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Purpose: Invasive micropapillary carcinoma (IMPC) of the breast is known for its high metastatic potential, but the definition of pure and mixed IMPC remains unclear. This retrospective cohort study aims to investigate the prognostic significance of the micropapillary component ratio and the expression of critical molecules of epithelial–mesenchymal transition (EMT), including E-cadherin (E-cad), N-cadherin (N-cad), CD44s, and β-catenin (β-cat), in distinguishing between pure and mixed IMPCs. Methods: We analyzed 100 cases of locally advanced IMPC between 2000 and 2018 and excluded patients who received neoadjuvant chemotherapy. Pure IMPC was defined as having a micropapillary component of over 90%. A comprehensive recording of prognostic parameters was conducted. The IMPC areas were analyzed using the immunohistochemical (IHC) staining method on the microarray set for pure and mixed IMPC patients. Pearson's chi-square, Fisher's exact tests, Kaplan–Meier analysis, and Cox proportional hazards analysis were employed. Results: The comparative survival analysis of the entire group, based on overall survival (OS) and disease-free survival (DFS), revealed no significant difference between the pure and mixed groups (P = 0.480, HR = 1.474 [0.502–4.325] and P = 0.390, HR = 1.587 [0.550–4.640], respectively). However, in the pure IMPC group, certain factors were found to be associated with a higher risk of short survival. These factors included skin involvement (P = 0.050), pT3&4 category (P = 0.006), a ratio of intraductal component (> 5%) (P = 0.032), and high-level expression of N-cad (P = 0.020). Notably, none of the risk factors identified for short OS in pure IMPC cases were observed as significant risks in mixed cases and vice versa. Furthermore, N-cad was identified as a poor prognostic marker for OS in pure IMPCs (P = 0.002). Conclusion: The selection of a 90% ratio for classifying pure IMPCs revealed significant differences in certain molecular and prognostic parameters between pure and mixed groups. Notably, the involvement of N-cadherin in the epithelial–mesenchymal transition (EMT) process provided crucial insights for predicting OS and DFS while also distinguishing between the two groups. These findings strongly support the notion that the pure IMPC subgroup represents a distinct entity characterized by unique molecular characteristics and behavioral patterns. [ABSTRACT FROM AUTHOR]

Background: Post-cardiac arrest syndrome (PCAS) after out-of-hospital cardiac arrest (OHCA) poses significant challenges due to its complex pathomechanisms involving inflammation, ischemia, and reperfusion injury. The identification of early available prognostic indicators is essential for optimizing therapeutic decisions and improving patient outcomes. Methods: In this retrospective single-center study, we analyzed real-world data from 463 OHCA patients with either prehospital or in-hospital return of spontaneous circulation (ROSC), treated at the Cardiac Arrest Center of the University Hospital of Marburg (MCAC) from January 2018 to December 2022. We evaluated demographic, prehospital, and clinical variables, including initial rhythms, resuscitation details, and early laboratory results. Statistical analyses included logistic regression to identify predictors of survival and neurological outcomes. Results: Overall, 46.9% (n = 217) of patients survived to discharge, with 70.1% (n = 152) achieving favorable neurological status (CPC 1 or 2). Age, initial shockable rhythm, resuscitation time to return of spontaneous circulation (ROSC), and early laboratory parameters like lactate, C-reactive protein, and glomerular filtration rate were identified as independent and combined Early Predictors of Outcome and Survival (EPOS), with high significant predictive value for survival (AUC 0.86 [95% CI 0.82–0.89]) and favorable neurological outcome (AUC 0.84 [95% CI 0.80–0.88]). Conclusion: Integration of EPOS into clinical procedures may significantly improve clinical decision making and thus patient prognosis in the early time-crucial period after OHCA. However, further validation in other patient cohorts is needed.

BACKGROUND: Male breast cancer (MBC) accounts for one percent of all breast cancers. Due to the lack of awareness and routine screening programs, most patients present with systemic disease at the time of diagnosis with low overall survival. OBJECTIVES: This study aims to investigate the prognostic factors of male breast cancer and its correlation with established prognostic parameters and patient outcomes. METHODS: Thirty-eight male breast cancer patients are identified from the MKA Breast Cancer Clinic database, and their corresponding clinical and pathological characteristics are obtained. Cut-off values of 1% and 10% are applied to further classify ER and PR results. RESULTS: Older men are more likely to develop MBC than younger men and are more likely to have spread to axillary lymph nodes. Invasive ductal carcinoma is a more common histologic type in MBC. All the tested patients have ER and PR positivity. Distant metastasis developed in 17/38 (44.7%) patients. Bone metastasis is seen commonly in metastatic MBC. CONCLUSIONS: According to our cohort, MBC is seen in older males, presents in later stages, and shows hormone receptor positivity and a tendency to bone involvement. MBC is a heterogenous but distinct biological entity requiring a specific clinical and pathological approach. [ABSTRACT FROM AUTHOR]

Recent studies have demonstrated that the combination of Cyclin-Dependent Kinase 4/6 Inhibitor (CDK4/6i) and endocrine therapy (ET) is more effective than ET alone and significantly improves progression-free survival (PFS) and overall survival (OS) in patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor-2 negative (HER2-) breast cancer (BC). Palbociclib is the first CDK4/6i approved for use, and its clinical advantages have been shown. However, 30% of patients will continue to develop secondary drug resistance. Therefore, exploring the parameters that can predict the efficacy of Palbociclib and developing a clinical prediction model is essential for evaluating the prognosis of patients. [ABSTRACT FROM AUTHOR]

Prognostic parameters are crucial in the choice of treatment in Graves' disease (GD), thus,these parameters may not be easily achievable in all situations. However hematological parameters is important in inflammation and easy to obtain. In this study we aimed to elucidate whether these parameters could determine the prognosis in patients with Graves Disease. This retrospective analysis consisted of 114 individuals with a diagnosed with GD. The enrolled patients were treated with anti-thyroid drugs for an average of 14 months and the mean follow-up period after treatment discontinuation was 17.4 months. After the follow-up period subjects have been segmented to 2 groups as: Group 1 relapsed (n:61) and Group 2 non-relapsed (n:53). The neutrophil to lymphocyte ratio (NLR) of the relapsing individual was statistically significantly higher compared to other group, while the eosinophil to monocytes ratio (EMR) was lower. In the multiregression analysis, both parameters were found to be independent risk factors in predicting relapse [(OR=3.1, p:0.026 for NLR) (OR=1.5, p [Med-Science 2022; 11(4.000): 1436-40]

· Definitions for occult hypoperfusion in trauma (tOH) differ markedly in the literature. · The described impact of tOH on outcome differs between studies, and it´s role in trauma remains unclear. · A systematic review was performed to identify utilized criteria for tOH in recent literature. · The following definition for tOH is proposed: Lactate > 2 mmol/l or BE 〈-3 mmol/l plus SBP 〉 90 mmHg and PR < 120 bpm. Occult hypoperfusion (OH) entails inadequate tissue oxygenation in the presence of normal vital signs. Numerous studies have demonstrated that this phenomenon is associated with impaired outcome and increased mortality, however definitions of OH differ between studies. The aim of the current study was to identify and evaluate the published definitions of the term 'occult hypoperfusion' in trauma (tOH). A review of literature was performed using the Medline database. The following MeSH terms have been used: occult hypoperfusion, severe trauma, polytrauma, resuscitation. Clinical studies on OH were included and utilized definitions have been compared. A predefined data-interpretation process was applied to create an integrative definition for tOH. A total of 43 publications used the term OH. A definition of OH was provided in 16 manuscripts. A pooled mean number of participants of 729 (SD: 1158) was found per study. The majority of manuscripts combine multiple parameters for inadequate tissue oxygenation and normal vital signs to define OH in trauma. In 12 manuscripts, specific cut-off values for hemodynamic parameters (SBP/PR/UP) and in 11/16 papers exact metabolic thresholds (lactate/B.E) were defined. The following definition best integrates definitions in current literature: Lactate > 2 mmol/l or BE <-3 mmol/l (to define inadequate oxygenation) plus SBP > 90 mmHg and PR < 120 bpm (to define normal macroperfusion). The current systematic review demonstrates that definitions of occult hypoperfusion in trauma differ in the literature. The following comprehensive definition for (tOH) is proposed: Lactate > 2 mmol/l or BE <-3 mmol/l plus SBP > 90 mmHg and PR < 120 bpm. This recommendation appears to represent current literature on tOH and may improve the identification of trauma patients at risk for OH and related complicated courses. Further validation studies are required to demonstrate the clinical role of tOH and the proposed definition. [ABSTRACT FROM AUTHOR]

Prognostic parameters are crucial in the choice of treatment in Graves' disease (GD), thus,these parameters may not be easily achievable in all situations. However hematological parameters is important in inflammation and easy to obtain. In this study we aimed to elucidate whether these parameters could determine the prognosis in patients with Graves Disease. This retrospective analysis consisted of 114 individuals with a diagnosed with GD. The enrolled patients were treated with anti-thyroid drugs for an average of 14 months and the mean follow-up period after treatment discontinuation was 17.4 months. After the follow-up period subjects have been segmented to 2 groups as: Group 1 relapsed (n:61) and Group 2 non-relapsed (n:53). The neutrophil to lymphocyte ratio (NLR) of the relapsing individual was statistically significantly higher compared to other group, while the eosinophil to monocytes ratio (EMR) was lower. In the multiregression analysis, both parameters were found to be independent risk factors in predicting relapse [(OR=3.1, p:0.026 for NLR) (OR=1.5, p<0.001 for EMR)]. In addition, a value of 0.17 EMR had 70% sensitivity and 80% specificity in determining recurrence. EMR was found to be an independent predictor of prognosis with high specificity. The calculation of EMR before initiating treatment could provide beneficial outcomes for the choice of treatment in patients with GD. [ABSTRACT FROM AUTHOR]

Abstract Background The aim of this retrospective study was to evaluate commonly used clinical and OCT-morphological parameters, including perifoveal pseudocysts, as prognostic factors for postoperative outcome after macular hole surgery in a retinal referral clinic in North Rhine-Westphalia, Germany. Methods and material This was a retrospective analysis of all patients who underwent surgery because of idiopathic MH between 2011 and 2017 in Augenklinik Tausendfensterhaus, Duisburg, Germany. Statistical evaluation of clinical and OCT-based parameters, including the areas of intraretinal pseudocysts, was conducted. The main statistical outcomes were surgical success and visual acuity. Only parameters with a highly significant correlation to the outcome parameters (postoperative visual acuity (VA); surgical success) in univariate analysis were entered in linear and logistic regression analyses. Results A total of 189 eyes of 178 patients (71.4% female; mean age 67.5 ± 8.2 a) who underwent surgery because of MH were included. The overall closure rate was 86.8%. The mean best corrected VA increased from 0.7 ± 0.3 logMAR before surgery to 0.5 ± 0.3 logMAR (p

Synovial sarcoma (SS) is a rare mesenchymal entity that represents 5–10% among soft tissue sarcomas (STS). Primary renal synovial sarcoma (PRSS) is an uncommon, rapidly growing tumor, with potential metastatic dissemination. The main prognostic factors of PRSS include tumor size and histologic grade, while translocation t (X; 18) (p11.2; q11.2) (fusion of SYT gene -chromosome 18- with SSX genes (1, 2 or 4)-chromosome X) is the most common pathognomonic sign. Aggressive surgical resection of the tumor along with concomitant regional lymphadenectomy is the treatment of choice for PRSS, while additional en bloc resection of the adjacent affected organs is often performed. To date, the role of preoperative or postoperative chemotherapy remains equivocal. The prognosis of patients with PRSS is poor, as the 5-year survival rate is only 20–30% and further deteriorates when a high mitotic activity is detected. Local recurrence even after complete R0 surgical excision remains the most frequent cause of death. The aim of this review was to meticulously discuss clinical features, histogenesis, and morphological and immunochemical findings of PRSS, while the role of current diagnostic and therapeutic management of this aggressive neoplasm was emphasized. [ABSTRACT FROM AUTHOR]

Endometrioid endometrial carcinomas (EEC) are common malignant lesions of the female genital tract, with incidence and risk factors that raise issues to improve histopathological prognostic factors. The study included 50 EEC cases, for which the clinicopathological parameters represented by age, risk factors, tumor grade, histological differences, invasion pattern, tumor stage and association of endometrial hyperplasia were analyzed statistically. The results indicated the predominance of EEC in the 7th decade of life, with associated risk factors (78%), more frequently well differentiated (52%), with no other specifications related to differentiation (NOS, 60%), with irregular invasion pattern (66%) in<50% of the myometrial wall (48%). Irregular pattern, microcystic, elongated, and fragmented (MELF) pattern and myoinvasion associated with vascular invasion (MVI) pattern were significantly associated with high grade and advanced stage tumors. With the exception of EEC-NOS and squamous differentiation, all other tumors were associated with low grade (G1). In this study there was a tendency to associate the age group of 60-69 years with the presence of endometrial hyperplasia and with high grade and advanced stage. Apart from the high grade and advanced stage, in the aggressive profile of the EEC can be included as the clinicopathological parameters the 7th decade of life and the irregular, MELF and MVI invasion patterns. [ABSTRACT FROM AUTHOR]

Background: Malignant solid pseudopapillary neoplasms (SPN) are rare tumor entities of the pancreas. The prognosis for SPN is generally excellent, although some tumors have malignant potential and tend to metastasize or relapse. Objective: The aim was to investigate whether there are histopathological or surgical risk factors that enable the biological potential of SPN to be estimated. Patients and methods: Data from patients with SPN treated in two large German pancreas centers from 2009 to 2018 were evaluated with respect to the occurrence of SPN, surgical management, histopathological tumor characteristics and the postoperative outcome. Results: A total of 22 patients with SPN (17 women, 5 men) were operated on. The median age of the patients was 37 years (range 19–69 years). At the time of surgery 20 patients showed tumor growth limited to the pancreas. A female patient with recurrence of an externally resected SPN had lymph node involvement. Another female patient had a hepatic metastatic recurrence (Union Internationale contre Cancer (UICC) stage IV) of an externally resected SPN. Although all patients survived recurrence-free during the follow-up, this patient developed liver metastases again. The survival rate up to the end of the follow-up (median 43 months; range 1–132 months) of this study was 100%. Conclusion: There is a lack of knowledge of the possible parameters that can be used to predict the biological behavior of SPN. Apart from an increased likelihood of recurrence after resection of an SPN recurrence, no clear risk factors could be identified in the examined patient collective that could indicate an increased malignant potential and a possibly poorer outcome. Only a radical surgical resection with lymphadenectomy enables a reliable assessment of the tumor stage and the removal of possibly affected lymph nodes, which could be the cause of a recurrence if left intact. [ABSTRACT FROM AUTHOR]

Background: The aim of this retrospective study was to evaluate commonly used clinical and OCT-morphological parameters, including perifoveal pseudocysts, as prognostic factors for postoperative outcome after macular hole surgery in a retinal referral clinic in North Rhine-Westphalia, Germany.Methods and Material: This was a retrospective analysis of all patients who underwent surgery because of idiopathic MH between 2011 and 2017 in Augenklinik Tausendfensterhaus, Duisburg, Germany. Statistical evaluation of clinical and OCT-based parameters, including the areas of intraretinal pseudocysts, was conducted. The main statistical outcomes were surgical success and visual acuity. Only parameters with a highly significant correlation to the outcome parameters (postoperative visual acuity (VA); surgical success) in univariate analysis were entered in linear and logistic regression analyses.Results: A total of 189 eyes of 178 patients (71.4% female; mean age 67.5 ± 8.2 a) who underwent surgery because of MH were included. The overall closure rate was 86.8%. The mean best corrected VA increased from 0.7 ± 0.3 logMAR before surgery to 0.5 ± 0.3 logMAR (p < 0.0001). While several clinical and OCT-based parameters as well as calculated indices showed a significant correlation with the outcome measures, the regression analysis showed that the minimum linear diameter was the only parameter that both predicted surgical success (p = 0.015) and was correlated with postoperative VA (p < 0.001).Conclusion: The minimum linear diameter serves as an easily assessed prognostic factor with the best predictive properties. This result is of great importance for clinical practice, as it simplifies the postsurgical prognosis. [ABSTRACT FROM AUTHOR]

Introduction:Colorectal carcinoma (CRC) is one of the most important causes of cancer-related deaths, and its incidence has been increasing in recent years. Considering the high mortality rates, new therapeutic targets are needed to improve survival in advanced disease. HER-2 is a member of the Epidermal Growth Factor Receptor family. Overexpression of HER-2 is related to malignant transformation, apoptosis and increased proliferation. In this study, the frequency of HER-2 expression in CRC and its relationship with prognostic parameters were examined.Methods:A total of 123 colorectal resection cases diagnosed as CRC in 2015-2016 in the Pathology Department of Haseki Research and Training Hospital were included in the study. Clinicopathological prognostic parameters were evaluated. Immunohistochemical staining of HER-2 was performed on slides obtained from selected paraffin blocks. The results of staining were scored as 0, 1+, 2+ or 3+. For statistical analysis, HER-2 scores of 0 and 1+ were considered as negative, (2+) scores as equivocal and (3+) scores as positive.Results:3+, 2+ and 1+ immunoreactivity (strong, medium and weak intensity of membrane staining, respectively) was detected in 13%, 21% and 16% of cases, respectively. When we compared the results of HER-2 status with the clinicopathological parameters, we found a correlation between HER-2 and distant metastasis. The distant metastasis rate was higher in HER-2-positive patients than in equivocal and negative patients. There was no significant relationship between HER-2 expression and other clinicopathological parameters we evaluated.Conclusion:Considering these HER-2 expression levels which not scarce, therapies targeting the HER-2 receptor can be a promising part of treatment regimes, although they are not the main treatment option in CRC.

Mucinous adenocarcinoma (MAC) has a worse prognosis than do classical adenocarcinoma. Increased tumor budding (TB) and lower number of tumor infiltrating lymphocytes (TIL) negatively affect prognosis in classical adenocarcinoma. In this study, we investigated whether TB and TIL values influenced prognosis in patients with MAC. Forty-five patients diagnosed with MAC between 2011 and 2015 were included in the study. TB and TIL values of the patients were re-evaluated. In assessing TIL, lymphocytes that infiltrated the stroma and tumor were evaluated separately. The effects of these findings on the prognostic parameters and the disease-free survival (DFS) and overall survival (OS) were evaluated. The mean follow-up period was 26.07 months (min: 1 max: 82, SD:24.86), OS 28.04 months (min: 1 max: 82 SD:24.81). The results between TB and OS (p = 0.066) and DFS (p = 0.205) were not significant. The relationship between sTIL and OS (p = 0.367) and DFS (p = 0.949) was not significant. The relationship between iTIL and OS (p = 0.502) and DFS (p = 0.870) was not significant. The only significant difference between clinicopathological parameters and TB, sTIL, and iTIL was between grade and TB (p = 0.016). In terms of clinicopathologic parameters, stage with OS (p = 0.008) and DFS (0.016), lymph node metastasis with OS (p = 0.010) and DFS (0.008), LVI (lymph vascular invasion) with OS (p = 0.034) and DFS (p = 0.015), PNI (perineural invasion) and DFS (p = 0.007) was significant. In this study, the effect of TB and TIL on the prognosis of MAC was investigated. We found that these data did not correlate with the prognosis of the tumor and the prognostic parameters (LVI, PNI, lymph node metastasis, stage) in the staging system remained as the gold standard for predicting prognosis. [Med-Science 2019; 8(4.000): 896-900]

Background: Post-cardiac arrest syndrome (PCAS) after out-of-hospital cardiac arrest (OHCA) poses significant challenges due to its complex pathomechanisms involving inflammation, ischemia, and reperfusion injury. The identification of early available prognostic indicators is essential for optimizing therapeutic decisions and improving patient outcomes., Methods: In this retrospective single-center study, we analyzed real-world data from 463 OHCA patients with either prehospital or in-hospital return of spontaneous circulation (ROSC), treated at the Cardiac Arrest Center of the University Hospital of Marburg (MCAC) from January 2018 to December 2022. We evaluated demographic, prehospital, and clinical variables, including initial rhythms, resuscitation details, and early laboratory results. Statistical analyses included logistic regression to identify predictors of survival and neurological outcomes., Results: Overall, 46.9% (n = 217) of patients survived to discharge, with 70.1% (n = 152) achieving favorable neurological status (CPC 1 or 2). Age, initial shockable rhythm, resuscitation time to return of spontaneous circulation (ROSC), and early laboratory parameters like lactate, C-reactive protein, and glomerular filtration rate were identified as independent and combined Early Predictors of Outcome and Survival (EPOS), with high significant predictive value for survival (AUC 0.86 [95% CI 0.82-0.89]) and favorable neurological outcome (AUC 0.84 [95% CI 0.80-0.88])., Conclusion: Integration of EPOS into clinical procedures may significantly improve clinical decision making and thus patient prognosis in the early time-crucial period after OHCA. However, further validation in other patient cohorts is needed., Competing Interests: JK received research funding from CytoSorbents; BM received research funding from Abiomed; JK, GC, BS, and BM receive speakers’ honoraria from Abiomed; JK and BM received speakers’ honoraria from Astra Zeneca, BS received speakers’ honoraria from Bayer and GSK. No other authors reported disclosures.The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Julian Kreutz reports a relationship with Abiomed Europe GmbH that includes: speaking and lecture fees. Birgit Markus reports a relationship with Abiomed Europe GmbH that includes: funding grants and speaking and lecture fees. Georgios Chatzis reports a relationship with Abiomed Europe GmbH that includes: speaking and lecture fees. Bernhard Schieffer reports a relationship with Abiomed Europe GmbH that includes: speaking and lecture fees. Julian Kreutz reports a relationship with CytoSorbents Europe GmbH that includes: funding grants. Julian Kreutz reports a relationship with AstraZeneca that includes: speaking and lecture fees. Birgit Markus reports a relationship with AstraZeneca that includes: speaking and lecture fees. Bernhard Schieffer reports a relationship with Bayer AG that includes: speaking and lecture fees. Bernhard Schieffer reports a relationship with GSK that includes: speaking and lecture fees. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Hürthle cells (HC) are characterized by abundant granular eosinophilic cytoplasm containing accumulated dysfunctional mitochondria and large nuclei with prominent nucleoli. Based on the distinct clinicopathologic and molecular characteristics of Hürthle cell neoplasms (HCN), the 2017 Endocrine World Health Organization (WHO) moved to categorizing HCN as a separate group of tumors. Hürthle cell carcinomas (HCC) are now subclassified as minimally invasive, encapsulated angioinvasive, and widely invasive. HCC have a low rate of driver mutations associated with follicular thyroid carcinoma. Instead, these neoplasms are characterized by widespread loss of heterozygosity due to whole-chromosome alterations and a high rate of mitochondrial DNA mutations. Increased understanding of the genomic underpinnings of HCC has translated into improvements in molecular testing of HCN. This review will focus on clinical, cytologic, and histopathologic features of HCN, concentrating on diagnostic challenges and prognostic parameters. In addition, the molecular characteristics and molecular testing of HCN will be reviewed. [ABSTRACT FROM AUTHOR]

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Prospective data about the prognostic value of immune-related adverse events (irAEs) in non-melanoma solid tumours are rare. The prognostic value of irAEs in patients treated with combined radiotherapy and immunotherapy is currently unknown. The prospective non-interventional ST-ICI trial investigates treatment response of tumour patients to anti–programmed cell death-ligand 1 (PD-L1) immune checkpoint inhibitors alone and in combination with radiotherapy and possible predictive markers. Patients undergoing immunotherapy or immunoradiotherapy were surveyed for irAEs. A total of 104 patients were included of whom 29 patients (28%) developed irAEs. Additional radiotherapy was performed in 50 patients (48%). Main tumour entities within the entire cohort were non–small cell lung cancer (NSCLC) (44%) and head and neck squamous cell carcinoma (42%). The rate of irAEs did not differ in patients with and without radiotherapy (p = 0.668). Patients who developed irAEs had longer overall survival (OS) (median: 22.8 months versus 9.0 months without irAEs, p = 0.001) and progression-free survival (PFS) (median: 7.8 months versus 3.2 months without irAEs, p = 0.002). In the subgroup with combined radiotherapy, patients with irAEs also had longer OS (median: 22.8 months versus 7.1 months without irAEs, p = 0.005) and PFS (median: 8.8 months versus 3.0 months without irAEs, p = 0.005). On multivariate analysis only PD-L1 on tumour cells (p = 0.049) and irAEs (p = 0.001) remained independent predictors of OS. The development of irAEs represents a favourable prognostic parameter in patients undergoing immunotherapy and immunoradiotherapy for solid tumours. • ST-ICI prospectively enrolled patients with non-melanoma tumour treated with anti-programmed cell death-ligand 1 (PD-L1). • Immune-related adverse events (irAEs) correlated with improved overall survival and progression-free survival. • Combination of radiotherapy with PD-L1 inhibitors did not increase irAEs. • In the subgroup with radiotherapy irAEs also had a positive prognostic value. [ABSTRACT FROM AUTHOR]

• Necrosis of basal ganglia are the typical MRI finding in survivors of methanol poisoning. • Survivors with toxic brain damage had lower volume of basal ganglia. • Positive correlation between the volume of putamen, markers of severity of poisoning. • Correlation between the basal ganglia volume and the thickness of retinal nerve fibers layer. Basal ganglia lesions are typical findings on magnetic resonance imaging (MRI) of the brain in survivors of acute methanol poisoning. However, no data are available on the association between the magnitude of damaged brain regions, serum concentrations of markers of acute methanol toxicity, oxidative stress, neuroinflammation, and the rate of retinal nerve ganglion cell loss. To investigate the association between MRI-based volumetry of the basal ganglia, retinal nerve fibre layer (RNFL) thickness and prognostic laboratory markers of outcomes in acute methanol poisoning. MRI-based volumetry of putamen, nucleus caudatus and globus pallidus was performed and compared with laboratory parameters of severity of poisoning and acute serum markers of oxidative damage of lipids (8-isoprostan, MDA, HHE, HNE), nucleic acids (8−OHdG, 8−OHG, 5−OHMU), proteins (o-Thyr, NO-Thyr, Cl-Thyr) and leukotrienes (LTC4, LTD4, LTE4, LTB4), as well as with the results of RNFL measurements by optic coherence tomography (OCT) in 16 patients with acute methanol poisoning (Group I) and in 28 survivors of poisoning two years after discharge with the same markers measured within the follow-up examination (Group II). The control group consisted of 28 healthy subjects without methanol poisoning. The survivors of acute methanol poisoning had significantly lower volumes of basal ganglia than the controls. The patients with MRI signs of methanol-induced toxic brain damage had significantly lower volumes of basal ganglia than those without these signs. A positive correlation was found between the volume of putamen and arterial blood pH on admission (r = 0.45; p = 0.02 and r = 0.44; p = 0.02 for left and right putamen, correspondingly). A negative correlation was present between the volumes of putamen and acute serum lactate (r = -0.63; p < 0.001 and r = -0.59; p = 0.01), creatinine (r = -0.53; p = 0.01 and r = -0.47; p = 0.01) and glucose (r = -0.55; p < 0.001 and r = -0.50; p = 0.01) concentrations. The volume of basal ganglia positively correlated with acute concentrations of markers of lipoperoxidation (8-isoprostan: r = 0.61; p < 0.05 and r = 0.59; p < 0.05 for left and right putamen, correspondingly) and inflammation (leukotriene LTB4: r = 0.61; p < 0.05 and r = 0.61; p < 0.05 for left and right putamen, correspondingly). The higher the volume of the basal ganglia, the higher the thickness of the RNFL, with the strongest positive association between global RNFL and the volume of putamen bilaterally (all p < 0.01). In the follow-up markers of oxidative stress and inflammation, only o-Thyr concentration negatively correlated with the volume of putamen bilaterally (r = –0.39; p < 0.05 and r = –0.37; p < 0.05 for left and right putamen, correspondingly). In survivors of acute methanol poisoning with signs of toxic brain damage, the magnitude of affected areas correlated with acute parameters of severity of poisoning, markers of oxidative stress and neuroinflammation. There was a positive association between the basal ganglia volume and the thickness of RNFL, making OCT an important screening test and MRI-based volumetry the confirmative diagnostic method for the detection of CNS sequelae of methanol poisoning. [ABSTRACT FROM AUTHOR]

Background: Drowning is the second leading cause of unnatural death in childhood worldwide. More than half of the drowned children, who were in need of cardiopulmonary resuscitation (CPR) at the scene suffered from lifelong neurological sequelae. There are few data about prognostic predictors in the pediatric population of drowning victims. The objective of the study was to assess incident characteristics, prognostic parameters, and long-term outcome of children recovering from a drowning incident. Methods: We carried out a retrospective analysis of data of the cohort of pediatric cases (age 0-18) of drowning victims admitted in the years 2000-2015 to the emergency room/intensive care unit/pediatric ward at the University Children's Hospital of Zurich, Switzerland. Outcome was classified by the Pediatric Cerebral Performance Category Scale (PCPCS). New subcategories of severity for known prognostic parameters have been defined. A correlation analysis was performed between the subcategories of the prognostic parameters and the PCPCS. Results: A total of 80 patients were included in the analysis. Of these, 64% were male, most of the patients were at the age of 0-5 years. More than 80% of the patients were unattended at a public or private pool when the drowning incident happened. In all, 61% (n = 49) needed cardiopulmonary resuscitation (CPR). Of the resuscitated children, 63% showed good to mildly impaired long-term outcome (PCPCS 1-3). Furthermore, 15% (n = 12) were transferred to rehabilitation. Seven children died during the hospital stay and another four died due to complications in the ten years following the incident. The newly defined subcategories of the parameter submersion time, Glasgow Coma Scale (GCS) at time of admission, body temperature at time of admission, blood pH, blood glucose, and blood lactate level correlated significantly with the PCPCS. Conclusions: Supervision of children, especially boys of the age 0-5 years, next to public or private pools is most important for prevention of drowning incidents in Switzerland. Cardiopulmonary resuscitation done by trained staff leads to a better long-term outcome. Medical decision making in severe cases of drowning should consider submersion time, GCS at time of admission, body temperature at time of admission, blood pH, blood glucose, and blood lactate levels, as these parameters correlate with long-term outcome. [ABSTRACT FROM AUTHOR]

Aim: To determine the relationship between established prognostic markers and Ki67 proliferative index in breast cancer patients and investigate variations of prognostic parameters between material types (tru-cut biopsy or resection). Material and Methods: Breast cancer cases reported in our laboratory between July 2015 and December 2019, as well as estrogen receptor (ER), progesterone receptor (PR), CerbB2, Ki-67 staining results, tumor type, histologic grade, tumor size, lymph node metastasis status parameters were obtained from the automation system. Tru-cut biopsy and resection materials were evaluated and the parameters were compared. Results: 726 materials taken from 571 adult patients were included in this study. 297 (40.9%) of the cases were evaluated by tru-cut biopsy and 430 (59.1%) were resection material. The mean ER staining percentage was 86.5 (± 10.36) and it was 61.65 (± 22.84) for PR. Ki-67 proliferative index had an average value of 26.58 (± 17.67). There was no difference between the material types in terms of immunohistochemical markers, whereas there were differences between the two material types in histological grade results. Conclusion: Besides established immunohistochemical prognostic markers, Ki67 proliferative index should be utilized in breast cancer cases and determination of histological grade in tru-cut biopsies is valuable for the clinical management of the tumor. [ABSTRACT FROM AUTHOR]

Introduction: Colorectal carcinoma (CRC) is one of the most important causes of cancer-related deaths, and its incidence has been increasing in recent years. Considering the high mortality rates, new therapeutic targets are needed to improve survival in advanced disease. HER-2 is a member of the Epidermal Growth Factor Receptor family. Overexpression of HER-2 is related to malignant transformation, apoptosis and increased proliferation. In this study, the frequency of HER-2 expression in CRC and its relationship with prognostic parameters were examined. Methods: A total of 123 colorectal resection cases diagnosed as CRC in 2015-2016 in the Pathology Department of Haseki Research and Training Hospital were included in the study. Clinicopathological prognostic parameters were evaluated. Immunohistochemical staining of HER-2 was performed on slides obtained from selected paraffin blocks. The results of staining were scored as 0, 1+, 2+ or 3+. For statistical analysis, HER-2 scores of 0 and 1+ were considered as negative, (2+) scores as equivocal and (3+) scores as positive. Results: 3+, 2+ and 1+ immunoreactivity (strong, medium and weak intensity of membrane staining, respectively) was detected in 13%, 21% and 16% of cases, respectively. When we compared the results of HER-2 status with the clinicopathological parameters, we found a correlation between HER-2 and distant metastasis. The distant metastasis rate was higher in HER-2-positive patients than in equivocal and negative patients. There was no significant relationship between HER-2 expression and other clinicopathological parameters we evaluated. Conclusion: Considering these HER-2 expression levels which not scarce, therapies targeting the HER-2 receptor can be a promising part of treatment regimes, although they are not the main treatment option in CRC. [ABSTRACT FROM AUTHOR]

Currently, about 50% of patients with metastatic renal cell carcinoma (mRCC) receive a second-line therapy. Therefore, the choice at each subsequent treatment line remains an important issue. In this retrospective study, we sought to identify pretreatment clinical parameters that could predict the likelihood of a patient receiving a second-line therapy. One hundred and sixty-one mRCC patients who received targeted therapy were evaluated. Descriptive statistics, Kaplan–Meier overall survival (OS), Cox regression, and binary logistic regression models were used for data analysis. Second-line therapy was given to 105 patients (65%). Patients with grade 1 tumor received second-line therapy more frequently than those with grade 2/3 tumors (P = 0.03). Only tumor grade was significantly different between patients receiving, or not receiving, second-line treatment. Median OS was significantly superior in patients receiving second-line therapy (32 versus 14 months; P = 0.007; hazard ratio [HR], 1.75; P = 0.008), patients with grade 1 tumors (130 versus 29 months in G2/3 tumors; HR, 3.85; P = 0.009), and in patients without early tumor progression (41 versus 11 months; HR, 5.04; 95% confidence interval [CI], 3.06–8.31; P < 0.001). In binary logistic regression, we identified early progression to be significantly associated with a higher probability of not receiving a second-line therapy (HR, 2.50; 95% CI, 1.01–6.21; P = 0.048). This study hypothesizes that pretreatment grade and early progression are predictive parameters for the selection of patients for second-line therapy.

Objective: Primary gastrointestinal non-hodgkin lymphomas (PGI-NHL) are uncommon diseases with treatment modalities including chemotherapy surgery, and radiotherapy. Our aim is to analyze the demographic and clinical features and treatment results of PGI-NHL. Materials and Methods: 286 patients diagnosed with lymphoma who referred to Ataturk University Medical Faculty Hospital between July 2001 and April 2014 were surveyed retrospectively and 22 (7.6%) PGI-NHL cases whose primary lesions were in gastrointestinal system were included. Results: Mean age was 47 (min.25- max.77) and 14 (63.6%) of them were men. The origin was determined as small intestines (50%), stomach (31.8%) and colon (18.2%), respectively The most common complaint and pathologic subtype were abdominal pain (68.2%) and diffuse large B cell lymphoma (86.4%), respectively. The Lugano Classification was as follows: stage 1 (18.2%), stage 2 (59.1%), and stage 4 (22.7%). Surgery and chemotherapy were administered to 40.9% of patients. Complete and partial response and disease progression were established in 72.1%, 4.5% and 13.6% of the patients, respectively. Mean survival time was 99.6±16 months. Mean overall survival time was determined significantly longer in small bowel group than gastric group (119±15 vs. 50±24 months) (p=0.039). Age, gender Eastern Cooperative Oncology Group performance status, International Prognostic Index, stage, histological type, tumor size, LDH level, albumin level, Hemoglobin level and treatment options were not associated with survival. Conclusion: Demographic and clinical characteristics of our series were similar with Middle Eastern and African countries. Optimal treatment options or prognostic factors for PGI-NHL are not clear. There is a need for randomized prospective studies including large number of patients and long follow-up period. [ABSTRACT FROM AUTHOR]

Background and Aims: Advances in the diagnosis and treatment of multiple myeloma (MM), place increasing demands on accurate stratification of patients as the starting point for optimal individualized therapy. The present study focused on assessing the association between HLC levels and the HLC-r to parameters of MM activity, prognosis and tumor mass volume.The objective was to assess the correlation of immunoglobulin (Ig), heavy/light chain (HLC) pairs (IgG-κ and-λ, IgA-κ and -λ HLC) and the ratio of monoclonal involved-HLC (i-HLC) to polyclonal uninvolved (u-HLC) Ig concentrations assessed by the HevyliteTM method with the free light chain κ/λ ratio (FLC-r), selected prognostic laboratory parameters i.e. Hb, platelets, albumin, β2-microglobulin (β2-M), Ca, lactate dehydrogenase (LDH), creatinine and the Durie-Salmon (D-S) and International Staging System (ISS), stages (1-3) for MM. Methods: HevyliteTM assays were done on the sera of 132 MM patients at the time of diagnosis (IgG 94, IgA 38). HLC-r was calculated in the case of i-HLC-κ from the i-HLC-κ/u-HLC-λ ratio and for i-HLC-λ from the i-HLC-λ/u-HLC-κ ratio. D-S and ISS stages were evenly distributed. Results: Md IgG-κ HLC-r was 64.8 (2.7-2222) and of IgG-λ HLC-r 49.6 (0.7-465.1), in the case of IgA-κ, Md HLC-r was 408.9 (3.4-3966) and for IgA-λ HLC-r the Md was 180.0 (0.1-3110). Normal levels of HLC pairs and HLC-r did not always rule out the diagnosis of MM. HLC-r correlated with FLC-r in IgG (r = 0.244, P = 0.018), but not in the IgA type. For IgG, HLC-r values were significantly different in patients with abnormal vs normal levels of Hb (P < 0.0001), albumin (P < 0.043), β2-M (P < 0.0001) and creatinine (P = 0.034) but not thrombocyte count, Ca or LDH. For the IgA isotype, we found a significant difference in HLC-r values only for thrombocyte count (P = 0.026) and β2-M (P = 0.016) but not for Hb, albumin, Ca, LDH or creatinine. For the IgG isotype there was a significant relationship of HLC-r index to stages 1-3 (P = 0.038) and substage A vs B (P = 0.048) according to D-S, and with high significance to stages 1-3 according to ISS (P = 0.005) and between stages 1 vs 3 (P = 0.001). For the IgA isotype, we found significant differences in HLC-r only between stages 1-3 (P = 0.025) according to D-S but not in the case of ISS. There were no significant correlations between i-HLC Ig levels and D-S or ISS stages in both IgG-κ and λ and IgA-κ and λ. Exceptions were significant differences for stages 1 vs 3 (P = 0.012) and 2 vs 3 (P = 0.017) for the IgG-λ isotype. There were no correlations of the HLC-r and u-HLC levels for either D-S or ISS stratifications in all HLC isotypes. Conclusion: We found a significant positive contribution of HLC-r using the i-HLC/u-HLC ratio even in the case of i-HLC-λ i.e. i-HLC-λ/u-HLC-κ. Variable results for the relationship of important laboratory parameters and D-S and ISS stratifications (stage 1-3) to HLC-r values in IgG and IgA isotypes make sep

Background: Drowning is the second leading cause of unnatural death in childhood worldwide. More than half of the drowned children, who were in need of cardiopulmonary resuscitation (CPR) at the scene suffered from lifelong neurological sequelae. There are few data about prognostic predictors in the pediatric population of drowning victims. The objective of the study was to assess incident characteristics, prognostic parameters, and long-term outcome of children recovering from a drowning incident. Methods: We carried out a retrospective analysis of data of the cohort of pediatric cases (age 0–18) of drowning victims admitted in the years 2000–2015 to the emergency room/intensive care unit/pediatric ward at the University Children’s Hospital of Zurich, Switzerland. Outcome was classified by the Pediatric Cerebral Performance Category Scale (PCPCS). New subcategories of severity for known prognostic parameters have been defined. A correlation analysis was performed between the subcategories of the prognostic parameters and the PCPCS. Results: A total of 80 patients were included in the analysis. Of these, 64% were male, most of the patients were at the age of 0–5 years. More than 80% of the patients were unattended at a public or private pool when the drowning incident happened. In all, 61% (n = 49) needed cardiopulmonary resuscitation (CPR). Of the resuscitated children, 63% showed good to mildly impaired long-term outcome (PCPCS 1–3). Furthermore, 15% (n = 12) were transferred to rehabilitation. Seven children died during the hospital stay and another four died due to complications in the ten years following the incident. The newly defined subcategories of the parameter submersion time, Glasgow Coma Scale (GCS) at time of admission, body temperature at time of admission, blood pH, blood glucose, and blood lactate level correlated significantly with the PCPCS. Conclusions: Supervision of children, especially boys of the age 0–5 years, next to public or private pools is most important for prevention of drowning incidents in Switzerland. Cardiopulmonary resuscitation done by trained staff leads to a better long-term outcome. Medical decision making in severe cases of drowning should consider submersion time, GCS at time of admission, body temperature at time of admission, blood pH, blood glucose, and blood lactate levels, as these parameters correlate with long-term outcome.

Gastric carcinomas are frequent tumors with variable growth patterns that may interfere with the evaluation of histopathological prognostic parameters of the lesions. In this study we analyzed the incidence and statistical relation of histological growth patterns depending on the prognostic parameters of gastric carcinomas for 95 cases. Pure forms were present in 82.2% of cases, from which more frequent subtypes were low grade tubular carcinomas and poorly cohesive with signet-ring cells carcinomas. Mixed forms were present in 17.8% of cases, with the highest incidence of tumors containing well differentiated tubular carcinoma and poorly differentiated papillary carcinoma areas. Analysis of the identified types and subtypes in relation to the histological prognostic parameters indicated significant differences regarding the tumor stage, the mixed subtypes being more frequent in advanced stages. Although mixed subtypes were more commonly associated with vascular and perineural invasion, the aspects were statistically insignificant. Together with tumor stage, the lymphovascular and/or perineural invasion should be taken into consideration as prognostic indicators in the postoperative management of gastric cancer. [ABSTRACT FROM AUTHOR]

Background: Regional lymph node (LN) metastasis is the single most prognostic factor for oral squamous cell carcinoma (OSCC). An analysis of the prognostic factors is important for predicting prognosis and reducing the mortality in these patients. Objectives: (1) To compare the value of various grading systems in predicting LN metastasis. (2) To evaluate histopathological parameters, which could help in predicting LN metastasis. Materials and Methods: A total of 20 excisional biopsies of OSCCs, were graded according to the four grading systems that is, Broder′s, Jakobsson′s, Anneroth and Hansen′s, and Brynes. We also evaluated various histopathological parameters, which could help in predicting LN metastasis. Results: Grading at the invasive front was most prognostic of LN metastasis. Tumors with total malignancy score ≥8 showed higher incidence of metastases. Conclusion: The histopathological parameters that could help in predicting lymph node metastases (LNM) are keratinization, nuclear pleomorphism (NP), and the pattern of invasion (POI) when assessed at the invasive front. When the whole tumor was considered, histopathological parameters like NP and POI were significant in predicting LNM.

Purpose: Hepatic arterial infusion chemotherapy (HAIC) is an option for patients with liver-predominant metastatic breast cancer (LMBC), when no further systemic treatment is available. But systematic reports are limited. Here we conducted a retrospective analysis of LMBC patients treated at an expert center. Methods: Individual patient data were retrieved from the clinical data base of the West German Cancer Center. Primary endpoints included hepatic response (RECIST), progression-free survival (PFS), overall survival (OS), and toxicity. A score based on LDH, AST, ALT and bilirubine was developed to estimate the hepatic metastasis load. Results: Data from 70 consecutive patients were included. All patients were heavily pretreated (median 7 treatment lines for LMBC). HAIC protocols included mitomycin/5-FU (70%), mitomycin (14.3%), melphalan (12.9%) and 5-FU (7.1%), with selection based on patient characteristics. Partial hepatic remission was obtained as best response in 14 patients (20.0%), stable disease in 27 patients (38.6%), and progressive disease in 29 patients (41.4%). Median PFS and OS from initiation of HAIC were 2 (range 0-10) and 7 months (range 1-37). Mainly hepatic and hematopoietic HAIC-related toxicities were observed; there was no treatment-related death. The hepatic metastasis score effectively separated two prognostic groups: Patients with a score <3 had significantly superior PFS (15 vs 7 weeks, p = 0.017) and OS (12 vs 5 months, p = 0.002). Conclusion: HAIC offers a safe and effective salvage treatment strategy in heavily pretreated patients with LMBC and no further treatment options. The hepatic metastasis score may help to identify patients with sustained clinical benefit. [ABSTRACT FROM AUTHOR]

Objective This study critically evaluates the long-term results of standalone anterior lumbar interbody fusion (ALIF), without use of rhBMP-2, as a therapeutic option for symptomatic patients with degenerative disc disease (DDD). Furthermore, this study intends to identify predictive parameters for anterior lumbar interbody fusion outcome. Methods A retrospective cohort study with additional telephone interview to obtain missing data was performed. All patients who underwent an L4–L5 or L5–S1 ALIF-procedure, or both, in the period between 2006 and 2011 were identified. The medical files of 123 patients with 154 fusion levels were reviewed. All patients were contacted by telephone to gather supplementary and missing information. Pain and functionality scores (Visual Analogue Scale [VAS] and Oswestry Disability Index [ODI]), radiologic (intervertebral disc height, Modic and Pfirrmann classifications), and different clinical parameters were gathered. Results The mean age of the population at surgery was 46.2 years. Overall, 59 female and 64 male patients were included in the study. The mean VAS score for back and leg pain improved significantly ( P < 0.001) with 5 and 4.4 points respectively at 3-year follow-up. Modic-type I changes are associated with a better improvement in VAS score for back pain ( P = 0.026), Pfirrmann-grades IV and V and an intervertebral disc height of less than 5 mm are associated with a better improvement in leg pain (respective P -values: 0.045 and 0.033). Overall, 89% of patients would reconsider the surgical intervention. Conclusions The ALIF technique is a durable treatment option for patients with DDD. This study suggests different predictive parameters for treatment outcome. [ABSTRACT FROM AUTHOR]

ABSTRACT Background The minority of head and neck cutaneous squamous cell carcinomas (SCC) metastasize to regional lymph nodes. The purpose of this study was to describe the clinical outcomes and prognostic factors for patients with node-positive head and neck cutaneous SCC who underwent lymphadenectomy. Methods We conducted a retrospective single center study using the Kaplan-Meier method for the investigation of the overall survival (OS) and locoregional control rates. The Cox proportional hazards model was evaluated to identify prognostic factors. Results The median number of positive lymph nodes from 149 lymphadenectomies was 2 in the neck and 1 in the parotid gland. The 5-year OS and locoregional control rates were 50% and 77%, respectively. OS was worse among older patients (hazard ratio [HR], 1.04; p = .015), immunosuppressed patients (HR, 2.06; p = .034), and patients with a high total lymph node ratio (calculated from the number of positive lymph nodes divided by the total number of nodes; multivariate analysis [MVA]; HR, 1.13; p = .019). Conclusion Low total lymph node ratio is associated with improved outcomes in node-positive head and neck cutaneous SCC. © 2017 Wiley Periodicals, Inc. Head Neck 39: 772-778, 2017 [ABSTRACT FROM AUTHOR]

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Echocardiography is the key tool for the diagnosis and evaluation of aortic stenosis. Because clinical decision-making is based on the echocardiographic assessment of its severity, it is essential that standards are adopted to maintain accuracy and consistency across echocardiographic laboratories. Detailed recommendations for the echocardiographic assessment of valve stenosis were published by the European Association of Echocardiography and the American Society of Echocardiography in 2009. In the meantime, numerous new studies on aortic stenosis have been published with particular new insights into the difficult subgroup of low gradient aortic stenosis making an update of recommendations necessary. The document focuses in particular on the optimization of left ventricular outflow tract assessment, low flow, low gradient aortic stenosis with preserved ejection fraction, a new classification of aortic stenosis by gradient, flow and ejection fraction, and a grading algorithm for an integrated and stepwise approach of artic stenosis assessment in clinical practice. [ABSTRACT FROM AUTHOR]

Background: Pulmonary metastases occur in 10-20% of patients with colorectal cancer and significantly influence long-term survival. In this study, the immunological architecture of colorectal lung in comparison to liver metastases and its impact on patient survival were examined. Methods: Specimens of patients with colorectal lung and liver metastases were stained for HE, CD4, CD8, CD20, CD68 and CD45RO. Besides histomorphological evaluation, immunohistochemical stainings were analyzed for the respective cell numbers separately for tumor area, infiltrative margin and distant lung or liver stroma. These findings were correlated with clinical data and patient outcome. Results: In colorectal lung (n = 69) in comparison to liver (n = 222) metastases, the immunological focus is located in the tumor region. A high CD4 + cell infiltration of this area is associated with prolonged survival of patients after resection of colorectal lung metastases [103 ± 33 (high) vs. 37 ± 6 months (low); p = 0.0246]. Patients who were treated with preoperative chemotherapy did not show differences in immune infiltrates compared to chemotherapy-naïve patients. Conclusion: Colorectal lung and liver metastases showed a distinct immunological architecture. A dense cell infiltration of colorectal lung metastases by CD4 + cells was related to prolonged patient survival. Preoperative chemotherapy did not influence cellular immune infiltrates. [ABSTRACT FROM AUTHOR]

The present study aimed to examine hypoxiainducible factor (HIF)-1α expression and its association with glucose uptake in invasive breast cancer. In addition, connections between glucose uptake and several other prognostic parameters of breast cancer were studied. Between August 2013 and April 2015, 92 patients with biopsy-diagnosed breast cancer were subjected to 18F-fluorodeoxyglucose positron emission tomography/computed tomography. The primary tumor and nodal maximum standardized uptake values (SUVmax) were recorded, and HIF-1α expression and clinical parameters, including tumor mass, estrogen receptor (ER) and progesterone receptor (PgR) levels, human epidermal growth factor receptor-2 (HER-2), Ki-67 index, grade and histology, were analyzed. SUVmax was compared with clinicopathological parameters and HIF-1α expression. The median SUVmax values of the ER-negative and PgR-negative tumors were significantly increased compared with ER and PgR-positive tumors, respectively (P=0.004 and P=0.008). SUVmax differed significantly between the T2 and T3 tumors and the T1 tumors. The median SUVmax levels were higher in the Ki-67 expression >10% group than the Ki-67 index <10% group (P=0.001). Although the median SUVmax values in HER-2-positive and -negative tumors were similar, triplenegative tumors demonstrated significantly higher values (P=0.04). With regard to tumor grade, the median SUVmax was greater in the high-grade tumors compared with the low-grade tumors. SUVmax did not exhibit a significant correlation with HIF-1α expression; however, HIF-1α expression was associated with tumor size and PgR expression. HIF-1α expression increased with a larger tumor size (r=0.27; P=0.008) and decreased PgR expression (r=-0.26; P=0.0002). The axillary nodal SUVmax of the N1 tumors was significantly lower than the N2 and N3 tumors (P<0.0001). In the multivariate analysis, tumor size, Ki-67 expression and ER Allred score were independent factors that impacted SUVmax. The results of the present study indicated strong associations between tumor size, tumor grade, Ki-67 expression, triple-negativity, downregulated hormone receptor expression and SUVmax values. Conversely, there was no association observed between glucose uptake and levels of HIF-1α. Based on these results, it is suggested that the lack of assiocation between hypoxia and glucose uptake indicates phenotypic independence. [ABSTRACT FROM AUTHOR]

Background: The multifunctional hepatocyte growth factor (HGF) is the ligand of c-Met receptor; it plays important role in mammary differentiation. HGF-Met signaling is a critical downstream function of c-Src-Stat3 pathway in mammalian tumorigenesis. Aim: Evaluation of tissue c-Met receptor hepatocyte growth factor receptor (HGFR) and serum level of HGF in female breast ductal carcinoma. Materials and Methods: Sixty-eight premenopausal females were divided as 30 control females subdivided into: [Group 1] 15 healthy volunteer females and [Group 2] five with fibrocystic disease and 10 having fibroadenoma of the breast and patients group [Group 3] consisted of 38 female patients with breast ductal carcinoma. Thorough clinical examination, preoperative fine needle aspiration cytology, estimation of fasting serum glucose, urea, creatinine, and uric acid levels, alanine aminotransferase activities, C-reactive protein, HGF level, before surgery and histopathological examination of the breast masses, and immunohistochemical detection of HGFR were done. Results and Conclusions: Significant increase in serum HGF levels were found in patients with breast cancer as compared with controls. Significant increase was also seen in patients with breast cancer with and without lymph node metastasis when each subgroup was compared with controls. Serum level of HGF is an independent prognostic indicator of breast cancer. Fibrocystic disease of the breast showed weak HGFR expression, while in normal tissue, HGFR was scanty; meanwhile, breast invasive ductal carcinoma showed homogenous strong reaction to HGFR. HGF is only one of a number of key factors involved in breast cancer and preoperative high serum HGF levels and malignancy occur usually together.

Aim: The cells are either in dividing or resting state. p 16 INK4a, arrests the cell cycle in late period of G1 stage, by inhibiting RB phosphorylation. The studies in recent years have shown that, in 30-50% of colorectal cancer, CpG portion of promoter region of p16 gene is hypermethylated. In developed countries, colorectal carcinoma is the third most common cancer. In most cases, colorectal carcinoma develops from dysplastic adenomatous polyps. The major treatment of colorectal carcinoma is surgical excision. In order to estimate the prognosis of this cancer, some prognostic parameters are used. In our study, the prognostic significance of expression of p16 tumor suppressor gene in colorectal cancer cases was investigated by comparing it with other prognostic factors. Methods: In 2 of 54 cases included in the study, staining was not observed. In the rest of the cases, the expression of p16 was compared with the other prognostic factors by diffusiveness and intensity. Results: As a result, no statistically significant relationship was observed between the diffusiveness and the intensity of p16 and the age, sex, diameter, macroscopic type, histological grade, depth of invasion, lymph node metastasis, lymphovascular invasion, perineural invasion, pattern of spread, inflammatory and desmoplastic reaction, existence of dysplasia in adjacent mucosa, number of mitosis. Conclusion: No relationship was observed between p16 expression in colorectal cancers and prognostic parameters. (The Medical Bulletin of Haseki 2010; 48: 34-40)

O linfoma primário do sistema nervoso central (LPSNC) é um linfoma extralinfonodal que, ao diagnóstico, encontra-se restrito ao parênquima cerebral, às meninges e/ou cordão espinhal e/ou olhos. Sua incidência triplicou nas últimas três décadas para 0,4 casos por 100.000 habitantes, representando 4% dos tumores do sistema nervoso central (SNC). Embora pacientes infectados pelo HIV tenham 3.600 vezes maior risco para o desenvolvimento do LPSNC, a incidência não aumentou apenas neste grupo de pessoas. Dados sugerem reduções da incidência de LPSNC em pacientes infectados após a introdução de drogas anti-retrovirais. Cerca de 90% dos casos de LPSNC são classificados como linfoma difuso de grandes células B, 10% têm envolvimento ocular e 10% são HIV positivos. A apresentação clínica depende da localização tumoral, prevalecendo os sintomas neurológicos em detrimento aos sistêmicos. Os exames de tomografia computadorizada (TC) e ressonância nuclear magnética (RNM) são essenciais para o diagnóstico, porém o exame confirmatório deve ser o anatomopatológico. O estadiamento deve ser feito com exames de imagem e biópsia de medula óssea (BMO) bilateral. Os principais fatores de mau prognóstico são: performance status do paciente acima de 1, idade superior a 60 anos, DHL elevada, hiperproteinorraquia e acometimento de área cerebral não hemisférica. Alguns fatores de prognóstico biológicos também podem influenciar na sobrevida, a exemplo da expressão de Bcl-6, que confere melhor prognóstico. O tratamento de escolha é a combinação de quimioterapia contendo altas doses de metotrexate e radioterapia (RDT). Devido às altas taxas de neurotoxicidade associada à RDT, seu uso tem ficado mais restrito aos pacientes idosos, e os recidivados ou refratários.Primary Central Nervous System lymphoma (PCNSL) is an extranodal non-Hodgkin lymphoma in the brain, leptomeninges, spinal cord or eyes. The incidence of PCNSL increased approximately three-fold in the last decades. Nowadays, it represents 0.4 case per 100,000 people and accounts for 4% of all primary brain tumors. Although individuals infected with HIV have a 3,600-fold increased risk of developing PCNSL compared with the general population, the incidence has not increased only in AIDS group. Recent data suggest that the incidence of PCNSL declined in the AIDS group after the introduction of anti-retroviral drugs. Around 90% of PCNSL cases are classified as diffuse large B-cell lymphoma, 10% involve the eyes and 10% of patients are HIV positive. The clinical presentation depends on the location of the tumor with neurological rather than systemic symptoms. Computed tomography (CT) and magnetic resonance imaging (RMI) are essential in diagnosis, however the gold standard is tumor biopsy. Staging should be made with imaging and bilateral biopsy of bone marrow. The main poor prognosic parameters are performance status greater than 1, age older than 60 years, elevated DHL, high liquor protein concentration and tumor located within the deep regions of the brain. BCL-6 expression identified in the tumor confers a better prognosis. Currently, a combined therapy with high doses of methotrexate and whole-brain radiotherapy is the therapy of choice. Nowever, whole-brain radiotherapy should be carefully analyzed because neurotoxity is a frequent problem in the elderly and in relapsed and refractory patients.

Breast cancer (BC) is a disease underlined by a complex aetiology, natural history and disease behaviour. Age is the greatest risk factor, which coupled with genetic predisposition, hormonal phenotype, reproductive profile and extrinsic factors, make BC the commonest malignancy in women (23%). The most frequent presenting symptom of BC is a hard, painless, irregular lump. Profile of BC, respective of it's growth and invasiveness capacity is diverse. Principle prognostic indicators are nodal status, tumour size histological grade and hormonal receptor status. Diagnosis is achieved by the combination of physical examination, FNAC or core biopsy and breast imaging (mammography/ ultrasound). Surgery remains the mainstay of BC treatment, with or without radiation therapy, chemotherapy, hormonal manipulation, and state-of-the-art targeted treatment. Even in this day-and-age, less than 55% of BC sufferers have an overall survival longer than 5 years. This raises an alarm to bring the long awaited and much researched patient-tailored treatment to the clinic at the fastest possible pace.

Purpose: Locally advanced carcinomas arising in the hypopharynx have been traditionally treated by resection of the hypopharynx, larynx, and cervical esophagus. However, the prognosis of these patients is still low. In the present study, we retrospectively analyzed the long-term survival of patients with locally advanced hypopharyngeal squamous cell carcinoma (HSCC) reconstructed by jejunal graft. Methods: Between 2004 and 2014, 68 patients with HSCC were treated at Tottori University Hospital. Nine patients with synchronous esophageal cancer were excluded. We analyzed the overall survival of 59 patients with clinical stage III and IV HSCC who underwent pharyngo-laryngo-cervical esophagectomy with definitive tracheostomy followed by free jejunal graft reconstruction. Additionally, prognostic significances of preoperative patients' Glasgow prognostic score (GPS), neutrophil-lymphocyte ratio (NLR), and prognostic nutritional index were analyzed. Results: Postoperative complications occurred in 18.6 % of 59 patients. There were no cases of graft loss, and no patient died from complications. Preoperative poor performance status of patients was a risk factor for postoperative complications. The 5-year overall survival rate of the 59 patients was 46.1 %, and the median survival time was 28 months. In univariate and multivariate survival analyses, high GPS (1 or 2), and high NLR (≥5) were recognized as independent poor prognostic markers for patients with HSCCs. Conclusions: Pharyngo-laryngo-cervical esophagectomy followed by free jejunal reconstruction was performed safely. Additional treatment, such as chemoradiotherapy, should be introduced for patients with high preoperative GPS or NLR after curative operation. [ABSTRACT FROM AUTHOR]

Background and Aims. Advances in the diagnosis and treatment of multiple myeloma (MM), place increasing demands on accurate stratification of patients as the starting point for optimal individualized therapy. The present study focused on assessing the association between HLC levels and the HLC-r to parameters of MM activity, prognosis and tumor mass volume. The objective was to assess the correlation of immunoglobulin (Ig), heavy/light chain (HLC) pairs (IgG-ê and-ë, IgA-ê and -ë HLC) and the ratio of monoclonal involved-HLC (i-HLC) to polyclonal uninvolved (u-HLC) Ig concentrations assessed by the HevyliteTM method with the free light chain ê/ë ratio (FLC-r), selected prognostic laboratory parameters i.e. Hb, platelets, albumin, â2-microglobulin (â2-M), Ca, lactate dehydrogenase (LDH), creatinine and the Durie-Salmon (D-S) and International Staging System (ISS), stages (1-3) for MM. Methods. HevyliteTM assays were done on the sera of 132 MM patients at the time of diagnosis (IgG 94, IgA 38). HLC-r was calculated in the case of i-HLC-κ from the i-HLC-κ/u-HLC-λ ratio and for i-HLC-λ from the i-HLC-λ/u-HLC-κ ratio. D-S and ISS stages were evenly distributed. Results. Md IgG-κ HLC-r was 64.8 (2.7-2222) and of IgG-λ HLC-r 49.6 (0.7-465.1), in the case of IgA-κ, Md HLC-r was 408.9 (3.4-3966) and for IgA-λ HLC-r the Md was 180.0 (0.1-3110). Normal levels of HLC pairs and HLC-r did not always rule out the diagnosis of MM. HLC-r correlated with FLC-r in IgG (r = 0.244, P = 0.018), but not in the IgA type. For IgG, HLC-r values were significantly different in patients with abnormal vs normal levels of Hb (P < 0.0001), albumin (P < 0.043), β2-M (P < 0.0001) and creatinine (P = 0.034) but not thrombocyte count, Ca or LDH. For the IgA isotype, we found a significant difference in HLC-r values only for thrombocyte count (P = 0.026) and β²-M (P = 0.016) but not for Hb, albumin, Ca, LDH or creatinine. For the IgG isotype there was a significant relationship of HLC-r index to stages 1-3 (P = 0.038) and substage A vs B (P = 0.048) according to D-S, and with high significance to stages 1-3 according to ISS (P = 0.005) and between stages 1 vs 3 (P = 0.001). For the IgA isotype, we found significant differences in HLC-r only between stages 1-3 (P = 0.025) according to D-S but not in the case of ISS. There were no significant correlations between i-HLC Ig levels and D-S or ISS stages in both IgG-κ and λ and IgA-κ and λ. Exceptions were significant differences for stages 1 vs 3 (P = 0.012) and 2 vs 3 (P = 0.017) for the IgG-λ isotype. There were no correlations of the HLC-r and u-HLC levels for either D-S or ISS stratifications in all HLC isotypes. Conclusion. We found a significant positive contribution of HLC-r using the i-HLC/u-HLC ratio even in the case of i-HLC-λ i.e. i-HLC-λ/u-HLC-κ. Variable results for the relationship of important laboratory parameters and D-S and ISS stratifications (stage 1-3) to HLC-r values in IgG and IgA isotypes make separate interpretation of the HevyliteTM method results necessary in clinical practice. [ABSTRACT FROM AUTHOR]

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Objectives: To evaluate the outcome of patients after nephrectomy and removal of tumour thrombus and to assess the prognostic value of preoperative parameters. Patients and methods: Ninety-eight patients who were surgically treated between 2002 and 2011 were included. Patients' charts were reviewed, and patients with renal cell carcinoma (RCC) and concomitant tumour thrombus in the renal vein (RV) were compared with those with extended inferior vena cava (IVC) thrombus. Wilcoxon rank-sum test, Kaplan-Meier analysis and uni- and multivariate Cox regression analysis were used for statistical evaluation. Results: Follow-up was 36 months (20-122 months), and 5-year disease-specific survival (DSS) and overall survival were 68.4 and 54.1 %, respectively. Patients with extended thrombus (levels 2-4) had higher intraoperative transfusion rates of concentrated red cells (CRC) and fresh-frozen plasma (FFP) compared with patients with thrombus confined to the RV (CRC: 5.8 vs. 1.5, p < 0.0001; FFP: 2.3 vs. 0.4, p = 0.0032). Surgery time (190 vs. 107 min, p < 0.0001), duration of hospitalisation (16 vs. 11 days, p = 0.0269), serum phosphate (3.64 vs. 3.29 mmol/l, p = 0.0369) and CRP levels (6.7 vs. 4.4 mg/dl, p = 0.0194) as well as aPTT were increased (33.7 vs. 29.6 s, p = 0.0059) in extended thrombus disease. In multivariate analysis, the presence of distant metastasis ( p = 0.03) and lymphovascular invasion ( p = 0.001), high platelet counts ( p = 0.001) and high serum potassium levels ( p = 0.032) proved to be independent prognostic factors. Conclusion: The surgical treatment of RCC with tumour thrombus in the RV or IVC has favourable results. Extended thrombus disease requires multidisciplinary approach. High serum potassium levels and platelet counts are associated with reduced DSS. [ABSTRACT FROM AUTHOR]

Background and purpose Positive surgical margins (PSM) after radical prostatectomy have been shown to be associated with impaired outcome. In pT3pN0 patients with PSM either immediate radiotherapy or clinical and biological monitoring followed by salvage radiotherapy is recommended by the latest guidelines of the European Association of Urology. Materials and methods A retrospective, multicenter study of eight urological centers was conducted on 536 prostatectomy patients with pT3aN0/NxR1 tumors and no neoadjuvant/adjuvant therapy. A pathological re-review of all prostate specimens was performed. Association of clinical and pathological features with biochemical recurrence (BCR) was analyzed using univariate and multivariate analysis. Results With 48 months median follow-up, BCR occurred in 39.7%. Preoperative PSA value, performance of pelvic lymph node dissection and Gleason score were significantly associated with BCR. In multivariate analysis, Gleason score was the only independent prognostic factor ( p < 0.001) for BCR. Five-year BCR-free survival rates were 74%, 70%, 38%, and 51% with Gleason score 6, 3 + 4 = 7a, 4 + 3 = 7b, and 8–10, respectively. Conclusions In pT3aN0/NxR1 patients with no adjuvant/neoadjuvant treatment, Gleason Score permits independent prediction of the risk for BCR. These findings could help to estimate and discuss the individual risk for BCR with our patients on an individual basis. [ABSTRACT FROM AUTHOR]

Purpose To correlate the apparent diffusion coefficient (ADC) of endometrioid carcinoma with histological tumor grade and degree of myometrial invasion. Materials and Methods 3T diffusion-weighted (DW) magnetic resonance (MR) images of 63 patients were retrospectively reviewed. Two readers measured tumor ADC according to a freehand region of interest (ROI) and a round ROI. Mean and minimum ADCs were correlated with prognostic parameters. Results The minimum ADC was 0.64 × 10−3mm2/s for grade 1 (G1, n = 42), 0.62 for grade 2 (G2, n = 14), 0.46 for grade 3 (G3, n = 7) on freehand ROI. There were significant differences between G1 and G3 ( P = 0.007), and G2 and G3 ( P = 0.038). No significant correlation was found between tumor grade and mean ADC (0.85 for G1, 0.82 for G2, and 0.72 for G3, P = 0.166). The minimum ADC was significantly lower for patients with deep ( n = 21, 0.54) than for those with superficial ( n = 39, 0.65) myometrial invasion. Conversely, mean ADC did not differ significantly (0.84 for superficial and 0.78 for deep myometrial invasion, P = 0.081). The same tendency was shown on round ROI. Conclusion The minimum ADC correlates with prognostic parameters of endometrial carcinoma more strongly than mean ADC. Lower minimum ADC is associated with higher histological tumor grade and higher degree of myometrial invasion. J. Magn. Reson. Imaging 2015;41:213-219. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]