Immunotherapy is a recently developed treatment against most forms of cancer. Although since the early 1990s, many advances have been made with the finding of new drugs as chemotherapy and molecular targeted therapies, the latest drugs approved for cancer treatment are mostly immunotherapy. These immunotherapies, including drugs directed against immune checkpoint Programmed cell death protein 1 (PD- 1), Programmed cell death protein 1 ligand (PD-L) 1, and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), have become a consolidated treatment strategy regarding various kinds of tumors, with an effective response, and good tolerability towards patients. Patients over 65 years old constitute a large portion of the neoplastic population, and are increasingly represented in medical oncology clinics. Unfortunately, however, these patients are underrepresented in randomized clinical trials. We also know that with aging, the microenvironment and immune cells undergo marked changes that are defined by the term immunosenescence. In this review, we will consider the various studies on im- munotherapy in elderly patients, while evaluating the subgroup analyses to better clarify the efficacy and safety that immunotherapy shows in this frail population in which the treatment strategy must be carefully selected.

Endothelial cells (EC) are key elements of vascularized tissues that form a single-cell layer that connects the vessels to the surrounding tissues. EC participate in the regulation of blood hemostasis, leukocyte homing, acute inflammation, wound healing, and antigen presentation. EC subpopulations are characterized by diverse structures, functions, and molecular profiles. In bone marrow, EC are part of the hematopoietic stem cell vascular and endosteal niche, where they play well-defined roles in hematopoietic stem cell functioning and maintenance, and reside surrounding sinu- soids and blood vessels. In the past years, the clinical and pathophysiological roles of EC have been explored due to their contribution to neoangiogenesis and alterations in the vascular endothelium functions in hematological diseases. The present review discusses the EC contribution to pathogenesis of hematological malignancies and their potential use as therapeutic target in these diseases.

Faced with the complexity of emergency surgery and the aging of the population, it is increasingly common to have to deal with critically ill patients who require intensive care postoperatively. Surgical stress amplifies senescence mecha- nisms where the organism is called to face the establishment of both early and late pathophysiological mechanisms disrupting homeostasis. In this scenario, sarcopenia represents a prognostic factor with a multifactorial etiology that can lead to fearful com- plications in the early postoperative period. As an octogenarian adaptation, its multifactorial genesis allows to act and counterbalance the action of concomitant modifiable factors through post-operative optimization strategies.

Objectives: Colorectal cancer is the most frequent and mortal cancer in Portugal. Both angiogenesis and cellular prolif- eration are core mechanisms to tumoral progression, with VEGF (Vascular Endothelial Growth Factor) and Ki-67, respec- tively, being widely known markers of those two processes. The purposes of this study are to comprehend VEGF and Ki-67’s impact on colorectal cancer prognosis which include assessing its expression in primary colorectal cancer of pa- tients who underwent surgery, establishing associations between the expression of VEGF and Ki-67 and discovering hy- pothetical associations between these biomarkers and clinicopathological aspects, relapse, and mortality of patients. Methods: A retrospective study was conducted in our hospital by including 512 patients submitted to surgery, from 2005 to 2010, with a post-operatory diagnosis of colorectal adenocarcinoma. The evaluation of expression of VEGF and Ki-67 in the obtained tissue was made through immunohistochemistry technique. The statistical analysis resourced to association tests and survival analysis. Results: VEGF-A showed association with the variable gender (p-value of 0.016), with its expression being more fre- quent in men. VEGF-C expression is more common in colon than in rectum (p- value of 0.042). VEGF-C is significantly associated with Ki-67 (p-value of 0.036), with 69.7% of cases where both are positive. All markers are significantly as- sociated with the grade of differentiation, with the VEGF family generally more present in well or moderately differenti- ated tumours and Ki-67 in the poorly differentiated. While the survival time was generally lower in the presence of any marker or combination, no significant differences were found among the survival analysis. Conclusion: VEGF-A, VEGF-C and Ki-67 expression did not show impact on the prognosis of this sample of patients. There was no significant association with a poorer overall survival or a reduced disease-free survival.

Objectives: This simulated study has mechanistically evaluated the molecular dynamics effects of rutin on CDKs 2, 4, and 6 in cell cycling. Methods: Protein Data Bank (http://www.rcsb.org) was used to obtain the PDB file of CDK 2, 4, and 6. After simulation of CDKs in Gromacs software, AutoDock 4.2 was used to run 200 stages of molecular docking of CDKs in the presence of the rutin. CDK 2, 4, and 6 were simulated in the presence of rutin after docking. Results: Rutin had the highest tendency to bind the CDK-2 and CDK-6 via binding 16 and 18 residues in the binding site with hydrogen and hydrophobic bonds (respectively). Also, they had the highest amount of binding energy released. Rutin decreased total energy in CDKs and reduced the radius of gyration in CDK-2 and CDK-6 after docking. The second- ary coil structure increased in CDK-2 and decreased in CDK-4 and 6. Conclusion: Conformational changes in CDK2 and 6 via rutin can inhibit the activity of these proteins and subsequent- ly arrest the cell cycle in phases G1, S, and G2, which can lead the damaged cell to cell repair or Apoptosis.

Objectives: Current literature regarding the assessment of changes in gall bladder polyps is minimal in Pakistan, which is known to have one of the highest risk of developing gall bladder carcinoma. The aim of this study is to determine the occurrence of cancer in incidentally detected Gall Bladder (GB) polyps identified by sonography and to propose surveil- lance guidelines in high risk population for gall bladder cancer. Methods: Radiological data of all “gall bladder polyps” detected on ultrasounds done between January 2001 and Feb- ruary 2015 was taken at a tertiary care institution and it was evaluated to see changes in the size of GB polyps. Patho- logic and clinical follow-up was reviewed from the medical record files. Results: GB polyps from 155 patients (Age range, 18–92 years) were included. US follow-up was performed with minimum follow-up duration of 2 years. The polyps ranged in size from 2-19 mm (mean size, 4 mm). Polyp size remained unchanged in 65 (42 %) polyps, decreased in 25 (16 %), increased in 12 (7 %) and resolved in 53 (34%). None of the polyps ranging in size from 1-6 mm turned out to be neoplastic. One polyp of 7 mm showed increase in size and progressed to carcinoma. Conclusion: The risk of malignancy of gall bladder resulting from incidentally detected polyps is very low. Hence, gall bladder polyps measuring upto 6 mm require no additional follow-up. Follow up may be indicated for polyps that are greater than or equal to 7 mm in size.

Objectives: Interleukin-10 (IL10) is a pro-inflammatory cytokine that plays a pivotal role in inflammatory diseases as well as in the pathogenesis of diverse tumors, including nasopharyngeal carcinoma (NPC). The present study was de- signed to evaluate the importance of the functional promoter polymorphisms of IL10 (-1082 A>G and -592 A>C) in the development of NPC. Methods: A total of 384 patients with NPC were recruited into this study, together with 375 matched control subjects. Polymorphisms within the promoter region of IL10 gene were analysed using PCR-RFLP method. Results: We report a lack of association between IL10 polymorphisms and NPC in the overall population (P>0.05). How- ever, the 1082 A>G polymorphism was significantly associated with the susceptibility to NPC among young patients (age ≤30 years). The GG genotype was found to be associated with a significantly higher risk of NPC as compared with the AA genotype among young patients (OR=2.534; 95% CI, 1.189–5.398, P=0.016). Conclusion: The results of the present study indicate an association between IL10 -1082 GG genotype and NPC among young North African subjects. This difference in IL10 polymorphism association with different ages at the onset of NPC suggests that the younger and older onset patients are genetically different and may involve different mechanisms.

Objectives: Treatment of multiple brain metastases more than 10 is challenging. Whole brain radiotherapy (WBRT) is generally believed to be the first treatment choice. In order to escape from mental deterioration after WBRT, we have performed Gamma Knife stereotactic radiosurgery (GKS) for numerous small brain metastases. Methods: Twelve cases of numerous (more than 30) brain metastases were treated by GKS. Mean total session number was 5.42 times, ranging 2 to 17. Each tumor was treated with the margin dose between 14 to 20 Gy. The tumor number treated in whole sessions was ranged from 31 to 144 (mean, 70.8). Results: Almost all the irradiated tumors either disappeared or shrank at the patient’s death or at the last follow-up, though new metastatic tumors were subsequently developed in some cases which required an additional treatment with GKS. At the last follow-up (3 to 51 months after GKS), nine cases were alive and well and three were dead. As adverse effects, two cases demonstrated seizures by radiation brain injury and another showed a gait disturbance. No apparent mental deterioration was observed during follow-up. Conclusion: Radiosurgery for numerous small brain metastases may be preferable rather than WBRT.

Objectives: We performed a planning study to evaluate the dosimetric differences between Volumetric Modulated Arc Therapy (VMAT) and Intensity Modulated Radiation Therapy (IMRT) using simultaneous Integrated Boost (SIB) for prostate cancer cases. Methods: 20 prostate cancer patients scheduled for SIB-VMAT treatment on the HalcyonTM 2.0 linear accelerator were recruited for this study and SIB-IMRT plans were generated for comparison purpose. The pelvic lymph nodes (PTV46), the seminal vesicle (PTV50), and the prostate (PTV60) were simultaneously treated to 46 Gy 50 Gy, and 60 Gy delivered in 20 fractions respectively. Results: SIB-VMAT was better due to its higher (1.41%) CI, lower (2.7%) HI, and lower (26%) GI than SIB-IMRT for PTV60. For PTV50, a higher (7.3%) CI, lower (48%) HI, and a lower (31.73%) GI for SIB-VMAT compared to SIB-IMRT. Also, for PTV46, a higher (9.4%) CI, lower (2.5%) HI, and a lower (16.4%) GI were achieved by SIB-VMAT compared to SIB-IMRT. Conclusion: Better conformal and slightly similar homogeneous dose distribution were noticed in SIB-VMAT plans compared to SIB-IMRT plans. However, SIB-IMRT provided better OARs sparing of the bladder and the femoral heads while SIB-VMAT had better sparing for rectum.

Numerous epidemiological studies examining the etiology of ovarian cancer and the role of pregnancy related factors in ovarian cancer has been one of the topics of interest to many researchers. Various articles have only mentioned the link between some risk factors and ovarian cancer, but no study has addressed the various dimensions of this issue to this day. Therefore, due to the important position of ovarian cancer among gynecological cancers, this study was con- ducted to investigate the pregnancy-related risk factors for ovarian cancer. To determine the relationship between pregnancy characteristic and ovarian cancer, a comprehensive search was car- ried out in English databases such as; Medline, Web of Science Core Collection, and Scopus using keywords; pregnancy, ovarian cancer (or 'carcinoma of the ovary' or 'ovarian neoplasm' or 'ovarian tumor'), risk factor, pregnancy characteris- tic terms and a combination of these terms. Full-text, English language, and original articles were included in this study. In total, 35 articles were entered into the study. The relationship between pregnancy related factors and ovarian cancer were studied. Although there was a weak association between some factors such as preterm birth and the risk of ovar- ian cancer, only the strong protective effect of parity was seen in the articles. The results of this study did not show that pregnancy related factors increase the risk of ovarian cancer. In summary, the findings are inadequate regarding some risk factors such as gender of fetus, multiple pregnancy, placental and fetal weight, parity, miscarriage, preeclampsia, and gestational diabetes, and raised questions for future research.

Objectives: DKK-1, a negative regulator of β-catenin in the Wnt pathway is commonly upregulated in cancer cells but its expression and association to chemoresistance have not been investigated extensively. Our aim was to evaluate the expression of DKK-1 and β-catenin as well as the effect of the Wnt pathway modulators iCRT-14 (iCRT) and WAY626611 (WAY) alone or in combination with Nigericin (NIG) on the viability of cancer cells grown under routine conditions (RC) or as floating spheroids (FSs). Methods: RC or FSs from human prostate (PC3 and LnCAP) and breast (MCF-7 and MDA-MB231) cells were treated for 72 hs with WAY or iCRT. Cell viability was determined by the MTT or the CCK-8 assays and protein expression was determined by western blot analysis. Results: DKK-1 was expressed at different basal levels in RC but was undetectable in FSs. β-catenin expression was in- creased in FSs. RC of PC3 and MCF-7 were sensitive to both iCRT and WAY but FSs generated from these cell lines were resistant to both drugs. NIG potentiated the effect of both Wnt inhibitors in FSs. Conclusion: Marked changes in the expression of Wnt pathway proteins, DKK-1 and β-catenin in FSs are associated with resistance to WAY and iCRT.

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Objectives: To aim to show the survival outcomes of ifosfamide, carboplatin and etoposide (ICE) therapy and the characteristics of treatment-related hematological side effects in patients with relapsed/refractory bone sarcomas (BSs) andsoft tissue sarcomas (STSs). Methods: Patients who were treated at the Department of Medical Oncology, Gulhane School of Medicine betweenJanuary 2017 and June 2021 were included. Post-ICE progression-free survival (PFS), overall survival (OS) rates and treatment-related hematological side effects were determined. Results: Fifty-six adult patients were included (thirty-four of them BSs). PFS was determined as 6.7 ± 4.4 months and 7.1±3.6 months for STSs and BSs, respectively. OS was 11.4±5.6 monhts and 12.6±7.1 for STSs and BSs, respectively. PFS and OS were not found to be better between groups (p=0.84 and p=0.517, respectively). The median OS and PFS after ICE protocol in patients with two or less systemic chemotherapy lines were significantly higher than those who received three or more lines (7.85±1.66 vs 3.74 ±2.89, p=0.001 and 13.80±8.45 vs 6.73, p=0.001). Conclusion: In addition to its contribution for all patients, ICE may contribute to longer survival, especially in patients receiving ≤2 lines of systemic chemotherapy.

Objectives: The aim of this study is to investigate the incidence of asymptomatic COVID 19 patients who underwent CT and PET/CT for oncological indications and to detect lung changes in CT and PET/CT in these patients. Methods: Between March 2020 and September 2021, 3135 patients admitted to the nuclear medicine department were retrospectively analyzed. Our study involved the oncology patients with a history of contact, clinical and labora- tory findings and possible COVID-19 disease, whose radiological findings at PET/CT and CT were compatible with viral pneumonia and confirmed by PCR testing. Results: Lung imaging findings suspicious of SARS-Co V-2 infection were found in 78 of 3135 patients (2,48%) included. The most frequent finding was multiple ground glass opacities (GGOs). In our study, we found characteristic peripheral ground-glass opacities with high FDG activitiy with increased nodal FDG uptake in favor of reactive lymphadenitis in FDG-PET/CT. Conclusion: Chest CT is used in the initial diagnosis and monitoring of COVID-19 progression as well as in the evalu- ation of complications. Although PET imaging is not typically considered among the primary research methods for the diagnosis of lower respiratory tract infections, it has made a significant contribution to the incidental diagnosis of especially asymptomatic COVID-19 oncological cases

Objectives: The knowledge of the possible differences in the clinical course of COVID-19 infection in cancer patients receiving treatment has not been sufficient to conclude. In this study, we retrospectively evaluated lymphocyte counts, LDH levels, neutrophil/lymphocyte ratios (NLR), platelet lymphocyte ratios (PLR), CRP albumin ratios (CRP/Alb), LDH/ albumin ratios in COVID-19 infected cancer patients actively treated in our clinic. Methods: Cancer patients who were currently under treatment in Department of Medical Oncology, Faculty of Medicine, Pamukkale University during the period between September 2020 and April 2021 were included in the study. During the period, 1363 stage 3-4 patients were received parenteral treatment and 60 patients were diagnosed with COVID-19 infection. Results: The median age of the patients was 60 years (range 19-82 years). Stage of cancer (p=0.028), lymphopenia (p<0.001), elevated LDH (p=0.002), elevated NLR (p<0.001); and elevated LDH/Alb ratios (p<0.001) were identified as the factors affecting mortality. Conclusion: In patients actively under treatment for cancer, clinical course of COVID-19 infection was found to be af- fected by the stage of the cancer, neutrophil lymphocyte ratios and by LDH/albumin ratios. We think that neutrophil lymphocyte ratios and LDH/albumin ratios are the important prognostic markers in the course of COVID-19 infection in cancer patients.

Many dental procedures invariably include a "bleeding event." The chance and severity of such events should be assessed on a relative risk rather than absolute risk. For example, when patients using antithrombotic agents for the management of their systemic illness (like coronary artery disease, cerbero vascular disease and major surgeries like hip joint /knee joint replacement) require any dental treatment, the dentist should weigh bleeding risk associated with the particular dental procedure together with the thrombotic risk. The dentist should also engage with the patient as well as patient`s consulting physician to decide whether the antithrombotic agent needs temporary withdrawal

For more than a decade, the targeted drug sorafenib[1, 2] has been the dominant first-line treatment for patients with advanced hepatocellular carcinoma (HCC). However, due to the low overall response rate and high drug resistance rate, many new targeted drugs have been developed, including sunitinib, brivanib, linifanib, nintedanib, dovitinib, sorafenib plus erlotinib, lenvatinib, and donafenib. On the other hand, with the increasing use of immune checkpoint inhibitors in solid tumors, several trials investigated the efficacy and safety of immune checkpoint inhibitors in advanced HCC. Among these trials, only lenvatinib and donafenib as monotherapy were non-inferior to sorafenib in overall survival in untreated advanced HCC. Most of other trials did not meet their primary end point of overall survival. However, the efficacy of the combination therapy with PD-1 or PD-L1 inhibitor plus bevacizumab (VEGF inhibitor) is amazing.[3, 4] An expert panel convened by the American Association for the Study of Liver Diseases recommended time to progression as the primary endpoint in randomized phase 2 trials and overall survival as the main endpoint to measure effectiveness in phase 3 trials.[5, 6] In real world clinical practice, subsequent antitumor therapies after tumor progression and/or therapies for concurrent liver disease can confound the assessment of clinical benefit. In the recent issue of Journal of Hepatology, on behalf of EASL, Bruix and coworkers updated the recommendations of systemic treatment of HCC.7 This review proposed that “overall survival is the sole robust endpoint to assess the benefit from any intervention in advanced HCC” and “all proposed surrogates lack adequate validation”. Here, we tried to reveal the relationship among objective response rate (ORR), median overall survival (OS) time and median progression-free survival (PFS) time by presenting them in a same curve graph. The potential relationship between PFS and OS is revealed by representing the hazard ratio (with 95% confidence interval) of PFS and OS with a forest plot. We systematically searched PubMed and EMBASE databases and analyzed phase 3 clinical trials with large sample size. A total of 11 trials about first-line systemic therapies for advanced HCC published from 2008 to 2021 were included into analysis. All these 11 trials included a group of patients treated with sorafenib. In addition, 7 trials about second-line systemic therapies published from 2015 to 2021 were also included into analysis. The control group received placebo treatment in all these 7 trials. All these 18 trials reported ORR, median PFS and OS time. The ORR according to RECIST 1.1 in the sorafenib group ranged from 0.7% to 11.9% (median 6.1%). Among patients with sorafenib therapy, the median PFS and OS time was 3.75 (range 2.8 to 5.5) and 10.4 (range 6.5 to 14.7) months, respectively.

Chromophobe renal cell carcinoma (ChRCC) accounts for 4-6% of RCC1. Most of ChRCC have good prognosis, but sarcomatoid transformation implies poor prognosis factor2. Although sarcomatoid RCC was initially described as an own histological entity3, despite the fact that its transformation mechanism is not known, it is nowadays recognized that this histology represents a transformation or dedifferentiation of a high-grade malignant neoplasia originating from any other histological subtype of RCC2. ChRCC with sarcomatoid differentiation is very rare, with a few reported cases and there is no consensus about the treatment of patients affected by this variant of RCC in the guidelines. Therefore, we consider appropriate to present these two cases and review the literature, focusing on the incidence and the current therapeutic options.

Atypical chronic myeloid leukemia (aCML) is a BCR-ABL1 negative myelodysplastic/myeloproliferative (MDS/MPN) neoplasm. Patients typically present with elevated neutrophil counts and hypercellular bone marrow, but there are no specific genetic or molecular markers available to diagnose aCML and it is therefore a diagnosis of exclusion. Atypical CML is rare and carries a poor prognosis, and there is currently no standard of care for treatment. In the absence of an available clinical trial, current consensus is for patients with a suitable donor to undergo allogeneic stem cell transplantation, and a comprehensive evaluation for driver mutations should be performed to screen for the potential use of targeted agents. Without an actionable driver mutation, hypomethylating agents are an emerging treatment option based on four reports showing complete hematologic remission in 7 of 8 patients treated with decitabine.

Objectives: Breast cancer is a dreadful public health issue that kills plenty of women all around the world. The peril of breast cancer is strongly linked to lipids, lipoproteins, and glycoproteins. Capsaicin (CAP), a natural alkaloid isolated from chilies, has been reported to possess excellent anti-cancer activity. Unfortunately, the clinical application of this compound is strictly limited due to its low solubility and poor bioavailability. Nanoparticle-based drug delivery systems have set the path for a revolution in cancer therapy by improving its therapeutic value. The aim of the present study was to investigate the effect of CAP encapsulated chitosan nanoparticles (CAP@CS-NP) on lipids, lipoproteins and glycoproteins abnormalities in 7,12-dimethylbenz(a)anthracene (DMBA) induced mammary carcinogenesis. Methods: A mammary tumor was induced by a single dose of DMBA 25mg/kg b.wt injected subcutaneously near the mammary gland. The levels of lipid profile, lipoproteins and glycoprotein components were analyzed in the plasma, liver and mammary tissues. Results: We observed higher levels of total cholesterol (TC), triglycerides (TG), phospholipids (PL), free fatty acids (FFA), hexose, hexosamine and sialic acid in DMBA induced tumor-bearing rats. Moreover, low-density lipoprotein cholesterol (LDL-C) and very low-density lipoprotein cholesterol (VLDL-C) levels were raised and high-density lipoprotein cholesterol (HDL-C) levels were dropped in tumor-bearing rats. The result shows that, CAP@CS-NP 4mg/kg b.wt administration significantly recouped abnormal levels to near-normal levels. It was additionally verified by histological staining in mammary tissues. Conclusion: Our findings suggest that nanoencapsulation of CAP@CS-NP successfully regulates lipid profile, lipoproteins, and glycoproteins levels.