Ugur Coskun

Random-start controlled ovarian hyperstimulation for emergency fertility preservation in letrozole cycles.

OBJECTIVE To report an emergency approach of random-start controlled ovarian hyperstimulation (COH) in the late follicular or luteal phase of the menstrual cycle for embryo cryopreservation in patients with cancer. DESIGN Case series. SETTING Academic tertiary referral centers. PATIENT(S) Three patients with a diagnosis of breast cancer requiring emergency fertility preservation in the late follicular or luteal phase of the menstrual cycle. INTERVENTION(S) After baseline pelvic ultrasound and hormonal evaluation, random-start COH was commenced immediately on menstrual cycle days 11, 14, or 17 with use of letrozole 2.5 mg/d and recombinant FSH 150 to 300 IU/d. Gonadotropin-releasing hormone antagonist was administered to prevent ovulation in all cases. Ovulation was triggered with either 250 μg of recombinant hCG or 10,000 IU of urinary hCG. MAIN OUTCOME MEASURE(S) Number of oocytes harvested, maturity and fertilization rates, number of embryos frozen. RESULT(S) Nine to 17 oocytes were harvested, resulting in the freezing of seven to 10 embryos with the mean maturity and fertilization rates of 58.8% to 77.7% and 69.2% to 87.5%, respectively. CONCLUSION(S) In an emergent setting, ovarian stimulation can be started at a random cycle date for the purpose of fertility preservation without compromising fertilization rates in letrozole cycles.

Serum YKL-40 levels as a prognostic factor in patients with locally advanced breast cancer.

IntroductionYKL-40 is a growth factor for connective tissue cells; it also stimulates the migration of endothelial cells. YKL-40 is secreted by cancer cells, and elevated serum levels have been associated with poorer prognosis in metastatic breast cancer. In the present study we evaluated the prognostic role of serum YKL-40 levels in patients with locally advanced breast cancer.MethodsYKL-40 levels were measured using ELISA in serum samples obtained from 45 breast cancer patients prior to surgery and chemotherapy. The median follow-up time was 46 months (range, 10–96 months). All patients underwent surgery after chemotherapy. During the follow-up period, 21 patients relapsed and there were 17 deaths.ResultsThe median serum YKL-40 concentration in patients with locally advanced breast cancer was 149.5 μg/l (range, 25.0–1021.3 μg/l). This was higher than levels observed in healthy female controls but the difference was not significant (P=0.44). Serum YKL-40 levels were also higher in patients with tumour size >2 cm and node-positive disease but again the differences were not significant (P>0.05). Tumour volume was correlated with serum YKL-40 levels (r=0.308, P=0.039). High serum YKL-40 levels were associated with shorter disease-free and overall survival although this trend failed to reach significance (P>0.05). Multivariate analysis including tumour size, lymph node status, oestrogen and progesterone receptor status, tumour grade, and serum YKL-40 levels indicated that serum YKL-40 levels were an independent prognostic variable for overall survival (hazard ratio, 1.004; 95% confidence intervals: 1.00, 1.07; P=0.027). Tumour size, lymph node status and oestrogen receptor status were also independent prognostic variables for overall survival (P<0.05).ConclusionOur results show that serum levels of the growth factor YKL-40 may be a useful prognostic indicator of outcome for patients with locally advanced breast cancer. Further studies are required to fully elucidate the biological function of YKL-40 in breast cancer.

Imatinib mesylate-induced acute liver failure in a patient with gastrointestinal stromal tumors

Imatinib mesylate is a drug that has been approved for treatment of chronic myeloid leukemia, Philadelphia-positive acute lymphoblastic leukemia, and advanced gastrointestinal stromal tumors. Several cases of hepatotoxicity, including fatal liver failure, have been reported with the long-term use of imatinib mesylate. Generally hepatotoxicity resolves after discontinuation of imatinib. Despite discontinuation of imatinib, hepatotoxicity can be progressive. Steroid may be useful in these patients and should be started early. We report a 53-year-old woman with advanced gastrointestinal stromal tumors who developed hepatotoxicity while receiving imatinib and subsequently acute liver failure. Ten weeks after commencing imatinib treatment, hepatotoxicity was determined. Imatinib was immediately ceased. Subsequently, a week later hepatic encephalopathy, jaundice, and coagulopathy occurred. Prednisolone was commenced. Liver biopsy was performed five weeks after the determining of hepatotoxicity. Biopsy showed sinusoidal congestion, necrosis of hepatocytes, inflammation, and hepatocyte drop out around the hepatic venule consistent with drug toxicity. Her liver function tests normalized with a nine-week prednisolone treatment. The patient was discharged. Her liver enzymes remained in normal range following visits. In cases of imatinib-induced acute hepatitis, the administration of prednisolone may be useful in the resolution of the acute episode and allow the reintroduction of a drug without risking recurrence of hepatitis.

Is the Pretreatment Neutrophil to Lymphocyte Ratio an Important Prognostic Parameter in Patients with Metastatic Renal Cell Carcinoma

BACKGROUND Tyrosine kinase inhibitor is a standard treatment for mRCC. The NLR, an index of systemic inflammation, is associated with outcome in several cancer types. To study the association of pretreatment NLR with PFS and overall survival (OS) of patients treated with VEGF-targeted therapy. PATIENTS AND METHODS We retrospectively studied an unselected cohort of patients with mRCC, who were treated with TKIs. Kaplan-Meier and log-rank analyses were employed on PFS and OS and multivariate Cox proportional hazard model analyzed clinical parameters for their prognostic relevance. RESULTS A total of 100 patients with mRCC who had early progressed after first-line therapy with interferon-α were included in this retrospective multicenter study conducted at 4 centers between February 2008 and December 2011. The median of the NLR was 3.04 and patients were divided into 2 higher and lower NLR groups according to median of NLR. Median PFS was 9 versus 11 months in patients with baseline NLR > 3.04 versus ≤ 3.04 (P = .009). The median OS was 16 months versus 29 months, in patients with NLR > 3.04 versus ≤ 3.04, respectively (P = .004). In the whole group OS was independently associated with higher NLR (hazard ratio [HR], 2.406; P = .004), PFS more than 6 months (HR, 4.081; P = .0001), and sex (HR, 2.342; P = .040). On the other hand in the higher NLR group (HR, 1.107; P = .009) Memorial Sloan-Kettering Cancer Center score (HR, 3.398; P = .0001) was associated with PFS. CONCLUSION In patients with mRCC treated with VEGF-targeted therapy, pretreatment NLR, the duration of PFS might be associated with OS. This should be investigated prospectively.

Radiation induced early necrosis in patients with malignant gliomas receiving temozolomide.

BACKGROUND Temozolomide is the major drug in the treatment of malignant gliomas. Radiation induced necrosis can behave radiologically and clinically like a recurrent tumor. The major problem is the differentiation between recurrence and radiation injury especially in early phases of treatment. The aim of this study was to evaluate the patients receiving temozolomide showing early clinical or radiological progression and impact of early necrosis on follow-up. PATIENTS AND METHODS We retrospectively evaluated medical records of 67 patients with malignant glioma receiving temozolomide. All patients received concomitant radiotherapy and temozolomide followed by adjuvant temozolomide. In case of any radiological or clinical progression, MRI spectroscopy evaluation was used to confirm tumoral progression. RESULTS Radiological or clinical progression was observed in 17 (25.4%) patients. Early radiation induced necrosis was diagnosed in 4 of 17 patients (23.5%) by surgery (n=3) and MRI spectroscopy (n=1). The observed incidence of pseudoprogression was 4 in 67 (6%) patients. Patients with diagnosis of early radiation injury had median progression-free survival of 7 months compared to 5 months in patients without radiation damage (p=0.004). However, there was no statistically significant difference in terms of overall survival between groups. CONCLUSION Temozolomide can cause early radiation induced injury which can mimic progressive tumor. Although the discrimination between two entities results in the accurate evaluation of response to therapy and benefits those patients, it did not affect overall survival. MRI spectroscopy is a valuable tool to define early radiation necrosis and should be further evaluated in larger prospective studies.

Prognostic value of serum IL-18 and nitric oxide activity in breast cancer patients at operable stage

Interleukin-18 (IL-18) is a multifunctional cytokine that was previously termed interferon-&ggr;-inducing factor. It has been suggested that serum IL-18 level may be used as a prognostic factor in some cancer types. Nitric oxide is a potent biologic molecule involved in the pathogenesis of cancer. In this study, we measured serum IL-18 and nitrate + nitrite levels in 56 patients with nonmetastatic breast cancer and 14 control subjects. Serum IL-18* and nitrate + nitrite** levels were significantly higher in patients with breast cancer when compared to the control subjects (*p < 0.05, **p < 0.001). Serum IL-18 levels were significantly higher in patients whose tumor size was greater than or equal to 5 cm when compared to patients whose tumor size was less than or equal to 2 cm (p < 0.05). Patients who were axillary lymph node negative (ALN) had lower serum IL-18 levels when compared to patients with positive ALN (p < 0.001). Serum IL-18 levels were significantly higher in patients with stage IIB or IIIA when compared to patients with stage I or IIA (p < 0.05). There was no significant difference in serum nitrate + nitrite levels in terms of age, tumor stage, estrogen receptor, and menopausal and ALN status (p > 0.05). In conclusion, serum IL-18 level may be a useful marker to predict prognosis of patients with breast cancer in complete remission after surgery. Long-term follow-up is required to clarify this hypothesis.

Cyclooxygenase-2 expression and its association with angiogenesis, Helicobacter pylori, and clinicopathologic characteristics of gastric carcinoma

Cyclooxygenase-2 (COX-2) is upregulated in gastric carcinoma, and its increased levels were found to have a prognostic significance in some studies. Both angiogenesis and Helicobacter pylori infection have been reported to be associated with COX-2 expression of gastric cancer in recent studies. In this study, COX-2 expression and its association with CD31 staining, H.-pylori infection, and well-known clinicopathological factors were investigated in 65 gastric cancer patients. COX-2 and CD31 expression assessment was done by immunohistochemical methods. Whartin Starry stain was performed for H.-pylori infection. Of 65 patients, 32 (49%) revealed intense COX-2 immunostaining. Among various clinicopathologic characteristics, COX-2 expression was inversely correlated with tumor size, TNM stage, and lymph node status. Thirty-two (49%) patients revealed intense CD31 immunostaining. Among various clinicopathologic characteristics, CD31 expression was associated only with lymph node metastasis. COX-2 expression was not correlated with CD31 staining and H.-pylori infection. Both COX-2 and CD31 staining had no prognostic significance. In conclusion, we found that COX-2 expression was significantly higher in earlier stages of gastric cancer. It can be suggested that COX-2 expression may be important in the initial development of gastric cancer but not in progression of the disease. Other factors which may be associated with COX-2 in gastric cancer, including angiogenesis and H.-pylori infection, should be investigated in further studies.

Prognostic Factors for Overall Survival in Patients With Metastatic Colorectal Carcinoma Treated With Vascular Endothelial Growth Factor-Targeting Agents

OBJECTIVE Angiogenesis represents a key element in the pathogenesis of malignancy. There are no robust data on prognostic factors for overall survival (OS) in patients with metastatic colorectal cancer treated with vascular endothelial growth factor (VEGF)-targeted therapy. The present study was conducted to establish a prognostic model for patients using an oxaliplatin-based or irinotecan-based chemotherapy plus bevacizumab in metastatic colorectal cancer. METHODS Baseline characteristics and outcomes on 170 patients treated with FOLFIRI or XELOX plus anti-VEGF therapy-naive metastatic colorectal cancer were collected from three Turkey cancer centers. Cox proportional hazards regression was used to identify independent prognostic factors for OS. RESULTS The median OS for the whole cohort was 19 months (95% CI, 14.3 to 23.6 months). Three of the seven adverse prognostic factors according to the Anatolian Society of Medical Oncology (ASMO) were independent predictors of short survival: serum lactate dehydrogenase (LDH) greater than the upper limit of normal (ULN; p<0.001); neutrophils greater than the ULN (p<0.0014); and progression free survival (PFS) less than 6 months (p =0.001). CONCLUSION Serum LDH and neutrophil levels were the main prognostic factors in predicting survival, followed by PFS. This model validates incorporation of components of the ASMO model into patient care and clinical trials that use VEGF-targeting agents.

Intrasellar plasmacytoma: an unusual presentation of multiple myeloma

IntroductionPlasmacytomas are unusual causes of a sellar mass. Occasionally, they can be misdiagnosed as a nonfunctioning adenoma because of radiological and clinical similarities.Literature reviewWe reviewed the pertinent literature and discuss here in the light of an illustrative case of our own.DiscussionA 70-year-old woman presented with a recurrent hypophysial mass. Initial diagnosis of a nonfunctioning pituitary adenoma was later overruled by a repeat biopsy, which showed a plasmacytoma. The tumor stained positively for CD138 and kappa light chain. Further studies confirmed the diagnosis of multiple myeloma. The patient was successfully treated with radiotherapy followed by systemic chemotherapy. Because they have different therapeutic implications, extramedullary plasmacytomas involving pituitary gland should be considered in the differential diagnosis of a nonfunctioning pituitary mass.

Interdigitating dendritic cell tumor with breast and cervical lymph-node involvement: a case report and review of the literature

Interdigitating dendritic cell tumor (IDCT) is an extremely rare malignancy. It occurs primarily in lymph nodes, but extranodal involvement has also been reported. A 38-year-old woman with IDCT with breast and cervical lymph-node involvement is reported in this paper. To our knowledge, this is the first case of IDCT originating from the breast. In the breast and lymph node, the tumor displayed diffuse sheets, fascicles and storiform growth pattern. It was composed of oval to spindle cells with pale to eosinophilic cytoplasm, ill-defined cell outlines, oval nuclei with vesicular chromatin and prominent eosinophilic nucleoli. Mitotic activity was three per ten high-power fields. The neoplastic cells were intermingled with small mature lymphocytes and plasma cells. Immunohistochemical studies showed that the tumor cells were strongly and diffusely positive for vimentin, CD68, S-100 protein, CD45/leukocyte common antigen and fascin and focally positive for lysozyme, alpha-1 antitrypsin and CD4. Ki-67 labeling index was 10%. The patient was treated with combined therapeutic approaches, including surgery, radiotherapy and chemotherapy. IDCT has the potential for an aggressive clinical course. However, 32 months after the initial diagnosis, the patient is still alive and being followed with a stable tumor burden.