Search

Colorectal cancer (CRC) is a common malignancy in both genders with a high death rate, accounting for about 56,000 each year in the USA only. In this study we examined the differences in CRC between the genders. We also looked for differences in the staining of the tumors and adjacent colonic mucosa to estrogen receptor β1 and its possible prognostic value. Fifty-five specimens from patients who underwent resection of colon cancer in our institute were sectioned and stained for estrogen receptor β1. The histopathological slides were evaluated for positive staining in the tumor and the normal colonic mucosa as well. The results were statistically analyzed. Positive estrogen receptor β1 stain was found in the nuclei of the tumor cells. We noted positive stain also in the cytoplasm of the tumor cells. Similar findings were observed in the normal colonic mucosa. Statistically significant differences were found regarding the positivity of the staining between the deceased and surviving patients, men/women and those who had metastases vs. the non-metastatic ones. Our data suggest that there is an estrogen influence on the development and progression of colon cancer. Furthermore, it was found to be higher in the more severe cases.

Gastric cancer (GC) in Israel remains incompletely characterized. The aim of this study was to define the clinical and pathological characteristics of GC in Israel and to compare them to the general Western population.This is a retrospective analysis of 461 consecutive GC patients treated at a single institution between 1995 and 2007. Epidemiological and clinical-pathological data were retrieved from the patients' medical files and the institutional electronic database and analyzed using standard statistical methods.Epidemiology, clinical manifestations, histopathological findings, clinical course, and prognostic factors for disease outcome were all similar to those reported in the Western literature. Findings unique to the Israeli population included: (1) rarity of GC-associated risk factors; (2) increased GC incidence in Ashkenazi Jews; (3) high incidence of second primary malignancy and family history of cancer; and (4) no dominancy of proximal GCs.There do not appear to be any major differences in the biology or clinical manifestations of GC in Israel. Western recommendations for diagnosis and treatment of GC may therefore be applied to the Israeli patient population.

PURPOSE: The role of local excision in patients with good histological response to neoadjuvant chemoradiation for locally advanced rectal cancer is unclear, mainly because of possible regional nodal involvement. This study aims to evaluate the correlation between pathological T and N stages following neoadjuvant chemoradiation for locally advanced rectal cancer and the outcome of patients with mural pathological complete response undergoing local excision. METHODS: This investigation was conducted as a retrospective analysis. Between January 1997 and December 2007, 320 patients with T3 to 4Nx, TxN+ or distal (≤6 cm from the anus) T2N0 rectal cancer underwent neoadjuvant concurrent chemoradiation followed by surgery. Radiotherapy was standard and chemotherapy consisted of common fluoropyrimidine-based regimens. RESULTS: After chemoradiation, 93% patients had radical surgery, 6% had local excision, and 3% did not have surgery. In the 291 patients undergoing radical surgery, the pathological T stage correlated with the N stage (P = .036). We compared the outcome of patients with mural complete pathological response (n = 37) who underwent radical surgery (group I) and those (n = 14) who had local excision only (group II). With a median follow-up of 48 months, 4 patients in group I had a recurrence and none in group II had a recurrence; one patient died in group I and none died in group II. Disease-free survival, pelvic recurrence-free survival, and overall survival rates were similar in both groups. CONCLUSION: In this retrospective study, nodal metastases were rare in patients with mural complete pathological response following neoadjuvant chemoradiation (3%), and local excision did not compromise their outcome. Therefore, local excision may be an acceptable option in these patients.

An optimal cancer vaccine should be able to induce highly potent, long-lasting, tumor-specific responses in the majority of the cancer patient population. One approach for achieving this is to use synthetic peptide vaccines derived from widely expressed tumor-associated antigens, that promiscuously bind multiple MHC class I and class II alleles. MUC1-SP-L (ImMucin, VXL100) is a 21mer peptide encoding the complete signal peptide domain of MUC1, a tumor-associated antigen expressed by over 90% of solid and non-solid tumors. MUC1-SP-L was predicted in silico to bind various MHC class I and MHC class II alleles, covering the majority of the Caucasian population. PBLs obtained from 13 naive donors all proliferated, with a Stimulation Index (SI≥2), to the MUC1-SP-L peptide, producing mixed CD4+ and CD8+ responses. Similar results were manifested by MUC1-SP-L in PBLs derived from 9 of 10 cancer patients with MUC1 positive tumors. CD4+ and CD8+ T cell populations exhibited CD45RO memory markers and secreted IFN-gamma and IL-2 following stimulation with MUC1-SP-L. These T cells also exhibited proliferation to the MUC1-SP-L inner 9mer epitopes and cytotoxicity against tumor cell lines expressing MUC1 and a concordant MHC class I allele. Cytotoxicity to MUC1-expressing human and murine tumors was shown also in T cells obtained from HLA-A2 transgenic mice and BALB/c syngeneic mice immunized with the MUC1-SP-L and GM-CSF. In an immunotherapy model, BALB/c mice inoculated with metastatic MUC1 transfected murine DA3 mammary tumor cells, exhibited significantly prolonged survival following vaccination with MUC1-SP-L. Our results indicate superior immunological and anti-tumor properties of MUC1-SP-L compared to previously published MUC1-derived epitopes.

This study was designed to characterize the entity of colorectal cancer (CRC) in young patients and to evaluate whether it has any unique epidemiological or clinicopathological features. The study population consisted of all consecutive young (≤50 years old at diagnosis) patients with CRC who were diagnosed during the years 1997–2007 and were treated at our institution, and a matching group of patients (>50 years at diagnosis). The medical files of these patients were reviewed, and the epidemiological, clinical, and pathological features of both groups were compared. There were 406 patients: 203 in each group. The features of the older group were typical for patients with CRC, but the younger group showed female predominance, different ethnic composition, prevalence of family history of cancer and hereditary CRC syndromes, and lower incidence of polyps. The incidence of left-sided tumors and advanced stages (III–IV) at diagnosis was higher in the younger patients. Mucinous/signet ring histology, grade, stage, lymphatic and vascular invasion were all predictive of survival, whereas age was not. Colorectal cancer in young patients was found to display a cluster of unique characteristics but fewer than previously reported and young age by itself was not found to impact patient outcome.

Background Hypermethylation of tumor suppressor genes' promoter and JC virus infection may be etiologic factors in the development of colorectal cancer (CRC). Objectives To look at both JC virus T antigen and hMLH1 promoter methylation in CRC tissue in Israeli ethnic groups with different incidence of CRC. Methods Twenty-four consecutive patients with sporadic CRC were included in the study. Genomic DNA was isolated from paraffin-embedded microdomains removed from five slides of 7 μm by deparaffinizing in multiple xylene washes. Isolated DNA was used as a template for PCR to amplify DNA sequences coding the amino terminus of JC virus T antigen. Methylation-specific PCR was performed on bisulfite-modified DNA templates from CRC tissue materials to study methylation status of hMLH1 promoter, using two sets of primers specific for amplification of methylated and unmethylated alleles. Results hMLH1 promoter methylation was observed in five patients (20.8%) who were also positive for JC virus T antigen, with even distribution among the ethnic groups. JC virus T antigen DNA was found in cancer tissues of 20 of the 24 patients; 50, 90.9, and 100% of Asia–Africa-born Jews, Europe–America-born Jews, and Israeli Arabs, respectively (P = 0.036 between the first group to the other). Conclusion Evidence for higher JC virus infection was shown among Europe-America-born Jews and Israeli Arabs. hMLH1 promoter methylation was evenly distributed between different ethnic groups in Israel.

Following the publication of the results of Women's Health Initiative in 2002 there have been gross changes in the attitude of women and physicians towards the risks and benefits of hormone replacement therapy (HRT). We evaluated the attitude of women gynecologist towards their own health, including adherence to recommended screening tests and self usage and prescription of hormone replacement therapy.Questionnaires regarding performance of screening tests, self usage and recommendation of HRT were posted by mail to all Israel's women gynecologists.Ninety questionnaires were eligible for analysis (43.2% response rate). Average age was 48+/-7.7 years. Only 7/90 (7.8%) gynecologists smoke regularly and average body mass index was 25+/-3.8 kg/m2. Most participants performed at least one screening tests in the past 2 years. The median interval from the last self breast exam, mammography, gynecologisy exam, Papanicolaou test, colonoscopy and bone density test was 0.2, 1.82, 1.79, 1.95, 3.27 and 1.41 years, respectively. Most of them (68.3%) did not routinely recommend HRT to their patients. The duration of self HRT usage ranged between 1-20 years (average 5.1+/-3.4 years). Most gynecologists (87.7%) recommended continuous estrogen and progesterone for women with their uterus in place.The health profile of Israeli women gynecologists is chracterized by a high performance of screening tests for cancer and low rate of smoking. Our study also demonstrates that the impact of the results of the WHI trial is still well manifested and most Israeli women gynecologists do not routinely recommend HRT to postmenopausal women.

Purpose This study assessed satisfaction of patients with cancer and the correlation between patient levels of satisfaction and the sociodemographic, medical, and psychological variables. Satisfaction measures were based on patient expectations for emotional and cognitive support by the oncologists. Patients and Methods A total of 1,027 patients with cancer were recruited from the outpatient departments and daycare treatment centers of four oncology institutes in Israel. Patient levels of expectations and satisfaction were assessed by using measures developed for this study. Patient psychological variables were assessed by using the Brief Symptoms Inventory, Impact of Events Scale, and Mental Adjustment to Cancer. χ2 and Student t tests were used to assess differences between the highly satisfied group and the less satisfied group. Results Lower values of satisfaction were reported on the dimensions that included the patient in the treatment plan and that included explanations to the family. Higher percentages of women, single patients, younger patients, and patients in stages II to III were found in the less satisfied group. This group reported significantly higher levels of psychological distress, anxious preoccupation, and helplessness and lower levels of fighting spirit. Conclusion Given the importance of patient satisfaction to treatment compliance, oncologists should consider evaluating patient expectations for support, especially in issues concerning planning the treatment and involving the family in medical decisions. Oncologists should take into account the possible interdependence between psychological variables and medical-care satisfaction.

We describe three patients with advanced Merkel cell carcinoma who were treated with etoposide given orally for recurrent regional lymph node involvement 18 to 30 months after exposure to etoposide given intravenously. Etoposide given orally (100 mg/day) was given for 10 to 14 consecutive days and repeated every 21 to 28 days for a median of three courses (range: two to four). Toxicity was minimal and mainly hematologic. Two patients showed a complete response and one a partial response, all of very rapid onset. All three patients are alive 6, 9, and 42 months from the start of oral treatment. Two remain progression free, and one had a recurrence 1 month after completion of chemotherapy. We suggest that orally administered etoposide, a topoisomerase II inhibitor, has a strong antitumor effect in advanced Merkel cell carcinoma, even in patients previously treated parenterally with the same drug. This action may be explained by the greater dependence of the drug's efficacy on the duration of administration rather than the dose intensity.

Background The aim of the current study was to strengthen the knowledge of oncologists concerning psychological distress and social support among married and unmarried male cancer patients and healthy male spouses of female cancer patients. Patients and methods Three groups of men were recruited from three major cancer centers in Israel: 185 married colon and rectal cancer patients, 54 single (unmarried) colon and rectal cancer patients, and 153 male spouses of female cancer patients. Participants were evaluated on four standardized instruments measuring psychological distress, coping, and social support. Results About 42.6% of the participants reported on a clinical level of psychological distress, with the highest rates (61.1%) among the single (unmarried) patients. Distress was negatively correlated to Karnofsky score and coping variables among all study groups. Distress was significantly and negatively correlated to social support variables among the spouses and married patients but not among the single patient groups. Conclusions Social support received by male cancer patients from friends and family may be mediated by spouse support. As a result, single male patients are at higher risk for psychological distress. Male spouses were also found to have high rates of distress. These two groups need special attention by oncologists.

B16-F10.9 is a highly metastatic clone of the B16-F10 melanoma line, that expresses low levels of MHC class-I antigens. F10.9 cells transfected with H-2Kb are highly immunogenic and consequently exhibit a low metastatic phenotype. Treatment with gamma-IFN elevated H-2Kb and H-2Db cell surface expression of F10.9 cells to levels much higher than did transfection of these genes. Yet, following intravenous injection, the gamma-IFN treated cells generated high loads of lung metastases. However, when tested for their immunogenic effect, they elicited CTL and were sensitive to CTL. Immunization with both the positive transfectant KI and the gamma-IFN-treated F10.9 cells protected in vivo against metastatic spread of a subsequent transplant of parental F10.9 cells. The protection elicited by KI transfectants was more effective than the protection by gamma-IFN-treated cells.

Background The majority of newly diagnosed patients with gastric cancer have disease that is not resectable because of local extension or metastatic (M1) disease. Laparoscopy is a recommended staging evaluation to identify occult peritoneal metastatic disease. We determined if endoscopic ultrasound (EUS) could improve the selection of patients for laparoscopy. Study Design Gastric cancer patients being screened for a preoperative chemotherapy clinical trial were prospectively examined. Patients underwent standard preoperative assessment. Those without obvious metastatic disease were referred for EUS and laparoscopy. EUS divided patients into risk categories for metastatic disease: low risk (T1–2, N0) and high risk (T3–4, N+, or both). Laparoscopy categories were M1 and M0. The ability of EUS to predict subradiographic peritoneal metastatic disease was evaluated. Results Ninety-four patients were studied. The majority were EUS high risk (72%). Occult metastatic disease was identified in 19 patients, 18 of whom had high-risk EUS stage. The yields of identifying M1 disease by laparoscopy in EUS high- and low-risk patients were 25% (95% CI, 15% to 37%) and 4% (95% CI, 0.1% to 20%), respectively. The negative predictive value of low-risk EUS for laparoscopy and pathologic M0 was 96% (exact 95% CI, 80% to 100%). Conclusions This study suggested that laparoscopy can be avoided in patients with EUS early-stage gastric cancer. Patients with more advanced disease are at higher risk of occult peritoneal disease and require laparoscopy. Validation with greater numbers is warranted, but, based on these data, we propose a new staging algorithm allowing EUS low-risk patients to proceed directly to resection.

SUMMARY Earlier reports have described an association between esophageal cancer (EC) and high incidence of other primary tumors (OPTs) of the upper aerodigestive tract and breast cancer. We evaluated the incidence of non-upper aerodigestive OPTs among Israeli EC patients; 2328 EC patients were retrieved from the Israeli National Cancer Registry between 1980 and 2004. The relative risk of OPTs for EC patients was measured using standardized incidence ratio (SIR). Two cohorts, Israeli National Cancer Registry registered colorectal cancer (CRC) patients and the general Israeli population, were used for reference; 297 EC patients (12.7%) had OPTs, including breast (18.9%), CRC (16.2%), prostate (8.8%), and bladder (8.4%) cancers. Upper aerodigestive OPTs were less common. Most OPTs were identified before (74.4%) or simultaneously with (13.8%) EC diagnosis. The median time interval between OPTs diagnoses and EC development was 6.0 years. The incidence of OPTs was significantly higher among EC patients compared with CRC patients (SIR: 2.05, P

To summarize our experience using a regimen of weekly 5-FU and leucovorin (LV) and biweekly cisplatin (CDDP) in advanced gastric cancer (AGC).Patients had previously untreated histologically confirmed AGC. Treatment consisted of intravenous weekly infusional 5-FU and LV and biweekly CDDP, given for 6 weeks followed by a 2-week rest. Initially, a lower dose level was used (5-FU 2000 mg/m(2), LV 500 mg/m(2), CDDP 40 mg/m(2)), which was later increased (5-FU 2600 mg/m(2), LV 500 mg/m(2), CDDP 50 mg/m(2)).Forty-five patients were treated, 18 at the lower dose level and 27 at the higher dose level. The median age was 67 years and 55% were male. Gradeor =3 toxicity was documented in 37% of patients but toxicity related hospitalizations or treatment discontinuation occurred in only 22% and 13%, respectively. There were no toxic deaths. The most common hematological toxicities were anemia and neutropenia and the most common non-hematological toxicities were nausea, vomiting and fatigue. Of the 39 patients evaluable for response, 13 (33%) had partial response (PR) and 11 (28%) had stable disease (SD). Control of disease (PR+SD) was achieved in 61%. The higher dose level was associated with a higher response rate (p=0.07) and an increased toxicity (p=0.01), mostly hematological and gastrointestinal. Median progression-free survival and overall survival were 3.5 and 9.2 months, respectively.This regimen appears safe, with a manageable toxicity profile. Efficacy data resemble those reported for more complex and toxic regimens. The higher dose level had enhanced activity, at the expense of increased toxicity.

To determine whether the use of adjuvant radiation in the treatment of invasive thymic tumors affects survival and to identify prognostic factors.The files of 47 patients with thymic tumors treated by adjuvant radiation in our institute from 1984 to 2003 were reviewed for data on prognosis and survival. All patients underwent thoracotomy followed by either total macroscopic resection (n = 42) or biopsy (n = 5). The radiation dose ranged from 26 to 60 Gy.Median duration of follow-up was 10.6 years. Overall 5-year survival was 73% (60%-88%): 77% for thymoma (n = 35/45) versus 33% for thymic carcinoma (n = 2/6) (P = 0.14). Better survival was associated with lower disease stage (II vs. III/IVA, P = 0.01), resection (P = 0.0004), myasthenia gravis at presentation (P = 0.04), and higher radiation dose (or=45 vs.45 Gy, P = 0.02); sex, smoking, tumor size, pathology, and margin status had no effect. Locoregional relapse occurred in 11 patients and distant metastasis in 4. The 5-year disease-free survival was 67% (52%-86%), with a median time to recurrence of 8.3 years. The better overall survival and disease-free survival associated with higher doses of radiation were also true for stage II patients. On multivariate analyses after adjusting for age, higher disease stage and lower radiation dose were found to adversely affect overall survival and disease-free survival. Thymic carcinoma had an impact only on disease-free survival.Postoperative radiation therapy to doses above 45 Gy may improve the disease-free and overall survival of patients with invasive thymoma, especially stage II. Thymic carcinoma has a worse prognosis.

Neoadjuvant chemoradiation with continuous infusion (CI) of 5-fluorouracil (5FU) is widely used in rectal cancer. The aim of this study was to evaluate the use of oral tegafur-uracil (UFT) and leucovorin (LV) instead of CI 5FU.Patients had resectable T3-4 or low T2 rectal adenocarcinoma. Chemoradiation consisted of pelvic irradiation (45 Gy in fractions of 1.8 Gy) and oral UFT (240 mg/m2/day) and LV (30 mg/day) given during the first 28 days of radiotherapy.Thirty-two patients were treated; 81% had T3-4 tumors and 25% had N+ disease. Toxicity, predominantly gastrointestinal, was generally mild. Grade 3 toxicity occurred in only one patient. Pathological down-staging was noted in 13 patients (42%) and pathological complete response in 3 (10%). Sphincter preservation was possible in 71% of patients undergoing surgery.Neoadjuvant chemoradiation with oral UFT/LV is well-tolerated and active against rectal cancer. Formal comparison with the current standard treatment is warranted.

Small cell undifferentiated carcinoma (SmCC) of the gastrointestinal tract (GIT) is a rare and highly aggressive malignancy. To date, fewer than 1,000 cases have been reported, with an estimated prevalence of 0.1% to 1% of all gastrointestinal (GI) tumors. Data on the disease are scarce due to its rarity and the fact that most authors have focused on one site within the GIT. In light of the limited data and its perceived similarity to SmCC of the lung, the disease has usually been treated as the latter. Nevertheless, recent clinicopathologic and molecular data imply several differences between the two entities, questioning the extent to which extrapolations from one to the other can be made. We review the available data on GI SmCC with emphasis on outlining its clinicopathologic features and the recommended treatment approach.

e14594 Background: The incidence of colorectal cancer (CRC) in young patients (pts) has increased significantly in the last decade. Several studies, including from our group, have evaluated whether CRC in young pts has unique features, with conflicting results. The aim of our study was to compare various characteristics of CRC between young and older pts, while emphasizing potential differences through a younger age cutoff and a larger database. Methods: This was a single center retrospective case control study. We searched our institutional database for all CRC pts 40 years old or younger who were diagnosed between 1997 and 2013. A control group consisted of consecutive pts older than 50 years at CRC diagnosis during the same period. These pts were matched to the study group by their year of diagnosis in a 1:2 ratio. Data on demographics, predisposing risk factors, clinical presentation, disease characteristics, treatment and outcome were compared between groups. Results: A total of 330 pts were included...

e20598 Background: Recent epidemiological studies indicate the rate of GI malignancies among younger population is constantly increasing, mainly due to colorectal cancer. There is paucity of data r...

e15050 Background: Esophageal cancer (EC) comprises two histopathological subtypes: squamous cell carcinoma (SqCC), usually located in the upper 2/3 of the esophagus, and adenocarcinoma (AdenoCa), ...

584 Background: Recent studies have indicated a significant increase of young colorectal cancer patients, who may then face unique survivorship issues as fertility concerns. The impact of oxaliplatin on gonadal function remains unclear. We prospectively evaluated oxaliplatin-induced gonadotoxicity in a cohort of young patients. In a preclinical setting, the impact of oxaliplatin on the gonads was prospectively studied in mice. Methods: Newly diagnosed female (< 43 years) and male (

Small bowel obstruction in an oncology patient is a common and serious medical problem which is associated with diagnostic as well as therapeutic dilemmas. While the condition is most commonly caused by postoperative adhesions and peritoneal carcinomatosis, other causes have been reported [Cormier WJ, Gaffey TA, Welch JM, et al. Linitis plastica caused by metastatic lobular carcinoma of the breast. Mayo Clinical Proceedings 1980;55:747-53; Clavien P-A, Laffer U, Torhos J, et al. Gastrointestinal metastases as first clinical manifestation of the dissemination of a breast cancer. European Journal of Surgical Oncology 1990;16:121-6; Bender GN, Maglinte DD, McLarney JH, et al. Malignant melanoma: patterns of metastasis to the small bowel, reliability of imaging studies, and clinical relevance. American Journal of Gastroenterology 2001;96:2392-400; Gatsoulis N, Roukounakis N, Kafetzis I, et al. Small bowel intussusception due to metastatic malignant melanoma. A case report. Technical Coloproctology 2004;8:141-3; Hung GY, Chiou T, Hsieh YL, et al. Intestinal metastasis causing intussusception in a patient treated for osteosarcoma with history of multiple metastases: a case report. Japanese Journal of Clinical Oncology 2001;31(4):165-7; Chen TF, Eardley I, Doyle PT, Bullock KN. Rectal obstruction secondary to carcinoma of the prostate treated by transanal resection of the prostate. British Journal of Urology 1992;70(6):643-7; Kamal HS, Farah RE, Hamzi HA, et al. Unusual presentation of rectal adenocarcinoma. Roman Journal of Gastroenterology 2003;12(1):47-50; Hofflander R, Beckes D, Kapre S, et al. A case of jejunal intussusception with gastrointestinal bleeding caused by metastatic testicular germ cell cancer. Digestive Surgery 1999;16(5):439-40]. One of these, reported thus far in only very few patients, is obstruction caused by secondary tumors, i.e. metastases from other organs to the small bowel wall. As cancer patients live longer with improved therapy, physicians are more likely to cope with rare phenomena of neoplasms, such as small bowel obstruction caused by secondary tumors. We hereby present a review of the relevant medical literature. The goal of this article is to define current knowledge on this phenomenon, with emphasis on its epidemiology and clinical characteristics, and to increase the awareness of the clinician treating cancer patients of such possibility.

The treatment of localized esophageal cancer (LEC) is under extensive debate. Treatment approaches include surgery or radiation alone, surgery with preoperative or postoperative radiation, preoperative or postoperative chemotherapy and definitive or preoperative chemoradiation. In fact, the type of therapy patients receive is often dependent on the actual medical field of the treating physician (surgery, oncology, etc.). The use of multiple treatment approaches toward LEC primarily reflects the scarcity of data that is derived from controlled randomized trials and the poor results of current therapies. In spite of the above, the cumulative data suggest that surgery and chemoradiation are the two treatment options in LEC and that their combined approach, i.e. preoperative chemoradiation, has not been proven to have a survival advantage over each one of these methods, and should therefore still be considered investigational. This article will review the available data on the various treatment approaches that are being used against LEC.

Colorectal carcinoma is one of the most common cancers in the world, and more than 50% of these patients develop liver metastases. Despite recent advances, systemic chemotherapy for metastatic disease without the use of surgery is considered palliative, as there are rarely long-term survivors. However, patients who are candidates for surgical resection of their liver metastases can have a prolonged survival or possibly a cure. Consensus guidelines on criteria for resection and prognostic scores help facilitate patient selection, yet only 25% of patients with liver metastases are considered to have resectable metastases. Neoadjuvant chemotherapy has been explored in an attempt to render more patients candidates for resection. First reports using neoadjuvant systemic chemotherapy in patients with unresectable disease found that 13% to 16% of patients could be rendered resectable. Efforts to increase response rates using hepatic arterial infusion or biologic agents may increase resection rates. This review summarizes the current data on neoadjuvant chemotherapy, the rationale for this approach, potential complications, and future prospects.

Merkel cell carcinoma (MCC) is an aggressive neuroendocrine tumor of the skin that is associated with a high incidence of recurrence and metastasis. The therapeutic arsenal for this malignancy is limited and once it spreads, there is no effective treatment. c-kit expression has been demonstrated previously in primary MCCs thus raising the possibility of treating MCCs with imatinib mesylate, the tyrosine kinase inhibitor that has shown promise in the management of c-kit expressing tumors. In this study we examine 25 additional primary MCCs and also 6 of their lymph node metastases. Formalin-fixed, paraffin-embedded tissues were stained immunohistochemically with an antibody directed against the KIT receptor. Percentage and intensity of staining were analyzed semiquantitatively using a three-tiered system. Twenty-one of the 25 (84%) primary tumors stained positively for KIT, of which 14 (67%) showed widespread positivity. Five of the 6 lymph nodes (83%) were similarly positive. High mitotic rate and vascular invasion in the primary tumors tended to be associated with prominent staining in the lymph node metastases. No association was found between c-kit expression and outcome. We confirm that the majority of primary MCCs express c-kit and further find that metastases are positive for the KIT receptor as well. Thus, c-kit expression may be an early event in the transformation of MCC, but not a marker for tumor progression.

The treatment of localized esophageal cancer (LEC) is controversial. The approaches that are used in daily practice include surgery or radiation alone, preoperative or postoperative radiation, preoperative or postoperative chemotherapy, and definitive or preoperative chemoradiation. The varied modalities used to treat LEC reflect both the lack of randomized trial data and the suboptimal results with current therapy. Nonetheless, the available data suggest that surgery and definitive concurrent chemoradiation represent two standard treatment options. The use of preoperative chemoradiation remains investigational, with phase III trials failing to demonstrate a consistent benefit for this option over chemoradiation or surgery alone. This review will examine the available data on the current treatment approaches in LEC.

Small-cell carcinoma (SmCC) of the gastrointestinal tract is a very rare and aggressive malignancy. To better define its clinicopathological features, the records of all patients with this disease seen at Memorial Sloan Kettering Cancer Center between 1980 and 2002 (n=64) were reviewed. The most common primary tumour locations were in the large bowel and oesophagus. Predisposing medical conditions for non-small-cell cancers, positive family cancer history, and metachronous tumours were common. In all, 37% had mixed tumour histology and 48% presented with extensive disease, according to the Veterans' Administration Lung Study group (VALSG) staging system used for small-cell lung cancer. Treatment outcome in limited disease (LD) suggested a role for surgery and chemotherapy. Platinum-based regimens resulted in a 50% response rate. The 2-year survival was 23% and two prognostic factors were identified, the extent of disease according to the VALSG system (P

High dose rate (HDR) endobronchial brachytherapy is widely used as a palliative treatment for symptomatic airway obstruction by primary or secondary malignant tumors. We report on a successful use of HDR brachytherapy in patients with nonmalignant airway obstruction.Case seriesSix patients received HDR brachytherapy for airway obstruction caused by granulation tissue around a metal stent placed for restoration of the airway patency for nonmalignant causes. In four patients, brachytherapy was performed following recurrent occlusion of the airway by granulation tissue formation; in two patients, it was done as a prophylactic procedure.HDR brachytherapy catheters were passed through the metal stents under direct fluoroscopic guidance. Simulation and computerized treatment planning were done, and a single dose of 10 Gy was administered using a brachytherapy remote afterloader with a (192)Ir source. The dose was prescribed to a distance of 1 cm from the center of the source, with a margin of 1 cm from the proximal and distal ends of the stent.At a median follow-up of 15 months, moderate granulation tissue formation was observed in only one patient; in four others, it was categorized as minimal, 5 to 30 months from the procedure. Restoration of the lumen was complete in four patients, near complete in one patient, and partial in one patient. In one patient, previously treated by external radiotherapy, local tissue necrosis was evident.HDR brachytherapy can be used safely for nonmalignant airway obstruction. Further studies including more patients and longer follow-up are needed.

Of the numerous prognostic factors for patients with localized malignant melanoma (LMM), none is superior to the simple parameter of tumor thickness. The aim of the present study was to better define prognostic factors for this disease. Between January 1992 and December 1994, 188 consecutive patients with LMM were treated at the Rabin Medical Center. Patient and tumor characteristics were retrospectively examined as potential prognostic factors. Patients (n=173) who had had at least two-year follow-up were included in the overall survival (OS) analysis, and 159 patients for whom accurate data on recurrent disease were available were included in the disease-free survival (DFS) analysis. At a median follow-up of 85 months (range 24-114), 48 patients (30%) had recurrent disease which resulted in death in 35 (20%). The five-year OS and DFS rates for the entire group were 82 and 72%, respectively. On univariate analysis, female gender, age younger than 75 years, metachronous or synchronous second skin cancer (including melanoma), light skin color, tumor thickness and TNM stage were predictive of both OS and DFS. Tumor location and ulceration, correlated with only one endpoint, OS or DFS, respectively. On multivariate analysis, three factors retained statistical significance with regard to both OS and DFS: tumor thickness (p=0.000 for both), second skin cancer (p=0.02 for both), and age (p=0.04 for both). Alongside the well-established predictive factor of tumor thickness in LMM, older age and the presence of a second skin cancer also have prognostic significance. The prognostic importance of the latter is reported here for the first time.

Amifostine is the best known radioprotector and chemoprotector which has already been incorporated into general oncology practice. However, the data regarding its action at the cellular level remain unclear. The present study examined the effect of amifostine with and without ionizing radiation on the growth of malignant and non-malignant cell lines. Amifostine was found to have a remarkable cytotoxic effect on malignant epithelial cell lines but a modest cytotoxic effect on malignant melanoma and non-malignant cell lines. It demonstrated an additive effect with radiation therapy on the malignant cell line and a variable effect on the non-malignant cell line. Endothelial cells were not affected by amifostine, but the myoblast cells showed a synergistic effect of amifostine and radiation. These findings demonstrate that the cytotoxic as well as the radioprotective effect of amifostine are cell-specific. Thus, caution should be exercised in the use of amifostine as a radioprotector, and it should be tested for each model of disease.

The aim of this prospective study was to record the pattern of failure associated with high-dose interferon-alpha2b (IFN) adjuvant therapy after surgery. It included 55 consecutive patients with stage IIB and III melanoma (median age 50 years) rendered disease-free by surgery but considered at high risk for relapse from a tertiary referral, university-affiliated medical centre. Intervention consisted of IFN 20 mU/m(2) per day intravenously, 5 days a week for 4 weeks, followed by subcutaneous IFN 10 mU/m(2) per day three times a week for 48 weeks. Treatment was stopped at completion of protocol, at disease progression or due to unacceptable toxicity. Dose modification followed treatment-related toxicity. Twenty-six of the 55 patients (47%) relapsed: 14 during treatment and 12 after completion of the protocol. Eighteen of these 26 patients (69%) relapsed initially in a single organ, most commonly in soft tissue or the CNS. A single metastasis was noted in 12 of the 18 patients, and multiple metastases confined to a single organ were detected in the other six. No statistically significant survival advantage could be demonstrated in association with any of the patterns of relapse. Patients treated for stage IIB disease fared better than those treated for stage III disease, regardless of whether the regional metastases were microscopic or palpable. IFN seems to be more commonly associated with a single-organ/single-metastasis pattern of failure, and more soft tissue and CNS relapses. This pattern did not translate into a survival advantage in this series. Larger databases should be explored to validate these trends.

BACKGROUND Classical Kaposi sarcoma (CKS) is a rare indolent neoplasm that is particularly prevalent among Jews of Ashkenazi and Mediterranean origin. Data regarding prognostic factors for CKS are scarce. The aim of the current retrospective analysis was to better define prognostic subgroups among patients with CKS. METHODS Between 1960 and 1995, 248 consecutive patients with CKS were treated at the Rambam and Rabin Medical Centers in Israel. Although treatment options included local excision, radiotherapy, and chemotherapy, observation alone was used for 31% of patients. For prognostic factor analysis, disease progression was classified as any progression and dissemination, and progression-free survival was calculated for each. RESULTS At a median follow-up of 20 months, four patients (1.6%) died of CKS. Of the patients eligible for analysis, 94 of 220 (39%) had any progression and 23 of 120 (18%) had dissemination. Only 8 of 202 (4%) had visceral spread. On univariate analysis, age was a statistically significant prognostic factor for any progression (P = 0.04), whereas immunosuppression and visceral involvement at presentation had only borderline significance. Immunosuppression was the only prognostic factor for dissemination (P = 0.003). On multivariate analysis, both age and immunosuppression were significant prognostic factors for any progression (P = 0.001 and 0.01, respectively). Immunosuppression was also predictive of dissemination (P = 0.006). CONCLUSIONS Immunosuppression and older age (50 years and older) are strongly associated with poorer outcome among CKS patients. The two end points used in this study may be used for future prognostic factor analyses. Cancer 2002;95:1982–7. © 2002 American Cancer Society. DOI 10.1002/cncr.10907

The human milk fat globule membrane protein BA46 (lactadherin) is highly overexpressed in human breast tumors, making it a potential target for tumor immunotherapy. We have identified BA46-derived peptides that contain the motif recognized by the MHC class I molecule HLA-A2.1 and that are processed and presented by human breast carcinoma cells. In mice lacking normal class I molecules but expressing an HLA-A2.1/D(b)-beta2 microglobulin single chain (HHD mice), three peptides elicited specific CTL activity. Two of these peptides also stimulated cytotoxic activity in peripheral blood lymphocytes from HLA-A2.1-positive breast carcinoma patients. Adoptive transfer of HHD-derived bulk CTLs to nude mice bearing human breast carcinoma transplants reduced tumor growth. These peptides therefore represent naturally processed BA46-derived CTL epitopes that can be used in peptide-based antitumor vaccines.

Tularemia is a zoonosis, caused by the Gram-negative bacterium, Francisella tularensis. The organism penetrates the human body through interrupted skin or mucous membranes, via animal contact or bites from ticks, deer-flies and mosquitoes. Contaminated aerosol and water are alternative modes of transmitting the germ through the respiratory and alimentary tracks. In light of its high infectivity in aerosol and its offensive occupation in the past, tularemia may appear in a biological warfare context. After an incubation period of 3-5 days, the disease begins with systemic symptoms, which abate, leaving a clinical picture, dominated by one of the listed patterns: ulceroglandular, typhoidal, glandular, occuloglandular, pharyngeal or pneumonic. Diagnosis and identification of the bacterium is difficult and even hazardous. Most diagnoses are established by serology which is positive in 50-70% of the patients after 2 weeks of illness, and in most of them by 4-8 weeks. The treatment of choice is streptomycin intra-muscular, or gentamicin intra-venous for 10-14 days. Prophylaxis may be achieved by tetracycline treatment, beginning up to 24 hours from exposure, for 2 weeks, or by a live attenuated, investigational vaccine. Nevertheless, post-exposure, or even better so, pre-exposure intervention is the most effective way of preventing the devastating results of the attack.

The viruses that cause hemorrhagic fever belong to four virus families: the Arenaviridae, Bunyaviridae, Filoviridae and Flaviviridae. These viruses are candidates for biological warfare agents because they are stable when aerosolized and cause severe debilitating disease. Research and development regarding the use of these viruses as warfare agents has been performed in the former Soviet Union and other countries. The introduction of these agents into non endemic countries poses a major public health threat to that country. Israel is not endemic for these agents, and therefore, local infection can occur from a traveller (human or animal) from an endemic country or due to intentional dissemination. Major clinical manifestations of hemorrhagic fevers are that of fever, rash, malaise and hemorrhagic signs. Due to the similarity between syndromes, any person with a history of persistent fever and any sign of hemorrhage should be considered as having viral hemorrhagic fever, and appropriate care instituted. Definitive diagnosis requires laboratory testing and is important to identify a possible biological warfare attack and to prepare for appropriate defense. This paper reviews the viruses that cause hemorrhagic fever, and their role as possible warfare agents.

It is difficult to detect bioterrorism attacks and to identify the castoff biological agent. The principal enigmas are the wide variety of the clinical symptoms associated with various biological agents and the fact that the attack is likely to be a covert event. The first and major indication of a bioterrorism attack could be the presence of affected patients. It is, however, extremely important to detect and identify an attack using a biological agent as early as possible. Therefore, it is crucial to be alert to such possibilities and to maintain high levels of suspicion. The aim of this article is to list all the clues, which will help us highlight the suspicion that a disease or clinical symptoms are the result of a bioterrorism attack and not a "natural" outbreak. These clues involve the recognition of a wide range of clinical patterns pertinent to biological agent attacks on the individual victim and the overall integrated epidemiological picture. Further signs also include the identification of the roots of transmission, the contagious patterns of bioterrorism agents and possible unusual findings in laboratory tests and in animals.

Smallpox has played a notorious role in human history. It has been the cause of millions of deaths throughout the centuries, yet, it was the first infectious disease that was ever eradicated thanks to a worldwide program. Smallpox vaccine, manufactured from the vaccinia virus, was the first vaccine ever produced. Recent bioterrorism events in the USA have brought smallpox back into the limelight, both medically and politically, because of the fear of the return of this horrific disease through the unscrupulous actions of terrorists who might spread variola virus. This article presents the history of smallpox, emphasizing its clinical variants. We also review the treatment of the disease, especially the vaccine--its efficacy and its disadvantages, and the public health measures that must be taken in order to control the disease. In conclusion, we will discuss the possibility of the resurgence of smallpox and global preparedness for such an outbreak.

There are hundreds of potential agents that could be used in biological warfare or bioterrorism: bacteria, viruses and toxins. There are no similarities between clinical presentations of organisms or toxins belonging to specific microbial families. Therefore, it is important for the physician, required to cope with an unusual disease or outbreak among his patients, to become familiar with the various symptoms that victims of biological warfare or bioterrorism may present.To describe the six most common groups of symptoms expected in the above setting. The most common symptoms will be described as they appear in nature, because of a fortunate lack of experience with the majority of these agents in biological warfare. Hence, variations of these presentations may be possible.The six most common presentations reviewed are: 1) respiratory tract symptoms; 2) hemorrhagic fevers; 3) meningitis and encephalitis; 4) flaccid paralyses; 5) fever syndromes with rash; and 6) diarrheal syndromes. Additional presentations may be possible due to alterations made in these organisms or development of new agents and mixtures. A list is provided of features that may alert a physician of the possibility of biological warfare or bioterrorism.Knowledge of the principal clinical presentations of victims of biological warfare or bioterrorism is essential to all physicians. This knowledge may contribute to the early recognition of a cluster of patients, an epidemic, an unusual disease, or biological warfare; quick referral to the emergency department, leading to early microbiological diagnosis; and rapid notification of the Ministry of Health. All these, and the institution of appropriate measures, will ultimately contribute to the survival of individual patients and at-risk populations.

Ricin toxin, found in the bean of the castor plant, is one of the most toxic and easily produced plant toxin. It is composed of two polypeptide chains linked by a disulfide bond. The toxin irreversibly blocks protein synthesis. Oral intoxication is the most frequent mode of exposure, but direct contact and inhalation have also been described. A single intramuscular exposure was reported, related to an assassination event in 1978. The clinical signs of intoxication begin hours after the exposure, and include gastrointestinal signs, dyspnea, fever, vasculatory collapse, neurological signs, liver necrosis and renal failure. Treatment is mainly supportive. A vaccine has been developed and found effective in animal studies. Ricin may be used as a biological weapon due to its heat stability and worldwide availability. A more friendly use, which has been tested in clinical trials, is the incorporation of ricin-immunotoxin for the treatment of cancer patients.

Aim: The PETACC-6 trial investigates the role of oxaliplatin in addition to preoperative chemoradiation (CRT) and adjuvant chemotherapy (CT) with capecitabine to improve disease-free survival (DFS) in locally advanced rectal cancer. Methods: Patients with rectal adenocarcinoma within 12 cm from the anal verge, T3/4 and/or node-positive, without evidence of metastatic disease, considered either resectable at the time of entry or expected to become resectable, were randomized to 5 weeks of preoperative CRT with capecitabine, followed by surgery and 6 cycles of adjuvant CT with capecitabine (standard control arm 1) or capecitabine + oxaliplatin before and after surgery (arm 2). 440 DFS events were required to have 80% power to detect an improvement in 3-year DFS from 65% to 72% (HR = 0.763), with two-sided alpha of 5% and allowing for an interim analysis for early efficacy at 200 events. Results: 1094 patients were randomized (547 in each arm). From 1081 eligible patients, 543 in arm 1 and 528 in arm 2 started preoperative treatment (3/528 patients without oxaliplatin in arm 2), and of these 77.3% and 72.6%) patients started postoperative chemotherapy within protocol. In arm 2, 11.8% patients did not receive the planned postoperative oxaliplatin. Major reasons for protocol discontinuation were progressive disease (3.9% in arm 1 vs. 3.8% in arm 2), toxicity (7.7% vs. 16.5%), surgery complication (8.7% vs. 9.1%), patient's refusal (5.9% vs. 10.8%). At planned interim analysis, the independent data monitoring committee recommended the early release of the results. At a median follow-up of 31months, 124 and 121 DFS events were observed in arm 1 and 2 (adjusted HR = 1.036, 95% CI: 0.81 -1.33, P = 0.78). 3-year DFS was 74.5% (95% CI: 70.1% - 78.3%) in arm 1 (which is higher than anticipated) vs. 73.9% (95% CI: 69.5% - 77.8%) in arm 2; conditional power under HR = 0.763 is only 7%. Less locoregional and distant failures were recorded in the experimental arm with oxaliplatin (95 in arm 2 vs. 109 in arm 1) but a higher rate of deaths without progression (26 in arm 2 vs. 15 in arm 1). Conclusions: Interim results at a median follow up of 2.6 y currently indicate no DFS-benefit for the addition of oxaliplatin to capecitabine-based CRT and adjuvant CT. However, with actually only 245 out of the required 440 events, final evaluation cannot be done before at least 2 further years follow-up. Disclosure: H.J. Schmoll: has a consultant or advisory relationship to disclose with Roche, Sanofi and Bayer; has honoraria to disclose from Roche; has research funding to disclose from Merck and Roche; K. Haustermans: has research funding to disclose from Roche; T.J. Price: has a consultant or advisory relationship to disclose with Roche; R. Hofheinz: has a consultant or advisory relationship to disclose with Roche; has honoraria and research funding to disclose from Roche; B. Brenner: has a consultant or advisory relationship to disclose with Sanofi-Aventis; has research funding to disclose from Sanofi-Aventis; J. Zalcberg: has a consultant or advisory relationship to disclose with Sanofi-Aventis and Roche; has honoraria, research funding and other remuneration to disclose from Sanofi-Aventis and Roche. M.P. Lutz: has a consultant or advisory relationship to disclose with Roche; E. Van Cutsem: has research funding to disclose from Roche and Sanofi.All other authors have declared no conflicts of interest.

3501 Background: The PETACC-6 trial investigates whether the addition of oxaliplatin to preoperative oral fluoropyrimidine-based chemoradiation (CRT) followed by postoperative adjuvant fluoropyrimidine-based chemotherapy (CT) improves disease-free survival (DFS) in locally advanced rectal cancer. Methods: Between 11/2008 and 09/2011, patients with rectal adenocarcinoma within 12 cm from the anal verge, T3/4 and/or node-positive, with no evidence of metastatic disease and considered either resectable at the time of entry or expected to become resectable, were randomly assigned to receive 5 weeks of preoperative CRT with capecitabine, followed by 6 cycles of adjuvant CT with capecitabine with (arm 2) or without (arm 1) the addition of oxaliplatin before and after surgery. 440 DFS events were required to have 80% power to detect an improvement in 3-year DFS from 65% with capecitabine alone to 72% with capecitabine and oxaliplatin (HR=0.763) using a two-sided alpha of 5% and owing for an interim analysis for ...

e14548 Background: Many metastatic CRC pts progress after exhausting all approved standard therapies but maintain a good performance status and could be candidates for further therapy. We hypothesized that a comprehensive NGS assay (FoundationOne) could identify novel therapy targets not routinely considered for CRC pts. Methods: Hybridization capture of 3,769 exons from 236 cancer-related genes and 47 introns of 19 genes commonly rearranged in cancer was applied to ≥ 50 ng of DNA extracted from CRC FFPE specimens and sequenced to high, uniform coverage. Genomic alterations (GA) including base substitutions, small indels, copy number alterations, and select gene fusions, were characterized and reported for each pt sample. Actionable GAs were defined as those identifying anti-cancer targeted therapies on the market or in registered clinical trials. Results: Thirty three CRC pts were included in the analysis(mean age, 54.2 years; range, 28-81; 52% male). Clinical samples used for NGS originated from colon (...

Background Although recurrent laryngeal carcinoma is a common clinical problem, the data regarding its natural history and prognostic factors are limited. The aim of the study was to describe the clinical course of patients with recurrent laryngeal carcinoma and determine the impact of various factors on their survival. Methods The medical files of 65 patients with recurrent laryngeal cancer treated at the Rabin Medical Center between 1975 and 1996 were reviewed. The possible risk factors for survival were analyzed using univariate and multivariate models. Results The estimated 2- and 5-year survival rates of the patient population were 67% and 56%, respectively. On univariate analysis, primary tumor site, T stage and nodal status, duration of disease-free interval, site of recurrence, and operability of recurrent tumor were all powerful prognostic factors for survival. On multivariate analysis, three variables retained statistical significance: primary tumor site (p < .001), site of recurrence (p < .001), and its operability (p = .005). Conclusions We found several disease-related factors to be predictive of poor outcome in patients with recurrent laryngeal cancer. Our data emphasize the need for early detection not only of primary tumors but also of their recurrences. © 2001 John Wiley & Sons, Inc. Head Neck 23: 531–535, 2001.

BACKGROUND Merkel cell carcinoma (MCC) has been associated with a high incidence of other skin tumors and hematological malignancies. The purpose of this study was to analyze data from the Israel Cancer Registry regarding the incidence of second neoplasms in patients with MCC and their impact on survival. METHODS Sixty-seven patients in whom MCC was diagnosed between 1983 and 1999 were included. Data were collected on age, gender and ethnic origin, dates of diagnosis of MCC and any other neoplasm, and date and cause of death, if applicable. Comparison of MCC-specific survival, estimated by the Kaplan–Meier product limit method, between patients with no other neoplasm and those with second primary tumors was performed by log rank test. Age-specific standardized incidence ratio (SIR) was calculated using 5751 age- and ethnic-matched malignant melanoma patients as a control group. RESULTS Seventeen patients (25%) had a second neoplasm before, concomitant with, or after the diagnosis of MCC; 2 of them also had a third primary tumor. The SIR was 2.8 (95% CI; range, 1.38–4.22), significantly higher than the control group. Almost half the tumors were squamous cell carcinomas, either skin or head and neck, and most of the remainder were hematological malignancies or breast and ovarian adenocarcinomas. On univariate analysis, the presence of another neoplasm, regardless of its chronology, was associated with higher MCC-specific mortality (65% vs. 40% for patients with MCC only; P = 0.022). Analysis of only those patients in whom a second neoplasm developed during follow-up after treatment for MCC yielded an estimated actuarial risk of developing a second primary of 2.1% for each year of observation. CONCLUSIONS There is a high incidence of second neoplasms, including noncutaneous solid tumors, in patients with MCC. The presence of these neoplasms, whether they appear before, after, or simultaneously with MCC, is associated with a higher MCC-specific mortality. Cancer 2001;91:1358–62. © 2001 American Cancer Society.

We evaluated the effects of Biafine and Lipiderm ointments in preventing radiation dermatitis. The study population included 74 patients after conservative surgery for early breast carcinoma who were referred for adjuvant external beam irradiation. Patients were randomized to receive Biafine or Lipiderm or no treatment. Both study preparations were applied twice daily, starting 10 days before onset of radiotherapy and continuing until 10 days after its completion. The skin treatment was upgraded, if clinically necessary, to steroids (grade 3), antibiotics (grade 4), or pause in therapy (grade 5). Success of treatment was evaluated according to the maximal level of skin treatment, the number of gaps in radiation therapy, the impression of the patients and the subjective skin reaction, and scores of the study nurse and radiotherapist. The three groups were comparable for all clinical features, except for a lower mean age of the Biafine group. Comparative analysis of the results showed no advantage for either preparation compared to the control arm other than maximal treatment level required for a skin reaction (mean 1.7 and 1.6 vs. 2.2), which did not reach statistical significance (p=0.145). Nevertheless, 86% of the patients in both the Biafine and Lipiderm arms expressed satisfaction with the respective ointments. In conclusion, neither Biafine nor Lipiderm seems to have a radioprotective effect.

We sought to compare the epidemiological and clinical features of patients with carcinoma of the larynx treated at a major Israeli tertiary facility with other series in the literature. The charts of 361 consecutive patients from 1974 to 1995 were reviewed. Our population was distinguished from other series by a low rate of alcohol abuse (12%), high incidence of second malignancies in sites other than the upper aerodigestive tract (53%) and high rate of early-stage tumors (82%). Overall 5-year survival and local control rates were 88% and 85%, respectively. Our study suggests that the low alcohol consumption and high proportion of early-stage tumors at diagnosis, characteristic of the Israeli population of patients with laryngeal carcinoma, may explain, in part, the relatively high survival and local control rates.