Gastrointestinal quality of life after laparoscopic-assisted sigmoidectomy for diverticular disease.

PURPOSE: Laparoscopic-assisted sigmoidectomy is a widely applied technique in the operative treatment of diverticular disease. Treatment guidelines recommend operation of complicated diverticulitis and after recurrent attacks of uncomplicated diverticulitis. These guidelines have become subject to controversy. The objective of this study was to assess disease-related quality of life after laparoscopic sigmoidectomy. METHODS: Data were collected retrospectively. Patients filled in a form describing their quality of life. All patients undergoing elective operation for diverticular disease between 1999 and 2006 at the Department of Surgery of the Uster Hospital, a regional medical center in Switzerland were included. The measurement tool we used is the Gastrointestinal Quality of Life Index (GIQLI). Wilcoxon-Mann-Whitney test or unpaired t-tests were applied to determine statistical significance of differences observed. RESULTS: A total of 130 patients were included and 120 questionnaires were available for analysis. Mean follow-up was 40 months. Of the total, 48% reported a GIQLI >100 before the operation, which rose to 83% after the operation (p < 0.0001). Mean GIQLI was 95 before and 114 after the operation (p < 0.0001). Female patients reported lower GIQLI rates. Overall, 96% were satisfied with the operation. CONCLUSIONS: The results in this study population show that in a majority of patients who underwent elective laparoscopic-assisted sigmoidectomy for recurrent diverticulitis gastrointestinal quality of life improved with the operation.

Phase II clinical trial of intratumoral application of TG1042 (adenovirus-interferon-gamma) in patients with advanced cutaneous T-cell lymphomas and multilesional cutaneous B-cell lymphomas.

Cutaneous lymphomas (CLs) are a heterogeneous group of lymphoproliferative disorders that are manageable by immunotherapy. Twenty-one patients were enrolled in a prospective open-label, dose-escalation multicenter study evaluating the effects of repeated TG1042 [adenovirus-interferon (IFN)-gamma] intralesional injections in patients with primary CLs, of which 18 were of T-cell and 3 of B-cell type. Repeated intralesional therapy using TG1042 consistently results in local tumor regressions in about half of treated patients and one-third of patients also in regressions in noninjected distant lesions, likely reflecting the systemic immune activation after intralesional therapy. Treatment was well tolerated with few adverse events including injection site reactions, chills, lymphopenia, and fever. Immune monitoring in the peripheral blood demonstrated systemic immune activation and the induction of antibodies against tumor antigens in some patients without clear association with clinical responses. CLs, in particular B-cell lymphomas with high objective response rates, seem to be excellent targets for this type of immunotherapy.

Identification of selectively expressed genes and antigens in CTCL.

The knowledge of tumor-associated antigens is required for most types of immunotherapy and can substantially facilitate diagnosis. To identify potential tumor-associated genes expressed in cutaneous T-cell lymphoma (CTCL), we used three complementary strategies: antigens which elicit a humoral immune response in CTCL patients were detected by serological analysis of a recombinant cDNA expression library. cDNAs differentially expressed in CTCL but not peripheral blood monocytes were identified by comparative cDNA hybridization and suppression subtractive hybridization. We identified 43 genes selectively expressed by CTCL cells, that have not yet been described in the context of CTCL development, but most of which had been reported to be associated with cancer. Expression analysis by database mining and subsequently RT-PCR on selected clones confirmed their selective expression in CTCL tissues. Serological tests showed that 15 clones were recognized by sera of CTCL patients but not of healthy donors. Analysis of serological tests for 11 clones using serum antibody detection array (SADA) and 100 sera of controls and CTCL patients each revealed up to 5% reactive sera in the tumor group. The expression pattern of the detected clones and their immunogenicity demonstrates that they might be relevant for the understanding of CTCL and suggests particularly three clones, HD-CL-41 (DRAK2), HD-CL-49 (nudC) and HD-CL-12 (ZNF195) for further analysis with respect to their prognostic and therapeutic value for CTCL.

Expression of GAGE family proteins in malignant melanoma.

Cancer/testis antigens are considered as promising targets for immunotherapy against tumors including malignant melanoma. One group of these antigens is the GAGE antigen family. In this study, we obtained recombinant GAGE-7b protein against which a rabbit antiserum was generated. The polyclonal, monospecific antibodies were used to analyze the expression of GAGE family proteins in human melanoma tissues and cell lines. GAGE expression in melanoma cell lines ranged from 41% to 58% and in melanoma tissues from 22% to 53%. Immunohistochemical analysis of melanoma tumors revealed a rather heterogeneous expression of GAGE resulting in individual positive cells or foci of stained cells. Furthermore, we could show that autoantibodies against GAGE family proteins are detectable in 6% of melanoma patients. Besides, we first demonstrated that the expression of GAGE family proteins can be stimulated with 5'-aza-2'-deoxycytidine and trichostatin A. Through upregulation of protein expression GAGE family proteins might develop into promising targets for immunotherapy of melanoma and other tumors.

Serological analysis of human renal cell carcinoma.

Serological analysis of cDNA expression libraries (SEREX) has proven to be a useful technique in the quest to elucidate the repertoire of immunogenic gene products in human cancer. We have applied the SEREX method to human renal cell carcinoma (RCC) in order to identify associated immunogenic gene products. cDNA expression libraries were prepared from a RCC tumor, a RCC cell line and human testis. The 3 libraries were screened with sera from 35 RCC patients and 15 healthy controls. Approximately 4.5 x 10(6) phage plaques were screened resulting in 234 positive clones, which corresponded to 74 different gene products. The seroreactivity toward 49 of these antigens was assessed. Seroreactivity to 21 (43%) of the antigens was similar in RCC patients and healthy controls, 9 antigens (18%) elicited antibodies more frequently and 19 antigens (39%) solely in RCC patients. In the reverse setting, reactivity of RCC patients' sera was tested against a panel of 44 previously identified "tumor-associated" antigens via the SADA (serum antibody detection array) method; 6 antigens reacted with RCC patients' and healthy donors' sera, 8 were reactive only with RCC patients' sera. From the 27 antigens identified by SEREX and SADA, which did not react with sera from healthy controls, 10 antigens reacted with a significant proportion of RCC patients' sera and 77% of RCC patients' sera reacted at least with one of these antigens. Sera from patients with non-malignant renal diseases or an autoimmune disease did not react with these 10 antigens.