Abstract: BACKGROUND/AIM Lung cancer is one of the most common malignant neoplastic diseases and by far the leading cause of cancer death worldwide. Recently, immune checkpoint inhibitors (ICIs) have received increasing attention for playing a crucial role in non-small cell lung cancer (NSCLC). Biomarkers, such as programmed cell death-ligand 1 (PD-L1) and tumor mutational burden (TMB), seemed to be helpful in selecting patients who are more likely to benefit from ICI treatment: however, their role has not yet been fully clarified. PATIENTS AND METHODS In this retrospective study, we evaluated the relationship between pre-treatment peripheral blood neutrophil-to-lymphocyte ratio (NLR) and survival in 252 patients suffering from advanced NSCLC who had received pembrolizumab as their first-line immunotherapy. RESULTS Compared to their NLR low counterparts who had a median overall survival (OS) of 34.8 months, patients with NLRs above 4.8 had a median OS of 7.6 months (HR=3.26, 95%Cl=2.3-4.6, p-value<0.0000001). In multivariate Cox regression analysis, alongside other variables, such as metastatic sites, age, and sex, NLR and PD-L1 predicted progression-free survival and OS; furthermore, a very high NLR - over 10 - seemed to forecast a very dismal prognosis in patients undergoing immunotherapy, with sudden deaths in the days immediately following therapy (median OS=3.8 months). CONCLUSION NLR acts as a valuable and reliable prognostic factor in non-small cell lung carcinoma patients undergoing first line immunotherapy with pembrolizumab. Additional investigation is necessary to fully elucidate the underlying biological rationale, which can be found in myeloid derived suppressor cells, a heterogeneous population of cells with neutrophil-like immunophenotypic features.

Abstract: Malignancies are among the leading causes of mortality worldwide. Early detection and treatment are the primary targets of clinical and translational research, and may be facilitated by the recognition of novel diagnostic and prognostic biomarkers. Decoy receptor 3 (DcR3) is a soluble receptor of the tumor necrosis factor receptor superfamily of proteins (TNFRSF), which associates with its respective TNF-like ligands, Fas-L, LIGHT, and TL1A. DcR3 has been recognised as a significant anti-apoptotic factor with prominent involvement in various inflammatory and neoplastic conditions. Increased intratumor expression of DcR3 and elevated soluble DcR3 protein content in the sera of patients has been reported for various malignancies. Recent published work has suggested that monitoring of local and systemic DcR3 may provide an attractive biomarker, mainly for defining subgroups of patients with aggressive tumor behaviour and poor prognosis. The aim of the present review is to summarize and critically present existing evidence regarding the potential clinical importance of monitoring DcR3 expression in patients with malignancies of the gastrointestinal tract, as well as liver and pancreatic cancer. We also present a detailed description of the pathophysiological basis that may underlie the involvement of DcR3 in gastrointestinal carcinogenesis. Based on these data, we comment on the potential applicability of DcR3 monitoring in the diagnosis and, most importantly, the prognostic stratification of patients.

Abstract: One of the major hallmarks of many cancer cells is dedifferentiated cells (immature cells) with little or no resemblance to normal cells. Besides the poor differentiation, malignant cells also have important features such as aggressiveness and resistance to different therapeutics. Differentiation potentiators hold great promise for cancer treatment. Dimethyl sulfoxide (DMSO) is a well-characterized pharmaceutical solvent. It is used as a component of numerous cancer therapeutic approaches, including cancer treatment and several approved cancer immune therapeutics such as Car-T cell therapy and the FDA-approved drug Mekinist (trametinib DMSO) for melanoma treatment. It is also biologically recognized as a pharmaceutical solvent and cryoprotectant. In the current literature, there are no mentions of DMSO's possible ability to potentiate therapeutic activity as a component of these cancer treatments. This review aimed to summarize scientific evidence and substantiate the concept that DMSO can contribute positively to the overall efficacy of cancer treatment as an adjuvant that is safe, inexpensive, and an effective differentiation-inducing therapeutic agent.

Abstract: Aim To evaluate the preoperative predictors of pathological lymph node (LN) metastasis and prognostic factors for postoperative biochemical recurrence (BCR) in robot-assisted radical prostatectomy with extended pelvic LN dissection in patients with D'Amico high-risk prostate cancer (PCa). Patients and Methods Overall, 107 patients with D'Amico high-risk PCa underwent robot-assisted radical prostatectomy with extended pelvic LN dissection without neoadjuvant or adjuvant therapy. BCR was defined as a prostate-specific antigen (PSA) level ≥0.2 ng/ml. Moreover, BCR-free survival rates were determined using Kaplan-Meier analysis. Logistic regression analysis was used to evaluate preoperative predictors of pathological LN metastasis. Cox regression analysis was used to evaluate the effects of preoperative and pathologic variables on BCR. Results The median follow-up was 21 months, and the 5-year BCR-free survival rate was 59.8%. The positive LN rate was 21.5%. In multivariate analysis, the percentage of positive cores was a significant preoperative predictor of positive LNs. Patients with >50% positive cores (p=0.004) and PSA density (PSAD) >0.5 ng/ml/cc (p=0.005) had a high risk of having ≥3 positive LNs. In multivariate analysis, PSAD >0.5% was a significant preoperative predictor of BCR. Among the postoperative predictors, the number of positive LNs was significantly associated with BCR. Patients with ≥3 positive LNs (n=7) had significantly lower BCR-free survival rates than patients with one or two positive LNs (n=16) (p<0.001). Patients with >50% positive cores and PSAD >0.5 ng/ml/cc had a risk for a high number of positive LNs (≥3) that was strongly associated with shorter BCR-free survival (p<0.001). Conclusion The percentage of positive cores may be useful as a preoperative predictor of pathological LN metastasis in patients with high-risk PCa. Patients with >50% positive cores and PSAD >0.5 ng/ml/cc were found to have a high risk for ≥3 positive LNs and shorter BCR-free survival.

Abstract: BACKGROUND/AIM It is well established that around one-third of patients with atypical endometrial hyperplasia (AEH) go on to develop endometrial cancer (EC). PATIENTS AND METHODS This retrospective cohort study included 119 patients recruited from the University Hospitals of Leicester from 01/01/2015 to 01/01/2020 with a diagnosis of AEH by endometrial biopsy. Patients were divided into two groups according to the management modality: Primary surgery (n=99), and conservative treatment (n=20). The aim of this study was to determine the incidence of EC in patients with AEH in University Hospitals of Leicester, UK, and to explore the reasons why patients with AEH opted for conservative management. RESULTS EC was diagnosed in 34.4% of patients with AEH managed by primary surgery. Moreover, the incidence of EC in patients with AEH managed conservatively was 25%. The main reason for opting for conservative management was that patients were unfit for surgery when assessed in the high-risk Anaesthetic Clinic (35%). CONCLUSION AEH is a pre-malignant lesion that has high risk of EC regardless of the mode of management. Total hysterectomy is the safest first line of treatment in AEH due to the high risk of concurrent EC and progression to EC. Currently, there is no reliable follow-up intervention to distinguish between concurrent EC and progression of AEH. Adequate discussion and counselling are essential when discussing conservative management for women with complex AEH. Patients should be counselled regarding the high risk of developing concurrent EC and risk of progression to EC.

Abstract: Background/Aim Several articles have assessed the prognostic significance of the expression of sirtuin 1 (SIRT1) in esophageal squamous cell carcinoma (ESCC). However, evidence in this field is insufficient. Thus, we conducted a meta-analysis to investigate the prognostic and clinical impact of SIRT1 expression in ESCC. Materials and Methods We searched the PubMed, Cochrane Library, and Web of Science databases for articles on the expression of SIRT1 and clinicopathological features in patients with ESCC. A meta-analysis was conducted. Results Four studies with 429 patients were included. The meta-analysis revealed a significant relationship between the high expression of SIRT1 and higher T-stage (odds ratio=2.39. 95% confidence interval=1.12-5.13, p=0.02), more advanced TNM stage (odds ratio=2.35. 95% confidence interval=1.20-4.60, p=0.01), and a poor overall survival (hazard ratio=1.90, 95% confidence interval=1.45-2.47, p<0.00001). Conclusion SIRT1 expression may be a promising prognostic biomarker for patients with ESCC.

Abstract: BACKGROUND/AIM Tyrosine kinases have crucial functions in cell signaling and proliferation. The phosphatidylinositol 3-kinase (PI3K) pathway is frequently deregulated in human cancer and is an essential regulator of cellular proliferation. We aimed to determine which tyrosine kinases contribute to resistance elicited by PI3K silencing and inhibition. MATERIALS AND METHODS To mimic catalytic inactivation of p110α/β, specific p110α (BYL719) and p110β (KIN193) inhibitors were used in addition to genetic knock-out in in vitro assays. Cell viability was assessed using crystal violet staining, whereas cellular transformation ability was analyzed by soft-agar growth assays. RESULTS Activated zeta chain of T-cell receptor-associated protein kinase 70 (ZAP70) generated resistance to PI3K inhibition. This resistance was via activation of the Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) axis. We demonstrated that activated ZAP70 has a high transforming capability associated with the formation of malignant phenotype in untransformed cells and has the potential to be a tumor-initiating factor in cancer cells. CONCLUSION ZAP70 may be a potent driver of proliferation and transformation in untransformed cells and is implicated in resistance to PI3K inhibitors in cancer cells.

Abstract: BACKGROUND/AIM The association between tumor PD-L1 expression and the rate of acquisition of the T790M mutation during treatment with first-/second-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) is a matter of study. This retrospective study was conducted to evaluate the association of tumor PD-L1 expression with the time on treatment under EGFR-TKIs in patients with EGFR-mutant non-small cell lung cancer (NSCLC), treated with first-/second-generation EGFR-TKIs. PATIENTS AND METHODS We conducted a retrospective review of the medical charts of patients with EGFR-mutant NSCLC treated with first- /second-generation EGFR-TKIs. Time on treatment with EGFR-TKIs was defined as the sum of progression-free survival period (PFS) from the start of treatment with first- /second-generation EGFR-TKIs and the PFS from the start of osimertinib treatment after acquisition of the T790M mutation. Tumor PD-L1 expression was evaluated using the 22C3 antibody. RESULTS Data of a total of 49 patients were analyzed, including 20 patients with negative tumor PD-L1 expression (tumor proportion score <1%) and 29 patients with positive tumor PD-L1 expression (tumor proportion score ≥1%). In the negative tumor PD-L1 expression group, the T790M mutation was detected in 12 (75%) of the 16 patients. In the positive tumor PD-L1 expression group, the T790M mutation was detected 6 (31.6%) out of the 19 patients in whom it was tested. The median (95% confidence interval) time on treatment with EGFR-TKIs was 21.7 (12.9-24.8) months and 12.3 (5.6-22.2) months in the negative and positive tumor PD-L1 expression groups, respectively. Analysis using a Cox proportional hazards model identified performance status and presence/absence of tumor PD-L1 expression as significantly associated with the time on treatment with EGFR-TKIs. CONCLUSION EGFR-mutant NSCLC patients with negative tumor PD-L1 expression showed a higher rate of acquisition of the T790M mutation and implementation rate of osimertinib therapy, leading to a longer time on treatment with EGFR-TKI.

Abstract: Background/Aim We aimed to assess the risk factors for postoperative complications and long-term outcome of patients aged ≥80 years after curative resection for gastric cancer (GC). Patients and Methods Patients aged ≥80 years who underwent curative gastrectomy for stage I-III GC between 2013 and 2020 were included. Clinical factors were retrospectively analyzed. Results Of all 109 patients, 29 (26.6%) had 33 postoperative complications (Clavien-Dindo grade ≥2). The rate of postoperative complications was higher in those with greater blood loss (≥170 ml, p<0.001). In multivariate analysis, greater blood loss was confirmed as an independent predictor of postoperative complications (p<0.001). The 30-day, 180-day, 1-year, and 3-year cumulative overall survival rates were 100%, 97.0%, 91.6%, and 74.7%, respectively. Multivariate analysis showed postoperative complications (p=0.014) and low prognostic nutritional index (PNI, p=0.044) were independent prognostic factors for poor overall survival. Conclusion Performing operations with less bleeding is important to reduce postoperative complications. According to the analysis of long-term survival, patients who experience postoperative complications and patients with a low preoperative PNI require special attention in the follow-up period. Nutritional support should be considered in patients with malnutrition.

Abstract: BACKGROUND/AIM Primary mediastinal non-seminomatous germ cell tumors (PMNSGCTs) are occasionally complicated by a hematologic malignancy, as with somatic-type malignant tumors called germ cell tumors with somatic-type malignancy (GCTSTM) and are known to have a poor prognosis. PATIENTS AND METHODS Data obtained between September 1997 and February 2020 for patients with mediastinal germ cell tumor at our institution were retrospectively analyzed. Key outcome measures included survival rates and the clinical features of non-seminoma cases. RESULTS Of 16 patients, 9 had pure seminoma, and 7 had non-seminoma. At the median follow-up of 56.2 months, the 5-year survival rate was significantly higher in patients with seminoma (100%) than in those with non-seminoma (37%) (log-rank test, p=0.0153). Regarding PMNSGCT, two patients evolved into GCTSTM and three had concomitant hematological malignancies. CONCLUSION Patients with PMNSGCTs, GCTSTM complications, and hematologic malignancies showed poor survival, suggesting the need for the development of treatment strategies.

Abstract: Prolactin (PRL) is a polypeptide hormone synthesized in the lactotrophs of the adenohypophysis and in extrahypophyseal glands (such as the prostate and breasts) where it promotes their development. PRL is also involved in cancer development in these glands. It has been shown to stimulate cancer cell migration, suggesting its possible involvement in metastasis, in which cell migration plays an essential role. However, the role of PRL in cell migration is still unclear. Moreover, the intracellular mechanisms activated by PRL to carry out cell migration are less well understood. PRL exerts its effects via the PRL receptor (PRLR), which leads intracellularly to phosphorylation of Janus protein kinase 2 (JAK2), which in turn phosphorylates p21-activated protein kinase (PAK1), leading to an increase in cell migration. Although several studies have described the involvement of the PRL-PAK1 pathway in breast cancer cell migration, the molecular mechanisms have not been fully elucidated and there is no integration of these into signaling pathways. This study was conducted based on literature search of review articles and original research in the PubMed database, using the following keywords: PRL, cell migration, PRL and cell migration, PAK1 and signaling pathways. The aim of this review article was to describe the major signaling pathways controlled by PRL-PAK1 and propose a comprehensive model of the signaling pathways associated with PRL-PAK1.

Abstract: Background/Aim Pulmonary enteric adeno-carcinoma (PEAC) is a rare type of non-small cell lung cancer (NSCLC), for which no established standard treatment exists. Combination therapy with the anti-programmed cell death protein 1 antibody pembrolizumab and platinum-containing chemotherapy is the standard treatment for NSCLC patients, but its effectiveness in PEAC is uncertain. Case Report We present a 68-year-old man with chemotherapy-naïve advanced PEAC who responded to a combination of pembrolizumab and platinum-containing chemotherapy. Conclusion The number of PEAC cases is small, and no clinical trials have been conducted to determine an optimal chemotherapy regimen. In this case, we showed that pembrolizumab combined with platinum-containing chemotherapy might effectively treat PEAC.

Abstract: BACKGROUND/AIM Prophylactic cranial irradiation (PCI) is a well-established treatment of small cell lung cancer (SCLC) patients following response to initial chemoradiotherapy. The benefit of PCI does, however, come at the cost of cognitive decline. This has been attributed to radiation-induced toxicity at the hippocampus, a crucial anatomic area for cognition. Modern radiotherapy techniques allow dose reduction at the hippocampal region. In this review, the safety profile, effect on cognition, and changes on brain imaging modalities of hippocampal avoidance-PCI (HA-PCI) will be presented, aiming to identify a potential clinical rationale for SCLC patients. MATERIALS AND METHODS A systematic review of the literature was performed in Pubmed, Cochrane library databases and ClinicalTrials.gov with no past date limitations until 07/01/2022. Principles as outlined in the preferred reporting items for systematic reviews and meta-analysis (PRISMA) statement were followed. RESULTS Eight studies published from 2015 to 2021 were included. CONCLUSION HA-PCI is safe, yet its effect on neurocognition and imaging remains unclear, as studies have shown contradictory results.

Abstract: Background/Aim: Postoperative pancreatic fistula (POPF) is the most serious complication of distal pancreatectomy (DP). When POPF occurs and becomes severe, it causes secondary complications and leads to a longer treatment period. This study aimed to identify early predictive factors of POPF after DP for pancreatic cancer (PC). Patients and Methods: This retrospective, single-institution study comprised of 55 patients with PC who underwent DP between 2010 and 2021 at the Gifu University Hospital. We statistically analyzed pre-, intra-, and post-operative factors to identify early predictive factors for POPF. Results: According to the definition and grading of the International Study Group of Pancreatic Fistula (ISGPF), 12 (21.8%) of 55 patients had POPF grades B and C. In the univariate analysis, POPF was significantly associated with the pancreas-to-muscle signal intensity ratio on T1-weighted magnetic resonance imaging (SIR on T1-w MRI), the drainage fluid amylase (D-Amy) levels on postoperative day 3 (POD3), C-reactive protein (CRP) on POD3, and heart rate on POD3. In multivariate analysis, pancreas-to-muscle SIR on T1-w MRI [>1.37; odds ratio (OR)=17.08; 95% confidence interval (CI)=1.64-598.16; p=0.02], D-Amy levels on POD3 (>1,200 U/l; OR=20.00; 95% CI=1.73-563.83; p=0.02) and heart rate on POD3 (>100 bpm; OR=15.33; 95% CI=1.53-258.45; p=0.02) were identified as independent early predictive factors. Conclusion: Preoperative pancreas-to-muscle SIR on T1-w MRI and postoperative D-Amy levels and heart rate significantly correlated with POPF after DP for PC. Postoperative management based on these predictive factors may improve the postoperative course.

Abstract: BACKGROUND/AIM Surgical treatment of renal cell carcinoma (RCC) with inferior vena cava (IVC) thrombus is associated with high morbidity and mortality rates, therefore presurgical systemic therapies are required in order to improve the safety and feasibility of the surgical procedure by decreasing the thrombus level and burden. The efficacy of presurgical combination therapy of immune checkpoint inhibitors (ICI) and tyrosine kinase inhibitors (TKI) for advanced renal cell carcinoma with IVC thrombus remains unclear. CASE REPORT We report a case of a 69-year-old male with cT3bN0M0 locally advanced RCC. We successfully performed a less invasive nephrectomy with thrombectomy, because nivolumab plus cabozantinib administration remarkably reduced the primary tumor and IVC thrombus, resulting in complete pathological response, as assessed with perioperative immunohistochemistry. CONCLUSION To the best of our knowledge, this is the first report showing that nephrectomy could be safely performed for RCC with IVC thrombus after presurgical nivolumab plus cabozantinib therapy, leading to pathological complete response.

Abstract: Among intra-cellular homeostasis mechanisms, ubiquitination plays a critical role in protein metabolism regulation by degrading proteins via activating a broad spectrum of ubiquitin chains. In fact, ubiquitination and sumoylation signaling pathways are characterized by increased complexity regarding the molecules and their interactions. The Ubiquitin-Proteasome System (Ub-PS) recognizes and targets a broad spectrum of protein substrates. Ubiquitin conjugation modifies each substrate protein determining its biochemical fate (degradation). A major functional activity of Ub-PS is autophagy mechanism regulation. Interestingly, Ub-PS promotes all stages of bulk autophagy (initiation, execution, and termination). Autophagy is a crucial catabolic process that provides protein degradation and for this reason the interaction with Ub-PS is crucial. Furthermore, ubiquitination controls and regulates specific types of protein targets. Ub-PS is also involved in oxidative cellular stress and DNA damage response. Additionally, the functional role of Ub-PS in ribosome machinery regulation seems to be crucial. Concerning carcinogenesis, Ub-PS is involved in malignant disease development and progression by negatively affecting the corresponding TGF-B-, MEEK/MAPK/ERK-JNK- dependent signaling pathways. In the current review article, we describe the role of Ub-PS biochemical modifications and alterations in oral squamous cell carcinoma (OSCC).

Abstract: BACKGROUND/AIM Several studies have reported on the relationship between HOXB13 variants and an increased prostate cancer (PC) risk. To our knowledge there are not many studies on HOXB13 mutations in Japanese patients with prostate cancer, and there many issues remain uninvestigated. We herein clarified the association between HOXB13 genetic variants and PC risk in a Japanese population. PATIENTS AND METHODS PC patients were diagnosed at the Gunma University Hospital and affiliated hospitals from 1994 to 2016. Sanger sequencing was performed on the coding regions of the HOXB13 gene in 152 familial PC (FPC) patients. Genotyping was performed on single nucleotide variants (SNVs) found in Sanger sequencing in 230 FPC patients from 152 pedigrees and 197 sporadic PC (SPC) patients and 144 controls. Allelic frequency and clinical data for each variant were studied in cases and controls. RESULTS G132E and F127C were identified in FPC patients. The frequencies of G132E and F127C were significantly higher compared to the control group (p=0.039). In three families, seven PC patients shared the G132E variant, within second-to-third-degree relatives. It was not possible to clarify to pathogenicity of each SNV alone. CONCLUSION We found two significant variants of the HOXB13 gene, G132E, F127C by analyzing and comparing gene samples from PC and non-PC patients. Furthermore, the HOXB13 G132E variant was found significantly increased in the FPC group.

Abstract: BACKGROUND/AIM Cervical cancer is the most common gynecological indication for pelvic exenteration (PE). It is an ultima ratio approach to cure advanced or recurring tumors. This study aimed to evaluate data from a Single Center Institution in order to assess morbidity, mortality and survival data. PATIENTS AND METHODS Data of 24 patients, who underwent anterior (APE) or total PE (TPE) for cervical cancer at the University Hospital Marburg between 2011 and 2016, were extracted and retrospectively evaluated. Survival analysis was conducted using the Kaplan-Meyer method. RESULTS Lymph node status was pN0, pN1 and pNX in 33.3%, 20.8% and 45.8% respectively. Negative margins could be achieved in 70.8%. A total of 16.7% of patients presented with metastatic disease, while 20.8%, 37.5% and 20.8% received 1, 2 or 3 modalities of treatment respectively; 20.8% underwent up-front PE. Predominant urinary diversion was an ileum conduit (66.7%). No complications were noted for 16.7%, major complications (≥Clavien Dindo 3) in 41.7%. Overall survival was 29.2% with a median overall survival (mOS) of 19.1 months. Curative PE was undertaken in 20 cases, with 2- and 3-year survival rates of 52.6% and 29.4% respectively. and a mOS of 24 months. Positive margins, metastatic disease, positive lymph nodes, TPE and a surgical time >6 h had a significant impact on OS. CONCLUSION PE for cervical cancer remains a feasible option in cases of advanced or recurring tumors when alternative treatment options would fail. For selected patients it may represent a chance of cure with acceptable complication and satisfactory survival rates.

Abstract: BACKGROUND/AIM There are few studies on artificial intelligence-based prediction models for colon cancer built using clinicopathological factors. Here, we aimed to perform a preliminary evaluation of a novel artificial intelligence-based prediction model for surgical site infection (SSI) in patients with stage II-III colon cancer. PATIENTS AND METHODS The medical records of 730 patients who underwent radical surgery for stage II-III colon cancer between 2000 and 2018 at our institute were retrospectively analyzed. Kaplan-Meier curves were used to examine the association between SSI and oncological outcomes (recurrence-free survival time). Next, we used the machine learning software Prediction One to predict SSI. Receiver-operating characteristic curve analysis was used to evaluate the accuracy of the artificial intelligence model. RESULTS The prognosis in terms of recurrence-free survival time was poor in patients with SSI (p=0.005, 95% confidence interval=4892.061-5525.251). The area under the curve of the artificial intelligence model in predicting SSI was 0.731. CONCLUSION As SSI is an important prognostic factor associated with oncological outcomes, the prediction of SSI occurrence is important. Based on our preliminary evaluation, the artificial intelligence model for predicting SSI in patients with stage II-III colon cancer was as accurate as the previously reported model derived through conventional statistical analysis.

Abstract: BACKGROUND/AIM Radiotherapy is one of the main treatments for estrogen receptor-positive (ER+) breast cancer. However, in some ER+ breast cancer cases, radiotherapy is insufficient to inhibit progression and there is a lack of markers to predict radiotherapy insensitivity. Solute carrier family 20 member 1 (SLC20A1) is a sodium/inorganic phosphate symporter, which has been proposed to be a viable prognostic marker for luminal A and B types of ER+ breast cancer. The present study examined the possibility of SLC20A1 as a novel biomarker for the prediction of radiotherapy efficiency. PATIENTS AND METHODS The Molecular Taxonomy of Breast Cancer International Consortium dataset was downloaded from cBioportal and the prognosis of patients with high SLC20A1 expression (SLC20A1 high ) was compared with that of patients with low SLC20A1 expression, without or with radiotherapy and tumor stages I, II, and III, using the Kaplan-Meier method and multivariate Cox regression analyses of disease-specific and relapse-free survival. RESULTS Patients in the SLC20A1 high group with radiotherapy showed poor clinical outcomes in both luminal A and luminal B breast cancers. Furthermore, in luminal A breast cancer at tumor stage I, patients in the SLC20A1 high group with radiotherapy also showed poor clinical outcomes. Therefore, these results suggest that radiotherapy is insufficient for patients in the SLC20A1 high group for both luminal A and B types, and especially for the luminal A type at tumor stage I. CONCLUSION SLC20A1 can be used as a prognostic marker for the prediction of the efficacy of radiotherapy for luminal A and luminal B breast cancers.

Abstract: Background Langerhans cell histiocytosis (LCH) is a rare disease, especially in adults. It is often associated with non-fatal bone and skin lesions and has relatively good radiosensitivity. In contrast, brain and lymph node metastases from LCH lesions are considered to be less sensitive to radiotherapy. Case Report At our institution, 30 Gy radiotherapy was used to treat bone lesions with dural invasion in a patient with adult-onset LCH. The patient was treated with chemotherapy and radiotherapy for 21 years since the initial diagnosis. After radiotherapy, the tumor shrank rapidly, and a complete response was achieved 1 year after treatment. The patient survived without local recurrence. Conclusion Here, we report the details of this case, along with a review of the literature. We suggest that even with invasion of the tissues around the bone lesions in LCH, local recurrence can be prevented by middle radiation doses.

Abstract: Gynecological cancer is the cancer that originates in the female reproductive system. According to the anatomical location of the cancer, it is distinguished into cervical, uterine, vaginal, ovarian, and vulvar cancer. Oncogenes and tumor catalytic genes play a key role in the genesis and development of gynecological cancer. This article presents the signaling pathways and expression of oncogenes that take place in the carcinogenesis of the female reproductive system.

Abstract: BACKGROUND/AIM Chondrosarcoma (CS) is a rare primary malignant bone tumor, which is the second most common tumor after osteosarcoma. Since chemotherapy and radiotherapy have poor efficacy for CS, amputation or surgical wide resection is the main strategy for localized high-grade CS, making CS therapy difficult. As studies on high-grade CS are limited owing to its rare nature, there are many unknown prognostic factors for survival. PATIENTS AND METHODS This retrospective cohort study included 44 patients with high-grade CS who underwent surgery at a single institution. Overall survival (OS), distant failure-free survival (DFFS), and local failure-free survival (LFFS) were evaluated using the Kaplan-Meier method. Furthermore, we evaluated prognostic factors for survival in patients with high-grade CS using univariate and multivariate analyses. RESULTS The 5-year OS, LFFS, and DFFS rates of high-grade CS were 75.9%, 90.8%, and 66.5%, respectively. Univariate analysis revealed that tumor size, tumor grade, and surgical margin were significant prognostic factors for OS and DFFS, and distant metastasis was significantly associated with OS. Furthermore, the multivariate analysis indicated that the presence of local recurrence and distant metastasis was significantly associated with OS. CONCLUSION Local recurrence and distant metastasis were significant prognostic factors for high-grade CS.

Abstract: BACKGROUND/AIM Circulating cell-free DNA (cfDNA) isolated from serum by noninvasive procedures can serve as a potential biomarker for the early detection of many cancers. The aim of this study was to implement a simple, yet effective quantitative method for measuring the cfDNA in serum and to investigate the relationship between cfDNA and the occurrence of recurrence in breast cancer (BrCa) patients. PATIENTS AND METHODS A total of 240 cases were selected, which comprised different subtypes of BrCa patients and control individuals. We selected 20 serum samples from patients which showed recurrence after 4-7 years of disease-free survival. SYBR green was used as a reporter molecule to estimate the amount of cfDNA in these serum samples. RESULTS A global Wilcoxon analysis was performed to compare the cfDNA abundance between non-recurrent and recurrent patients. The amount of cfDNA was higher in recurrent patients (recurrent vs. non-recurrent ratio=1.3; p=0.03; AUC=0.76) compared to non-recurrent patients. The data between normal/healthy controls and non-recurrent patients indicated no significant differences (n=20 in each group, healthy to non-recurrent ratio=1.03; p=0.20; AUC=0.61). CONCLUSION We implemented a straightforward one-step technique to measure the amount of cfDNA in serum, which can translate into a clinical diagnostic tool in the near future. The high levels of cfDNA in the serum of recurrent BrCa patients compared to non-recurrent BrCa patients indicates a possible uncovered role for circulating genetic information, which either contributes to the cancer recurrence phenomenon or at the very least, serves as an identifier for the potential of recurrence.

Abstract: BACKGROUND/AIM To investigate the association between androgen deprivation therapy (ADT) and changes in the estimated glomerular filtration rate (eGFR) in male Japanese patients with prostate cancer, based on post-hoc analysis of data from a previous prospective study. PATIENTS AND METHODS Among 103 patients with prostate cancer in whom renal function changes were tracked over 5 years, 88 were divided into a group who completed ADT within 3 years (short ADT group; n=47) and a group who continued with ADT for more than 5 years (continuous ADT group; n=41). We compared the groups in terms of the eGFR, calculated based on age and serum creatinine (mg/dl) before ADT initiation and every other year over the next 5 years. RESULTS The eGFR decreased by 4.91 and 2.89 ml/min in the short and continuous ADT groups, respectively, over the 5-year period following ADT initiation. The respective decreases in the eGFR were 0.98 and 0.58 ml/min/year. No significant difference in the eGFR was observed between the two groups at any measurement point. Patients treated with ADT showed a decrease in the eGFR of 0.58-0.98 ml/min/year over a 5-year period, which is about twice as high as that of normal Japanese males. No significant difference in the eGFR by ADT duration was observed. CONCLUSION The eGFR decreased by 0.58-0.98 ml/min/year in our ADT patients, which was about twice as high as the rate of decrease in normal Japanese males, and approximately the same as in urine protein-positive male patients. We suggest that a large decrease in the eGFR may not play a role in the development of acute kidney injury. In addition, the duration of ADT does not appear to have a significant effect on the eGFR.

Abstract: BACKGROUND/AIM Triple-negative breast cancer (TNBC) prevalence and risk of relapse are greatest in African American (AA) patients. Doxorubicin (DOX) and abemaciclib (ABE) synergism in Rb-positive TNBC cells (MDA-MB-231), and antagonism in Rb-negative TNBC cells (MDA-MB-468) have been previously shown. Here, we assessed Kinesin-like protein 1 (KIFC1) as an ethnic-specific prognostic biomarker of the DOX+ABE combination for the Rb-status in TNBC. MATERIALS AND METHODS Literature search for TNBC prognostic biomarkers in the AA population was conducted. MDA-MB-231 and MDA-MB-468 cells were exposed over 72 h to four treatment arms: 1) control (medium without drug), 2) DOX at 50% inhibitory concentration in MDA-MB-231 (0.565 μM) and MDA-MB-468 (0.121 μM), 3) ABE alone (2 μM), and 4) DOX+ABE combination at their corresponding concentrations in each cell-line. KIFC1 protein expression and temporal changes were quantified in MDA-MB-231 cells using western blot. RESULTS KIFC1, Kaiso, and Annexin A2 are literature-identified AA-specific TNBC prognostic biomarkers. KIFC1 was found to be uncorrelated to other proposed biomarkers, suggesting it may predict risk independently of other TNBC biomarkers. In both cell lines, DOX alone did not significantly change KIFC1 expression relative to control. Conversely, ABE reduced KIFC1 expression in MDA-MB-231 but not in MDA-MB-468 cells. The combination DOX+ABE resulted in a greatest reduction in KIFC1 in MDA-MB-231 cells with a more rapid time-to-full inhibition of KIFC1 compared to ABE alone. CONCLUSION Change in KIFC1 expression is primarily driven by ABE in Rb-positive TNBC cells. DOX increases ABE speed to achieve a full inhibition of KIFC1 in Rb-positive, yet, without influencing its expression in Rb-negative TNBC cells.

Abstract: Background/Aim We investigated the clinical efficacy of inflammation-based indexes in predicting unfavourable relapse-free survival (RFS) in patients with stage II/III colorectal cancer (CRC) receiving oxaliplatin-based adjuvant chemotherapy. Patients and Methods A retrospective analysis was performed on 45 patients who underwent curative resection for stage II/III CRC followed by oxaliplatin-based adjuvant chemotherapy after 8 weeks. Upon adjuvant chemotherapy initiation, all patients were evaluated for lymphocyte count (LC), neutrophil/lymphocyte ratio (NLR), lymphocyte/monocyte ratio (LMR), platelet/lymphocyte ratio (PLR), modified Glasgow Prognostic Score (mGPS) and prognostic nutritional index (PNI), after which their correlation with relapse was analysed. Results Univariate analysis identified LC <1,350/mm 3 , NLR ≥2.03, LMR <5.15, PLR ≥209, mGPS 2, and early discontinuation of chemotherapy within two months as significant risk factors for RFS. Multivariate analysis identified LMR <5.15, PLR > 209 and mGPS 2 as significant independent risk factors for unfavourable RFS. Conclusion Measurement of LMR, PLR, and mGPS upon adjuvant therapy initiation can be a useful tool for predicting recurrence after curative surgery for stage II/III CRC.

Abstract: BACKGROUND/AIM Although CDK4/6 inhibitors have been increasingly used in combination with hormonal agents to treat hormone-receptor positive and human epithelial growth factor receptor 2-negative breast cancer, the mechanism of CDK4/6 inhibitor resistance and its impact on established therapy for post-resistance, especially bevacizumab combined with chemotherapy, are unclear. MATERIALS AND METHODS Sensitivity of RB knockout MCF7 clones to CDK4/6 inhibitors was evaluated in vitro. One RB knockout clone was subcutaneously implanted in nude mice and the effects of bevacizumab on volume and microvessel density (MVD) of tumors were investigated. RESULTS Palbociclib did not exhibit antitumor efficacy against the RB knockout tumor, in contrast to the parental MCF7 xenograft model. Bevacizumab significantly exhibited antitumor efficacy and suppressed the MVD both in RB knockout and parental MCF7 xenograft models. CONCLUSION Bevacizumab inhibited tumor growth by suppressing MVD in the CDK4/6 inhibitor-resistant tumor acquired due to RB loss, suggesting its efficacy also in patients after treatment with CDK4/6 inhibitors.

Abstract: AIM To report the detection of dysplastic crypts in asymmetric branching (DCAB) in biopsies from patients with ulcerative colitis (UC). PATIENTS AND METHODS One hundred consecutive endoscopic biopsies from patients with UC undergoing surveillance were reviewed. RESULTS Three biopsy/cases showed DCAB. The frequency of DCAB varied from two in one case, three in another case, and five in the remaining case. CONCLUSION The final outcome of DCAB is to generate two or more dysplastic asymmetric offspring-crypts. Repeated DCAB offspring formation, together with new DCAB, would boost the pool of dysplastic crypts, resulting in an exponential expansion of the mucosal area occupied by dysplasia in UC.