of SCI are discussed, drawing on evidence from thoraco-abdominal aortic aneurysm surgery. The risk of long-term neurological deficit should be discussed with prospective pancreas recipients given the potential impact on posttransplant quality of life.

High expression of mesothelin in advanced serous ovarian cancer is associated with poor prognosis.

PURPOSE: Mesothelin is a cell surface glycoprotein which is highly expressed in various types of epithelial cancers. Its expression level is associated with poor prognosis in many cancer types. The aim this study was to evaluate the association of the level of mesothelin expression with clinicopathological characteristics and its prognostic significance in patients with advanced serous ovarian cancer (SOC). METHODS: Tissue blocks from a total 42 patients with advanced SOC treated at the medical oncology clinic of Izmir Katip Celebi University Ataturk Training and Research Hospital between 2006 and 2013 were evaluated. Immunohistochemical staining for mesothelin was performed. Clinical characteristics, optimal or suboptimal operation, response to platinum-based chemotherapy, and overall survival (OS) were analyzed. RESULTS: The cut-off value of 45 for mesothelin H-score determined by ROC analysis predicted survival with 86% sensitivity and 75% specificity (p=0.020). We found a notable negative correlation between mesothelin H-score and OS (r = -0.570, p=0.0001). The median OS was 67 months (95%CI, 36.114 to 97.886) in the low-staining mesothelin H-score group and 27 months (95%CI, 22.238 to 31.762) in the high-staining mesothelin H-score group (p=0.002). Univariate analysis showed that the clinical stage IV disease (p=0.023), platinum chemoresistance (p=0.001), higher mesothelin H-score (p=0.002), and suboptimal surgery (p=0.024) were associated with worse OS. In the multivariate Cox regression model, mesothelin H-score (B=1.15, 95%CI=1.016 to 9.850, p=0.047) and the status of platinum sensitivity (B=-.916, 95%CI=.185 to -.864, p=0.020 were statistically significant predictors for OS. CONCLUSION: These results indicated that high mesothelin H-scores were significantly associated with poor prognosis in patients with advanced SOC.

Impact of Regional Organ Sharing and Allocation in the UK Northern Liver Alliance on Waiting Time to Liver Transplantation and Waitlist Survival.

BACKGROUND: In the United Kingdom, liver transplantation (LT) is undertaken in 7 supraregional centers. Until March 2018, liver grafts were offered to a center and allocated to a patient on their elective waiting list (WL) based on unit prioritization. Patients in Newcastle, Leeds, and Edinburgh with a United Kingdom Model for End-Stage Liver Disease (UKELD) score ≥62 were registered on a common WL and prioritized for deceased-donor liver allocation. This was known as the Northern Liver Alliance (NLA) "top-band scheme." Organs were shared between the 3 centers, with a "payback" scheme ensuring no patient in any center was disadvantaged. We investigated whether the NLA had improved WL survival and waiting time (WT) to transplantation. METHODS: Data for this study were obtained from the UK Transplant Registry maintained by National Health Service Blood and Transplant. This study was based on adult patients registered for first elective liver transplant between April 2013 and December 2016. Non-NLA centers were controls. The Kaplan-Meier method was used to estimate WL survival and median WT to transplant, with the log-rank test used to make comparisons; a Bonferroni correction was applied post hoc to determine pairwise differences. RESULTS: WT was significantly lower at NLA centers compared with non-NLA centers for top-band patients (23 versus 99 days, P < 0.001). However, WL survival was not significantly different for top-band patients (P > 0.999) comparing NLA with non-NLA centers. WL survival for nontop-band patients was no different (P > 0.999) comparing NLA with non-NLA centers. CONCLUSIONS: The NLA achieved its aim, providing earlier transplantation to patients with the greatest need. Nontop-band patients did not experience inferior survival.

The clinical importance of serum galectin-3 levels in breast cancer patients with and without metastasis.

OBJECTIVE: Studies have investigated expression status of galectin-3 (Gal-3), but very little is known about the importance of circulating Gal-3 in patients with breast cancer (BC). The purpose of the study was to investigate the clinical significance and potential diagnostic value of plasma Gal-3 levels in patients with BC. MATERIALS AND METHODS: Fifty-two patients with BC and 35 age-matched healthy controls were enrolled. Levels of Gal-3 were investigated in BC patients and healthy controls. Gal-3 levels were determined using ELISA method. RESULTS: Serum Gal-3 levels were significantly higher in BC patients than in controls (P = 0.002). Gal-3 levels did not significantly differ according to patients' statuses of lymph node involvement, hormone receptor, lymphovascular invasion, e-cadherin, menopausal, stage, serum hemostatic markers (prothrombin time, partial thromboplastin time, and international normalized ratio), platelet counts, mean platelet volume, lactate dehydrogenase, carcinoembryonic antigen, and carbohydrate antigen 15-3 values (P > 0.05 for all). A cut-off value of Gal-3 to predict BC was determined at ≥3.17 ng/ml with a sensitivity of 75.0%, a specificity of 65.71%, a positive and negative predictive values of 76.5 and 63.9%, respectively (area under the curve: 0.705 [95% confidence interval, 0.598-0.798], P = 0.0002). CONCLUSION: Serum Gal-3 levels were significantly higher in BC patients and did not significantly differ according to clinical and tumoral characteristics of patients. Furthermore, there was no difference in Gal-3 levels between BC patients with and without metastatic disease. Serum Gal-3 levels can be used as an adjunct to other diagnostic or screening tests for BC regardless of clinical and tumoral characteristics of patients.

Presentation, diagnostic assessment and surgical outcomes in primary hyperparathyroidism: a single centre's experience.

OBJECTIVE: Primary hyperparathyroidism (PHPT) is a common reason for referral to endocrinology but the evidence base guiding assessment is limited. We evaluated the clinical presentation, assessment and subsequent management in PHPT. DESIGN: Retrospective cohort study. PATIENTS: PHPT assessed between 2006 - 2014 (n = 611) in a university hospital. MEASUREMENTS: Symptoms, clinical features, biochemistry, neck radiology and surgical outcomes. RESULTS: Fatigue (23.8%), polyuria (15.6%) and polydipsia (14.9%) were associated with PHPT biochemistry. Bone fracture was present in 16.4% but was not associated with biochemistry. A history of nephrolithiasis (10.0%) was associated only with younger age (P = 0.006) and male gender (P = 0.037). Thiazide diuretic discontinuation was not associated with any subsequent change in calcium (P = 0.514). Urine calcium creatinine clearance ratio (CCCR) was <0.01 in 18.2% of patients with confirmed PHPT. Older age (P < 0.001) and lower PTH (P = 0.043) were associated with failure to locate an adenoma on ultrasound (44.0% of scans). When an adenoma was identified on ultrasound the lateralization was correct in 94.5%. Non-curative surgery occurred in 8.2% and was greater in those requiring more than one neck imaging modality (OR 2.42, P = 0.035). CONCLUSIONS: Clinical features associated with PHPT are not strongly related to biochemistry. Thiazide cessation does not appear to attenuate hypercalcaemia. PHPT remains the likeliest diagnosis in the presence of low CCCR. Ultrasound is highly discriminant when an adenoma is identified but surgical failure is more likely when more than one imaging modality is required.

Substantial Metabolic Activity of Human Brown Adipose Tissue during Warm Conditions and Cold-Induced Lipolysis of Local Triglycerides.

Current understanding of in vivo human brown adipose tissue (BAT) physiology is limited by a reliance on positron emission tomography (PET)/computed tomography (CT) scanning, which has measured exogenous glucose and fatty acid uptake but not quantified endogenous substrate utilization by BAT. Six lean, healthy men underwent 18fluorodeoxyglucose-PET/CT scanning to localize BAT so microdialysis catheters could be inserted in supraclavicular BAT under CT guidance and in abdominal subcutaneous white adipose tissue (WAT). Arterial and dialysate samples were collected during warm (∼25°C) and cold exposure (∼17°C), and blood flow was measured by 133xenon washout. During warm conditions, there was increased glucose uptake and lactate release and decreased glycerol release by BAT compared with WAT. Cold exposure increased blood flow, glycerol release, and glucose and glutamate uptake only by BAT. This novel use of microdialysis reveals that human BAT is metabolically active during warm conditions. BAT activation substantially increases local lipolysis but also utilization of other substrates such as glutamate.

[Leptomeningeal metastasis of EGFR (+) lung adenocarcinoma: a case report]. / EGFR (+) akciger adenokarsinomunun leptomeningeal metastazi: Olgu sunumu.

Leptomeningeal metastasis is a very rare complication of infiltration of leptomeninges and subarachnoid space with malignant cells. It is an indicator of poor prognosis. Its incidence is 3.8% in non-small cell lung carcinoma (NSCLC). This rate is higher in patients with epidermal growth factor receptor (EGFR) mutation. Brain magnetic resonance imaging (MRI) is the first choice in the diagnosis. The diagnosis of leptomeningeal metastasis is difficult and often bypassed because it is rare and does not cause gross mass lesions such as brain metastasis. Systemic chemotherapy, intrathecal therapy, cranial radiotherapy and targeted treatment agents are an option in the treatment. It has been shown that targeted therapies can be promising because of the ability to switch to cerebrospinal fluid in appropriate patients. We present the case with EGFR positive lung adenocarcinoma whit leptomeningeal metastasis (LM) due to its rarity, difficulty in diagnosis and its association with EGFR mutation.