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2. Ann Oncol. 2004 Apr;15(4):610-2.


Targeting pulmonary metastases of renal cell carcinoma by inhalation of



Merimsky O(1), Gez E, Weitzen R, Nehushtan H, Rubinov R, Hayat H, Peretz T,

Ben-Shahar M, Biran H, Katsenelson R, Mermershtein V, Loven D, Karminsky N,

Neumann A, Matcejevsky D, Inbar M.


Author information:

(1)Unit of Bone and Soft Tissue Oncology, Division of Oncology, Tel-Aviv Sourasky

Medical Center, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv,



INTRODUCTION: Pulmonary metastases of renal cell carcinoma (RCC) are associated

with poor prognosis. Inhalation therapy with interleukin-2 (IL-2) is thus an

appealing method for palliation. This multicenter study summarizes the national

experience of IL-2 inhalation in patients with lung metastases of RCC.

PATIENTS AND METHODS: Forty patients (median, 66.5 years of age) with

radiologically documented progressing pulmonary metastases were enrolled. All

patients had to be able to comply with inhalation technique, and were not

candidates for other treatment options. Twenty-eight patients were systemic

treatment-naïve. The protocol included three daily inhalations of IL-2 to a total

dose of 18 MU. Treatment had to be continued until one of the following occurred:

progression; a complete response; a life threatening toxicity; or patient

refusal. Response was assessed using the Response Evaluation Criteria in Solid

Tumors (RECIST) system.

RESULTS: The disease-control rate reached 57.5%, with a partial response rate of

2.5% and a disease stabilization rate of 55%. Median time to progression was 8.7

months. The main side-effects were cough and weakness.

CONCLUSIONS: Inhalation of IL-2 for the treatment of pulmonary metastases in RCC

is feasible, tolerable and beneficial in controlling progressive disease for

considerable periods of time. The definition of response of biological therapy

may need to be re-assessed and modified: stable disease should be regarded as a

favorable response.


PMID: 15033668  [PubMed - indexed for MEDLINE]



3. Isr Med Assoc J. 2002 May;4(5):376-8.


Bone metastases of renal cell carcinoma: the role of surgery.


Bickels J, Merimsky O.


Comment on

    Isr Med Assoc J. 2002 May;4(5):385-6.


PMID: 12040831  [PubMed - indexed for MEDLINE]



4. Cancer. 2001 Apr 1;91(7):1363-71.


Multiple primary malignancies in association with soft tissue sarcomas.


Merimsky O(1), Kollender Y, Issakov J, Bickels J, Flusser G, Gutman M,

Lev-Chelouche D, Inbar M, Meller I.


Author information:

(1)Department of Oncology, The Tel-Aviv Sourasky Medical Center, the Sackler

School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.


BACKGROUND: Modern cancer treatment has increased the survival of patients with

various malignancies substantially. One of the late sequelae of successful

treatment is the development of a second malignant tumor. However, in many cases

of second primary tumors, exposure to chemotherapy or radiation therapy is not

evident, and it should be postulated that the putative mechanism for the

development of the second tumor is different. In the current series, the

association between soft tissue sarcoma (STS) in adults and the development of

other primary malignancies was studied.

METHODS: A retrospective search of the data files of 610 patients with STS or

bone sarcomas who were treated at the study institution between January 1995 and

December 1999 was performed. All files regarding patients with STS who developed

a second malignant tumor were retrieved for analysis.

RESULTS: Of 375 patients with STS, 28 (7.5%) developed other malignant neoplasms

either before or after the diagnosis of STS. STS as the first tumor occurred in

14 patients (ages 16-72 years). Only three patients were treated with

chemotherapy for their sarcoma. Radiation therapy was administered to five

patients as an adjuvant to surgery for the first tumor. The second tumor types

mainly included STS and renal cell carcinoma. The time interval between the

diagnosis of the STS and the second malignancy was 0 (for synchronous tumors) to

21 years. Three patients developed a third primary tumor within 3 years after the

diagnosis of the second tumor. The median overall survival was > 78 months.

Fourteen patients (ages 35-87 years) had a first primary tumor other than STS

(mainly breast carcinoma and genitourinary malignancies). The second tumors

(mainly STS) appeared within 0 (for synchronous tumors) to 27 years. The median

overall survival for the 14 patients in this group from the time of diagnosis of

the first tumor was > 102 months.

CONCLUSIONS: The phenomenon of two or three primary neoplasms developing in

patients in whom one of the tumors was STS occurs at a rate of 7.5%, a

significantly higher rate than that reported for the occurrence of STS among the

general cancer population (1%). The majority of cases occur incidentally. The

clinical implication includes the need to search for an occult second primary

tumor in patients with STS as an integral part of their follow-up. This is

especially true in patients with primary malignant fibrous histiocytoma who

demonstrate a risk for developing a renal cell carcinoma.


Copyright 2001 American Cancer Society.


PMID: 11283938  [PubMed - indexed for MEDLINE]



5. J Urol. 2000 Nov;164(5):1505-8.


Metastatic renal cell carcinoma of bone: indications and technique of surgical



Kollender Y(1), Bickels J, Price WM, Kellar KL, Chen J, Merimsky O, Meller I,

Malawer MM.


Author information:

(1)National Unit of Orthopedic Oncology and Departments of Urology and Oncology,

Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel.


PURPOSE: We describe the efficacy of surgical excision of metastatic renal cell

carcinoma of bone for achieving local tumor control, pain control and functional

outcome with emphasis on the indications and techniques of surgical intervention

as well as oncological outcome.

MATERIALS AND METHODS: Between 1980 and 1997 we performed surgery on 45 patients

(56 lesions) with metastatic renal cell carcinoma of bone. Indications for

surgery were solitary bone metastasis, intractable pain, or impending or present

pathological fracture. Surgery involved wide excision in 29 cases, marginal

excision with adjunctive liquid nitrogen in 25 and amputation in 2.

RESULTS: None of the patients had significant bleeding intraoperatively. Mean

hospital stay was 9.8 days, during which there was no flap necrosis, deep wound

infection, nerve palsy or thromboembolic complication. Postoperatively pain was

significantly relieved in 91% of patients, while 89% achieved a good to excellent

functional outcome, and 94% with metastatic lesions of the pelvic girdle and

lower extremities were ambulatory. Local recurrence developed in only 4 of the 56

lesions (7.1%), including 3 after marginal resection. Survival was more than 2

years in 22 patients (49%) and more than 3 in 17 (38%).

CONCLUSIONS: Surgical excision is safe and reliable for restoring mechanical bone

stability, relieving pain and providing good function in most patients with

metastatic renal cell carcinoma who meet the criteria for surgical intervention.

Relatively prolonged survival in these cases justifies considering surgical

intervention when feasible.


PMID: 11025692  [PubMed - indexed for MEDLINE]



6. Anticancer Drugs. 1992 Dec;3(6):567-70.


Neurotoxicity of interferon-alpha.


Merimsky O(1), Chaitchik S.


Author information:

(1)Department of Oncology, Tel-Aviv Sourasky Medical Center, Israel.


Interferon (IFN) related neurotoxicity includes somnolence and confusion,

fatigue, lethargy, psychiatric symptoms, conceptual disorganization, neurological

deficits, cortical blindness, coma and, rarely, death. The neurologic syndromes

seem to be more common in elderly patients, following intramuscular or

intravenous administration, at higher doses of frequent injections of IFN-alpha

and in primary renal cell carcinoma. The duration of the treatment was not

strongly related to neurotoxicity. Computed tomography findings were non-specific

and included atrophy or periventricular lucencies. Electroencephalograph studies

demonstrated a generalized increase in slow wave activity which returned to

normal after cessation of treatment. Behavioral and mental changes in patients

treated with IFN are warning signs, and indicate the need to withdraw treatment.


PMID: 1288726  [PubMed - indexed for MEDLINE]



7. Mol Biother. 1992 Sep;4(3):130-4.


Our experience with interferon alpha: renal cell carcinoma.


Merimsky O(1), Chaitchik S.


Author information:

(1)Department of Oncology, Ichilov Hospital, Tel Aviv Sourasky Medical Center,



Our 3-year clinical experience using recombinant interferon (rIFN) alpha-C in

patients with metastatic renal cell carcinoma (RCC) is summarized. This type of

IFN is a new subspecies of the IFN-alpha protein family. Its specific activity is

1-2 x 10(9) U/mg protein, the highest among IFN-alpha species presently

available. Pharmacokinetic study indicated good bioavailability of the

preparation from the intramuscular injection. A phase II study was performed to

assess the response rate related to rIFN-alpha C at a low dosage. A dose of 3 x

10(6) U daily was administered, followed by 3 x 10(6) U/m2 every other day to

avoid severe toxicity. Among 33 treated patients, a partial remission rate of

9.7% and stable disease rate of 25.8% were achieved. Side effects were usually

mild and the treatment was well tolerated by the patients. However, mental

deterioration and behavioral changes were observed in five patients with RCC

treated by rIFN-alpha C and were related to neurotoxicity of IFN. The role of

vinblastine in addition to IFN in the treatment of RCC was assessed in nine

patients who had failed on IFN alone. No response was observed. It appeared that

vinblastine had little if any effect in being added to IFN as second-line

therapy. We conclude that rIFN-alpha C has moderate activity in the treatment of

RCC. Familiarity with the possible toxicity of this agent will lead to more

careful management of patients.


PMID: 1445666  [PubMed - indexed for MEDLINE]



8. Mol Biother. 1992 Jun;4(2):95-6.


Metastases to skeletal muscles and interferon treatment.


Merimsky O(1), Inbar M, Chaitchik S.


Author information:

(1)Department of Oncology, Tel-Aviv Sourasky Medical Center, Israel.


Blood-borne metastases to a skeletal muscle are rare and may originate in various

primary tumors. Recurrent solitary metastasis of renal cell carcinoma, and

metastatic lesion as part of disseminated malignant melanoma in skeletal muscles

are reported in two patients. In both cases interferon treatment with or without

chemotherapy failed in arresting the disease.


PMID: 1515101  [PubMed - indexed for MEDLINE]



9. Cancer Chemother Pharmacol. 1992;29(4):329-30.


Interferon-related cortical blindness.


Merimsky O(1), Nisipeanu P, Loewenstein A, Reider-Groswasser I, Chaitchik S.


Author information:

(1)Department of Oncology, Tel-Aviv Medical Center, Israel.


The term cortical blindness indicates loss of sight due to bilateral lesions in

the occipital lobes. It is a rare but severe side effect produced by

chemotherapeutic agents. Cortical blindness was diagnosed in a 75-year-old man

who had been treated with alpha-interferon for metastatic renal-cell carcinoma.

The absence of focal neurological signs and of abnormal findings as determined by

two repeated computed tomography (CT) scans of the brain, which excluded

structural damage to the occipital lobes, suggest that metabolic or toxic

reactions may have caused the cortical blindness diagnosed in our patient. The

temporal relationship between the treatment with alpha-interferon and the

development of cortical blindness indicates that this substance may have been the

causative agent for this phenomenon.


PMID: 1537083  [PubMed - indexed for MEDLINE]



10. Tumori. 1991 Aug 31;77(4):361-2.


Interferon-related leukoencephalopathy in a patient with renal cell carcinoma.


Merimsky O(1), Reider I, Merimsky E, Chaitchik S.


Author information:

(1)Department of Oncology, Tel-Aviv Sourasky Medical Center, Tel-Aviv University,



A 75-year-old patient with metastatic renal cell carcinoma was treated with

recombinant interferon alpha-C and thereafter developed a neurologic syndrome of

dementia, ataxia, confusional state, loss of concentration ability and cortical

blindness. CT scan findings were compatible with leukoencephalopathy, which is

reported as being a toxic effect of interferon.


PMID: 1746062  [PubMed - indexed for MEDLINE]



11. Mol Biother. 1991 Mar;3(1):34-7.


Does vinblastine add to the potency of alpha interferon in the treatment of renal

cell carcinoma?


Merimsky O(1), Shnider BI, Chaitchik S.


Author information:

(1)Department of Oncology, Tel-Aviv Sourasky Medical Center, Sackler School of

Medicine, Tel-Aviv University, Israel.


The combination of alpha interferon and vinblastine has been reported to yield a

response rate of 30-40% in previously untreated patients with metastatic renal

cell carcinoma. This combination was given to nine patients with advanced

metastatic renal carcinoma after they failed or relapsed on alpha-interferon

alone, to attempt to evaluate the role of vinblastine in this combination.

Neither complete nor partial response was observed. Two patients had disease

stabilization for two and seven months. Our preliminary results suggest that

vinblastine did not add to the efficacy of interferon in this group of patients.


PMID: 2069758  [PubMed - indexed for MEDLINE]



12. Cancer Chemother Pharmacol. 1991;27(5):406-8.


Pharmacokinetics of recombinant interferon alpha-C.


Merimsky O(1), Rubinstein M, Fischer D, Danon A, Chaitchik S.


Author information:

(1)Department of Oncology, Tel-Aviv Sourasky Medical Center, Israel.


Recombinant interferon alpha-C (rIFN alpha-C, Interpharm), is a new type of

alpha-interferon that has a specific activity of 1-2 x 10(9) units/mg protein.

The pharmacokinetics of rIFN alpha-C were studied in 11 patients with metastatic

renal-cell carcinoma. A total of 10 million units IFN alpha-C were injected

intramuscularly and the serum level of IFN was evaluated up to 72 h

post-administration. Measurable IFN concentrations appeared in the serum as early

as 0.5 h, and levels peaked at 4-6 h (Cmax = 53.2 +/- 4.6 units/ml). Relatively

high levels persisted for 24 h and declined thereafter with an apparent half-life

of 3-4 h. The mean area under the serum-concentration curve (AUC) was 1,259 +/-

145 units h ml-1, indicating good bioavailability of the preparation from the

intramuscular injection.


PMID: 1999003  [PubMed - indexed for MEDLINE]



13. J Surg Oncol. 1990 Dec;45(4):279-81.


The use of interferon alpha-C in patients with metastatic renal cell carcinoma

arising in a congenital solitary kidney.


Merimsky O(1), Merimsky E, Chaitchik S.


Author information:

(1)Department of Oncology, Ichilov Hospital, Tel-Aviv Sourasky Medical Center,



Three cases of renal cell carcinoma in a congenital solitary kidney are

presented. Treatment with recombinant interferon alpha-C was administered in two

cases. A subjective response occurred in one case. The literature is reviewed

with respect to treatment options and prognostic factors.


PMID: 2250479  [PubMed - indexed for MEDLINE]



14. Mol Biother. 1990 Sep;2(3):155-9.


Phase II study of recombinant interferon alpha-C in patients with metastatic

renal cell carcinoma.


Merimsky O(1), Inbar M, Merimsky E, Kovner F, Spitzer E, Laufer R, Braf Z,

Chaitchik S.


Author information:

(1)Department of Oncology, Tel-Aviv Sourasky Medical Center, Sackler School of

Medicine, Tel-Aviv University, Israel.


Recombinant interferon alpha-C is a new strain of the alpha interferon family. It

was given to 33 patients with measurable metastatic renal cell carcinoma of whom

31 were evaluable. Protocol consisted of 3 million U/d for 2 weeks, then 3

million U/m2 every other day until progression. No complete response was

observed. Three patients (9.7%) had partial response for a mean duration of 5.6

months and eight patients (25.8%) were stabilized for a mean of 4.3 months.

Responsive sites were mainly lung, bone, and kidney, while side effects were

generally mild. better results were observed in previously nephrectomized

patients who had not received chemotherapy or hormonotherapy for recurrent or

metastatic disease (p less than 0.05), and also in patients with a brief

disease-free interval and short delay from presenting symptoms of the primary

tumor until interferon treatment (p less than 0.05). Median survival was

significantly longer in responders than in progressors (p less than 0.05). We

suggest that the efficacy of recombinant interferon alpha-C in a low-dose regime

versus other types of interferon as first-line therapy for inoperable,

metastatic, or locally recurrent renal cell carcinoma should be investigated in a

prospective, controlled, randomized study.


PMID: 2222899  [PubMed - indexed for MEDLINE]



15. Tumori. 1990 Aug 31;76(4):407-9.


Recurrent solitary metastasis of renal cell carcinoma in skeletal muscles.


Merimsky O(1), Levine T, Chaitchik S.


Author information:

(1)Department of Oncology, Ichilov Hospital Tel-Aviv Medical Center, Israel.


Metastatic carcinoma to skeletal muscle is uncommon and may originate from

breast, colon, lung, pancreas and other sources. Recurrent solitary metastases of

renal cell carcinoma in the biceps femori and gluteus muscles are described in a

69 year-old man. The tendency of metastases to occur merely in muscles could not

be explained in our case. The relative immunity of muscle to the metastatic

process should be further investigated.


PMID: 2399572  [PubMed - indexed for MEDLINE]



16. Eur J Cancer. 1990;26(8):921.


Interferon plus vinblastine in renal carcinoma patients who had failed on

interferon alone.


Merimsky O, Chaitchik S.


PMID: 2145941  [PubMed - indexed for MEDLINE]



17. Eur J Cancer. 1990;26(5):596-600.


Interferon-related mental deterioration and behavioral changes in patients with

renal cell carcinoma.


Merimsky O(1), Reider-Groswasser I, Inbar M, Chaitchik S.


Author information:

(1)Department of Oncology, Tel Aviv Sourasky Center, Ichilov Hospital, Israel.


Five out of 38 patients (13%) with metastatic renal cell carcinoma had mental

deterioration 3 weeks to 13 months after the start of treatment with recombinant

interferon alpha-C. Metastatic spread to the brain, paraneoplastic effect of the

tumor on the central nervous system and other causes of dementia were excluded.

Computed tomography of the brain in these patients was normal and the width of

the cerebral sulci and ventricles did not correlate with the severity of

dementia. Specific patterns of atrophy were not seen. General deterioration,

assessed by the change in Karnofsky performance status, was associated with

dementia. The dementia may have been caused by a neurotoxic effect of interferon.


PMID: 2144747  [PubMed - indexed for MEDLINE]



18. J Urol (Paris). 1989;95(4):243-5.


Metastatic renal cell carcinoma arising in a congenital solitary kidney.

Treatment with interferon-containing combinations. A case report and a review of

the literature.


Merimsky O(1), Laufer R, Chaitchik S.


Author information:

(1)Department of Oncology, Tel-Aviv Medical Center, Israel.


Renal Cell Carcinoma (RCC) in a single kidney is a rare occurrence, more so when

it concerns agenesis of the kidney. Chemotherapy of metastatic renal cell

carcinoma has a poor effect. We report a case of a man, 49 years of age, with

agenesis of one kidney, admitted with a metastatic RCC of his only kidney.

Survival of 15 months duration was achieved by therapy combining Provera,

Vinblastine and Alpha-C-Recombinant Interferon.


PMID: 2529317  [PubMed - indexed for MEDLINE]



19. J Urol (Paris). 1984;90(5):341-3.


[Sarcomatoid carcinoma of the kidney].


[Article in French]


Golomb J, Merimsky E, Baratz M, Greenstein A, Braf Z.


Sarcomatoid renal carcinoma is an uncommon renal malignancy with an aggressive

biological behaviour and very poor survival rate. We treated lately 4 patients,

three of which died shortly after the operation. The case reports are presented

and the histology and the clinical implications are discussed.


PMID: 6501912  [PubMed - indexed for MEDLINE]



20. AJR Am J Roentgenol. 1981 Oct;137(4):781-5.


Infarction of renal tumors using isobutyl-2 cyanoacrylate and lipiodol.


Papo J, Baratz M, Merimsky E.


Percutaneous transcatheter embolization of the renal artery in clear cell

carcinoma was performed in nine patients. The occlusive material used was a

suspension of 1 ml of isobutyl-2-cyanoacrylate in 3 ml of Lipiodol. Six patients

were operated on 2-5 days after the embolization, and in three patients the

procedure was palliative. In one of the latter, follow-up arteriography 4 months

later showed that the artery was still occluded. There were no complications

attributed to the glue or to oil emboli in this series.


PMID: 6270991  [PubMed - indexed for MEDLINE]


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