Catheter-Directed Ionic Liquid Embolic Agent for Rapid Portal Vein Embolization, Segmentectomy, and Bile Duct Ablation.

Embolic materials currently in use for portal vein embolization (PVE) do not treat the tumor, which poses a risk for tumor progression during the interval between PVE and surgical resection. Here, is developed an ionic-liquid-based embolic material (LEAD) for portal vein embolization, liver ablation, and drug delivery. LEAD is optimized and characterized for diffusivity, X-ray visibility, and cytotoxicity. In the porcine renal embolization model, LEAD delivered from the main renal artery reached vasculature down to 10 microns with uniform tissue ablation and delivery of small and large therapeutics. In non-survival and survival porcine experiments, successful PVE is achieved in minutes, leading to the expected chemical segmentectomy, and delivery of a large protein drug (i.e., Nivolumab) with LEAD. In cholangiocarcinoma mouse tumor models and in ex vivo human tumors, LEAD consistently achieved an effective ablation and wide drug distribution. Furthermore, various strains of drug-resistant patient-derived bacteria showed significant susceptibility to LEAD, suggesting that LEAD may also prevent infectious complications resulting from tissue ablation. With its capabilities to embolize, ablate, and deliver therapeutics, ease of use, and a high safety profile demonstrated in animal studies, LEAD offers a potential alternative to tumor ablation with or without PVE for FLR growth.

Bioengineered Ionic Liquid for Catheter-Directed Tissue Ablation, Drug Delivery, and Embolization.

Delivery of therapeutics to solid tumors with high bioavailability remains a challenge and is likely the main contributor to the ineffectiveness of immunotherapy and chemotherapy. Here, a catheter-directed ionic liquid embolic (ILE) is bioengineered to achieve durable vascular embolization, uniform tissue ablation, and drug delivery in non-survival and survival porcine models of embolization, outperforming the clinically used embolic agents. To simulate the clinical scenario, rabbit VX2 orthotopic liver tumors are treated showing successful trans-arterial delivery of Nivolumab and effective tumor ablation. Furthermore, similar results are also observed in human ex vivo tumor tissue as well as significant susceptibility of highly resistant patient-derived bacteria is seen to ILE, suggesting that ILE can prevent abscess formation in embolized tissue. ILE represents a new class of liquid embolic agents that can treat tumors, improve the delivery of therapeutics, prevent infectious complications, and potentially increase chemo- and immunotherapy response in solid tumors.

Advances and Challenges in Interventional Immuno-Oncology Locoregional Therapies.

Interventional immuno-oncology is making strides in locoregional therapies to address complex tumor microenvironments. Long-standing interventional radiology cancer therapies, such as tumor ablation and embolization, are being recharacterized in the context of immunotherapy. Intratumoral injections, such as those of genetically engineered or unaltered viruses, and the delivery of immune cells, antibodies, proteins, or cytokines into targeted tumors, along with advancements in delivery techniques, have produced promising results in preliminary studies, indicating their antitumor effectiveness. Emerging strategies using DNA scaffolding, polysaccharides, glycan, chitosan, and natural products are also showing promise in targeted cancer therapy. The future of interventional immuno-oncology lies in personalized immunotherapies that capitalize on individual immune profiles and tumor characteristics, along with the exploration of combination therapies. This study will review various interventional immuno-oncology strategies and emerging technologies to enhance delivery of therapeutics and response to immunotherapy.

Silk Embolic Material for Catheter-Directed Endovascular Drug Delivery.

Embolization is a catheter-based minimally invasive procedure that deliberately occludes diseased blood vessels for treatment purposes. A novel silk-based embolic material (SEM) that is developed and optimized to provide tandem integration of both embolization and the delivery of therapeutics is reported. Natural silk is processed into fibroin proteins of varying lengths and is combined with charged nanoclay particles to allow visibility and injectability using clinical catheters as small as 600 µm in diameter at lengths >100 cm. SEMs loaded with fluorochrome labeled bovine albumin and Nivolumab, which is among the most used immunotherapy drugs worldwide, demonstrate a sustained release profile in vitro over 28 days. In a porcine renal survival model, SEMs with labeled albumin and Nivolumab successfully embolize porcine arteries without recanalization and lead to the delivery of both albumin and Nivolumab into the interstitial space of the renal cortex. Mechanistically, it is shown that tissue delivery is most optimal when the internal elastic membrane of the embolized artery is disrupted. SEM is a potential next-generation multifunctional embolic agent that can achieve embolization and deliver a wide range of therapeutics to treat vascular diseases including tumors.

Effects of Primary Tumor Resection on Metastatic Breast Cancer Survival and the Predictive Power of Neutrophil: Lymphocyte Ratio on Prognosis.

OBJECTIVE: The aim was to investigate the effect of primary tumor resection (PTR) on survival in metastatic breast cancer patients and to assess the power of the neutrophil-to-lymphocyte ratio (NLR) regarding the prediction of prognosis in this patient group. MATERIALS AND METHODS: Female patients diagnosed with and starting treatment for metastatic breast cancer from 2003 to 2016 in the general surgery and oncology clinics at a single center were retrospectively reviewed. Pre-treatment NLR value and survival situations were evaluated. RESULTS: A total of 117 patients were enrolled. The disease-specific survival (DSS) of the patients was 41.4 months. When stratified into PTR and systemic treatment (ST) groups, there was no difference in the survival (p = 0.054); 43.5 months in the PTR group vs 30.7 months in the ST group. When hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative subgroups were analyzed, DSS was significantly longer (p = 0.02) in the PTR group (55.4 months) compared to the ST group (41.8 months). Finally, in patients with an NLR of <2.3, DSS was significantly longer (p = 0.03) in the PTR group (56.1 months) compared to the ST group (25.2 months). CONCLUSION: These results suggest that DSS can be increased with PTR in selected patients with a diagnosis of metastatic breast cancer. NLR may be useful in selecting patients for appropraite treatment modality.

Prognostic factors in patients with metastatic urothelial carcinoma who have treated with Atezolizumab.

BACKGROUND: Atezolizumab (ATZ) has demonstrated antitumor activity and manageable safety in previous studies of patients with metastatic platinum-resistant urothelial carcinoma. However, the response rate of Atezolizumab was modest. In the current study, we evaluated the pretreatment prognostic factors for overall survival in patients with metastatic urothelial carcinoma who have progressed after first-line chemotherapy in the Expanded-Access Program of Atezolizumab. PATIENTS AND METHODS: In this study, we present a retrospective analysis of 113 patients with urothelial cancer treated with ATZ after progression on first-line chemotherapy. Data of the patients was obtained from patient files and hospital records. Eligible patients included metastatic urothelial carcinoma patients treated with at least one course of ATZ. Univariate analysis was used to identify clinical and laboratory factors that significantly impact OS. Variables were retained for multivariate analysis if they had a statistical relationship with OS (p < 0.1), and then included a final model of p < 0.05. RESULTS: The median follow-up duration was 23.5 months. Of the patients, 98 (86.7%) were male and 13.3% were female. The median age was 65 years of age (37-86). In univariate analysis, primary tumor location in the upper tract, increasing absolute neutrophil count (ANC), increasing absolute lymphocyte count, neutrophil-to-lymphocyte ratio (NLR) > 3, liver metastases, baseline creatinine clearance less (GFR) than 60 ml/min, Eastern Cooperative Oncology Group (ECOG) performance status (1 ≥), and hemoglobin levels below 10 mg/dl were all the significantly associated with OS. Three of the five adverse prognostic factors according to the Bellmunt criteria were independent of short survival: liver metastases HR 3.105; 95% CI 1.673-5.761; p < (0.001), ECOG PS (1 ≥) HR 2.184; 95% CI 1.120-4.256; p = 0.022, and Hemoglobin level below 10 mg/dl HR 2.680; 95% CI 1.558-4.608; p < (0.001). In addition, NLR > 3 hazard ratio [HR] 2.092; 95% CI 1.031-4.243; p = 0.041 and GFR less than 60 ml/min HR 1.829; 95% CI 1.1-3.041; p = 0.02, maintained a significant association with OS in multivariate analysis. CONCLUSIONS: This model confirms the Bellmunt model with the addition of NLR > 3 and GFR less than 60 ml/min and can be associated with clinical trials that use immunotherapy in patients with bladder cancer.

Pembrolizumab alone or combined with chemotherapy versus chemotherapy as first-line therapy for advanced urothelial carcinoma (KEYNOTE-361): a randomised, open-label, phase 3 trial.

BACKGROUND: PD-1 and PD-L1 inhibitors are active in metastatic urothelial carcinoma, but positive randomised data supporting their use as a first-line treatment are lacking. In this study we assessed outcomes with first-line pembrolizumab alone or combined with chemotherapy versus chemotherapy for patients with previously untreated advanced urothelial carcinoma. METHODS: KEYNOTE-361 is a randomised, open-label, phase 3 trial of patients aged at least 18 years, with untreated, locally advanced, unresectable, or metastatic urothelial carcinoma, with an Eastern Cooperative Oncology Group performance status of up to 2. Eligible patients were enrolled from 201 medical centres in 21 countries and randomly allocated (1:1:1) via an interactive voice-web response system to intravenous pembrolizumab 200 mg every 3 weeks for a maximum of 35 cycles plus intravenous chemotherapy (gemcitabine [1000 mg/m2] on days 1 and 8 and investigator's choice of cisplatin [70 mg/m2] or carboplatin [area under the curve 5] on day 1 of every 3-week cycle) for a maximum of six cycles, pembrolizumab alone, or chemotherapy alone, stratified by choice of platinum therapy and PD-L1 combined positive score (CPS). Neither patients nor investigators were masked to the treatment assignment or CPS. At protocol-specified final analysis, sequential hypothesis testing began with superiority of pembrolizumab plus chemotherapy versus chemotherapy alone in the total population (all patients randomly allocated to a treatment) for the dual primary endpoints of progression-free survival (p value boundary 0·0019), assessed by masked, independent central review, and overall survival (p value boundary 0·0142), followed by non-inferiority and superiority of overall survival for pembrolizumab versus chemotherapy in the patient population with CPS of at least 10 and in the total population (also a primary endpoint). Safety was assessed in the as-treated population (all patients who received at least one dose of study treatment). This study is completed and is no longer enrolling patients, and is registered at ClinicalTrials.gov, number NCT02853305. FINDINGS: Between Oct 19, 2016 and June 29, 2018, 1010 patients were enrolled and allocated to receive pembrolizumab plus chemotherapy (n=351), pembrolizumab monotherapy (n=307), or chemotherapy alone (n=352). Median follow-up was 31·7 months (IQR 27·7-36·0). Pembrolizumab plus chemotherapy versus chemotherapy did not significantly improve progression-free survival, with a median progression-free survival of 8·3 months (95% CI 7·5-8·5) in the pembrolizumab plus chemotherapy group versus 7·1 months (6·4-7·9) in the chemotherapy group (hazard ratio [HR] 0·78, 95% CI 0·65-0·93; p=0·0033), or overall survival, with a median overall survival of 17·0 months (14·5-19·5) in the pembrolizumab plus chemotherapy group versus 14·3 months (12·3-16·7) in the chemotherapy group (0·86, 0·72-1·02; p=0·0407). No further formal statistical hypothesis testing was done. In analyses of overall survival with pembrolizumab versus chemotherapy (now exploratory based on hierarchical statistical testing), overall survival was similar between these treatment groups, both in the total population (15·6 months [95% CI 12·1-17·9] with pembrolizumab vs 14·3 months [12·3-16·7] with chemotherapy; HR 0·92, 95% CI 0·77-1·11) and the population with CPS of at least 10 (16·1 months [13·6-19·9] with pembrolizumab vs 15·2 months [11·6-23·3] with chemotherapy; 1·01, 0·77-1·32). The most common grade 3 or 4 adverse event attributed to study treatment was anaemia with pembrolizumab plus chemotherapy (104 [30%] of 349 patients) or chemotherapy alone (112 [33%] of 342 patients), and diarrhoea, fatigue, and hyponatraemia (each affecting four [1%] of 302 patients) with pembrolizumab alone. Six (1%) of 1010 patients died due to an adverse event attributed to study treatment; two patients in each treatment group. One each occurred due to cardiac arrest and device-related sepsis in the pembrolizumab plus chemotherapy group, one each due to cardiac failure and malignant neoplasm progression in the pembrolizumab group, and one each due to myocardial infarction and ischaemic colitis in the chemotherapy group. INTERPRETATION: The addition of pembrolizumab to first-line platinum-based chemotherapy did not significantly improve efficacy and should not be widely adopted for treatment of advanced urothelial carcinoma. FUNDING: Merck Sharp and Dohme, a subsidiary of Merck, Kenilworth, NJ, USA.

Atezolizumab in Patients with Metastatic Urothelial Carcinoma Who Have Progressed After First-line Chemotherapy: Results of Real-life Experiences.

BACKGROUND: Atezolizumab (ATZ) has demonstrated antitumor activity and manageable safety in previous studies in patients with locally advanced or metastatic platinum-resistant urothelial carcinoma. OBJECTIVE: To compare the real-life experience and data of clinical trials on ATZ treatment in metastatic urothelial carcinoma. DESIGN, SETTING, AND PARTICIPANTS: Patients with urothelial cancer treated with ATZ after progression on first-line chemotherapy from an expanded access program were retrospectively studied. Data of patients were obtained from their files and hospital records. Safety was evaluated for patients treated with at least one cycle of ATZ. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was objective response rate (ORR). The secondary endpoints are overall survival (OS), progression-free survival (PFS), duration of response, and safety profile of patients. Kaplan-Meier methods were used to calculate median follow-up and estimate PFS and OS. RESULTS AND LIMITATIONS: Data of 115 enrolled patients were analyzed. Most of the patients (92.3%, n = 106) had received chemotherapy regimen only once prior to ATZ. The median follow-up duration was 23.5 mo. The complete response rate, partial response rate, and ORR were 8.7% (n = 10), 20.0% (n = 23), and 28.7% (n = 33), respectively. The median duration of response was 20.4 mo (95% confidence interval [CI], 6.47-28.8). Of the 33 patients who responded to treatment, 60% (n = 20) had an ongoing response at the time of the analysis. PFS and OS with ATZ were 3.8 mo (95% CI, 2.25-5.49) and 9.8 mo (95% CI, 6.7-12.9), respectively. All-cause and any-grade adverse events were observed in 113 (98%) patients. Of the patients, 64% experienced a treatment-related adverse event of any grade and 24 (21.2%) had a grade 3-4 treatment-related adverse event. Limitations of the study included its retrospective design, and determination of treatment response based on clinical notes and local radiographic studies. CONCLUSIONS: In these real-life data, ATZ was effective and well tolerated in patients with metastatic urothelial carcinoma who have progressed with platinum-based first-line chemotherapy. ATZ is an effective and tolerable treatment for patients with locally advanced or metastatic platinum-resistant urothelial carcinoma in our study, similar to previously reported trials. PATIENT SUMMARY: Atezolizumab is effective and well-tolerated in patients with metastatic urothelial cancer who progressed with first-line chemotherapy, consistent with the outcomes of the previous clinical trials in this setting.

Efficacy of Palbociclib and Endocrine Treatment in Heavily Pretreated Hormone Receptor-positive/HER2-negative Advanced Breast Cancer: Retrospective Multicenter Trial

Background: The synthesis of CDK4/6 inhibitors with endocrine treatment in two series of treatment has been widely accepted as the standard for patients with estrogen receptor-positive metastatic breast cancer. In spite of this, the activity of CDK4/6 inhibitors in patients with metastatic breast cancer who have progressed despite receiving multiple lines of treatment is not well understood. Aims: To report the activity and safety of a CDK4/6 inhibitor (palbociclib) in patients in whom at least three lines of treatment for ER+ metastatic breast cancer had failed. Study Design: Multicenter retrospective observational cohort study. Methods: In this retrospective observational cohort study, we included 43 patients who received palbociclib after at least three lines of systemic treatment for ER+/HER2− metastatic breast cancer. Results: The median progression-free survival in our population was 7 months (25th-75th percentile, 4-10), and the median overall survival was 11 months (25th-75th percentile, 6-19). Although there were some adverse events, palbociclib was generally well tolerated, so dose reduction was needed for only six patients (14%). Conclusion: The efficacy of palbociclib among heavily treated hormone receptor-positive/HER2− patients with advanced breast cancer was acceptable in terms of clinical benefit, and it was generally well tolerated among this population.

Hyperprogression after immunotherapy: A comprehensive review.

Immune checkpoint inhibitors have revolutionized cancer treatment with patient improved survival, quality of life, and a longer response. However, up to 30% of patients experience paradoxical accelerated tumor progression early after immune-checkpoint blockade therapy. This phenomenon is also known as hyperprogression (HP). Unlike other responses, such as pseudoprogression or natural progression, HP causes worse survival outcomes in patients. Older age, higher metastatic burden, and previous radiation have been independently associated with HP. Even though the exact molecular mechanism underlying HP after immune-checkpoint blockade therapy remains unknown, oncogenic signaling activation including MDM2 amplification or EGFR alterations, the modification of tumor microenvironment by radiotherapy with immune checkpoint inhibitors, and alterations in immune landscape of tumors have been hypothesized as the biological mechanisms behind HP. Patients with HP have been presented with poor prognosis and increased deleterious mutations in cancer genes, along with alterations in the tumor microenvironment. As immune checkpoint inhibitors have been more widely accepted by oncologists, proper assessment of this unique tumor response remains challenging in clinical practice. This work documents the recent findings on epidemiology, biological and clinicopathological factors of HP after immunotherapy.

Adding taxane to platin-5-fluorouracil combination does not improve survival rate in patients ≥ 65 years of age with advanced gastric cancer: A retrospective-multicenter study.

PURPOSE: Advanced gastric cancer (AGC) has a dismal prognosis. Platin-5-fluorouracil (CF) combination chemotherapy is the most widely used protocol and addition of a taxane (TCF) seems to increase survival and toxicity rates. We aimed to evaluate efficacy and toxicity of TCF as compared to CF in patients older than 65 years and compare them with the patients younger than 65 years. METHODS: A total of 341 patients with AGC have been treated at six different oncology centers in Turkey between 2010 and 2014 and evaluated retrospectively. The characteristics of the patients whose tumors were histologically confirmed and whose survival data were available were registered and analyzed. The study group consisted of 234 patients younger than 65 years (group 1) and 107 patients older than 65 years (group 2). All of the data obtained from the patients were statistically analyzed. RESULTS: The median age of the patients was 58.2 years and the mean follow-up time 14.4 months. For the entire group, progression-free survival (PFS) and overall survival (OS) were 9 and 13 months, respectively. Using TCF over CF regimen increased the OS by 4.2 months (i.e., group 1 and 2 together). For group 2, patients with liver metastases and without surgery of the primary tumor were treated with significantly more TCF as compared to CF, respectively. Although TCF yielded significantly higher PFS and OS in group 1 (p=0.0001 and p=0.017), there was no significant difference in group 2 as compared to CF. Also, grade 3-4 toxicity was statistically defined as one of the possible reasons of worsened OS in patients older than 65 years and receiving TCF. CONCLUSIONS: The addition of taxanes to CF backbone leads to a significant increase in both PFS and OS in patients younger than 65 years of age but the triplet regimen with taxanes does not provide superior survival in patients older than 65 years of age.

Effectiveness of Platinum-Based Treatment for Triple Negative Metastatic Breast Cancer: a Meta-Analysis

Background: Triple-negative breast cancer (TNBC) is a sub-group of breast cancers with a particularly poor prognosis. The results of studies investigating the role of platinum-based chemotherapy (PBC) in metastatic TNBC (mTNBC) have been conflicting. In this meta-analysis, our aim was to assess the effectiveness of PBCs for mTNBCs. Methods: The PubMed, Cochrane Controlled Trials Register Databases, and EBSCOhost databases were accessed. The English language was used as the search language and only human studies were included. The Newcastle­Ottawa Quality Assessment Scale and the Jadad scoring system were used to evaluate the quality of the included randomized controlled studies. Results: Seven studies and 1,571 patients were included in this meta-analysis. The pooled hazard ratio (HR) for overall survival (OS), evaluated on the basis of six studies, showed the use of PBC regimes to be related to OS in mTNBCs (HR 0.620; 95% CI 0.513-0.749; p:<0.001). Four studies containing HR and abstract statistics used for HR calculation were included in the meta-analysis for progression-free survival (PFS). The pooled HR again indicated a significant relation (HR, 0.628; 95% CI, 0.501-0.786; p:<0.001). Conclusions: In this meta-analysis, we confirmed that PBC regimes provide OS and PFS advantages compared to non-PBC regimes. The use of PBC regimes could be a good choice in mTNBC patients for better quality of life and survival.

Two Uncommon Sites of Metastasis: Breast and Hypophysis Metastases of Head and Neck Adenoid Cystic Carcinoma Detected by FDG PET/CT.

Adenoid cystic carcinoma (ACC) is a rare epithelial malignancy arising from secretory glands, particularly the salivary glands. It tends to invade nerves and has a high potential for distant hematogenous metastasis, especially to the lungs, bone, liver and brain. The breast and hypophysis are not common sites of ACC metastatic disease. Herein, we report a case of ACC of the head and neck region with two unusual sites of metastases, the hypophysis and breast.

Docetaxel plus cisplatin plus fluorouracil versus carboplatin plus fluorouracil-cetuximab in first-line setting in patients with recurrent or metastatic head and neck squamous cell cancer who did not previously receive neoadjuvant or adjuvant chemotherapy, which is standard?

BACKGROUND: The prognosis of recurrent or metastatic head and neck squamous cell cancer (HNSCC) is very poor. In the present retrospective study, we compared the impact of docetaxel plus cisplatin plus fluorouracil (TCF), and cisplatin plus fluorouracil plus cetuximab (CF-Ctx) regimens on the prognosis of patients with recurrent or metastatic HNSCC in first-line. MATERIALS AND METHODS: A total of 70 patients were evaluated as two groups, according to treatment protocol: TCF (n: 47) and CF-Ctx (n: 23). The groups were compared regarding survival. RESULTS: The median progression-free survival was 7.3 and 8.3 months, TCF and CF-Ctx groups, respectively, (P = 0.280). The median overall survival (OS) was 15.6 and 9.3 months for TCF and CF-Ctx groups, respectively, (P = 0.029). The dose reduction and using of granulocyte colony stimulating factor were significantly higher in TCF group (P = 0.048 and P = 0.018, respectively). CONCLUSION: In first-line setting, TCF regimen is superior to CF-Ctx regimen in terms of OS in patients with recurrent or metastatic HNSCC, who did not previously receive neoadjuvant or adjuvant chemotherapy.

Expression of claudin 1, 4 and 7 in thyroid neoplasms.

The distinction of thyroid carcinoma from benign thyroid neoplasm, as well as the subtyping of papillary carcinoma (PC) and follicular carcinoma (FC), may be performed histopathologically in the majority of cases. However, in certain cases, it is difficult to histopathologically distinguish between PC and FC, as well as follicular adenoma (FA), FC and the dominant nodule of multinodular goiter (MNG-DN). The present study aimed to determine the roles of the expression levels of the tight junction proteins claudin 1, 4 and 7 in the differential diagnosis of PC, FC, FA, MNG-DN, medullary carcinoma (MC) and anaplastic carcinoma (AC). The current study included 114 cases of histopathologically diagnosed thyroid neoplasia, which were distributed as follows: 29 FA, 18 MNG-DN, 47 PC, 10 FC, 5 MC and 5 AC. The expression levels of claudin 1, 4 and 7 were examined using immunohistochemical methods. The results revealed a significant difference in claudin 1 expression between malignant and benign thyroid neoplasms (P<0.001). Claudin 1 expression was not detected in any of the MNG-DN cases, and no significant difference in claudin 1 expression levels was identified between FA and FC (P=0.653). However, a statistically significant difference was observed between FC and PC (P<0.001). Claudin 4 expression did not differ between malignant and benign thyroid neoplasms, neither between MNG-DN, FA and FC, nor between FC and PC (P=0.068, P=0.502 and P=0.481, respectively). Claudin 7 exhibited positive immunohistochemical staining in 107 patients (94%); however, no significant difference in claudin 7 expression §levels was identified between malignant and benign thyroid neoplasms among MNG-DN, FA and FC (malignant, P=0.135; benign, P=0.470). Claudin 7 exhibited positive staining in all PC and FC cases. Therefore, claudin 1 expression levels may be useful in distinguishing cases of FC and PC with overlapping histopathological features, and provide a novel immunohistochemical marker for the subtyping of thyroid carcinoma.

Platelet Distribution Width as a Predictor of Metastasis in Gastric Cancer Patients.

INTRODUCTION: There are few known predictors of gastric cancer (GC). In this study, we evaluated the relationship between peripheral blood parameters and disease in patients with GC. Our aim was to identify a predictor of the development of metastasis. MATERIALS AND METHODS: Pretreatment peripheral blood parameters, including neutrophil, lymphocyte, and platelet counts; median platelet values (MPVs); and platelet distribution width (PDW), of patients diagnosed with GC were assessed. The independent T test was used in comparisons between two groups with a normal distribution, the Mann-Whitney U test in comparisons between two groups without a normal distribution, the Kruskal-Wallis test to compare more than two groups, and the Dunn's multiple comparison test to compare subgroups. A p value <0.05 was considered statistically significant. RESULTS: In GC patients, neutrophil and platelet counts, but not lymphocyte counts and MPVs, increased significantly with disease stage progression. Among patients who developed a metastasis during follow-up, the relationship between PDW and the risk of metastasis was statistically significant (p = 0.04). Both lymphocyte and platelet levels had a statistically significant relationship to survival (p = 0.04 and p = 0.02, respectively). CONCLUSIONS: Our results showed that in patients with GC, PDW, one of the standard parameters measured in a complete blood count, is a predictor of metastasis. Therefore, the PDW may be an important consideration in the surgical and chemotherapeutic treatment planning of patients with GC. Treatment strategies should also take into account lymphocyte and platelet levels, both of which were shown to be significantly related to survival.

Preoperative neutrophil-to-lymphocyte ratio and plateletto- lymphocyte ratio as new prognostic factors for patients with colorectal cancer.

PURPOSE: The objective of this study was to preoperatively evaluate blood platelet to lymphocyte ratio (PLR) and neutrophil to lymphocyte ratio (NLR) for their prognostic value in patients with colorectal cancer (CRC). METHODS: We retrospectively reviewed 347 patients who underwent colorectal surgery for CRC in the Istanbul Education and Research Hospital and the Antalya Education and Research Hospital. The prognostic value of preoperative PLR, NLR, and other clinical and laboratory parameters was assessed with univariate and multivariate analysis. RESULTS: Median overall survival (OS) was 61.8 months [95% CI for hazard ratio (HR) 46.24-77.14]. Significant parameters in univariate analysis, which were the preoperative levels of carcinoembryonic antigen (CEA) (p=0.055), albumin (p=0.003), hemoglobin (p=0.012), PLR (p=0.004), and NLR (p=0.054) were assessed by multivariate analysis which showed that only albumin retained its significance (p=0.008). Median OS was 70.1 vs 44.8 months with PLR ? 180 vs PLR > 180 (log rank; p=0.005). Median OS was "Not reached" (NR) vs 43.5 months with NLR ? 3 vs NLR > 3 (log rank; p=0.012). CONCLUSIONS: This study showed that preoperative levels of CEA, albumin, PLR, and NLR have significant prognostic value for patients with CRC.

Primary Tumor Resection and Survival in Patients with Stage IV Gastric Cancer.

PURPOSE: The aim of this study was to determine whether surgical resection of the primary tumor contributes to survival in patients with metastatic gastric cancer. MATERIALS AND METHODS: A total of 288 patients with metastatic gastric cancer from the Akdeniz University, Antalya Training and Research Hospital, and the Meram University of Konya database were retrospectively analyzed. The effect of primary tumor resection on survival of patients with metastatic gastric cancer was investigated using the log-rank test. Kaplan-Meier survival estimates were calculated. Multivariate analysis was performed using Cox proportional hazards regression modeling. RESULTS: The median overall survival was 12.0 months (95% confidence intewrval [CI], 10.4~13.6 months) and 7.8 months (95% CI, 5.5~10.0 months) for patients with and without primary tumor resection, respectively (P<0.001). The median progression-free survival was 8.3 months (95% CI, 7.1~9.5 months) and 6.2 months (95% CI, 5.8~6.7 months) for patients with and without primary tumor resection, respectively (P=0.002). CONCLUSIONS: Non-curative gastrectomy in patients with metastatic gastric cancer might increase their survival rate regardless of the occurrence of life-threatening tumor-related complications.

A new marker for breast cancer diagnosis, human epididymis protein 4: A preliminary study.

Breast cancer is the most frequently diagnosed cancer type in women. Tumor markers have been widely used for assessing the treatment response and early diagnosis of recurrence. Human epididymis protein 4 (HE4) is expressed in ductal carcinoma of the breast tissue; however, its serum levels and their diagnostic and prognostic potential in breast cancer have not been investigated, which was therefore the aim of the present study. The serum levels of HE4 were determined in 36 breast cancer patients, 11 ovarian cancer patients and 16 healthy volunteers. The association between clinicopathological characteristics of breast cancer and serum HE4 levels was investigated. A significant difference in the median serum levels of HE4 was identified between breast cancer patients, ovarian cancer patients and healthy volunteers (P=0.013). The cutoff value for the prediction of breast cancer was determined at >13.24 pmol/l for HE4, with a sensitivity of 61.11%, specificity of 68.75%, positive predictive value of 81.48%, negative predictive value of 44.0% and accuracy of 63.46%. Furthermore, a positive correlation between the serum levels of HE4 and cancer antigen 15-3 was determined (r=0.399, P=0.026). To the best of our knowledge, the present study was the first to determine the diagnostic value of serum HE4 for breast cancer. A significant elevation of serum HE4 levels in patients with breast cancer compared with that in healthy controls was identified. HE4 may serve as a novel biomarker for the diagnosis of breast cancer.

Mean Platelet Volume as an Independent Predictive Marker for Pathologic Complete Response after Neoadjuvant Chemotherapy in Patients with Locally Advanced Breast Cancer.

BACKGROUND: The impact of mean platelet volume (MPV) on prognosis, diagnosis and response to therapy in cancer patients has been widely investigated. In the present study, we evaluated whether MPV at diagnosis has predictive value for pathologic complete response (pCR) after neoadjuvant chemotherapy in patients with locally advanced breast cancer (LABC). MATERIALS AND METHODS: A total of 109 patients with LABC from Akdeniz University and Antalya Research and Training Hospital were evaluated retrospectively. RESULTS: ROC curve analysis suggested that the optimum MPV cut-off point for LABC patients with pCR (+) was 8.15 (AUC:0.378, 95%CI [0.256- 0.499], p=0.077). The patients with MPV <8.15 had higher pCR rates (29.2% vs. 13.1%, p=0.038). After binary logistic regression analysis, MPV and estrogen receptor absence were independent predictors for pCR. CONCLUSIONS: MPV has an independent predictive value for pCR after neoadjuvant chemotherapy in patients with LABC.