Search

Cancer is a major factor of morbidity and mortality worldwide. Over 90% of cancer-related deaths are due to metastatic disease. Observations made more than 140 years ago described cancer cells from solid tumors in the bloodstream. yet, the significance of these circulating and disseminated cells and their contribution to the generation of metastasis remained a mystery. Recently, substantial technological advances have enabled the detection and isolation of circulating tumor cells from the peripheral blood. Currently, this technology allows quantitative analysis of circulating cancer cell content and permits a view of the genetic and phenotypic changes in this accessible population. In the future, researchers hope to use circulating tumor cells as a powerful tool for early detection, prognosis, tumor response assessment and even for treatment selection. The discovery of cancer cells in the bloodstream holds many promises in the study, diagnosis and treatment of cancer, but, at the same time, raises difficult questions regarding the identity of these cells, their contribution to the process of metastasis and their ability to aid medical decisions. This review aims to introduce the topic of circulating tumor cells to the Israeli medical community and encourage active participation in basic and translational research in this field. We believe this field holds great potential for promoting the practice of surgical oncology, tumor surveillance and clinical oncology.

Ipilimumab (Yervoy) is a monocLonal antibody designed to block cytotoxic T cell antigen 4 (CTLA-4), an inhibitory receptor of T lymphocytes. This drug is the first to receive US FDAs approval for advanced stage malignant melanoma in the last 13 years. So far, no survival benefit was achieved for this patient group with single drug or combination chemo- and chemo-immunotherapy. In phase II and III trials, up to 15% of patients had melanoma regressions, with a decreased hazard ratio of death of 0.72 compared to the standard chemotherapy with Dacarbazine. The development of Ipilimumab marks a success in deciphering the check-point control on the immune response. Activated T cells over-express CTLA-4 molecule on their surface and become susceptible to its inhibitory effect. CTLA-4 decreases the signaling network derived by antigen recognition of T cells. Alongside of its therapeutic effect, the CTLA-4 blockade enhances autoimmune responses. Severe diarrhea results from toxicity to the colonic mucosa which may eventuate in perforation and, in rare cases, death. Other adverse events of varying severity occur in many patients and include skin eruption, uveitis, endocrinopathies such as thyroiditis and hypophysitis and autoimmune hepatitis. Ipilimumab toxicity is reversible with systemic use of corticosteroids, but the use of TNF inhibitors is sometimes indicated in the absence of resolution. The clinical success of the CTLA-4 blockade motivated intense searches for additional check-point modifiers, such as PD-1 molecule, with encouraging preliminary results. Ipilimumab's entry into the clinic is the opening of a new chapter in the immunotherapy of melanoma in particular, and of cancer, in general.

Some of the women who undergo surgery for the removal of breast cancer will need adjuvant treatment with chemotherapy, hormonal therapy, biological therapy or radiation therapy. In patients whose tumor expresses HER2, the adjuvant treatment will include Trastuzumab. In a number of prospective randomized trials performed in recent years, Trastuzumab was proven to have a significant effect in reducing by half the incidence of the recurrence of the disease and reducing the risk of death by a third. It is important to provide Trastuzumab as early as possible, together with the chemotherapy, unless treatment with doxorubicin is needed and then Trastuzumab is given later. The most significant side effect of Trastuzumab is cardiac toxicity, which is manifested in most cases by an asymptomatic decrease of the left ventricular ejection fraction in 2.3-17.3% of patients, although in most cases this has no clinical significance. Symptomatic heart failure is a rare event in Trastuzumab treated patients, occurring in 0-4% of patients and it is generally reversible with Trastuzumab discontinuation. In this review we summarize the current perspective on Trastuzumab and discuss adjuvant treatments in HER2-positive early breast cancer.

Carbohydrate antigen (CA) 19-9 is produced by adenocarcinomas of the pancreas, stomach, gall bladder, colon, ovary and lung. Serum CA 19-9 is considered the most sensitive marker for pancreatic cancer, being elevated in 75% or more of patients with pancreatic cancer. In all three cases of pancreatic cancer presented, patients died of their disease quite shortly after diagnosis. Preoperative imaging was unsuccessful in exposing the actual advanced state extent of the disease and even during surgery its real extent was underestimated. The only prognostic indicator of the observed rapid disease progression was a very significant elevation of preoperative serum CA 19-9.

Metastatic testicular cancer can be associated with a variety of complications due to obstruction or invasion of adjacent structures. This is a case study of 2 patients with testicular cancer who presented with venous thromboembolism.

Background: During the past few years, the genes BRCAI and BRCA2 were cloned. Mutations in each gene are responsible for the syndrome of familial breast and ovarian carcinoma. Among women who carry such a mutation, there is a 56%-80% life-time risk of developing breast cancer and a 16%-60% risk of developing ovarian cancer. Recently, it has been proven that prophylactic mastectomy and/or oophorectomy might reduce such risks of developing cancer. Neither of these treatments offers full protection and furthermore, compliance of carriers is partial, considering the physical and mental consequences of such treatment., Goals and Methods: This study describes the sociodemographic profile of 30 healthy carriers of BRCA1/2 mutations that underwent prophylactic salpingo-oophorectomy. We also examined the pathological specimens and point out the ratio of significant pathological findings, especially the presence of cancer. The women are being followed-up at Hadassah Medical Center, Jerusalem., Results: Pathological examination of the ovaries and fallopian tubes of 30 healthy carriers of BRCA1/2 mutations who underwent prophylactic salpingo-oophorectomy revealed tumor in three cases (10%). Two tumors were in the ovaries and one in the fallopian tube. One of these tumors was in an advanced stage and two were small and confined to the organ., Conclusions: Based on the above results, we noted that salpingo-oophorectomy, despite being quite a radical preventive method, might offer protection for the carriers against life-threatening silently-developing cancer. We found cancer in 10% (3) of the women, and in two of these cases, prophylactic salpingo-oophorectomy became the definitive treatment for a small occult tumor.

Background: Breast cancer is the leading cancer among Israeli women. Mammography is the most widely used tool for early diagnosis of breast cancer. Eight published randomized controlled trials followed nearly 500,000 women over 7 to 18 years. Most trials found that screening mammography decreases breast cancer mortality by 20 to 40%. A recent study examined the methodology of the randomized clinical trials and found that most trials were flawed in the methodology of data collection and analysis in a way that might have influenced the results of those trials., Purpose: To review the studies, clarify the issues, and reach a conclusion regarding the utility of screening mammography in reducing breast cancer-related mortality in Israel., Methods: A review of the world literature, and analyses of the Israeli data., Results: Seven out of eight published randomized controlled trials found a significant decrease in breast cancer mortality among women who underwent screening mammography. A meta-analysis of the trials also supports the utility of screening mammography in decreasing breast cancer mortality. The criticism over the methodology of these trials does not necessarily invalidate their conclusions., Conclusions: The data indicate that screening mammography does indeed assist in early diagnosis, and most published studies show a significant reduction in breast cancer-related mortality in the screened population. Due to the high incidence of breast cancer in the Israel, especially among young women, the national screening program should continue. Moreover, consideration should be given to expanding it to women starting at age 45, instead of 50, as is practiced today.

Tamoxifen is a selective estrogen receptor modulator (SERM) with pro- and anti-estrogenic properties. Currently it is the most widely used agent for first line treatment against hormone sensitive metastatic breast cancer and the only approved hormonal agent for adjuvant treatment of organ confined breast cancer. Furthermore, its uses have been extended for the treatment of intraductal breast carcinoma patients. In such settings the most worrisome side effect of tamoxifen is its ability to increase the rates of uterine cancers. It has been claimed that most of these cancers are found at an early stage because of vaginal bleeding. Moreover, it has been shown that for most women transvaginal ultrasound is an ineffective screening method for the early detection of uterine carcinomas. It is important, however, to notice that long term tamoxifen treatment can cause metastatic uterine cancer--not only carcinomas but also sarcomas (mainly malignant mixed mesodermal tumors. It should be noted that, at least for the special population of BRCA mutation carriers, transvaginal ultrasound can increase our ability for the earlier discovery of ovarian cancer. Thus, we believe that there is still a place for the use of transvaginal ultrasound in special populations. This is specifically for long term tamoxifen users (more than the usually recommended five years), women with a higher chance of having uterine carcinomas (namely very high body weight, strong family history) and women with a high index of suspicion as carriers of a BRCA mutation. Until new second generation SERMs and aromatase inhibitors are shown to possess better anti-cancer abilities than tamoxifen, this drug will remain in wide use, however, we must not overlook its possible rare side effects.

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 [8 patients 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 significant advantage in overall actuarial survival.

About 5-10% of the most common cancers, such as breast, colon and melanoma, result from mutations in inherited predisposition genes. Recently some of these genes have been mapped or even cloned. These advances in cancer genetics have made more precise genetic counseling possible for cancer patients and their families. In our clinic for specific genetic counseling 180 families with a history of cancer were seen during a 10-month period. In counseling sessions, the family history was confirmed and interpreted, personal risk was estimated and the availability of molecular genetic testing was presented. Blood samples for DNA testing were drawn from those with certain criteria who wished to be tested. Instructions for early detection were also given, depending on the personal risk of cancer as compared to that of the general population.