Biomedical subjects

D Elias

Publications and source records attributed to D Elias.

At least 109 records · Page 6Linked to original sources

PubMed1998

Resection of liver metastases from a noncolorectal primary: indications and results based on 147 monocentric patients.

BACKGROUND: Very few series have reported indications for and results of hepatectomy for isolated unique or multiple liver metastases (LM) from a noncolorectal primary. We performed a prospective analysis of 147 patients submitted to hepatectomy for LM to evaluate the results and indications for this unusual type of treatment. STUDY DESIGN: Of 538 patients submitted to hepatectomy for a malignant tumor between 1984 and 1996, 147 underwent operations for noncolorectal LM. Conventional and unconventional hepatectomy procedures were used with intermittent clamping of the hepatic pedicle, and in some patients with intermittent vascular occlusion of the liver. RESULTS: Postoperative hospital mortality was 2%. The crude 5-year survival was 36%, and survival without progressive disease was 28%. No difference was observed in survival when synchronous and metachronous LM were compared, or when patients with more or fewer than three LM were compared. Five-year survival rates were 20% for 35 breast cancers, 74% for 27 neuroendocrine tumors, 46% for 20 testicular tumors, 18% for 13 sarcomas, and slightly less than 20% for 11 gastric carcinomas, 10 melanomas, and 7 tumors of the gallbladder, according to the primary. Survival exceeded 20% for 6 gynecologic tumors but was disappointing for head and neck cancers, when the primary was unknown, or when the tumor was truly undifferentiated. CONCLUSIONS: Certain guidelines emerge from this series on the indications and uses of adjuvant chemotherapy. Indications for hepatectomy are relatively straightforward for neuroendocrine, testicular, and renal tumors. Hepatectomy for LM from other primaries appears beneficial in certain sarcomas, breast and gynecologic cancers, and perhaps melanoma, for which selection criteria, unfortunately, remain obscure.

Adolescent↗

PubMed1998

[What are the real indications for hepatectomies in metastases of colorectal origin?].

AIM: To ascertain the real impact of classical contraindications (relative or absolute according to various authors) represented by: a high number of liver metastases (LM), the presence of associated extra-hepatic localizations (EHL), and a surgical margin less than 10 mm. METHODS: A prospective study was conducted in 269 consecutive hepatectomized patients. Inclusion criteria were only the resection of all tumoral tissue, and lack of major operative risk. Fifty-nine patients had at least 4 LM, 62 had an associated EHL, and 187 had a surgical margin < 10 mm. Altogether, 83% of the patients did not match the classical selection criteria. Sixty-two parameters were registered. A uni- and multivariate study of prognostic factors was performed. RESULTS: Although 18% of the resections were palliative (R1 or R2 according to the UICC classification), and the hospital mortality was 3.3% (2.2% during the first postoperative month), global and disease-free 5-year survival rates were 34.4% and 23.3%, respectively. The number of LM had no prognostic implication. A surgical margin > 9 mm improved significantly the prognosis. Between 0 and 9 mm, it had no important prognostic impact if the cut surface was histologically disease-free. A margin < 10 mm was greatly associated with a high number of LM, a bilateral localization of LM, and extended hepatectomy. Among the EHL, only those discovered during laparotomy had a significant adverse impact on prognosis. CONCLUSION: Fundamental principles of the indications of hepatectomy for colorectal LM are to resect all the lesions and to avoid major operative risk. In complex cases, the most frequent, these principles can only be completely followed in a specialized center.

Adolescent↗

PubMed1998

[Esophagectomy for epidermoid cancer discovered during evaluation of ENT cancer].

UNLABELLED: The treatment of synchronous esophageal and head and neck carcinomas is difficult. MATERIAL AND METHOD: Retrospective study of 33 patients treated with esophagectomy for an intrathoracic squamous cells carcinoma discovered during pan-endoscopy for a synchronous head and neck cancer. RESULTS: In 7 cases (21%) it was advanced (pT3-4) esophageal cancers. The hospital mortality was 9%. Five year survival was 18% without stabilization of the survival curve, 60% of patients died of recurrence of tumor. CONCLUSION: Esophagectomy is suitable for usT1-2 tumors if surgery is also indicated for the head and neck tumor. Radiochemotherapy is indicated for advanced usT3-4 esophageal tumors or when the treatment of the head and neck tumor is not surgery.

Adult↗

PubMed1998

[Impact of tumor doubling time on the therapeutic strategy: application to so-called synchronous metastases of colorectal cancers].

An exhaustive review of tumor doubling time (TDT) is presented, showing that growth of a solid malignancy remains subclinical for three-quarters of its duration and that tumor growth is close (but not strictly identical) to an exponential type. The TDT can be transiently accelerated after an aggression, particularly after surgery (which induces immunodepression and stimulation of growth factors during healing). In contrast, the TDT can be slowed by effective chemotherapy. Based on these elements, the classical attitude of waiting 3 to 6 months before resecting synchronous liver metastases from a colorectal primary is illogical, as it has only a 5 to 10% chance of detecting new metastases during this interval. Therapeutic decisions must therefore be exclusively based on surgical technical considerations, rather than erroneous oncologic considerations. In terms of the tumor growth, it is better to operate once rather than twice. In terms of the patient's quality of life and socio-economic aspects, one operation is also preferable to two. Resection of the primary tumor and synchronous metastases should therefore be performed during the same operative procedure whenever possible.

Colorectal Neoplasms↗

PubMed1998

[Importance of a multidisciplinary approach to metastatic cancer of the rectum].

Management of rectal cancers with synchronous metastasis is difficult. We evaluated in 23 patients a combination of pelvic radiotherapy at the dose of 45 Gy in 5 weeks and 25 fractions with chemotherapy by 5-fluorouracil (350 mg/m2/day) and folinic acid (20 mg/m2/day) for 5 days at the time of the first and the fifth week of the irradiation. Surgery was indicated firstly in cases of stricture or secondarily for resection of the primary location and, when possible, of the metastasis. General state of health of the patients improved in 35%, symptomatology in 86% and comfort in 72% of the cases. Response rates for the primary tumor were 41% of partial response and 50% of stable disease. For the metastatic lesions, they were 9% and 59% respectively. Sixty-one per cent of patients were secondarily operated with resection of the primary tumor in 12 cases and of hepatic metastases in 2 cases. The median survival and the median survival without progression were respectively 13 and 9 months. Radiochemotherapy combination as the first treatment was beneficial in 4/5 of the patients presenting a rectal cancer with synchronous metastasis and allowed us to select those that would secondarily benefit from a surgical resection.

Adult↗

PubMed1997

Chemoradiotherapy followed by surgery compared with surgery alone in squamous-cell cancer of the esophagus.

BACKGROUND: We conducted a multicenter, randomized trial to compare preoperative chemoradiotherapy followed by surgery with surgery alone in patients with stage I and II squamous-cell cancer of the esophagus. METHODS: The preoperative combined therapy consisted of two one-week courses; each involved radiotherapy, in a dose of 18.5 Gy delivered in five fractions of 3.7 Gy each, and 80 mg of cisplatin per square meter of body-surface area, administered 0 to 2 days before the first day of radiotherapy. The surgical plan included one-stage en bloc esophagectomy and proximal gastrectomy by the abdominal and right thoracic routes, to be performed immediately after randomization in the group assigned to surgery alone and two to four weeks after the completion of preoperative chemoradiotherapy in the group assigned to combined therapy. RESULTS: A total of 297 patients entered the study; 11 were found to be ineligible, and 4 were lost to follow-up. Of the remaining 282, 139 were assigned to surgery alone and 143 to combined therapy. After a median follow-up of 55.2 months, no significant difference in overall survival was observed; the median survival was 18.6 months for both groups. As compared with the group treated with surgery alone, the group treated preoperatively had longer disease-free survival (P=0.003), a longer interval free of local disease (P=0.01), a lower rate of cancer-related deaths (P=0.002), and a higher frequency of curative resection (P=0.017). However, there were more postoperative deaths (P=0.012) in the group treated preoperatively with chemoradiotherapy. Three prognostic factors were found to influence survival in a multivariate analysis: the disease stage, based on computed tomography; the location of the tumor; and whether the surgical resection was curative. CONCLUSIONS: In patients with squamous-cell esophageal cancer, preoperative chemoradiotherapy did not improve overall survival, but it did prolong disease-free survival and survival free of local disease.

Antineoplastic Agents↗

PubMed1997

Accelerated fractionation in esophageal cancers: a multivariate analysis on 88 patients.

PURPOSE: Accelerated fractionation was used to shorten overall treatment time to increase locoregional control and cause-specific survival. METHODS AND MATERIALS: Eighty-eight patients with cancer of the esophagus ineligible for surgery were entered in the study between 1986 and 1993. Neoadjuvant chemotherapy was given to 64% of patients. Accelerated radiotherapy using the concomitant boost technique delivered a median dose of 65 Gy in a median overall treatment time of 32 days. RESULTS: The 3-year actuarial local control rate in patients with T1, T2, and T3 tumors was 71%, 42%, and 33%, respectively. The 3-year cause-specific survival rates were 40%, 22%, and 6%, respectively. Sixteen percent of patients experienced Grade 3 esophagitis. Late toxicity included esophageal stenosis and pulmonary fibrosis in 8% and 9% of the patients, respectively. Multivariate analysis demonstrated that T stage and overall treatment time were prognostic factors for cause-specific survival. T stage and neoadjuvant chemotherapy were independent prognostic factors for locoregional control. CONCLUSION: These findings suggest that accelerated fractionation given in an overall treatment time of <35 days might be beneficial for early-stage cancer of the esophagus. Neoadjuvant chemotherapy is not recommended, as it was a significant adverse prognostic factor in the multivariate analysis for local control. Accelerated fractionation can be carried out with moderate acute and late toxicity.

Adenocarcinoma↗

PubMed1997

T-cell receptor CDR3 size distribution analysis to evaluate specific T-cell response to cancer vaccines.

To evaluate immunization procedures in cancer patients, it is important to define which biological parameters reflecting a specific immune response to the vaccine should be followed. One of these may be the recruitment or expansion of clonally amplified T-cell subpopulations previously primed by tumor-specific antigen that could be detected in tiny samples by CDR3 length analysis of T-cell receptor Vbeta transcripts. To evaluate this procedure, we studied one patient with metastatic colorectal adenocarcinoma who had received 4 intradermal injections of irradiated autologous tumor cells plus IL-2 on days 1, 8, 15 and 36. Skin tests for delayed type hypersensitivity (DTH) reaction to irradiated autologous tumor cells were performed on days 1 and 43. Although no change was observed in day 43 PBMCs, some recurrent transcripts were detected with similar CDR3 size patterns in both vaccine and DTH sites. Fine analysis of these Vbeta-Cbeta PCR products with Jbeta primers confirmed that transcripts with similar length were recruited in both vaccine and DTH sites. Induction of an inflammatory response in both DTH and vaccine sites may therefore be associated with the recruitment of few T-cell clonotypes. In addition, a Vbeta15-Jbeta2.5 transcript similar to those detected in vaccine and DTH sites was also identified in enzymatically dissociated tumor cells and in a tumor fragment. Sequencing confirmed that an identical junctional sequence was shared by Vbeta15-Jbeta2.5 transcripts from both DTH and tumor samples. Our results indicate that a T-cell clone similar to the one amplified in the tumor was recruited at the vaccine and DTH reaction sites. We therefore suggest that such an approach would be useful in assessing specific expansion of T-cell clones induced by cancer vaccines.

Adenocarcinoma↗

PubMed1997

Abdominoperineal resection combined with pre- and postoperative radiation therapy in the treatment of low-lying rectal carcinoma.

PURPOSE: A series of patients with rectal carcinoma irradiated by a sandwich technique combined with surgery is retrospectively analyzed. METHODS AND MATERIALS: From 1978 to 1991, 155 patients with low or mid rectal carcinoma received abdominoperineal resection combined with a preoperative irradiation regimen of 35 Gy delivered in 14 fractions of 2.5 Gy each over a period of 3.5 weeks. The dose was increased to 45 Gy in the case of tumor fixation. According to histopathological findings, this irradiation was complemented in 87 cases by a postoperative dose of 25 Gy delivered in 10 fractions, for a total dose of 60 Gy delivered in the posterior pelvis. RESULTS: Five-year survival was 66.8% for the entire population. The 5-year actuarial local control rate was 77.6%. Carcinologic results and toxicity were analyzed according to the pathological findings and the modalities of radiation therapy. CONCLUSIONS: The postoperative boost after a preoperative moderate dose of irradiation seems to have no utility. Thus, this sandwich technique is not recommended.

Adult↗

PubMed1997

Treatment of NOD diabetes with a novel peptide of the hsp60 molecule induces Th2-type antibodies.

A peptide from the sequence of hsp60 molecule, designated p277, has been shown to be functionally involved in modulating the development of auto-immune diabetes in the NOD mouse: administration of p277 to NOD mice can arrest the diabetogenic autoimmune process, even when far advanced. Is p277 the only hsp60 peptide able to modulate the disease? We mapped T cell responses to peptides spanning the mouse hsp60 molecule and identified an immunogenic peptide, designated p12, that is also functional in arresting NOD diabetes. Although no spontaneous T cell reactivity to p12 could be detected in NOD mice, subcutaneous administration of 100 microg of p12 in mineral oil to 10-week-old female NOD mice, similar to treatment with p277, significantly prevented progression of the disease. Administration of other immunogenic peptides was not effective. A peptide from the glutamic acid decarboxylase (GAD65) sequence, GADp35, and a peptide from the myco-bacterial hsp60 molecule did not influence the development of diabetes. The effectiveness of hsp60 peptides p12 and p277 was associated with the induction of antibodies to the peptides of the IgG1 and IgG2b isotypes, antibodies which appear to be regulated by anti-inflammatory cytokines. There was a negative correlation between the amounts of antibodies induced by the hsp60 peptides and the level of blood glucose. Thus, more than one peptide of the hsp60 molecule can be used to inhibit the development of NOD diabetes, and the effect of peptide therapy appears to be associated with the induction of specific antibody isotypes.

Amino Acid Sequence↗

PubMed1997

Estrogen, progesterone and testosterone receptors in human fetal cartilaginous tissue: immunohistochemical studies.

Computerized image analysis was used to study the distribution in cartilage of receptors to estrogen, progesterone, and testosterone during human fetal development. We have examined three histologically distinct cell groups (hypertrophic, proliferating, and reserve zones) in long bones, vertebrae, and trachea from 19 fetuses. Comparisons were made across gender and gestational age. Contrasting with controls, we examined the density of receptors, the size of the nuclear area in which the receptors were detected, the number of hormone receptor-bearing cells, and the total receptor quantity per sample. We found that estrogen, progesterone, and testosterone receptors were detected in the nuclei of all cell types, in both female and male embryonic cartilaginous tissue. Gender differences were small and inconsistent. Changes associated with gestational age depicted a pattern of hormone receptor manifestation, shifting from the immature cell types to more differentiated cells. This was evident from the receptor densities and from the cellular area in which receptors were sighted. These dynamics are accompanied by a general increase in receptor content per sample, brought about by the concomitant increase in receptor containing area size and cell number. The increase in receptor levels seems to reflect the maturation and growth of the fetal skeleton.

Cartilage↗

PubMed1997

Peritoneal carcinomatosis treatment with curative intent: the Institut Gustave-Roussy experience.

The prognosis of peritoneal carcinomatosis (PC), classically treated with intravenous chemotherapy, is very poor (mean survival of 6 months). The aim of this study is to report the results of a phase II study in which PC was treated with complete cytoreductive surgery, with the residual microscopic disease treated by immediate intraperitoneal post-operative chemotherapy (IIPC) for 5 days (mitomycin with fluorouracil or Adriamycin with Platinol. Fifty-four patients with PC from miscellaneous origins were treated between January 1993 and April 1996. The PC was important (clinically evident) but with no extraperitoneal localization in 29 cases. The PC was moderate or minor in 25 cases having been fortuitously discovered during a laparotomy for extraperitoneal cancer localization. Operating time was 7:21 h, associated frequently with extensive peritonectomies, and with resection of invaded organs (four organs per patient). IIPC was complete (5 days) in 91 per cent of patients. Three post-operative deaths (5.5%) occurred. Morbidity was present in 61 per cent of patients, and was related to surgical extension (P < 0.001). A 2-year survival of 50% was mainly correlated with the importance of the PC (P < 0.01), and was the same for both groups of patients (isolated major PC vs moderate (or minor) PC associated with extraperitoneal localization). PC recurrence rates were 30 per cent at 2 years. Complete cytoreductive surgery associated with IIPC is a logical and promising treatment of moderate and minor PC. However, it appears that it is a heavy treatment for patients (and physicians), and its efficacy will be proved only after a randomized study for survival, quality of life, and cost (currently ongoing).

Adult↗

PubMed1997

Molecular characterization of the diabetes-associated mouse MHC class II protein, I-Ag7.

The MHC class II molecule of the non-obese diabetic (NOD) mice, I-Ag7, is associated with susceptibility to autoimmune diabetes. To try to understand the molecular basis of this association, we analyzed the peptide binding properties and intracellular behavior of I-Ag7 in comparison with other I-A haplotypes. We found that I-Ag7 molecules manifested normal intracellular trafficking and lifespan, and a small but clearly detectable fraction of I-Ag7 in the cells formed SDS-resistant compact dimers. The binding of an antigenic reference peptide to I-Ag7 was stable and was accompanied by compact dimer formation. Our analysis of the binding specificity of I-Ag7 revealed a peptide binding motif of nine amino acids with a degenerate position at P1 and three conserved anchor positions: P4, P6 and P9. An allele-specific preference for negatively charged residues was found at P9, apparently due to the presence of the rare Ser residue at position 57 of the I-Ag7 beta chain. These findings could have implications for the mechanisms of MHC-mediated susceptibility to autoimmune diabetes in the NOD mice.

Amino Acid Sequence↗

PubMed1997

Self-expanding metallic stents as palliative treatment of malignant gastroduodenal stenosis.

OBJECTIVE: Our objective was to evaluate the efficacy of self-expanding metallic stents as palliative treatment in 10 patients with malignant stenosis of the stomach (n = 2) or the duodenum (n = 8). CONCLUSION: Metallic stents appeared valuable for the treatment of malignant gastroduodenal stenosis in this preliminary study because they provided durable relief of symptoms in eight of 10 patients for a mean of 93 days, until death. Particular attention should be paid to evaluating the digestive tract meticulously downstream because this zone was the cause of failure in two patients. Further studies are needed using a larger series.

Abdominal Neoplasms↗

PubMed1997

Hsp60 peptide therapy of NOD mouse diabetes induces a Th2 cytokine burst and downregulates autoimmunity to various beta-cell antigens.

A peptide of the human 60-kDa heat-shock protein (hsp60), designated p277, was found to be useful as a therapeutic agent to arrest the autoimmune process responsible for diabetes in nonobese diabetic (NOD) mice. The effectiveness of peptide treatment was associated with the induction of peptide-specific antibodies of the IgG1 but not of the IgG2a isotype, suggesting the possibility that a Th2-type response may have been induced. We now report that the effectiveness of p277 treatment is associated with the transient activation of anti-p277 splenic T-cells that produce the Th2 cytokines interleukin-4 (IL-4) and IL-10. The Th2 response to p277 was associated with reduced Th1-type autoimmunity to hsp60 and to two other target antigens associated with diabetes: GAD and insulin. The Th2 shift appeared to be relatively specific; spontaneous T-cell reactivity to a bacterial antigen peptide remained in the Th1 mode in the p277-treated mice. Moreover, treatment with the bacterial peptide did not induce a change in cytokine profile, and it did not affect progression of the disease. Thus, effective peptide treatment of the diabetogenic process associated with the induction of antibodies may be explained by selective and transient activation of Th2 autoimmune reactivity.

Animals↗

PubMed1997

Intestinal helminths and their influence on the indicators of iron status in the elderly.

The intestinal helminthiasis and hematological status was assessed in 100 elderly residents of two low-land communities, one at sea-level and the other at 61; m, equally representative of men and women. These are beth low-income communities. The population showed a 48% helminth infection rate which consisted of hookworm, Trichuris, and Ascaris infection. The prevalence of each of the individual parasites was considered light to moderate and the intensity of infection was generally low in this population. A strong inverse association between intensity of hookworm infection and hemoglobin levels was observed but only at intensities greater than 2,000 eggs/gram feces. Lower intensities of infection had no apparent influence on hematological status. The evaluation of hematological status using hematocrit and hemoglobin showed different prevalences of risk of anemia of 14.1% and 43.8%, respectively. These differences may reflect the chosen cut-off values. Iron deficiency does not appear to be a major problem in this population with only 5% or 11% having absent stores using the low and high cut-off values of circulating serum ferritin, respectively.

Aged↗

PubMed1997

[Peritoneal carcinosis treated by complete excision and immediate postoperative intra-peritoneal chemotherapy. Phase II study in 54 patients].

OBJECTIVES: The short term prognosis of peritoneal carcinomatosis whose classical treatment is intravenous chemotherapy, is poor (mean survival of 6 months). The aim of this study was to report the results of a phase II prospective study in which peritoneal carcinomatosis was managed with complete reductive surgery associated with treatment of the residual microscopic disease with immediate intraperitoneal postoperative chemotherapy. PATIENTS AND METHODS: Fifty-four patients with peritoneal carcinomatosis from miscellaneous origins, were treated between January 1993 and April 1996. Major peritoneal carcinomatosis was important, clinically evident, but without extraperitoneal localization in 29 cases. It was moderate, fortuitously discovered during a laparotomy for an extraperitoneal recurrence in 25 cases. Immediate intraperitoneal postoperative chemotherapy was carried out continuously during 5 days, with 900 ml/m2 of ringer lactate, with either mitomycine C and 5-fluorouracil, or doxorubicin and platinum, according to histology. The treatment was complete in 91% of cases. RESULTS: Three patients died during the hospitalization (5.5%), and a high morbidity (61%) was observed, with 35% intra-abdominal complications necessitating surgery in 13% of the patients. The postoperative complications were correlated with the extension of the cytoreductive surgery (P < 0.001). After a mean follow-up of 12.3 months, 13 patients died. The 2-year survival rate was 50%. Survival was related to the importance of the peritoneal carcinomatosis (P < 0.01) and was identical for patients with isolated peritoneal carcinomatosis and for patients with moderate peritoneal carcinomatosis associated with resected extra-peritoneal disease. The incidence of recurrence of peritoneal carcinomatosis was 30% at 2 years, showing the efficiency of this new procedure to treat peritoneal carcinomatosis. CONCLUSIONS: Complete cytoreductive surgery with immediate intraperitoneal postoperative chemotherapy is a promising treatment of peritoneal carcinomatosis. However it appears that: a) it is a difficult treatment for patients and for physicians, b) its efficiency will be asserted only with a randomized study (currently ongoing), that only allows to suppress selection bias, c) it is able to cure some groups of peritoneal carcinomatosis (probably 20%), that will be difficult to identify, and d) improvement of immediate intraperitoneal postoperative chemotherapy is possible (mainly with hyperthermia). The main advantage of immediate intraperitoneal postoperative chemotherapy is that, after proving its efficiency, easy widespread use will be assured.

Adult↗

PubMed1997

[Primary anorectal melanoma. Apropos of 19 cases].

OBJECTIVE: The aim of this study was to determine the significant prognostic factors for primary anorectal melanoma and propose a standard surgical procedure. PATIENTS AND METHODS: From 1975 to 1995, 19 patients with primary melanoma of the anus were treated. Five patients were given palliative care, 6 had abdominoperineal amputation and 8 had curative local transrectal tumoral excision. Two patients also underwent inguinal node dissection. RESULTS: Overall 5-year survival was 21%. Univariate analysis showed a significantly poorer prognosis when: inguinal or pelvic nodes were invaded (p = 0.01), surgical margins were invaded (p = 0.003), visceral metastases were present (p = 0.01) and the tumor measured over 20 mm thick (p = 0.01). Prognosis was unchanged by the type of surgical exeresis. CONCLUSIONS: Local transrectal excision is the first ling choice for primary anorectal melanoma. Amputation of the rectum should be reserved for cases where complete tumor resection is technically impossible transrectally. Node dissection is indicated in cases with clinical invasion of the inguinal nodes.

Adult↗