Nil Mandel

Gallium-68 (68Ga) prostate-specific-membrane-antigen positron-emission-tomography/computed-tomography is a highly promising method for imaging primary and recurrent prostate cancer. These dual-modality imaging technologies enable whole-body functional and anatomical evaluation in a single session. This study investigated the performance of 68Ga-prostate-specific-membrane-antigen-11 positron-emission-tomography/computed-tomography for detecting prostate carcinoma in patients with rising prostate-specific-antigen after primary therapy. Six hundred sixty (660) patients with biochemical recurrence referred for positron-emission-tomography/computed-tomography with 68Ga-prostate-specific-membrane-antigen-11 were evaluated retrospectively. Prostate-specific-antigen-stratified cohorts of pathological scan results were analyzed, and relationships between prostate-specific-antigen kinetics and PSMA-positive tumor lesions were correlated. Gallium-68 prostate-specific-membrane-antigen-11 positr...

Background and Purpose: To investigate the role of postoperative concomitant chemoradioimmunotherapy in gastric adenocarcinoma patients. Patients and Methods: 59 patients, who underwent total or subtotal gastrectomy, with lymph node involvement, positive microscopic surgical margins or serosal involvement were included in the study. Radiotherapy started concomitantly with chemotherapy and levamisole. Extended-field radiotherapy was given to gastric bed and regional lymphatics via two anterior-posterior/posterior-anterior fields. A total dose of 45 Gy in 25 fractions with a fraction size of 1.8 Gy was planned. In 28 patients (48%) with positive surgical margins a 10-Gy boost dose was given to the anastomosis site. An adjuvant i.v. bolus of 450 mg/m2/day 5-fluorouracil (5-FU) was administered concomitantly during the first 3 days and at the 20th day of irradiation. After completion of radiotherapy, i.v. boluses of 450 mg/m2/day 5-FU and 25 mg/m2/day rescuvorin were continued for 6 months once a week. Levamisole 40 mg/day orally was started at the 1st day of radiotherapy and also continued for 6 months. Median follow-up was 37 months (7–112 months). Results: Median survival was 23 months. Overall 3- and 5-year survival rates amounted to 35% and 14%, respectively. Median survival of the patients with positive surgical margins was 22 months. The 3- and 5-year locoregional control rates were 59% and 55%, respectively. The most common toxicity was upper gastrointestinal system toxicity, which was observed in 42 patients (71%). Four patients (7%) died on account of early toxic effects, and six (10%) could not complete treatment. Conclusion: Although 48% of the study population involved patients with microscopic residual disease, the survival results as a whole were satisfactory. However, due to high toxicity, radiotherapy must be delivered with the most proper techniques along with adequate nutrition and supportive care. Hintergrund und Ziel: Untersuchung der Rolle der postoperativen Radiochemotherapie bei Patienten mit Adenokarzinom des Magens. Patienten und Methodik: 59 total oder subtotal operierte Patienten mit Adenokarzinom des Magens, die eine Invasion der Serosaoberfläche, einen Befall der regionären Lymphknoten oder positive Resektionsränder aufwiesen, wurden in die Studie eingeschlossen. Postoperativ wurde eine simultane Radiochemotherapie begonnen. Die Bestrahlung wurde in „Extended-field“-Technik über zwei Felder (anterior-posterior und posterior-anterior) mit einer Gesamtdosis von 45 Gy in 25 Fraktionen zu 1,8 Gy appliziert. 28 Patienten (48%) mit positiven Resektionsrändern erhielten zusätzlich einen 10-Gy-Boost auf den Anastomosenbereich. Die adjuvante Chemotherapie mit einem 450-mg/m2-Bolus 5-Fluorouracil (5-FU) wurde an den ersten 3 Tagen verabreicht und am 20. Tag wiederholt. Nach der Strahlentherapie erhielten die Patienten 450 mg/m2 5-FU i.v. und 25 mg/m2 Leukovorin i.v. wöchentlich für weitere 6 Monate. Die Immunmodulation mit 40 mg Levamisol p.o. wurde am 1. Bestrahlungstag begonnen und für 6 Monate weitergeführt. Der mediane Nachuntersuchungszeitraum lag bei 37 Monaten (7–112 Monate). Ergebnisse: Die mediane Überlebenszeit betrug 23 Monate. Die 3- und 5-Jahres-Gesamtüberlebensraten lagen bei 35% und 14%. Patienten mit positiven Resektionsrändern wiesen eine mediane Überlebenszeit von 22 Monaten auf. Die lokoregionale Kontrollrate betrug 59% nach 3 Jahren und 55% nach 5 Jahren. Die häufigsten Nebenwirkungen der Behandlung waren gastrointestinale Beschwerden bei 42 Patienten (71%). Vier Patienten (7%) starben infolge der Nebenwirkungen. Sechs Patienten konnten die Behandlung aufgrund von Nebenwirkungen nicht beenden. Schlussfolgerung: Obwohl 48% der Patienten in dieser Studie einen mikroskopisch nachweisbaren Resttumor aufwiesen, war die beobachtete Überlebenszeit verhältnismäßig gut. Aufgrund der hohen Toxizität sollte die Behandlung jedoch sehr sorgfältig unter Einsatz angemessener supportiver Maßnahmen durchgeführt werden.

Delftia tsuruhatensis is a non-glucose fermenting, oxidase positive, motile, gram-negative bacillus first isolated from activated sludge collected from a domestic wastewater treatment plant in Japan. To the best of our knowledge only one case of infection with Delftia tsuruhatensis exists in the medical literature. This is the second case report of human infection having Delftia tsuruhatensis as a causative agent.

We investigated predictive values of BRAF, PI3K and PTEN in cetuximab responses in KRAS wild-type (+) chemotherapy refractory, metastatic colorectal cancer (CRC) patients. Primary tumour tissues of 41 KRAS wild-type mCRC patients receiving cetuximab-based chemotherapy were investigated for PI3K, PTEN, KRAS and BRAF mutations. Progression-free survival (PFS) and overall survival (OS) periods were calculated with Kaplan-Meier method and the Cox proportional hazards model was used. PTEN and PI3K expressions were 63 and 42 %, respectively. BRAF mutation was observed as 9.8 % among patients. Tumours with BRAF mutation had statistically lower response rates (RR) for cetuximab-based treatment than tumours with BRAF wild type (0 vs. 58 %, p = 0.02). PTEN expressing tumours had statistically higher RR for cetuximab-based treatment than tumours with PTEN loss (42 vs. 12 %, p = 0.04). PI3K expression had worse significant effect on cetuximab RR than PI3K non-expressed tumours (15 vs. 44 %, p = 0.023). Median PFS was significantly longer in patients with PTEN expression (14 months) than in patients with PTEN loss (5 months) (HR, 0.4; p = 0.028). Median PFS was significantly longer in patients with PI3K non-expression (15.2 months) than in patients with PI3K expression (4.1 months) (HR, 0.31; p = 0.001). Significant difference in PFS and OS between patients with BRAF mutated and BRAF wild-type tumours was not detected. However, patients with PTEN expression had significantly longer OS (15.1 months) than patients with PTEN loss tumour (9.9 months) (HR, 0.34; p = 0.008). Patients without PI3K expression had significantly longer OS (18.2 months) than patients with PI3K expression (10.1 months) (HR, 0.27; p = 0.001). Multivariate analyses revealed that PTEN expression (HR, 0.48; p = 0.02) and absence of PI3K expression (HR, 0.2; p = 0.001) were independent prognostic factors for increased PFS. Similarly, PTEN overexpression (HR, 0.62; p = 0.03) and absence of PI3K expression (HR, 0.27; p = 0.005) were independent prognostic factors for increased OS. In PTEN loss, PI3K expression may be used as biomarkers to further select KRAS wild-type patients undergoing anti-epidermal growth factor receptor treatment.

Materials/Methods: Between January 1988 and May 2010, 486 patients had undergone radical surgery for stage IB-IIA cervical cancer. Of the 486 patients, 128 had intermediate recurrent factors which are deep stromal invasion (>2/3 thickness), lymph-vascular space invasion, bulky tumor and closed or positive margin of the vagina. There were 42 patients received who postoperative radiation therapy (PORT) of the small pelvic field (SP group), 69 patients received PORT of the standard whole pelvic field (WP group), and 17 patients without PORT (NRT group). The patients with more than two risk factors were 22 (52%) for SP group, 22 (32%) for WP group and 5 (29%) for NRT group. In both SP and WP groups, PORT was delivered with 10-MV X-rays by opposed pair technique and the median total dose was 45Gy per 25 fractions. The median follow-up period of the SP, WP, and NRT group was 63, 97 and 97 months. The significance of the late complications and overall survival and pelvic control rate of each group were analyzed. Results: Five-year overall survival rate was 97.6% for the SP group, 81.7% for the WP group and 100% for the NRT group (SP vs. WP, pZ0.023), and 5-year recurrence free survival rate was 95.2% for the SP group, 79.8% for the WP group and 62.8% for the NRT group (SP vs. NRT, pZ0.022; SP vs. WP, pZ0.051). Recurrence was identified in 2 patients (4.8%) for the SP group, 8 (11.6%) for the WP group and 5 (29.4%) for the NRT group (SP vs. NRT, pZ0.022). Of those patients, the intrapelvic recurrence was identified in 2 (100%) patients for the SP group, 3 (37.5%) for the WP group and 4 (80%) for the NRT group (SP vs. NRT, pZ0.072; WP vs. NRT, pZ0.021). Late complications of gastrointestinal tract (GI) with grade 3 or more were 0 (0%) for the SP group and 9 (13%) for the WP group (pZ0.030). Four of the 9 patients in the WP group underwent operation for severe ileus and fistel. No patients appeared to have grade 3 leg edema for the SP and WP group. In the rate of serious late complications for radiation therapy, the small pelvic field was less than the whole pelvic field, especially GI complications. Conclusions: Using small pelvic field radiation might be useful for early uterine cervical cancer patients with intermediate recurrent factors. Author Disclosure: H. Eto: None. G. Suzuki: None. E. Ogo: None. H. Suefuji: None. Y. Watanabe: None. C. Tsuji: None. C. Hattori: None. K. Ushijima: None. T. Kamura: None. N. Hayabuchi: None.

CA-125, a commonly used tumor marker for epithelial ovarian cancer, is a glycoprotein found in normal tissues derived from coelomic epithelia. Increased serum levels of CA-125 have also been found in nongynecologic tumors and nonmalignant diseases involving the peritoneum. A few recent studies and sporadic case reports have reported increased CA-125 levels in patients with non-Hodgkin's lymphoma (NHL). In our study, we aimed to evaluate the serum levels of CA-125 in patients with NHL and determine its potential role to show disease activity in NHL. Serum levels of CA-125 were measured in 61 patients with NHL and were found to be correlated with clinical stage, site of involvement, and disease activity.

We examined the expression pattern of cyclooxygenase-2 (COX-2) and c-kit in uterine smooth muscle neoplasms and tried to determine the role of these markers in differential diagnosis. Archival tissue from 64 patients with uterine smooth muscle neoplasms (20 leiomyomas (LMs), 22 atypical leiomyomas (ALMs), and 22 leiomyosarcomas (LMSs)) was immunostained with antibodies against estrogen (ER) and progesterone receptors (PR), COX-2 and c-kit. 7 of 20 LM cases and 5 of 22 ALM cases were immunopositive for COX-2, whereas none of the LMS cases stained immunopositive (p< or =0.05). 4 of 20 LM cases and 5 of 22 ALM cases were immunopositive for c-kit, whereas 15 of 22 LMS cases showed c-kit immunopositivity (p< or =0.05). In conclusion, very few LMs and ALMs show COX-2 immunopositivity. LMSs usually do not express COX-2. COX-2 expression in smooth muscle tumors is not a prominent feature. Therefore, COX-2 inhibitors may not be useful in LMS therapy. C-kit was significantly expressed in uterine LMSs.

Objective. The aim of this study was to evaluate clinicopathological findings and the efficacy of the treatment modalities used in patients with olfactory neuroblastomas. Study Design. Retrospective record review. Setting. Istanbul University, Cerrahpasa Medical Faculty, medical oncology outpatient clinic. Subjects and Methods. There were 3 stage A tumors, 5 stage B and 11 stage C according to the Kadish staging system. There were 5 grade I/II and 12 grade III/IV according to the Hyams' histopathologic system. Involvement to orbita was detected in eight patients at the time of diagnosis. Results. The median follow-up period was 23.7 months. The 5-year survival rate for the whole group was 26%. The stage A/B groups exhibited a better survival rate than the C group with 2-year survival rates being 25 versus 71% respectively (P=.008). The grade I/II groups exhibited a better survival rate than the grade III/IV groups with 2-year survival rates being 50 versus 16% respectively (P=.0...

We aimed to describe the effectiveness of our standardized protocol for febrile neutropenia (FN), which was targeted to minimize unintended outcomes and reduce antimicrobial consumption. The study was performed in a private hospital with 300 beds. We included all adult hematologic and oncologic cancer inpatients admitted between January 1, 2015-December 31, 2015, and January 1, 2016-May 31, 2017. The outcomes of the study were fatality, infections, and adherence to the antimicrobial stewardship program (ASP). We included 152 FN attacks of 95 adult inpatients from hematology and oncology wards; of these, 43% were women, and the median age was 57 years. The case fatality rate was 30% in the pre-ASP period and decreased to 11% in the post-ASP period (P = .024). The appropriate adding or changing (P = .006) and appropriate continuation or de-escalation or discontinuation of antimicrobials improved (P < .001). In the post-ASP period, Staphylococcus spp infections (from 22% to 8%, P = ...

Is there any in vitro evidence for or against ovarian protection by co-administration of a GnRH agonist with chemotherapy in human? The co-administration of GnRH agonist leuprolide acetate with cytotoxic chemotherapy agents does not preserve ovarian reserve in vitro. Randomized controlled trials of the co-administration of gonadotrophin-releasing hormone (GnRH) agonists with adjuvant chemotherapy to preserve ovarian function have shown contradictory results. This fact, together with the lack of a proven molecular mechanism of action for ovarian protection with GnRH agonist (GnRHa) places this approach as a fertility preservation strategy under scrutiny. We therefore aimed in this study to provide in vitro evidence for or against the role of GnRHa in the prevention of chemotherapy-induced damage in human ovary. This translational research study of ex vivo and in vitro models of human ovary and granulosa cells was conducted in a university hospital between 2013 and 2015. Ovarian cortical pieces (n = 15, age 14-37) and mitotic non-luteinized (COV434 and HGrC1) and non-mitotic luteinized human granulosa cells (HLGC) expressing GnRH receptor were used for the experiments. The samples were treated with cyclophosphamide, cisplatin, paclitaxel, 5-FU, or TAC combination regimen (docetaxel, adriamycin and cyclophosphamide) with and without GnRHa leuprolide acetate for 24 h. DNA damage, apoptosis, follicle reserve, hormone markers of ovarian function and reserve (estradiol (E2), progesterone (P) and anti-mullerian hormone (AMH)) and the expression of anti-apoptotic genes (bcl-2, bcl-xL, bcl-2L2, Mcl-1, BIRC-2 and XIAP) were compared among control, chemotherapy and chemotherapy + GnRHa groups. The greatest magnitude of cytotoxicity was observed in the samples treated with cyclophosphamide, cisplatin and TAC regimen. Exposure to these drugs resulted in DNA damage, apoptosis and massive follicle loss along with a concurrent decline in the steroidogenic activity of the samples. GnRHa co-administered with chemotherapy agents stimulated its receptors and raised intracellular cAMP levels. But it neither activated anti-apoptotic pathways nor prevented follicle loss, DNA damage and apoptosis induced by these drugs. Our findings do not conclusively rule out the possibility that GnRHa may offer protection, if any, through some other mechanisms in vivo. GnRH agonist treatment with chemotherapy does not prevent or ameliorate ovarian damage and follicle loss in vitro. These data can be useful when consulting a young patient who may wish to receive GnRH treatment with chemotherapy to protect her ovaries from chemotherapy-induced damage. This study was funded by the School of Medicine and the Graduate School of Health Sciences of Koc University, and the American Hospital Women's Health Center, Comprehensive Cancer Care and Fertility Preservation Programs, Istanbul, Turkey. The authors declare no competing interests.

Colorectal cancer metastasizes predictably, with liver predominance in most cases. Because liver involvement has been shown to be a major determinant of survival in this population, liver-directed therapies are increasingly considered even in cases where there is (limited) extrahepatic disease. Unfortunately, these patients carry a known risk of recurrence in the liver regardless of initial therapy choice. Therefore, there is a demand for minimally invasive, non-surgical, personalized cancer treatments to preserve quality of life in the induction, consolidation, and maintenance phases of cancer therapy. This report aims to review evidence-based conceptual, pharmacological, and technological paradigm shifts in parenteral and percutaneous treatment strategies as well as forthcoming evidence regarding next-generation systemic, locoregional, and local treatment approaches for this patient population.

OBJECTIVES: We evaluated the results of patients with gastric carcinoma who were treated with postoperative chemoradiotherapy. METHODS: Seventy-six patients with gastric carcinoma, treated with postoperative chemoradiotherapy between 2003 and 2007, were retrospectively ...

The first Phase I Trial with a combination of IL-2 and IFN-alpha was published in 1989. There are still some questions though, concerning the in vivo effects of this combination on lymphocytes. We designed a prospective pilot study to evaluate in vivo effects of low dose IL-2 and IFN-alpha combination on expression of Bcl-2, FAS (Apo-1/CD 95), Fas Ligand, IL-2 receptor (CD25), and HLA-DR on peripheral lymphocytes in patients with advanced renal cell carcinoma. After initiation of the immunomodulating therapy, Bcl-2 expressing lymphocytes increased significantly on day 3 (p < 0.025), Fas (Apo-1/CD95) expressing lymphocyte increased significantly on day 5 (p < 0.003), Fas ligand expressing lymphocytes increased significantly on day 3 (p < 0.004), HLA-DR expressing lymphocytes increased significantly on day 5 (p < 0.003), and IL-2 receptor (CD25) expressing cells increased significantly on day 5 (p < 0.01). We conclude that immunomodulating therapy induces in vivo expression of Bcl-2, Fas (Apo-1) and Fas Ligand in lymphocytes significantly.

The phosphatidylinositol 3'-kinase/Akt (PI3K/Akt) pathway is a key regulator for HER2- overexpressing breast cancer, but data about whether activation of PI3K/Akt is associated with poor prognosis and resistance to trastuzumab therapy is controversial. In this study we investigated predictive and prognostic significance of expression of p27, Akt, PTEN and PI3K, which are components of the PI3K/Akt signaling pathway, in HER2-positive metastatic breast cancer (MBC), retrospectively. Fifty-four HER2- positive MBC patients who had received first-line trastuzumab-based therapy were recruited for the study group. All of the patient's breast tissue samples were examined for p27 and Akt expression. In addition, twenty-five patients with sufficient amount of tumor tissue were also examined for PTEN and PI3K expression. p27, Akt, PTEN and PI3K were evaluated by immunohistochemistry and their relationship with patient demographic features, tumor characteristics, response to trastuzumab...

Epidural spinal metastasis of Ewing's sarcoma is rarely observed. We report on a rare case of purely epidural spinal metastasis of Ewing's sarcoma with pain and paraplegia, and describe the treatment and final outcome of the patient.

To evaluate the long term results among patients with soft tissue sarcoma of the thoracic wall. Twenty-six patients who were treated with pre-or postoperative radiotherapy between December 1980-December 2007, with a diagnosis of soft tissue sarcoma of the thoracic wall were retrospectively evaluated. The median age was 44 years (14-85 years) and 15 of them were male. A total of 50% of patients were grade 3. The most common histologic type of tumor was undifferentiated pleomorphic sarcoma (26.9%). Tumor size varied between 2-25 cm (median 6.5 cm). Seventeen of the cases had marginal and 9 had wide local resection. Four cases received preoperative radiotherapy and 22 postoperative radiotherapy. Six of the patients with large and high grade tumors received chemotherapy. Median follow-up time was 82 months (9-309 months). Local recurrence and metastasis was detected in 34.6% and 42.3% of patients, respectively. Five- year local control (LC), disease-free survival (DFS), overall survival...

There is limited data regarding outcomes of Ewing's sarcoma family of tumors in adolescents and adults compared with the same tumors in childhood. The aim of the study was to analyze prognostic factors and treatment results in a cohort of adolescents and adults with non-metastatic skeletal Ewing's sarcoma family of tumors. From 1992-2008, 90 adolescents and adults with Ewing's sarcoma family of tumors of the bone were referred to our institution. Sixty-five (72%) non-metastatic patients with analyzable data and treated in our institution were retrospectively evaluated. All patients were treated with alternated chemotherapy regimens administered every 3 weeks. The local treatment modality was selected according to tumor and patient characteristics. The median age was 21 years (range, 13-50). Most patients (74%) were >17 years of age. Forty-six percent of the tumors were located in the extremities. Local therapy was surgery in 45 patients and radiotherapy alone in 19 pa...

To assess the long term clinical outcome of preoperative radiotherapy with or without chemotherapy followed by limb sparing surgery in patients with non-metastatic soft tissue sarcomas (STS) of the extremities. Sixty patients with locally advanced STS were retrospectively analyzed. The median tumor diameter was 12 cm. All patients were treated with preoperative radiotherapy delivered with two different fractionation schedules (35Gy/10fr or 46-50Gy/23-25fr). Neoadjuvant chemotherapy was added to 44 patients with large and/or high grade tumors. Surgery was performed 2-6 weeks after radiotherapy. Chemotherapy was completed up to 6 courses after surgery in patients who had good responses. Median follow-up time was 67 months (8-268 months). All of the patients had limb sparing surgery. The 5-year local control (LC), disease free (DFS) and overall survival (OSS) rates for all of the patients were 81%, 48.1% and 68.3% respectively. 5-year LC, DFS and cause specific survival (CSS) were 81.7...

Unlike cetuximab, there is a paucity of biomarkers for bevacizumab as predictors of outcome in metastatic colorectal cancer (mCRC) patients. Obviously exploring the worth of some potential markers in this setting is warranted. The purpose of this study was to investigate the predictive value of the presence of K-RAS and B-RAF mutations on the outcome of patients with mCRC treated with FOLFIRI and bevacizumab combination therapy. A total of 172 patients with mCRC were evaluated. K-RAS and B-RAF mutations were analyzed by quantitative PCR. Median progression-free survival (PFS) and overall survival (OS) were compared utilizing chi-square and Mann-Whitney U tests, respectively. Forty-four percent (N=77) of the patients were found to harbor K-RAS mutations and 6 (7.5%) were positive for B-RAF mutations. In baseline no difference in PFS and OS was observed between the groups with or without K-RAS mutation. No relationship was established between K-RAS and B-RAF mutation status and baseli...

Cetuximab is currently approved for the treatment of metastatic colorectal cancer (mCR) with KRAS wild-type. Prior few studies demonstrated that G13D mutated tumors could benefit from cetuximab. This study aims to investigate whether KRAS G13D mutated tumors benefit from cetuximab in the chemotherapy refractory patients. We retrospectively compared progression-free survival (PFS), overall survival (OS) and response rate (RR) according to KRAS mutation status in 105 patients with mRC treated at the Cerrahpasa Medical School Hospital, between October 2008 and October 2011, with cetuximab alone or in combination with chemotherapy. PFS was significantly longer in patients G13D mutated tumors (6.81 months) than in patients with other KRAS mutated tumors (5 months) (p=0.027). No significant difference in PFS between patients G13D mutated and KRAS wild-type tumors was detected. No significant difference in OS was detected in patients between G13D mutated tumors and other KRAS mutated tumor...