דן ליבוביץ, אמנון זיסמן, יהודית קליינמן, אריה לינדנר

המח' לאורולוגיה, מרכז רפואי אסף-הרופא, צריפין

סרטן הערמונית הוא המחלה הממארת השכיחה ביותר בגברים והיארעותה מגיעה לכדי 900 חולים חדשים לכל 100,000 לשנה. איבחון מוקדם של המחלה בשלב בו השאת מוגבלת לבלוטת הערמונית, מאפשר ריפוי מלא בחלק ניכר מן החולים. האפשרויות הטיפוליות כוללות כריתת ערמונית רדיקלית, טיפול קרינתי והקפאה קריוגנית.

בניתוחים קריוגניים (נ"ק), מבוצעת הקפאת השאת בתוך הגוף על ידי החדרת גלאי לאיבר המטרה והשראת טמפרטורה נמוכה קיצונית בסביבות 180 – מ"צ. כדור הקרח הנוצר סביב הגלאי כולל בתוכו את ריקמת המטרה, וחשיפתה לטמפרטורה נמוכה קוטלת כל ריקמה ביולוגית. כיום, מהווים נ"ק אפשרות טיפולית מקובלת בחולים בסרטן הערמונית, והפעולה קיבלה את אישור מינהל המזון והתרופות בארה"ב (FDA). בסקירתנו, נדון הניסיון העולמי בנ"ק כטיפול בלוקים בסרטן הערמונית.

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. 
 

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%).
 

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.

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.

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.

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.

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.

Transarterial Oil Chemoembolization for Hepatocellular Carcinoma 

Izhar Levy, Anthony Verstandig, Talia Sasson, Dana Wolf, Ilia Krichon, Eugin Libson, Pinchas Levensart, Orit Papo, Oded Yurim, Ahmed Id, Daniel Shouval

Division of Medicine, Liver Unit and Invasive Radiology, Radiology, Pathology and Surgery Depts., Hadassah University Hospital, Ein Kerem, Jerusalem

Hepatocellular carcinoma (HCC) is a common malignancy with a grave prognosis. Most patients have both the malignant tumor as well as hepatic cirrhosis. Liver transplantation or hepatectomy are considered the only curative procedures, but can be applied in fewer than 10% of patients. In recent decades the most common treatments of HCC are transarterial chemoembolization with oil (TOCE) and percutaneous ethanol injection (PEI). We summarize our retrospective study of 100 patients (mean age 64) 3‏ treated by TE.

In 271 procedures between 1989-1998, in 16 patients hepatectomy was combined with TOCE and in 8 PEI was combined with TOCE, while the rest were treated by TOCE alone. Tumor mass was reduced in 36% of those treated by TOCE (tumor volume reduced 24-75%). Alpha-feto protein (AFP) was reduced 25-90% in 20/32 of those with elevated AFP levels. Median survival for the 100 in the entire group was 19 months (10.9 months in those with conservative treatment). Median survival in the 57 in Okuda stage 1 and the 43 in stages 2 or 3 was 30.1 months and 10.9 months, respectively (p<0.0001). Of the 57 in stage 1, 16 underwent hepatectomy in addition to TOCE and 41 were treated only by TOCE (median survival 15 and 26 months, respectively, p not significant).

Comparing Okuda 1 patients treated by TOCE only with the natural history of the disease and historical controls (Okuda 1 patients treated conservatively in 1984) median survival was 26 and 10 months respectively (p<0.001). The side effects of TOCE were relatively mild. There was 1 fatality (3 days after treatment), and quality of life was maintained. Despite progress in the treatment of HCC by TOCE, PEI, and liver transplantation, long-term survival has remained unsatisfactory.

Brief Preoperative Radiotherapy reduces Local Recurrences and Improves Survival in Rectal Cancer

T. Peretz, Z. Weshler,* Y. Goldberg, A.L. Durst, H.R. Freund

Depts. of Surgery and Oncology, Hadassah University Hospitals, and Hebrew University-Hadassah Medical School, Ein Kerem and Mt. Scopus, Jerusalem

Locoregional recurrence of rectal cancer ranges between 20%-50% following apparently radical surgery. Radiation has the potential of reducing this high rate of recurrence and residual disease. A retrospective analysis of 78 patients with locally advanced, biopsy proven, adenocarcinoma of the rectum treated between 1980-1987 was conducted. 28 (36%) were treated by surgery alone (surgery); 29 (37%) by surgery and postoperative radiotherapy (post-op); and 21 (27%) by surgery and preoperative radiotherapy (pre-op). 41 were females and 37 males. The median age was 62 years (range 25-90).

All tumors were resectable. 42 patients (54%) underwent abdomino-perineal resection and 36 (46%) anterior resection patients [8 Dukes B₁ (10%); 37 B₂ (47%); 2 C₁ (3%); 31 C₂ (40%]. Local recurrences were verified by transanal or ultrasound guided needle biopsy.

The 5-year actuarial survival rates by the Kaplan-Meier method for 75 evaluated patients was 55%. Overall 5-year actuarial survival was significantly higher (p=0.001) in pre-op radiotherapy (95%) compared to surgery alone (45%), or surgery with postoperative radiotherapy (32%). The data were significant (p=0.006) for patients with stage B tumors, but not stage C. This trend of improved survival held also at 8-year follow-up (80% pre-op; 32% post-op; 27% surgery). The 5-year actuarial local control was significantly better (p=0.03) for the pre-op irradiated patients (22%), compared with surgery only (56%) and post-op radiotherapy (38%). Local control was better (p=0.02) for Dukes B tumors in the preoperative group, but not Dukes C tumors.

Actuarial 5-year survival of those without distant metastases was 87% for pre-op patients, 62% for surgery alone and 48% for post-op radiotherapy. As all patients were clinically classified as advanced rectal tumors, tumor downstaging by preoperative radiotherapy seems to be paramount for local control. Improved local control translates into a siginificant advantage in overall actuarial survival.

*DECEASED.

Breast Conservation: Safe for Early Breast Cancer

Gil Bar-Sella, Georgetta Fried, Zipora Brotman, Anna Ravkin, Riva Borovik, Abraham Kuten

Dept. of Oncology, Rambam Medical Center; Dept. of Oncology, Lin Medical Center; and Rappaport Faculty of Medicine, Technion, Haifa

Between 1981-1993 581 women with primary breast cancer were treated by breast conservation. Their mean age was 56‏12 years and 63% were postmenopausal and 37% pre- or perimenopausal. The median follow-up time was 56 months. 45% had pathological Stage I disease, 49% Stage II, 2.5% Stage III and 3.5% clinical Stage I-II disease. 54% of lesions were excised with good margins, 10% with close margins (<0.5 cm), 9% with microscopic residual, 3% with macroscopic residual, and in 24% margins were not reported. Adjuvant therapy, consisting of combination chemotherapy and/or hormones, was given to 69%.

Radiotherapy, usually 50 Gy tangential photon irradiation to the whole breast, was given to 564 (97%); an electron or photon "boost" to the tumor with a median dose of 17.5 Gy was given to 378 (65%). Most of those with positive nodes received 50 Gy to the lymphatic drainage system.

1 year after radiotherapy cosmetic results were rated as "good" or "excellent" in 80%, "moderate" in 17% and "poor" in 3%. The 5-year actuarial survival was 97% in Stage I and 88% in Stage II. 37 patients (6.5%) developed breast recurrence; 11 of these (2%) had simultaneous distant metastases. 5 (<1%) developed axillary or supraclavicular lymph node metastases, and 81 (14%) developed distant metastases. Most local recurrences were in those younger than 40, and in those with primary tumors >1.75 cm.

The satisfactory level of local control achieved is attributed to the high doses of radiation (up to 75 Gy) administered to those with high risk lesions.

אברהם דומב

המח' לכימיה תרופתית, ביה"ס לרוקחות, הפקולטה לרפואה, האוניברסיטה העברית, ירושלים

Adjuvant Therapy of Large Bowel Carcinoma

G. Ezekiel, S. Walfisch, Y. Cohen*

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

The National Institutes of Health (NIH) held a consensus conference which recommended 5-FU and levamisole as adjuvant chemotherapy for colon cancer MAC (Modified Astler Coller) stage C.

From 1991-1994, 37 such patients diagnosed here were treated with 5-FU (intravenous dose of 450/mg/m²/d for 5 days and from day 29, once a week for 48 weeks) and oral levamisole (50 mg 3 times/d. for 3 days, every 2 weeks for a year), as suggested by NIH guidelines.

16 patients were males and 21 were females, mean age was 62 years and median 64. Cancer locations were: right colon (in 16, 43%), left colon (19, 51%), multiple colon primaries (2, 1%). 25 (68%) had 1-3 positive lymph nodes and 12 (32%) had 4 or more positive lymph nodes.

Only 20 (54%) finished treatment as prescribed. In the others, 1 or both drugs caused side-effects for which the drugs had to be stopped. 6 patients relapsed while on treatment.

The most common side-effects were diarrhea, stomatitis and bone marrow suppression. 3 were hospitalized due to neutropenic fever. 5-year actuarial survival of all patients was 61%; 5-year relapse-free survival was 61%; 5-year relapse-free survival of right versus left colon was 41% and 82%, respectively (p<0.01). There was no significant difference in 5-year survival of those with 1-3 positive lymph nodes as compared to those with 4 or more (62% and 56%, respectively). 5-year survival in those who finished or did not finish treatment (excluding those who stopped treatment because of progressive disease) was 83% and 70%, respectively (NS).

The 5-year survival of our series was similar to that of patients treated similarly elsewhere. The 5-FU and levamisole treatment was not tolerated well by our study population. It has recently been replaced in our service by a 5-FU and leucovorin regimen given for 6 months.

* Jules E. Harris Chair in Oncology.