Long-Term Sequelae of Malignant Tumors in Childhood

N. M. Peretz, H. Goldberg, A. Kuten, I. Meller, E. Krivoi, A. Lorber, L. Bentur, A. Lightman, V. Gorenberg, M. Ben Arush-Weyl

Pediatric Hematology-Oncology Dept., Oncology Center, Pediatric Cardiology Unit, Pulmonology and Gynecology Depts., and Pediatric Endocrinology Unit; Rambam Medical Center and Technion-Israel Institute of Technology, Haifa; and Orthopedic-Oncology Unit, Tel Aviv-Sourasky Medical Center and Tel Aviv University

110 children with malignant diseases (leukemia excepted) who survived 5-20 years (median 9) post-therapy were followed (1996-1998). Median age during follow-up was 15 years (range 5-23). The most common malignancies were brain tumors, lymphoma, retinoblastoma and Wilm's tumor.

The 174 late side-effects included endocrine disorders (19%), cognitive impairment (14%), orthopedic dysfunction (12%), alopecia (12%), dental damage (11%), psychological (8%) and neurological (8%) disturbances, and azoospermia or amenorrhea (5%). There was no cardiac or renal damage and no second malignancy.

29% of side-effects were severe. There was significant reduction in quality of life in 54 (49%), in 27 of whom it was severe enough to require psychological intervention. Treatment of brain tumor caused 98 late side-effects in 28 patients (sequelae-to-patient ratio [SPR] 3.3). Most cognitive, endocrine and neurological disorders, and most cases of alopecia, dental and psychological difficulties were in these patients. There were frequent late complications in those treated for retinoblastoma (SPR 1.8), and bone or soft tissue sarcomas (SPR 0.8). Those treated for Wilm's tumor had few side-effects (SPR 0.4).

Late side effects were most frequent after radiation, reaching as high as SPR 2.4. It averaged only 0.5 in those treated with chemotherapy alone or in combination with surgery.

Reduction of late side-effects in these patients requires using less toxic modalities, as long as cure rate is not compromised. When considering secondary strategies, screening for early detection of late complications would enable immediate solutions, such as hormonal replacement or providing compensating skills for post-treatment disability.
 

למעלה מ- 40,000 נשים נפטרו בשנה האחרונה מסרטן השד בארצות הברית. עובדה זו מעמידה את סרטן השד כסרטן השכיח ביותר בנשים והשני כגורם לתמותה מסרטן בנשים. נשים מעל גיל 60 הן בעלות הסיכון הגבוה ביותר ללקות בסרטן השד ואוכלוסייה זו היא אוכלוסיית המטרה לרוב המחקרים הקליניים שמטרתם טיפול מונע. הסיכון במהלך שנות החיים ללקות בסרטן שד פולשני הוא בשיעור של 12%, ולכן כל טיפול שיפחית או יגדיל את הסיכון הנ"ל, הוא בעל השפעה חשובה על בריאות האשה. טיפולים המשפיעים על עלייה או ירידה בסיכון לסרטן השד בנשים בעת חדלון הווסת כוללים: טיפול הורמוני חלופי, כריתת שד כטיפול מונע, ומתן טמוקסיפן וראלוקסיפן. בשנה האחרונה, פורסמו מספר מחקרים בנושא, אותם נסקור במאמר זה.

Photodynamic Therapy of Nasal Basal Cell Carcinoma

R. Haddad, M. Cohen, O. Kaplan, R. Greenberg, H. Kashtan

Dept. of Surgery, Tel Aviv-Sourasky Medical Center

Photodynamic therapy (PDT) is a noninvasive modality used topically for several skin cancers. We evaluated the effects of PDT on basal cell carcinoma (BCC) of the nose, using aminolevulinic acid (ALA) as a photosensitizer and a non-laser light source (Versa-LightTM). The advantages of this light source are synergistic, hyperthermia and fewer side effects.

A paste of 20% ALA was applied topically to biopsy-proven BCC of the nose. Lesions were covered with occlusive light-shielding dressing and after 18 hours they were submitted to 10 minutes of exposure to the light. Initial evaluation was made after 21 days and every 3 months thereafter. Patients who did not respond after 2 treatments were referred for surgery.

Mean follow-up in 31 patients was 19 months (range 6-36). There were no significant side-effects. There was complete response in 24/27 (88.9%), in whom there was recurrence in 2/27 (7.4%).
 

Screening for Early Detection of Prostatic Cancer

A. Neheman, Y. Shotland, Y. Metz, A. Stein

Dept. of Urology, Carmel Hospital, Lady Davis Medical Center, Haifa

Prostatic cancer (PC) is second only to lung cancer as a cause of cancer mortality in men word-wide. In Israel it is the most common cause of cancer mortality in men, after lung cancer and colo-rectal cancer.

We screened, for the first time in Israel, for prostatic cancer using serum levels of PSA and a digital rectal examination (DRE). The purpose was not only to diagnose PC but also to increase public awareness of the condition.

300 men in the Haifa area who met statistical criteria for early diagnosis of PC participated. They filled a questionnaire regarding risk factors for PC (age, family history (FH) of prostatic and breast cancer, cigarette smoking, alcohol consumption, previous PSA sampling) and were examined. Those who had out-of-ragne, age-related PSA values, or a pathologic DRE underwent trans-rectal ultrasound (TRUS) examination and guided biopsy of the prostate. Those with a positive biopsy for PC underwent radical prostatectomy or radiation therapy.

41 (14.3%) had out-of-range, age-related PSA levels and 10 (3.5%) had a pathologic DRE. 39 (13.3%) underwent TRUS and biopsy and 6 (2.04%) had clinically significant PC, all early stages (Gleason 4-6).

Correlation between age and PSA has been proven statistically significant (p<0.05). Symptoms of urinary tract obstruction and nocturia were related to a high PSA (p=0.035 and 0.002, respectively). Those with PC had at least 1 symptom of urinary tract obstruction; 6 (15.3%) who underwent TRUS and biopsy and a FH of prostate cancer. However, no subject with a FH of PC had biopsy-proven cancer. Those with PC had PSA values from 4.9 to 31.8 ng/ml (9.6 median). Age-related PSA had a positive predictive value of 17.1%.

Results of our annual screening for early detection of PC using age-related PSA, and DRE are encouraging: cases detected were clinically significant and treatable. It would appear that screening for PC will result in decreasing the incidence of metastatic cancer and therefore mortality. 
 

Pulmonary Adenocarcinoma in Myasthenia Gravis - Auto-Immunity and Late Development of Malignancy

Yitzhak Rosen, Yair Levy, Yehuda Shoenfeld

Dept. of Internal Medicine B, Sheba Medical Center, Tel Hashomer and Sackler Faculty of Medicine, Tel Aviv University

We report a 75-year-old man with myasthenia gravis for many years, who was hospitalized because of cough, fever, and dyspnea. Chest x-ray revealed a bilateral pleural effusion. Adenocarcinomatous cells were found in the pleural fluid. Computerized tomography of the chest showed widespread pulmonary dissemination of the tumor.

The relationship between myasthenia gravis, an autoimmune disease involving the motor end-plate, and malignancy (thymoma) has been widely recognized. Current literature documents few reports of lung malignancies with concurrent development of myasthenia gravis. A tentative explanation, based on current research, is provided for the possible role of myasthenia gravis and the late development of lung cancer. Moreover, a model for the autoimmune phenomenon and the development of late malignancies will be provided with explicit explanations. It is important to search for occult, developing malignancies in newly diagnosed autoimmune diseases.

Preservation of the Larynx in Advanced Cancer

Edward Rosenblatt, Nava Siegelmann-Danieli, Jemal Zidan, Nisim Haim, Abraham Kuten

Oncology Dept., Rambam Medical Center and Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa

The effectiveness of sequential chemo-radiotherapy in preserving the larynx in advanced laryngeal carcinoma was assessed. 4 Unselected patients (19 men and 2 women, mean age 60 years) with advanced squamous cell carcinoma of the larynx (T3-4/N0-3) received induction chemotherapy consisting of 2-3 cycles of cisplatin (100 mg/m²) and 5-flourouracil (1000 mg/m²/day) as a continuous infusion on days 1-5 followed by definitive radiotherapy: 50 Gy to the whole neck, 70 Gy to the larynx and clinically involved nodes, using a combination of 6 MV photons and 9-12 MeV electrons.

19 of The 21 patients responded to combined therapy but there was no response to induction therapy in 2 (10%) and 2 did not complete therapy due to severe toxicity. At a mean follow-up of 40 months, 7 had undergone total laryngectomy (33%), for an overall 5-year laryngeal preservation rate of 66%. Reasons for total laryngectomy in 2 patients were no response and in 5 tumor recurrence.

Mean survival was 39 months (range 11-46 months); at last follow-up 17 of 21 were alive and disease-free, 11 of whom had a functional larynx (65% of survivors). 2 died due to disease progression and 1 due to a cardiovascular event. Sequential chemo-radiation allows laryngeal preservation in about 2/3 of surviving patients without compromising survival.

Breaking Bad News - A Structured Course for Primary Care Physicians 

Lea Ungar, Mordechai Alperin, Gilad Amiel, Zvi Behrier, Shmuel Reiss

Family Medicine Dept., Kupat Holim Klalit Health Services, Western Galilee District; Medical Education Unit, Bruce Rappaport Faculty of Medicine, Technion Institute of Technology; and Urology, Dept., Bnei-Zion Medical Center, Haifa

Physicians are frequently required to break bad news to their patients. Previous research has shown that inconvenience, incompetence, and difficulty in dealing with patients' feelings are the main complaints expressed by physicians after such an encounter. Current educational programs dealing with breaking bad news are usually short, given in lecture format, and are inadequate in addressing essential issues such as knowledge, personal beliefs and attitudes, and previous personal experiences of physicians in such situations.

In the past 8 years our Dept. of Family Medicine has implemented a course in breaking bad news that addresses these issues. A senior family practitioner and a medical social worker conduct 14 sessions of discussions and role-playing for small groups of residents and primary care physicians. The program is based on: theory dealing with methods of managing stress and crisis intervention, clarifying personal attitudes, discussions of previous personal encounters of the participants, various modalities of communication, methods of addressing patients' feelings and emotions, and coping with the emotions of the one breaking the bad news.

On a 1-5 Likert scale questionnaire the course received an overall score of 4.47 (SD 0.51). Participants noted that they gained relevant communication skills for future patient encounters. A reliable examination of practitioners' competence in breaking bad news is mandatory in order to assess the efficiency of such courses.

Penile Prosthesis for Erectile Dysfunction: Long-Term Follow-Up 

Ofer N. Gofrit, Ofer Z. Shenfeld, Ran Katz, Amos Shapiro, Ezekiel H. Landau, Dov Pode

Urology Dept., Hadassah University Hospital, Jerusalem

Our armamentarium for the treatment of erectile dysfunction has recently been expanded by addition of Viagra and the MUSE. However, their long-term results are still unknown. The insertion of a penile prosthesis is invasive, expensive, and irreversible, but under optimal condition provides an acceptable, definitive solution for erectile dysfunction. We evaluated our long-term results with penile prosthesis insertion (PPI).

From 1987-1998, 57 patients underwent PPI in our department. Mean age was 55 years and the common causes of erectile dysfunction were atherosclerotic disease (23), radical pelvic surgery (15), and diabetes mellitus (14). Semirigid prostheses were inserted in 12 and inflatable prostheses in 45, including 42 single-component and 3 multi-component prostheses.

Recently we interviewed these patients by telephone, using a standard questionnaire. Those not satisfied with the surgical results (83% of the living patients) were examined in our clinic. Mean follow-up was 53 months. In 37 (84%) the prosthesis was mechanically functional (rates after 1, 5 and 10 years were 87.8%, 80%, and 75%, respectively). In only 2 (2.5%) had serious complications led to prosthesis removal.

All mechanical failures had occurred in those with inflatable prostheses after a mean of 48.5 months (range 4-113). At the time of the survey 68% were sexually active and 64% were satisfied with the surgical result. We conclude that PPI is safe treatment for erectile dysfunction. Although the rate of mechanically functioning prostheses decreases with time, modern multi-component prostheses may lead to better mechanical results.

Testicular Cancer: Self-Awareness and Testicular Self-Examination in Soldiers and Military Physicians

Thomas Tichler, Rony Weitzen, Aharon Feinstone, Raoul Orvieto, Marian Moskovitz, Adam Singer

Depts. of Oncology and Medicine B, Sheba Medical Center, Tel Hashomer; Medical Corps, Israel Defence Forces; Gynecology Dept., Hasharon Medical Center, Petah Tikvah; and Medical Dept. B, Fleaman Hospital, Haifa

Testicular cancer is the most common malignancy in young men. To evaluate knowledge and awareness of that cancer, and of the practice of testicular self-examination (TSE), we developed a questionnaire which was distributed to 717 male soldiers and 200 of their military physicians.

21% of the soldiers had received some explanation of the importance of TSE, but only 16% were actually instructed how to perform TSE, and only 2% practiced it regularly. 24% had never examined their testicles before, 185 only rarely, and 6% often. With increased age, TSE frequency increased, but previous education, type of military unit, and ethnic origin had no affect. 99% of military physicians had been taught how to examine breasts, but only 70% had been taught routine testicular examination. 22% performed it, but 27% never did. 84% had never taught their soldiers the importance of TSE, although 51% taught female soldiers breast self-examination.

There was a significant lack of awareness of the importance of regular practice of TSE among both soldiers and their army physicians.

Laparoscopic Ultrasound in Predicting Resectability of Choriocarcinoma

M. Shimonov, P. Schachter, G. Gvirtz, Y. Avni, A. Rosen, A. Czerniak

Depts. of Surgery, Ultrasound, and of Gastroenterology, Wolfson Medical Center, Holon and Sackler Faculty of Medicine, Tel Aviv University

Cholangiocarcinoma accounts for about 1% of all malignant tumors. They are difficult to diagnose because of their small size and their location. Although surgical resection is the best therapeutic approach, most patients undergo unnecessary exploratory laparotomy due to incorrect preoperative diagnosis.

We present our experience with laparoscopic ultrasound (LU) in the evaluation of cholangiocarcinoma and determination of tumor spread and vascular involvement. Of 25 patients referred for surgery, 6 were excluded following LU and were referred instead for palliative treatment. Diagnosis of the tumor was successful in 92%, and vascular involvement was diagnosed in 46%. LU should be an integral diagnostic test in the evaluation of choriocarcinoma.

Breast Tumors Demonstrated by Tc-99m Sestamibi Scintimammography 

Itzhak Pappo, Tifha Horne, Herbert Merdad, Ruben Orda

Dept. of Surgery A, Institute of Nuclear Medicine and Dept. of Pathology, Assaf Harofeh Medical Center, Zrifin; and Sackler Faculty of Medicine, Tel Aviv University

Breast cancer can be detected by scintimammography using Tc-99m sestamibi (MIBI). The method is highly accurate, sensitive and specific. Histologically, most of the tumors have been adenocarcinomas.

We present 2 women with rare breast tumors, primary squamous cell carcinoma and malignant phyllodes tumor. In both, mammography and cytological biopsy were not diagnostic, but MIBI scintimammography demonstrated focal uptake in the diseased breast.

Concomitant Coronary Artery Bypass Surgery and Pulmonary Lobectomy 

Amit Korach, Uzzi Izhar, Ehud Rudis, Amir Elami

Dept. of Cardiothoracic Surgery, Hadassah University Hospital, Jerusalem

Coronary artery disease amenable to percutaneous interventions or coronary artery bypass grafting, and resectable lung cancer are major causes of morbidity and mortality. We present our experience in the treatment of 3 patients (men aged 64 and 66 and a woman of 77) who each had significant coronary artery disease and a resectable lung tumor. They underwent combined coronary artery bypass grafting and pulmonary lobectomy.

We conclude from our experience and review of the literature that concomitant surgery in such cases is safe and effective, decreases suffering, and decreases the cost of 2 separate invasive procedures.

Breast Cancer after Mantle Field Irradiation for Hodgkin's Disease 

A. Katz, B. Brenner, A. Sulkes, H. Luria, G. Marshak, E. Fenig

Oncology Institute, Rabin Medical Center, Beilinson Campus, Petah Tikva and Sackler Faculty of Medicine, Tel Aviv University

Effective use of modern therapeutic modalities results in the cure of 75%-80% of Hodgkin's disease patients, regardless of stage. The major threat to continued survival is, therefore, not recurrent disease but development of second malignancies. Recent reports have firmly established the increased risk of breast cancer developing in women treated with mantle field irradiation.

We describe 3 women who developed breast carcinoma following mantle field irradiation for Hodgkin's disease. Their clinical course was consistent with that reported in larger series. They were relatively young when irradiated and there was a long interval between radiation therapy and the diagnosis of breast cancer.

Review of the literature shows that there may be a role for prophylactic mastectomy after irradiation for Hodkgin's disease.

Etoposide and Cisplatin for Non-Small Cell Lung Cancer 

David B. Geffen, Sofia Man, Yoram Cohen*

Dept. of Oncology, Soroka-University Medical Center and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheba

Etoposide and cisplatin (EP) has been the standard therapy for non-small cell lung cancer (NSCLC) at many cancer centers for over a decade. We analyzed our experience with EP in NSCLC to provide a baseline for comparison with new drugs. From 1986 through 1994, 46 of our patients with NSCLC received EP as first-line chemotherapy. Radiation therapy was administered to 25 of them, including 20 who received it immediately before or concomitantly with chemotherapy. Toxicity was mild and included only 1 episode of neutropenic fever and 1 case of reversible renal failure.

Overall response was 22%. In 3, response was complete (pathologically documented in 2 of them) and in 7 partial. Median survival in locally advanced (stage III) and metastatic disease (stage IV and recurrent) were 12 months and 7 months, respectively. 2 patients are alive and free of disease more than 6 years after diagnosis.

Our results are consistent with other published studies of EP in NSCLC. EP provides modest benefit in locally advanced NSCLC, with minimal toxicity.

Jules E. Harris Chair in Oncology.

Alopecia Due to Seroxat 

Leonid Umansky, Abraham Dorevitch, Avner Sella

Psychiatry Chronic Dept., Eitanim Mental Health Center, Jerusalem

There are 2 stages of alopecia, anagen and telogen effluvium, both of which may be associated with medication- related alopecia. We describe massive hair loss in a 51-year-old woman during treatment with Seroxat (paroxetine), which remitted after it was discontinued. Pathological mechanisms of drug-associated alopecia are complex and have yet to be fully elucidated.