Derya Kivrak Salim

The neutrophil to lymphocyte ratio has a high negative predictive value for pathologic complete response in locally advanced breast cancer patients receiving neoadjuvant chemotherapy.

BACKGROUND The neutrophil-to-lymphocyte ratio (NLR) is a strong predictor of mortality in patients with pancreatic, colorectal, lung, gastric cancer and renal cell carcinoma. The aim of this study was to determine the relationship between pathological complete response (pCR) and pretreatment NLR values in locally advanced breast cancer (BC) patients receiving neoadjuvant chemotherapy (NACT). MATERIALS AND METHODS Datawere collected retrospectively from the Akdeniz University School of Medicine Database for locally advanced BC patients treated with NACT between January 2000- December 2013. RESULTS A total of 78 patients were analyzed. Sixteen (20%) patients achieved pCR. Estrogen receptor (ER) positivity was lower in pCR+ than pCR- cases (p=0.011). The median NLR values were similar in both arms. The optimum NLR cut-off point for BC patients with PCR+ was 2.33 (AUC:0.544, 95%CI [0.401- 0.688], p=0.586) with sensitivity, specificity, positive predictive value and negative predictive value (NPV) of 50%, 51,6%, 21,1%, and 80%, respectively. CONCLUSIONS This study showed no relationship between the pCR and pretreatment NLR values. Because of a considerable high NPV, in the patients with higher NLR who had luminal type BC in which pCR is lower after NACT, such treatment may not be recommended.

Clinicopathologic features and molecular subtypes of breast cancer in young women (age ≤35).

INTRODUCTION Breast cancer in young women is a relatively rare disease; however it tends to be more aggressive and is the leading cause of cancer death in this population. The aim of this study is to investigate the clinical and biological features of breast cancer arising in young Turkish breast cancer patients. MATERIALS AND METHODS Patients with breast cancer aged 35 or less (≤35 years) were selected for the study. In total 211 cases were included. Pathologic features; histologic subtypes, grade, lymphovascular invasion, axillary involvement, and stage were recorded for each. RESULTS The most common subtype was luminal B (36.5%), followed by luminal A (30.8%), triple negative (23.2%) and HER2+(9.5%) subtypes. Twelve percent of the patients had stage 4, 32.7% had stage 3, 46.4% had stage 2, and 6.2% had stage 1 disease at the time of diagnosis. Mean tumour diameter was 3.87 cm (range 0.3-13 cm). The axillary lymph nodes were positive in 74.4% of the patients, while lympho-vascular invasion was seen in 56.4%. Some 9.5% of patients had grade 1, 51.2% had grade 2, and 31.8% had grade 3 tumors. CONCLUSIONS Young women with breast cancer in Turkey are more likely to present with luminal B subtype. Tumors in young women are more likely to present with advanced disease, to be high grade and and to have more lymphovascular invasion. Further research should focus on whether we need new treatment strategies for young patients with breast carcinoma.

The Neutrophil to Lymphocyte Ratio is an Independent Prognostic Factor in Patients with Metastatic Gastric Cancer

Inflammation can play an important role in cancer progression and the prognostic importance of neutrophil to lymphocyte ratio (NLR), a marker of inflammation, in cancer is a current investigation topic. In the present study, we aimed to determine whether there is a prognostic link between NLR and metastatic gastric cancer (mGC). A total of 143 patients from the Akdeniz University and Antalya Training and Research Hospital database were retrospectively analyzed. The median NLR value was 3.34. The median overall survival (OS) and median progression-free survival (PFS) were 11.6 and 7.9 months, respectively, in patients with NLR<3.34 while these values were 8.3 and 6.2 months respectively in patients with NLR >3.34 (p<0.001 and p=0.011, respectively). Our study showed that increased NLR is an independent prognostic factor associated with short survival in patients with mGC.

Ipilimumab may increase the severity of cutenaous toxicity related to radiotherapy

Ipilimumab, monoclonal antibody against cytotoxic T-lymphocyte antigen-4 and, radiotherapy are commonly used to treat unresectable and metastatic melanoma. As a result of upregulation of immune system with ipilimumab, many immune-related adverse effects, such as dermatitis, colitis, hepatitis, and hypophysitis, have been previously reported in literature. Typically, these effects are treated with high-dose steroids and mostly heal up. Here, we report a case who was receiving radiotherapy due to metastatic malignant melanoma with atypical generalized rash, which was enlarged with concurrent ipilimumab treatment.

Fatal posterior revesible leukoencephalopathy syndrome associated coma induced by bevacizumab in metastatic colorectal cancer and review of literature

Posterior reversible leukoencephalopathy syndrome (PRES) is a syndrome characterized by headache, hypertension, confusion, visual disturbance, and seizures accompanied by subcortical vasogenic edema, predominantly involving the parietal and occipital lobes. The syndrome is usually described in malignant hypertension, eclampsia, renal failure, immunosuppressive, and cytotoxic chemotherapies. Bevacizumab, a monoclonal antibody that binds to the vascular endothelial growth factor (VEGF) has been linked to PRES. We carried out review of reports documenting the occurrence of PRES in patients receiving bevacizumab. This literature review was conducted by utilizing PubMed Database. If early diagnosed, PRES is reversible. We present a case of fatal PRES-associated coma induced by bevacizumab in metastatic colorectal cancer.

Molecular types and neoadjuvant chemotherapy in patients with breast cancer- while molecular shifting is more common in luminal a tumors, the pathologic complete response is most frequently observed in her-2 like tumors.

BACKGROUND Pathologic complete response (pCR) is one of the most important target end-points of neoadjuvant chemotherapy (NACT) in patients with breast cancer (BC). In present study, we aimed to investigate the relationship between molecular subtypes and NACT in patients with BC. MATERIALS AND METHODS Using the Akdeniz University database, 106 patients who received NACT for operable breast cancer were retrospectively identified. Prognostic factors before and after NACT were assessed. According to the molecular subtypes, molecular shifting after NACT and tumoral and nodal response to NACT were analyzed. RESULTS The distribution of subtypes was: Luminal A, 28.3% (n=30); Luminal B, 31.1% (n=33); HER2-like, 24.5% (n=26); and basal like/ triple negative (BL/TN), 16.0% (n=17). According to molecular subtypes, pCR rates in both breast and axillary were 0%, 21.4%, 36.4% and 27.3% for luminal A, luminal B, HER2-like and BL/TN, respectively (p=0.018). Molecular subtype shifting was mostly seen in luminal A type (28.6%) after the NACT. The pCR rate in breast and axillary was significantly higher in patients with HER2-like type BC. CONCLUSIONS In patients with HER-2 like type BC, NACT may be offered in early stages. Additionally, due to molecular shifting, adjuvant treatment schedule should be reviewed again, especially in the luminal A group.

Metronomic maintenance chemotherapy in patients presenting with paraneoplastic autoimmune hepatitis with recurrent thymic carcinoma

Autoimmune hepatitis is a rarely seen autoimmune paraneoplastic syndrome of thymic carcinoma. Chemotherapy may be an effective choice in the treatment of primary tumor and paraneoplastic disorder. In this case, we report a 32-year-old man presented with increased liver enzymes and cholestasis with a history of thymoma surgically removed four years ago. Liver biopsy showed chronic active autoimmune hepatitis. Computed tomography scan showed pulmonary metastases and pleural mass as a recurrence of thymic carcinoma, proven by biopsy. After four cycles of cisplatin plus adriamycin plus cyclophosphamide plus vincristine and six cycles of paclitaxel plus gemcitabine, maintenance metronomic cyclophosphamide plus etoposide regimen was offered to the patient. Complete biological signs of hepatitis without need for steroids or immune suppressors and complete radiologic response in primary tumor were achieved. Maintenance metronomic chemotherapy regimens may be an alternative to the current treatment options in patients with thymic carcinomas.

Experience of bevacizumab in a patient with colorectal cancer after renal transplantation.

Bevacizumab is a drug that is widely used for the first-line treatment of metastatic colorectal cancer (mCRC). Bevacizumab neutralizes vascular endothelial growth factor and can lead to proteinuria and renal damage. In this case, experience on full dose short-time treatment of bevacizumab in a patient under immunosuppressive treatment for renal transplantation with chronic renal failure has been shared. The patients were diagnosed with mCRC 7 months ago. The patient had multiple liver metastases at the time of the diagnosis. He had a history of renal transplantation 2 years ago because of renal failure, and he had been under immunosuppressive treatment for this reason. 5-fluorouracil-leucovorin-irinotecan -bevacizumab regimen was begun for the treatment of mCRC. The dose of bevacizumab was 5 mg/kg/day for 14 days. There was 2.5 g/day of proteinuria at the start of the treatment. However, renal dysfunction progressed, and proteinuria increased to 4 g/day in the 3rd month of treatment. In this case, the experience of using bevacizumab in a patient under immunosuppressive treatment for renal transplantation with chronic failure has been presented.

The importance of stromal and intratumoral tumor lymphocyte infiltration for pathologic complete response in patients with locally advanced breast cancer

Objective: Increased tumor-infiltrating lymphocytes (TILs) in breast carcinoma tissues is an independent predictive factor for pathologic complete response (pCR). The increased intratumoral and stromal TILs (sTILs) in breast cancer (BC) have significant prognostic effects. In this study, we evaluated whether pCR rates to neoadjuvant chemotherapy (NACT) are higher in tumors with increased number of TILs in the pretreatment biopsy. Materials and Methods: We retrospectively evaluated the number of TILs in intratumoral TILs (iTILs) and sTILs compartments from pretreatment full-face hematoxylin and eosin-stained sections of 62 patients with locally advanced BC (LABC) who received NACT. The capacity of sTILs and iTILs in predicting pCR to NACT in LABC analyzed using receiver operating characteristic (ROC) curve analysis. Results: According to ROC curve analysis, the optimum sTILs and iTILs cut-off points (the number of positive cells per square millimeter of tissue) for patients with LABC patients with pCR (+) were 19 (area under the curve (AUC): 0.668, 95% confidence interval [CI] [0.501–0.835],P = 0.064) and 4 (AUC: 0.786, 95%CI [0.666–0.907],P = 0.002), respectively. Of the 62 patients, 26 had sTILs >19 and 25 had iTILs >4. The patients were divided into two according to percent of sTILs (sTILs >19 and sTILs ≤19 groups) and iTILs (iTILs >4 and iTILs ≤4 groups). Both sTILs >19 and iTILs >4 patients were associated with development higher pCR. While pCR was significantly higher in iTILs >4 patients (P = 0.002), it was not significantly in sTILs >19 patients (P = 0.107). Conclusions: There is significantly an association between pCR and increased number of intratumoral TILs (>4 cells/mm 2 of tissue) in BC who received NACT.

Fallopian tube metastasis in a patient with a history of breast cancer

Breast carcinoma metastasis to the fallopian tube is extremely rare. Distinction between a primary fallopian tumor and metastasis of breast cancer is crucial since treatment and prognosis are different. However, it is difficult to confirm pathologically without surgery. Herein, we report a 46-year-old woman with a history of left modified radical mastectomy for breast cancer 13 years ago, presenting with a left adnexial mass. She underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy. Pathology findings revealed cytokeratin (CK) 7, ER, and PR positive tumor cells. Mammoglobuline, P53, CK20, GCDFP-15 and, thrombomoduline were negative. HER2 was also 2+. Fluorescence in situ hybridization (FISH) for HER2 was negative. Based on the morphology and immunophenotype of the tumor, we established the diagnosis as metastasis of breast cancer to the fallopian tube.