Shlomo Walfisch

Coping with a threat to life: a longitudinal study of self-concept, social support, and psychological distress.

The relationship of self-concept (self-esteem and mastery) and social support to psychological distress was studied among 68 Israeli women immediately prior to undergoing biopsy for suspected cancer (acute stress) and 3 months later for the noncancer group (everyday stress). It was predicted that women with stronger self-concepts and more social support would experience less state depression and state anxiety during the acute crisis than women with weaker self-concepts and less social support. It was further predicted that self-concept would be more critical than social support due to the acute nature of the event. Finally, self-concept was predicted to be related to psychological distress both during the acute and everyday stress situations (a direct effect), while social support was predicted to be related to psychological distress only during the acute stress situation (a buffering effect). The hypotheses were generally confirmed. However, self-concept and social support were seen as complexly related to psychological distress during the acute phase, one not necessarily being more critical than the other. The selective employment of available resistance resources to fit the situation and implications for preventive intervention were discussed.

Tomato lycopene extract supplementation decreases insulin-like growth factor-I levels in colon cancer patients.

Epidemiological studies have shown that high serum levels of insulin-like growth factor-I are associated with an increased risk of colon and other types of cancer. The aim of this study was to determine whether short intervention with dietary tomato lycopene extract will affect serum levels of the insulin-like growth factor system components in colon cancer patients. The study had a double-blind, randomized, placebo-controlled design. Colon cancer patients (n=56), candidates for colectomy, were recruited from the local community a few days to a few weeks before surgery. Personal and medical data were recorded. Plasma concentrations of insulin-like growth factor-I and II and insulin-like growth factor-I-binding protein-3 were assayed by routine laboratory methods. Lycopene was assayed by high-performance liquid chromatography. Plasma lycopene levels increased by twofold after supplementation with tomato lycopene extract. In the placebo-treated group, there was a small nonsignificant increase in lycopene plasma levels. The plasma concentration of insulin-like growth factor-I decreased significantly by about 25% after tomato lycopene extract supplementation as compared with the placebo-treated group (P<0.05). No significant change was observed in insulin-like growth factor-I-binding protein-3 or insulin-like growth factor-II, whereas the insulin-like growth factor-I/insulin-like growth factor-I-binding protein-3 molar ratio decreased significantly (P<0.05). Given that high plasma levels of insulin-like growth factor-I have been suggested as a risk factor for various types of cancer including colon cancer, the results support our suggestion that tomato lycopene extract has a role in the prevention of colon and possibly other types of cancer.

Lycopene in serum, skin and adipose tissues after tomato-oleoresin supplementation in patients undergoing haemorrhoidectomy or peri-anal fistulotomy

Lycopene, the main carotenoid found in tomatoes and tomato-based products, has been reported to be protective against several types of cancer. Assessment of changes in plasma concentration of carotenoids following ingestion of lycopene-rich food sources does not necessarily predict changes in lycopene concentration or distribution of its isomers in other body tissues. Our aim was to determine the relationship between concentrations of lycopene and other tomato carotenoids in human serum and body tissues after tomato-oleoresin supplementation. Tomato lycopene oleoresin (30 mg/d) or a placebo was administered for 1 to 7 weeks to seventy-five volunteers undergoing elective haemorrhoidectomy or peri-anal fistulotomy. Carotenoid concentration and isomer distribution in blood and in the surgically removed skin and adipose tissues was measured by HPLC. The serum concentration of lycopene increased after supplementation from 0.26 (SD 0.12) to 0.52 (SD 0.25) micromol/l (n 35; P<0.0001). In the placebo group (n 40), lycopene serum concentration did not change significantly. Serum lycopene concentration after treatment was 2.2-fold greater in the lycopene group than in the placebo group, a slightly higher ratio than that found in skin and adipose tissue (1.6- and 1.4-fold higher than the placebo, respectively). A significant correlation between serum and tissue concentrations was found for both beta-carotene and lycopene in the placebo group, whereas in the lycopene-supplemented group the correlation between serum and tissues remained the same for beta-carotene but for lycopene was weak. Lycopene supplementation did not significantly change the proportion of all-trans v. cis isomers in the serum and tissues, despite the fact that more than 90 % of the supplemented lycopene was in the all-trans form. These results show that tomato-oleoresin supplementation increases lycopene concentrations in serum and in adipose tissue and skin. The ability to increase lycopene levels in tissues is one of the prerequisites for using it as a food supplement with health benefits.

FTIR Microscopic Studies on Normal, Polyp, and Malignant Human Colonic Tissues

Fourier-Transform Infrared Spectroscopy (FTIR) employs a unique approach tooptical diagnosis of tissue pathology based on the characteristic molecularvibrational spectra of the tissue. The biomolecular changes in the cellularand sub-cellular levels developing in abnormal tissue, including a majorityof cancer forms, manifest themselves in different optical signatures, whichcan be detected in infrared microspectroscopy. This report has two parts. Inthe first part, we report studies on normal, premalignant (polyp) andmalignant human colonic tissues from three patients with different stages ofmalignancy. Our method is based on microscopic infrared study (FTIR-microscopy)of thin tissue specimens and a direct comparison with traditional histopathologicalanalysis, which serves as a “gold” reference. The limited dataavailable showed normal colonic tissue has a stronger absorption thanpolypoid tumor and cancerous types over a wide region in a total of 100measurements. Detailed analysis showed that there is a significant decreasein total carbohydrate, phosphate and possibly creatine contents for polyp andcancerous tissue types in comparison to the controls. The same trend is maintainedin seven other patients studied. The second part consists of an analysis showingthe influence of various independent factors such as age, sex and grade of malignancy. Ourpreliminary results suggest that among the above three factors, age and gradeof malignancy have significant effect on the metabolites level, but sex has onlyminor effect on the measured spectra. Initial results on Linear DiscriminantAnalysis (LDA) showed good classification between normal and malignant cellsof human colonic tissues.

Detection of abnormal proliferation in histologically 'normal' colonic biopsies using FTIR-microspectroscopy.

Background: Abnormal crypt proliferation and development in the colon has been associated with premalignant stages of colon cancer. Conventionally, molecular markers are used to detect abnormal crypt proliferation. Methods: In the present work, feasibility studies of FTIR‐MSP to distinguish between normal and abnormal crypts from colon biopsies that show normal histopathological features have been undertaken. Results: The results indicate that abnormal crypts show deviations in the pattern of absorbance in the Mid IR region along the crypt height when compared with the normal crypts. The crypts could be empirically classified into three groups such as crypts having a normal absorbance pattern for all biochemical components, crypts with abnormal absorbance pattern for some biochemical components and crypts with completely abnormal absorbance pattern along the height for all or most biochemical components studied by FTIR. The utilization of FTIR‐MSP is proposed for diagnosis of abnormal metabolism at the molecular level of histologically completely normal‐looking crypts, especially from those biopsies that are taken from sites far away from cancer. Conclusions: This method could give rise to a reduction in false‐negative results during examination of biopsies using the conventional histopathological methods. The present method may be complementary to existing methods for precise demarcation of the zone of colostomy prior to colon cancer surgery.

Modulation of transcriptional activity by antioxidant carotenoids

It is widely accepted that diet changes are a powerful means to prevent cancer. The possible involvement of transcriptional activity in the anticancer activity of carotenoids will be the focus of this review. Carotenoids function as potent antioxidants, and this is clearly a major mechanism of their action. In addition carotenoids action involves interference in several pathways related to cancer cell proliferation and includes changes in the expression of many proteins participating in these processes such as connexins, phase II enzymes, cyclins, cyclin-dependent kinases and their inhibitors. These changes in protein expression suggest that the initial effect involves modulation of transcription by ligand-activated nuclear receptors or by other transcription factors. It is feasible to suggest that carotenoids and their oxidized derivatives interact with a network of transcription systems that are activated by different ligands at low affinity and specificity and that this activation leads to the synergistic inhibition of cell growth.

Combined Multimodal Approach to the Treatment of Metastatic Anal Carcinoma: Report of a Case and Review of the Literature

Background: We report on a patient with squamous cell anal carcinoma and liver metastases, who underwent multimodal treatment for cure, consisting of repeated partial hepatectomy in combination with chemoradiotherapy. Patients and Methods: A 54-year-old woman presented with squamous cell anal carcinoma and liver metastases. She was treated with a combination of chemoradiotherapy for the primary tumor and then underwent surgery for liver metastases. 2 and 5 years after presentation, the patient underwent repeated partial hepatectomies for recurrent liver disease. At present, 5 months after completing therapy and 71 months after the initial diagnosis, she is in good health with no evidence of disease. Results: Repeated partial hepatectomy led to prolonged survival in a patient with squamous cell anal carcinoma metastatic to the liver. Conclusions: This is the first report of aggressive partial hepatectomy for recurrent liver metastases resulting from anal cancer. Based on our experience, we suggest that in selected patients repeated hepatectomy should be part of an aggressive multimodal treatment program with curative intent.

Role of gene regulation in the anticancer activity of carotenoids

There is extensive evidence that high intake of fruits and vegetables is associated with decreased risk of many types of cancers. Thus, it is widely accepted that diet changes are a powerful means to prevent cancer. Although there is a growing interest in the role of the tomato carotenoid lycopene in cancer prevention and treatment, we hypothesize that a single micronutrient cannot replace the power of the concerted action of multiple agents derived from a diet rich in fruits and vegetables. Indeed, we found that lycopene can synergize with other phytonutrients in the inhibition of cancer cell growth. The mechanism underlying the inhibitory effects of lycopene and other carotenoids involves interference in several pathways related to cancer cell proliferation and includes changes in the expression of many proteins participating in these processes, such as connexins, cyclins, cyclin-dependent kinases, and their inhibitors. These changes in protein expression suggest that the initial effect involves modulation of transcription by ligand-activated nuclear receptors or by other transcription factors. It is feasible to suggest that carotenoids and their oxidized derivatives interact with a network of transcription systems that are activated by different ligands at low affinity and specificity and that this activation leads to the synergistic inhibition of cell growth.

Stressful events, mastery, and depression: An evaluation of crisis theory

The effect of prior stressful events and mastery on psychological distress during and following a threat to life was examined, and three competing models concerning the effect of prior stressful events on reactions to severe life crisis were compared. The stressful events model suggests that prior stressful events increase vulnerability to new threatening events. The traditional crisis model suggests no such effect of prior stressful events on crisis reaction due to the overwhelming effect of the crisis at hand. A facilitator model predicts that prior events decrease vulnerability to crisis due to a “practice effect.” Fifty-five Israeli women (not found to have cancer) were studied just prior to and 3 months following biopsy for suspected cancer. Those with greater prior stressful events were significantly more state depressed at both times than those experiencing fewer events, supporting the stressful events model. It was also found that mastery moderated the extent to which women were depressed and the period of time they remained depressed. However, mastery did not limit the stressful life event — depression relationship. Implications for research and intervention are discussed.

Double seton—A new modified approach to high transsphincteric anal fistula

Despite the fact that complicated extrasphincteric anal fistulas have been recognized and treated for many years, there is still a lack of consensus among colorectal surgeons as to the optimum surgical approach. We have devised a modification of the seton technique, which we used in 23 patients without complications or recurrence.