Avishay Sella

Publications (14)33.49 Total impact

• Article: Hyperbaric oxygen therapy for hemorrhagic radiation cystitis.

  Yaniv Shilo, Shay Efrati, Zvi Simon, Avishay Sella, Eliahu Gez, Eyal Fenig, Mark Wygoda, Arie Lindner, Gregori Fishlev, Kobi Stav, Amnon Zisman, Yoram I Siegel, Dan Leibovici
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  ABSTRACT: Hemorrhagic radiation cystitis (HRC) is a significant clinical problem that occurs after pelvic radiation therapy and is often refractory. To evaluate the efficacy and safety of hyperbaric oxygen therapy (HBO) for HRC. Daily 90 minute sessions of HBO at 2 ATM 100% oxygen were given to 32 HRC patients with ASTRO grades 3-4 hematuria. The median age was 72.5 (48-88 years). The median time interval between radiation therapy and HBO was 4 years (1-26 years). The patients received a median of 30 HBO sessions (3-53). Hematuria resolved in 27 patients (84%) and persisted in 5. Cystectomy was required in two, and ileal-conduit and bilateral percutaneous nephrostomies were performed in one and two patients, respectively. With a median follow-up of 12 months (5-74 months), the hematuria cleared completely in 16 patients (59%) and mild hematuria requiring no further treatment recurred in 10 others. Another patient with ASTRO grade 4 hematuria needed bladder irrigation and blood transfusions. Complications included eardrum perforation in four patients and transient vertigo and mild hemoptysis in one case each. None of them required HBO discontinuation. HBO controlled bleeding in 84% of the patients. A durable freedom from significant hematuria was achieved in 96% of the patients. HBO seems to be an effective and safe modality in patients with HRC.
  The Israel Medical Association journal: IMAJ 02/2013; 15(2):75-8. · 1.02 Impact Factor
• Article: Does sunitinib-induced hypothyroidism play a role in the activity of sunitinib in metastatic renal cell carcinoma?

  Avishay Sella, Aleck H Hercbergs, Ekaterina Hanovich, Svetlana Kovel
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  ABSTRACT: The objective of this study was to evaluate if hypothyroidism developing during sunitib therapy in patients with metastatic renal cell carcinoma (mRCC) is associated with a better outcome. Thirty-one consecutive patients with clear cell mRCC were retrospectively analyzed. Thyroid function was assessed prior to therapy, every 6 weeks during the first 6 months and every 2-4 months thereafter. Hypothyroidism was considered present if thyroid-stimulating hormone (TSH) exceeded the upper normal limit (UNL) with normal triiodothyronine (T3) and thyroxine (T4). Hypothyroidism occurred in 16 patients (52%) within 3 months (range 0.7-22.9) of treatment initiation. Thyroid replacement corrected TSH below the UNL in 10 patients (63%). The distribution according to Motzer prognostic criteria revealed good prognosis in 16 patients (52%), intermediate in 9 (29%) and poor in 6 (19%). The hypothyroid patients tended to have longer progression-free survival (PFS; median 12.2 vs. 9.4 months; p = 0.234) and longer survival (median 22.4 vs. 13.9 months; p = 0.234) than the euthyroid patients. Clinical benefits were similar in both groups. Hypothyroidism that develops in mRCC patients treated with sunitinib is associated with a trend toward prolonged PFS and survival, with a similar clinical benefit rate.
  Chemotherapy 06/2012; 58(3):200-5. · 1.82 Impact Factor
• Article: Serum DNA methylation for monitoring response to neoadjuvant chemotherapy in breast cancer patients.

  Ayelet Avraham, Ronit Uhlmann, Aino Shperber, Miriam Birnbaum, Judith Sandbank, Avishay Sella, Saraswati Sukumar, Ella Evron
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  ABSTRACT: Patients with large or nonoperable breast cancers often receive neoadjuvant chemotherapy to facilitate full resection of the tumor and enable conservation of the breast. However, currently available methods for evaluation of response during therapy are limited and the actual effect of the treatment is only recognized at surgery upon completion of chemotherapy. Timely assessment of response could allow individual tailoring of the treatment and save noneffective drugs and unnecessary toxicity. Here, we suggest that tumor derived DNA methylation in the serum may reflect changes in tumor burden and allow early recognition of responders versus nonresponders. In this pilot study, we collected 7 consecutive serum samples from 52 patients with locally advanced breast cancer during neoadjuvant chemotherapy. We selected RASSF1, which was methylated in more than 80% of the tumors, for serum analysis. Using the "methylation sensitive PCR and high resolution melting," we detected RASSF1 methylation in the serum of 21 patients prior to therapy. In four patients who achieved complete pathological response, RASSF1 methylation in the serum became undetectable early during therapy. In contrast, in 17 patients that had partial or minimal pathological response, serum RASSF1 methylation persisted longer or throughout the treatment (complete versus partial response p = 0.02). These findings support further development of this assay for monitoring response during neoadjuvant therapy.
  International Journal of Cancer 03/2012; 131(7):E1166-72. · 5.44 Impact Factor
• Article: Combination of gemcitabine and carboplatin in urothelial cancer patients unfit for cisplatin due to impaired renal or cardiac function.

  Avishay Sella, Svetlana Kovel
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  ABSTRACT: Combination of gemcitabine and carboplatin is the accepted treatment for metastatic urothelial cancer patients unfit for cisplatin-based chemotherapy. Gemcitabine 1000 mg/m² (days 1, 8) and carboplatin AUC- 4.5 (day 1) were given every 21 days to 23 patients with creatinine clearance < 60 mL/min, cardiac ejection fraction < 45% or active ischemia. Patient characteristics included: median age 73 (56-86) years; primary site: bladder 17 (73%), upper tract 6 (27 %) patients; Bajorin 's prognostic groups: good 6 (26%), intermediate 11 (48%) and poor 6 (26%) patients. Data was retrospectively documented. Patients were followed until they expired. We obtained objective responses in 8 (34.7%) patients, (95% CI, 16.3-57.2%), including one patient with complete response. The median progressionfree survival was 4 (0.2-16.5+) months and the overall survival 8.6 (0.2-45.3+) months. At time of analysis, 4 patients (17%) remained disease free; 3 of them underwent resection of residual disease. Toxicity included: infection in 9 (39%) patients; among them, one died from pneumonia; bleeding ≥ grade 2 in 3 (13%) patients and fatigue grade 3 in 2 (9%) patients. Hematologic toxicity included grade 4 thrombocytopenia in 2 (9%) patients and grade 4 neutropenia in 3 (13%) patients. Five (22%) patients discontinued therapy due to toxicity. Combination of gemcitabine and carboplatin demonstrated clinical activity in patients with advanced urothelial cancer unfit for cisplatin. It was associated with considerable toxicity. Resection of residual disease is feasible in this population.
  International braz j urol: official journal of the Brazilian Society of Urology 01/2012; 38(1):49-56.
• Article: A similar cell-specific pattern of HOXA methylation in normal and in cancer tissues.

  Ayelet Avraham, Judith Sandbank, Nirit Yarom, Avshalom Shalom, Tami Karni, Itzhak Pappo, Avishay Sella, Alexander Fich, Shlomo Walfisch, Larisa Gheber, Ella Evron
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  ABSTRACT: HOX genes are developmental genes that determine anterior-posterior embryonic pattern and govern the process of differentiation. Inappropriate expression of HOX genes has been implicated in developmental abnormalities and hematopoietic malignancies. In addition, HOX genes silencing by DNA methylation has been reported in cancers and related to disease aggressiveness and outcome. On the other hand, accumulating evidence suggests that epigenetic changes at HOX genes are linked to normal development and differentiation. To better understand the relationship between HOXA methylation and cancer, we analyzed the methylation pattern of HOXA genes in human primary breast and colon carcinomas, normal tissues, and normal white blood cells. Genome-wide methylation arrays of breast cancers and white blood cells demonstrated similar methylation patterns. Quantitative methylation analysis of seven representative HOXA genes revealed various levels of methylation in both normal tissues and cancers. Analysis of epithelial-enriched normal breast tissue and stroma indicated that the stroma was the major origin of HOXA methylation. Furthermore, in selected dense breast cancers, minimal increase in methylation of several HOXA genes did not correlate with the predominance of malignant epithelial cells in these tumors. Our results suggest that methylation of the HOXA cluster may be a normal developmental and cell type specific process rather than a cancer specific mechanism.
  Epigenetics: official journal of the DNA Methylation Society 01/2010; 5(1):41-6. · 4.58 Impact Factor
• Article: Epistaxis during treatment with paclitaxel.

  Nirit Yarom, Arnoldo Cyjon, Svetlana Kovel, Adelya Yachnin, Avishay Sella, Ella Evron
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  ABSTRACT: The purpose of this study was to determine the incidence and severity of epistaxis in patients treated with paclitaxel. Patients who were treated with paclitaxel filled a questionnaire regarding their general health, medications and incidents of epistaxis. Relevant clinical information was obtained from the patients' charts. Forty-seven consecutive patients were recruited to the study. Twenty-four (51%) of the patients reported epistaxis during paclitaxel therapy. Twenty-three of 39 (59%) patients who received weekly paclitaxel had epistaxis at least once during treatment, compared with one out of eight patients who were treated every 3 weeks (P = 0.045). All episodes of epistaxis were mild, occurred with normal platelets counts and did not require blood product transfusions or treatment modification. The majority of the patients experienced the first episode of epistaxis on the third week of weekly paclitaxel treatment and then repeatedly throughout therapy. It is concluded that epistaxis is a common mild side-effect of weekly paclitaxel that has not been reported previously. In this trial, epistaxis did not have any major clinical consequences. However, when paclitaxel is combined with other drugs that may cause bleeding, such as bevacizumab, physicians should be alerted to the potential risk of this phenomenon.
  Basic & Clinical Pharmacology & Toxicology 02/2009; 104(3):259-61. · 2.18 Impact Factor
• Article: Prostate-specific antigen flare phenomenon with docetaxel-based chemotherapy in patients with androgen-independent prostate cancer.

  Avishay Sella, Cora N Sternberg, Iwona Skoneczna, Svetlana Kovel
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  ABSTRACT: To evaluate the prostate-specific antigen (PSA) 'flare' phenomenon in patients with androgen-independent prostate cancer (AIPC) treated with docetaxel, as flare is a known effect of androgen-deprivation therapy in hormone-dependent prostate cancer. The charts of 56 patients who received docetaxel-based chemotherapy in three different centres from August 1999 to August 2007 were reviewed retrospectively. The biochemical response was characterized according to the Bubley criteria. There was an immediate PSA response (PSA decline >or= 50%) in 23 (41%) patients, PSA stabilization (PSA decline < 50%) in 16 (29%) and PSA progression in nine (16%). There was also a fourth response, i.e. PSA flare, defined as an increase in PSA level with no symptomatic progression, after starting docetaxel-based chemotherapy administered every 3 weeks. Eight (14%) patients with PSA flare were identified; all had osseous disease and five had additional soft-tissue disease. The PSA flare lasted a median (range) of 21 (21-42) days and it spread over a median of 1 (1-2) cycles. The temporary PSA surge exceeded baseline values by a median (range) of 61.5 (12-404)%. There was a subsequent PSA response in six of the eight patients and PSA stabilized in the remaining two. Patients with flare received a median of 8.5 (5-12) treatment cycles, vs a median of 8 (2-12) in the immediate PSA response group (P = 0.103, Student's t-test). The Response Evaluation Criteria in Solid Tumors criteria evaluation showed one patient with a partial response and six with stable disease. The median survival of patients with PSA flare was 12.5 months, while that of the immediate PSA responders was 20.1 months (not statistically significant, P = 0.168, log-rank test). Of patients with AIPC, 14% had an initial PSA flare after starting docetaxel-based chemotherapy. The occurrence of PSA flare had no effect on treatment duration or outcome. With lack of clinical progression, docetaxel-based chemotherapy should be administered for at least two 3-week cycles before further decisions are made about efficacy.
  BJU International 11/2008; 102(11):1607-9. · 2.84 Impact Factor
• Article: Muscle-invasive bladder tumour: can the bladder be preserved?

  Avishay Sella
  BJU International 09/2008; 102(9):1053-4. · 2.84 Impact Factor
• Article: Neoadjuvant chemohormonal therapy in poor-prognosis localized prostate cancer.

  Avishay Sella, Amnon Zisman, Svetlana Kovel, Nirit Yarom, Dany Leibovici, Arie Lindner
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  ABSTRACT: To conduct a trial of neoadjuvant chemohormonal therapy and radical prostatectomy for patients with poor-prognosis localized prostate cancer (prostate-specific antigen [PSA] value 20 ng/mL or greater, Gleason score 8 or higher, and clinical stage T2c or greater), who are at high risk for local and systemic relapse. Complete androgen blockage and four cycles of docetaxel (70 mg/m2) on day 2 and estramustine (280 mg three times daily) on days 1 to 5 every 21 days were given to 22 patients before radical prostatectomy and nerve preservation. Patient characteristics, as median (range), were as follows: age 61 (49 to 70) years, PSA value 21.2 (3.2 to 71.6) ng/mL, and Gleason sum 7 (6 to 9). Clinical stage was T3a-c in 14 patients (64%), T2c in 4 (18%), T2b in 3 (14%), and T1c in 1 (4%). Presurgery characteristics after chemohormonal therapy were as follows: PSA value 0.21 (0.05 to 0.6) ng/mL, clinical stage T1c in 14 patients (63.7%), T2a in 6 (27.3%), and T3a in 2 (9%). The pathologic specimens revealed viable disease in all patients, organ-confined disease in 14 (63.6%), specimen-confined disease in 16 (72.7%), seminal vesicle disease in 9 (40.9%), and lymph node involvement in 4 (18.1%). To date, at a median follow-up of 23.6 (12.1 to 54.7) months, 10 patients (45.4%) relapsed, with PSA doubling time of 1.5 (0.4 to 34.3) months. Of the relapsed patients, 8 (89%) had organ/specimen involvement. The neoadjuvant chemohormonal approach with nerve-preservation surgery is feasible in patients with poor-prognosis localized prostate cancer. It leads to clinical tumor downstaging. The pattern of relapse suggests that local therapy, with radiotherapy for patients with surgical or capsular involvement, and additional systemic therapy should be integrated.
  Urology 03/2008; 71(2):323-7. · 2.43 Impact Factor
• Article: The prevalence of malignancy in satellite renal lesions and its surgical implication during nephron sparing surgery.

  Orit Raz, Sonia Mendlovic, Dan Leibovici, Allan J Pantuck, Judith Sandbank, Avishay Sella, Arie Lindner, Amnon Zisman
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  ABSTRACT: We examined the prevalence of malignancy in a synchronous ipsilateral renal lesion identified during partial nephrectomy and evaluated its clinical significance. We retrospectively reviewed the records of 112 patients (114 renal units) who underwent nephron sparing surgery for a clinically localized sporadic renal mass between May 1995 and September 2005. In 37 patients (32%) an additional lesion was diagnosed and excised intraoperatively, while in 67% these lesions were known before the operation and believed to be simple cysts. During surgery the additional mass was suspicious in 8 cases and in the remainder the mass was described as simple cysts that were excised. The mean size of the primary mass was 3.1 cm (SD 1.4). In 29 (78%) cases the primary mass was malignant, in 23 (79%) of these the second mass was benign and in the remainder renal cell carcinoma was diagnosed. In 8 cases (22%) the primary mass was benign and in 2 (25%) the secondary mass was malignant. Overall 22% of all second masses were malignant, and all were low grade and low stage. We found that 7% of second ipsilateral masses could be expected to harbor malignancy. Based on our data it is questionable whether total nephrectomy is mandatory as an immediate response to an ipsilateral synchronous second renal mass. The present findings may represent an increased appreciation of ipsilateral multicentricity compared to historical data.
  The Journal of Urology 12/2007; 178(5):1892-5; discussion 1895. · 3.75 Impact Factor
• Article: Progression after docetaxel-based chemotherapy in androgen-independent prostate cancer.

  Avishay Sella, Cora Sternberg, Svetlana Kovel, Nirit Yarom, Iwona Skoneczna
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  ABSTRACT: To assess the clinical pattern of progression and prostate-specific antigen doubling time (PSA-DT) after exposure to docetaxel-based chemotherapy in patients with androgen-independent prostate cancer (AIPC). Fifty-five patients received docetaxel-based chemotherapy; data were collected retrospectively from three different departments. Progression was known in 44 (79%) and the PSA-DT was available in 33 patients. Of the 29 patients with soft-tissue and soft-tissue plus bone metastases, 22 (76%) developed soft-tissue progression. Among the 35 patients with bone and bone plus soft-tissue metastases, 27 (77%) had osseous progression. There was no difference between the PSA-DT at progression before and after docetaxel-based therapy (mean 3.1 vs 2.7 months, P = 0.592, Student's t-test.). However, the median (range) PSA-DT at progression after docetaxel-based therapy was 0.84 (0.3-4) months in patients with a PSA response, significantly shorter than the median of 3.1 (0.3-12) months of patients with no biochemical response (P = 0.002, Student's t-test). The PSA-DT dynamics at progression had no effect on survival (P = 0.63, log-rank test). The pattern of progression after docetaxel-based chemotherapy is predominantly osseous in patient with bone metastases and mostly soft-tissue in those with soft-tissue disease. Progression after docetaxel-based chemotherapy in AIPC does not modify the PSA-DT before docetaxel. Evaluation of a larger population is needed to assess the clinical relevance of PSA dynamics after docetaxel therapy.
  BJU International 10/2007; 100(3):533-5. · 2.84 Impact Factor
• Article: [Taxotere-based chemotherapy in androgen-independent prostate cancer].

  Nirit Yarom, Svetlana Kovel, Avishay Sella
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  ABSTRACT: Taxotere-based chemotherapy is the only approach which has recently demonstrated prolongation of survival in patients with androgen-independent prostate cancer. This article presents our experience with this therapy. Since August 1999 we treated 49 patients with Taxotere/Estramustine or Taxotere/Prednisone combinations. Biochemical response occurred in 27 (55.1%) patients, unaffected by prior exposure to chemotherapy. Among the 32 patients with measurable disease, 7 (21/8%) patients demonstrated partial response and an additional 16 (50%) patients obtained stable disease. Half of the patients withdrew morphine palliative therapy. The median survival of all patients was 12.6 months, significantly longer in patients with biochemical response (14.3 vs 5.4 months) and no prior chemotherapy (14.3 vs 9.1 months). The disease recurred equally among osseous and soft tissue sites (18 sites each group). The most significant toxicity was neutropenia grade 3-4 in 26 (53%) patients. Infection, among them one fatal, developed in 18 (37.3%) patients. Taxotere-based chemotherapy is active and tolerated in androgen-independent prostate cancer. Heavily pretreated patients are sensitive to therapy. Progression occurred in bone and soft-tissue sites.
  Harefuah 02/2006; 145(1):22-4, 79.
• Article: Novel concepts in the staging of renal cell carcinoma.

  Dan Leibovici, Arie Lindner, Avishay Sella, Amnon Zisman
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  ABSTRACT: The incidence of renal cell carcinoma (RCC) continues to rise steadily; unfortunately, our ability to cure patients with metastatic RCC remains limited. When developing and evaluating new treatment protocols, it is important to consider the role of prognostic factors, often defined as pretreatment features, that are predictive of outcome. The complexity and variability of patients' individual clinical outcome and the recently recognized limitation of conventional staging systems have lead to the formulation of integrated prognostic staging systems. In this review, we discuss the evolution of various clinically relevant integrated staging systems for RCC.
  Current Urology Reports 03/2003; 4(1):41-8.
• Article: Local anesthesia for prostate biopsy by periprostatic lidocaine injection: a double-blind placebo controlled study.

  Dan Leibovici, Amnon Zisman, Yoram I Siegel, Avishay Sella, Judy Kleinmann, Arie Lindner
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  ABSTRACT: We determined the efficacy of anesthesia for prostate biopsy by periprostatic lidocaine injection. A total of 90 consecutive patients undergoing prostate biopsies were randomized into lidocaine and placebo groups of 45 each in double-blind fashion. A 5 ml. dose of 1% lidocaine or 0.9% sodium chloride was injected via 23 gauge needles inserted through the transrectal ultrasound probe working channel and aimed at the prostatic neurovascular bundles bilaterally. Patients completed a symptom questionnaire applying a visual analog scale of 0-none to 10-maximal addressing pre-procedure anxiety, overall pain and discomfort throughout the procedure, pain during biopsy punctures and patient tolerance, as judged by the operator. Student's t test was used to analyze continuous variables and the chi-square test was applied for categorical data. Linear regression was done to determine intervariable influences. The average pain level throughout the procedure was 3.06 in the lidocaine group versus 4.15 in the control group (p = 0.04), while the pain level during biopsy punctures was 1.51 versus 3.98 (p = 0.0001) and patient tolerance was 1.06 versus 1.93 (p = 0.018). The level of discomfort throughout the procedure was lower in the lidocaine group with borderline significance (4.31 versus 5.24, p = 0.077). The lidocaine and control groups were comparable regarding average patient age (65 and 66 years, respectively). Prostate volume was similar in the 2 groups (68.5 versus 63 ml.). The median number of biopsy punctures was 7 and 8, respectively. Cancer was identified in 10 patients (22.2%) per group. Periprostatic lidocaine injection is an effective method of anesthesia for prostate biopsy.
  The Journal of Urology 03/2002; 167(2 Pt 1):563-5. · 3.75 Impact Factor