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D Elias

Publications and source records attributed to D Elias.

At least 163 records · Page 9Linked to original sources

T-cell receptor repertoire in colorectal adenocarcinoma patients with hepatic metastases and its changes induced by preoperative adjuvant interleukin-2 therapy.

The liver is the primary site for colorectal metastases and hepatic resection often fails to cure these patients. Little is known about T-cell immune response in these patients or its changes after interleukin-2 (IL-2) infusion. Using polymerase chain reaction methodology, we investigated T-cell receptor (TCR) V alpha and V beta gene segment subfamily usage in tumor, hepatic tissue, and blood of six patients undergoing hepatic resection and, in addition, in six patients receiving preoperative adjuvant IL-2 therapy (randomized phase I trial). The objectives were (a) to analyze the TCR repertoire in patients undergoing hepatic resection (without IL-2), (b) to analyze the TCR repertoire in patients undergoing hepatic resection after IL-2 therapy, (c) to analyze the effects of preoperative IL-2 infusion on the tumor-infiltrating lymphocyte (TIL) TCR repertoire by comparing TCR V gene segment usage in IL-2-treated versus nontreated patients, and (d) to analyze the effect of IL-2 infusion on the peripheral blood mononuclear cell (PBMC) TCR repertoire by comparing TCR V gene segment expression in pre- versus posttreatment PBMC of IL-2-treated patients. With regard to the first objective, we observed an unrestricted use of V alpha and V beta gene segment subfamily specificities in tumor hepatic tissue and blood of patients undergoing hepatic resection. In addition, we found that some V alpha and V beta specificities were overexpressed in tumor compared with hepatic tissue and blood, suggesting that the corresponding T-cell subpopulations were expanded at the tumor site. In IL-2-treated patients, in whom the tumor and liver were heavily infiltrated by T lymphocytes, the TIL TCR repertoire was also highly diverse and roughly similar to that detected in hepatic tissue and blood, except for a few overexpressions. To analyze the effect of IL-2 on TIL, we next compared the data obtained in IL-2-treated versus nontreated patients. No significant difference between the two groups was observed. Finally, no major changes in the PBMC TCR repertoire were found after IL-2 infusion. Further studies are needed to identify discrete T-cell subpopulations in these patients that may participate in either tumor immune surveillance or active immunotherapy mechanisms triggered by systemic IL-2 infusion.

Adenocarcinoma↗

Autoimmune diabetes induced by the beta-cell toxin STZ. Immunity to the 60-kDa heat shock protein and to insulin.

Administered at a suitably low dose, the toxin streptozotocin (STZ) can trigger an autoimmune process leading to destruction of the beta-cells of the pancreatic islets. In this study, we examined specific immunological reactions in mice before and during the development of STZ-induced autoimmune diabetes. We now report that the development of spontaneous autoantibodies to insulin can serve as a marker of susceptibility to a low dose of STZ. Susceptible male mice of the C57BL/KsJ strain manifested such anti-insulin antibodies, and resistant female mice did not. Administration of a low dose of STZ (five daily doses each of 30 mg/kg) induced transient hyperglycemia approximately 20-30 days later, which temporarily remitted but was followed by intractable diabetes approximately 2.5 months later. The diabetogenic process triggered by the low dose of STZ was associated with an increase in the level of anti-insulin antibodies bearing the Dana and Micha (DM) idiotype, later followed by the appearance of anti-idiotypic antibodies that peaked before the onset of diabetes. Antibodies and T-cells reactive to hsp60 (heat shock protein) were triggered by the low-dose STZ administration and persisted throughout the period that preceded clinical diabetes. T-cells reactive to the p277 peptide of hsp60 were also observed. Finally, active immunization to hsp60 caused transient hyperglycemia by itself and also aggravated the hyperglycemia induced by low-dose STZ. Thus, autoantibodies to insulin can indicate susceptibility to a toxic trigger of diabetes, and a low dose of a toxin can activate the insulin and hsp60 autoimmunity that has been detected previously in the spontaneous autoimmune diabetes of NOD strain mice.

Animals↗

[Intra-arterial hepatic chemotherapy. Experience of 200 cases].

OBJECTIVES: This retrospective study had three aims: a) to investigate whether one catheter, whatever the number of hepatic arteries, associated with miscellaneous arterial ligations, produced the same results as the implantation of multiple catheters, b) to study the survival rate after intra-arterial chemotherapy, and c) based on a multifactorial study of prognostic factors, to define the best indications of this treatment in the future. METHODS: Two hundred catheters were surgically implanted to perform intrahepatic arterial chemotherapy in patients with multiple unresectable isolated liver tumors. The origins of these tumours were colorectal cancer in 152 cases, neuroendocrine tumour in 13 cases, hepatocellular carcinoma in 9 cases, and miscellaneous tumours in 22 cases. The hepatic arteries were ligated in 32% of the cases. Resection of the primary or local recurrence was performed at the same time in respectively 41% and 16% of the cases. RESULTS: The use of only one catheter was always possible, and the ligations of miscellaneous accessory hepatic arteries did not modify the therapeutic results. There were no postoperative deaths. Numerous complications occurred during local chemotherapy, mainly digestive and hepatobiliary complications (38.5% of the cases). Early discontinuation of local chemotherapy was due to the occurrence of thrombosis of the hepatic artery in 23% of the cases (after a mean delay of 5.2 months) and to the occurrence of digestive or hepato-biliary complications in 11% of the cases. The rate of objective response was 44%, with 22 complete and 62 partial responses on morphologic examination. The crude survival rates were 65 +/- 3% at 1 year, 33 +/- 4% at 2 years and 5 +/- 2% at 5 years, with a median survival of 16 months. The median survival was different according to the primary tumour (34 months for neuroendocrine tumours, 17 months for colorectal tumours and 12 months for hepatocellular and miscellaneous carcinomas). For the 152 colorectal cancers, a multifactorial study identified 2 main independent adverse prognostic factors: an involvement of the liver greater than 50% (P = 0.006) and circulating carcinoembryonic antigen > 100 ng/L (P = 0.001).

Adult↗

[Intraperitoneal hyperthermic chemotherapy (IPHC), a promising treatment of peritoneal carcinomatosis].

Intraperitoneal hyperthermic chemotherapy (IPHC) appears to be a promising treatment of peritoneal carcinomatosis. This paper reports the physio-pathological background of IPHC and the various studies which have been published in the literature. It points out the heterogeneity of these series and discuss the most critical points as surgical indications, choice of the antineoplastic drugs, their doses, temperatures of the IPHC, extend of the cytoreductive surgery, morbidity and mortality. Finally, several options are proposed for those points which are not yet standardized.

Animals↗

Treatment of peritoneal carcinomatosis by intraperitoneal chemo-hyperthermia: reliable and unreliable concepts.

Intraoperative peritoneal chemo-hyperthermia (IPCH) is a promising treatment of peritoneal carcinomatosis arising from digestive tumors. After presenting the rationale for the use of IPCH, this review reports the results published to date by different groups. Unfortunately, data with respect to technical aspects, indications and results are unclear, inhomogeneous and questionable. The discussion presents reliable and unreliable points, mainly concerning the technical aspects of IPCH: what is the maximal desirable tumor thickness before initiating treatment? What is the ideal temperature? Is central hyperthermia beneficial? What is the ideal duration? What is the most effective antimitotic drug? A new classification of peritoneal seeding before cytoreductive surgery and before the initiation of IPCH, is proposed, and a suggestion concerning the reporting of drug concentrations made. Numerous prospective studies need to be conducted to test different technical modalities and to evaluate the results of IPCH.

Animals↗

[Surgical interventions for erroneous diagnoses of liver metastases].

Among 635 laparotomies carried out for liver metastases (LM) between June 1983 and December 1992, twenty three operations (with 6 hepatectomies) were performed for a false positive diagnosis of LM. They represented 3.6% of the whole population, but only 2.8% if the 5 patients operated for persistent diagnostic doubt are excluded. The 6 hepatectomies represented 2.2% of the 276 hepatectomies carried out for LM. The 23 false positive diagnosis of LM could be classified as follows: 14 complete errors (operation for the diagnosis of LM), 4 partial errors (the operation was also indicated for a concomitant disease), and 5 cases of real diagnostic doubt. Two groups of patients were differentiated according to the survey: one group had a regular survey and had a modification of their initial morphologic examinations of the liver, and one group had no reference morphologic examinations of the liver. The errors were more frequent in the first group. Atypical angiomas were the most frequent lesion (n = 10), followed by atypical cysts (n = 4), and nodular focal hyperplasia (n = 4): they represented 78% of all false positive diagnosis of LM. These false positive lesions were mainly detected in three carcinomas: colorectal carcinomas (n = 10), breast cancers (n = 5) and melanomas (n = 3): they represented 78% of the incorrect diagnosis. The relative frequency was high for melanomas (36%) and breast cancers (14%), but low for colorectal cancers (2%). The retrospective study of these cases shows that some errors could be eliminated by a more extensive imaging and systematic radio-clinical confrontation.(ABSTRACT TRUNCATED AT 250 WORDS)

Breast Neoplasms↗

[Cutaneous metastasis disclosing adrenal cortical carcinoma].

Metastases to the skin from internal malignant neoplasms are uncommon and often preterminal event. Cutaneous metastases from an adrenal cortical carcinoma have rarely been reported even in the advanced stages of the disease. A patient was initially seen with a small cutaneous lesion on the cheek and was found to have a large adrenal cortical tumor. Histologic comparison proved that the cutaneous lesion was a metastase from an adrenal cortical carcinoma.

Adrenal Cortex Neoplasms↗

[Contributions and limitations of transcutaneous ultrasonography in the preoperative evaluation for hepatic resections].

From October 1990 to January 1992, 36 patients were operated in order to perform an hepatectomy for hepatic metastases (n = 33) or primary malignant tumors (= 3). The authors evaluated the reliability of preoperative ultrasonography (US) by comparing US data to intraoperative findings without consideration of others preoperative examinations. Preoperative US detected 65 out the 78 nodules founded intra-operatively; 13 nodules (4 to 30 mm) and a micronodular dissemination were not detected (sensitivity 82% for the whole lesions). Probable causes of false negative cases (size, location and echogenicity of the nodules) are discussed. Sixty three out of the 65 nodules detected were correctly located in the hepatic segmentation by preoperative US. Hepatectomy was performed in 30 of the 36 patients (84%). The resection previously planned by preoperative US was realized in 24 patients, 5 hepatic resections (14%) had to be enlarged and one completed by a lymphadenectomy; in 6 cases (16.5%) the hepatectomy was not possible because of intraoperative findings of lesions previously not detected by preoperative examinations including US (3 with not removable hepatic nodules, 3 with lymph nodes metastases). This study confirms the reliability of US for anatomical location of hepatic lesions. US sensitivity for the detection is satisfactory. However the number of nodules was underestimated in one third of the patients. The hepatic resection previously planned was effectively realized in only 67% of the cases, in one case out of 6, the resection had to be enlarged and in one case out of 6, the resection was not possible.

Adult↗

[Total esophagoplasty using a double pedicled free graft from the jejunum: the last resort].

After repeated failures of classic oesophagoplasties (gastroplasty and coloplasty) a last chance reconstruction could rely on a free jejunal transplant. We report an exceptional and original case where digestive tract was re-established between the orostoma and the epigastric antrum. The patient has four neoplasms in the throat, thoracic oesophagus. After circular pharyngolarynectomy and total oesophagectomy, all the usable vascularized plasties had necrosed. The ultimate reconstruction was performed with a free jejunal transplant carrying two vascular bundles revascularized with the cervical vessels and the internal thoracic vessels. Several recommendations are proposed: Save as much of the digestive tube as possible; preserve the physiological gastroduodenal circuit; redissect the residual plasty in order to raise the new one as high as possible; perform a sub-cutaneous insertion of the residual plasties and the jejunal transplant; and if the loss of digestive substance is greater than 30 cm, a long free jejunal transplant with two vascular bundles should be used.

Adult↗

[Resectable liver metastases and synchronous extra-hepatic sites of colorectal origin. Surgical indications].

Twenty-two patients with liver metastases and synchronous extra-hepatic localizations or colorectal cancer underwent complete resection of all their cancerous lesion. Their survival was not significantly different from that of 87 patients in whom single or multiple metastases involving only the liver had been resected. Analysis of our 22 patients showed that they fell into two subgroups: those with lung metastases (n = 5) and those with pediculate colonic nodes (n = 6), who benefited from the double resection since their disease-free survival rate at 5 years was 35 percent. In contrast, patients who had a few peritoneal nodules (n = 8) relapsed during the first 13 postoperative months. The presence of one or a few extra-hepatic lesions does not necessarily preclude resection of the liver metastases, provided they can be resected during the same operation in case of intra-abdominal lesions and during a later operation in case of lung metastases. A single peritoneal nodule may be the first manifestation of peritoneal dissemination and contra-indicates the resection of liver metastases.

Adult↗

Repeat hepatectomy for cancer.

In a series of 279 hepatectomies performed for cancer between June 1984 and March 1992, 46 were repeat operations, for metastases in 41 patients. The primary tumour was in the colon and rectum (28 patients), APUDoma (five) and miscellaneous (eight). Repeat hepatectomies were performed in 26 per cent of patients who had recurrence after the first liver resection and in 40 per cent of those who had liver recurrence. An unsuspected extrahepatic recurrence was discovered and resected in eight instances and in two other cases a known extrahepatic recurrence was resected during the second hepatectomy. The hospital mortality rate was 2 per cent (one patient); the death was from nosocomial pneumonia. The total morbidity rate including minor complications was 32 per cent, with a higher frequency of haemorrhagic problems after secondary liver resection (12 per cent) than after primary hepatectomy (5 per cent). The rate of postoperative complications after repeat hepatectomy was related significantly to operative blood loss greater than 1500 ml (P = 0.04). The technical problems of repeat hepatectomy were: (1) re-exposure of the liver, considered to be difficult in 67 per cent of second liver resections and 80 per cent of third procedures; (2) the liver parenchyma, which often had histological modifications between first and second resections and was more difficult to 'work' as shown by the mean duration of clamping of the hepatic pedicle (54 min for secondary versus 36 min for primary liver resection); and (3) modification of the intraparenchymal vasculobiliary anatomy following liver regeneration after major hepatectomy. Intraoperative ultrasonography was of great benefit. Rates of crude and recurrence-free survival were relatively encouraging at 47 and 33 per cent 3 years after the second liver resection for the whole group. These values were lower for colorectal cancer (37 and 21 per cent 3 years after the second hepatectomy). These figures do not, however, convey the complete picture of the outcome for these patients. During the same follow-up period, 143 recurrences were detected and a mean of 2.9 resections per patient were performed. The indications for repeat hepatectomy are still to be clarified, although the surgical technique is safe.

Adult↗

Potential contribution of 131I-labelled monoclonal anti-CEA antibodies in the treatment of liver metastases from colorectal carcinomas: pretherapeutic study with dose recovery in resected tissues.

20 patients with liver metastases from colorectal carcinoma undergoing laparotomy received 15-60 mg intravenously, either intact or fragments of, anti-carcinoembryonic antigen (anti-CEA) monoclonal antibodies labelled with 0.55-1.48 GBq (15-40 mCi) of 131I, 3-8 days prior to operation. The uptake measured per gram of metastases ranged from 0.33 to 6.6 x 10(-3%) of injected dose. Tumour to liver uptake ratios ranged from 2 to 33. The radiation dose, estimated in 6 patients (3 of each group), for an extrapolated dose of 3.7 GBq (100 mCi) of 131I ranged from 0.3 to 0.8 Gy in normal liver or spleen (an acceptable estimate for bone marrow radiation dose) and from 3.4 to 8.2 Gy to the hepatic metastases, indicating that probably other therapeutic modalities should be associated with radioimmunotherapy.

Antibodies, Monoclonal↗

Portal vein embolization: utility for inducing left hepatic lobe hypertrophy before surgery.

Right portal vein embolization (PVE) was performed in patients in need of wide hepatectomy to induce preoperative hypertrophy of the future remnant liver (FRL), which would have been insufficient for safe resection. PVE was achieved with cyanoacrylate or gelatin sponges by using a percutaneous subxiphoid approach in 10 patients with tumors in noncirrhotic liver. Surgery was performed in nine patients 17-48 days (mean, 34 days) after PVE. Computed tomographic liver volumetric studies were performed before embolization and before surgery. Clinical and biologic tolerance of PVE was excellent except in one case. Histopathologic studies showed occlusion of portal veins with minimal parenchymal ischemia in eight of nine patients. The FRL volume increased by 64%, which represented 31% of the preresection volume of the liver. Better hypertrophy was seen after cyanoacrylate embolization. The authors conclude that PVE is safe and well tolerated and induces marked hypertrophy of the unembolized parenchyma in noncirrhotic patients. This hypertrophy allows hepatectomy to be performed under safe conditions when the FRL volume is initially insufficient.

Adolescent↗

Transcatheter chemoembolization of progressive carcinoid liver metastasis.

PURPOSE: The authors report their experience treating progressive liver metastases from carcinoid tumor with doxorubicin, iodized oil, and gelatin sponge embolization. MATERIALS AND METHODS: Of 23 patients, 18 had carcinoid syndrome and 19 had elevated urinary 5-hydroxyindoleacetic acid (5-HIAA) levels. Relief of symptoms, changes in 5-HIAA levels, and changes in tumor size could be evaluated in 10, 11, and 17 patients, respectively. RESULTS: Symptomatic response was complete (average duration, 29 months) in 70% and partial in 30% of evaluated patients. Biologic response was complete (average duration, 21 months) in 73%, partial in 18%, and minor in 9% of evaluated patients. Morphologic response was complete in 11%, partial in 24%, and minor in 24% of evaluated patients. Survival after diagnosis of primary tumor, diagnosis of hepatic metastases, and first chemoembolization was 81, 47, and 24 months, respectively. Eight patients were alive at the end of the study. No mortality was related to chemoembolization. CONCLUSION: Chemoembolization is safe and effective for palliation of carcinoid liver metastases.

Adult↗

Surgical treatment of hepatic metastases: impact of intraoperative sonography.

OBJECTIVE: A prospective study was done to determine the influence of intraoperative sonographic findings on surgical decision making in patients with hepatic metastases. SUBJECTS AND METHODS: Thirty-seven consecutive patients with hepatic metastases who underwent surgery (for hepatic resection or intraarterial catheter placement) were prospectively evaluated. For each patient, the resectability of the metastases and the surgical approach were determined preoperatively on the basis of the combined results of sonography, bolus dynamic CT, and CT during arterial portography (CTAP). Those determinations were compared with the decisions made during surgery, which were based on the intraoperative sonographic findings. The surgical procedure that was actually performed was compared with the procedure decided on preoperatively. RESULTS: Eighty-two metastases were surgically and pathologically proved. Preoperatively, 73 (89%) of the 82 metastases were detected with a combination of sonography, bolus dynamic CT, and CTAP. Seventy-nine metastases (96%) were detected with intraoperative sonography. Six metastases in four patients were detected only with intraoperative sonography. Furthermore, in two patients, intraoperative sonography showed four additional metastases, which changed the initial surgical approach decided on preoperatively. CONCLUSION: Our study suggests that intraoperative sonography provides important data that cannot be obtained with preoperative imaging techniques and affect the surgical decision making in patients with hepatic metastases.

Adult↗