Transpleurodiaphragmatic radiofrequency thermoablation of a liver metastasis.
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Adenocarcinoma↗
Biomedical subjects
D Elias
Publications and source records attributed to D Elias.
Reflections and proposals for the standardization of lymphadenectomy for gastric carcinoma.
In this paper, I consider: the value of various histological procedures; the feasibility and reproducibility of lymphadenectomies according to the Japanese Research Society for Gastric Cancer; the minimal number of lymph nodes (LNs) which should be resected for each type of lymphadenectomy; and the best way to present the results concerning the LN status. A reproducible lymphadenectomy is proposed for simplified anatomical level I (anterior plane, along the gastric curves) and level II (intermediate plane, along the gastric arteries), without spleno-pancreatectomy for the majority of cases. The LN status must be based on the total number of involved nodes, as recommended by the 1997 UICC classification. These simple, reproducible guidelines offer a basis for the standardization of procedures used for the treatment and classification of gastric carcinomas.
Feasibility Studies↗
Reply to Professor Bozzetti.
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Journal Article↗
Usefulness of intraoperative radiofrequency thermoablation of liver tumours associated or not with hepatectomy.
INTRODUCTION: A probe emitting radiofrequency (RF) waves is able to destroy tumour tissue by thermal ablation. The purpose of this study was to undertake a prospective estimation of the benefit of RF thermoablation of liver tumours during hepatic and extrahepatic resections aimed at obtaining an R0 status in patients in whom disease is notoriously considered unresectable. METHOD: Twenty-one patients underwent surgery between January 1997 and September 1999. In 17 cases, RF was associated with a hepatectomy and in nine of these cases with resection of extrahepatic lesions. In two cases, extensive resection of extrahepatic lesions was associated with RF to treat liver metastases, and in two cases RF was ultimately performed alone. The mean number of liver metastases was 6.2+/-4.3 (range 1-15) per patient. A total of 32 lesions were treated with RF. The mean size of the 33 RF-thermoablated tumours was 13.6+/-9.7 mm (range 5-52 mm), and in all but one case, a Pringle manoeuvre was performed during the RF procedure. RESULTS: A probable R0-resection was obtained in 18 cases. No operative deaths or any RF-related complications occurred. If we exclude the case in which it was clearly impossible to destroy liver metastases intraoperatively, only one local recurrence occurred (3%) among the 32 thermoablated lesions after a mean follow-up of 17.3 months. The 2-year overall and disease-free survival rates for this initially unresectable population were 94.7% and 22%, respectively. CONCLUSION: Intraoperative use of RF to destroy unresectable liver tumours increases the rate of curative resections. Future progress in RF technology and adequate vascular clamping during RF should increase this rate.
Adult↗
Radiofrequency ablation of 100 hepatic metastases with a mean follow-up of more than 1 year.
OBJECTIVE: The objective of our study was to evaluate the efficacy and safety of radiofrequency ablation of hepatic metastases performed either percutaneously for treatment of hepatic metastases in patients deemed ineligible for surgery or intraoperatively during partial hepatectomy to destroy unresectable metastases. SUBJECTS AND METHODS: Sixty-eight patients with 121 hepatic metastases (<5 metastases per patient) that were mainly colorectal in origin underwent 76 sessions of radiofrequency ablation with cooled-needle electrodes under sonographic guidance. Twenty-one patients with 33 metastases of 5-20 mm in diameter (mean +/- SD,13 +/- 7 mm) underwent intraoperative radiofrequency ablation. Forty-seven patients with 88 metastases of 10 to 42 mm in diameter (mean +/- SD, 26 +/- 9 mm) were treated with percutaneous radiofrequency ablation. Procedure efficacy was evaluated with dynamic enhanced CT and MR imaging performed 2, 4, and 6 months after treatment and then every 3 months. RESULTS: Radiofrequency ablation allowed eradication of 91% of the 100 treated metastases that were followed up for 4-23 months (mean, 13.7 months). Tumor control was equivalent for percutaneous radiofrequency ablation (90%) and for intraoperative radiofrequency ablation (94%). Failure to achieve tumor control occurred mostly with the largest tumor nodules. One bilioperitoneum and two abscesses were the major complications encountered after treatment of 121 metastases with a follow-up of more than 2 months. CONCLUSION: Radiofrequency ablation appears to be a promising therapeutic modality capable of extending the possibilities of partial hepatectomy and of efficiently treating small metastases percutaneously.
Adult↗
[Complications and tolerance of heated intraperitoneal chemotherapy and cytoreductive surgery for peritoneal carcinomatosis: results of a phase I-II study of peritoneal carcinomatosis from different sources].
Peritoneal carcinomatosis represents the terminal stage of adenocarcinomas of the gastrointestinal tract. A new treatment combining cytoreductive surgery and intraperitoneal chemotherapy-hyperthermia has been used with encouraging results. The purpose of this study was to report the complications associated with this treatment. Fourty procedures were carry out in 37 patients. Death occurred in 3 patients. Major medical complications were 13 pulmonary infections, 11 acute renal failure (with only 3 who needed dialysis) and 10 patients with neutropenia grade 3 and 4 toxicity. Intra-abdominal complications occurred in 16 patients (there were 11 anastomotic leak and/or bowel perforation, and 12 intra-abdominal infections). Some complications like secretory diarrhea or tubulopathia which were related to these treatment need further investigations. Six procedures were without any complications, 6 presented minor ones and 22 major complications. Adverse effects were relatively important with this new treatment strategy. This was maybe due to a learning process; there is no death and only one anastomotic leak in our last study including 30 patients with cytoreductive surgery and intraperitoneal chemotherapy-hyperthermia.
Adolescent↗
Research on the best chemohyperthermia technique of treatment of peritoneal carcinomatosis after complete resection.
BACKGROUND: The complete or almost complete resection of peritoneal carcinomatosis (PC) followed by intraperitoneal chemohyperthermia (IPCH) is potentially capable of curing some patients presenting with disease confined to the peritoneum. AIMS: The aim of this prospective phase I-II study was to develop an efficient IPCH procedure with good thermal homogeneity and good spatial diffusion, that would be reproducible (and thus could be standardized and exported), and to evaluate patient tolerance and its efficiency in eradicating tumor tissue. METHODS: Seven IPCH procedures were tested successively in 32 patients (up to a total of 35 IPCH). Each procedure was tested in at least 4 patients before modifications for technical reasons or due to inacceptable tolerance. Five of them were followed by early postoperative intraperitoneal chemotherapy (EPIC) lasting 4 days. Thermal homogeneity was measured with 6 thermal probes placed in different positions inside the abdominal cavity. Spatial diffusion was studied in the last patients by adding methylene blue to the IPCH liquid. The mean follow-up was 23.85 months for the series. RESULTS: From the technological point of view, we have progressively shown that procedures with closure of the abdomen are not satisfactory: it was impossible to obtain thermal homogeneity when the entire parietal wound was closed, but markedly improved when only the skin was closed. However, these "closed" procedures did not allow us to treat all surfaces at risk. The peritoneal cavity "expander" did not permit treatment of the parietal wound and an indeterminate amount of the perfusion oozed out at its periphery. The open technique with traction of the skin upwards was superior. Using different procedures successively undermined the quality of the postoperative results. Three patients (8.6%) died and morbidity (albeit minimal) occurred in 27 patients (77%) during the postoperative course. Mortality and morbidity were significantly correlated (P = 0.02) with the peritoneal index (scoring the extent of PC). The 2-year survival rate was 60% and PC did not recur in 49% of the patients. The survival rate was correlated with the extent of PC (peritoneal index greater than or below 15) (P = 0.004), and with the absence of extraperitoneal disease (P = 0.01).
Adolescent↗
[Neuro-endocrine tumors and von Hippel-Lindau disease. 3 cases].
BACKGROUND: Neuroendocrine tumors can occur in patients with hereditary syndromes predisposing to multiple endocrine neoplasia (MEN) and Von Hippel-Lindau disease (VHL). CASE REPORTS: We report the cases of three men with pheochromocytomas, one with an associated neuroendocrine tumor of the pancreas. In one case, diagnosis was suggested by the familial context of VHL in the patients father. In the two other cases, the bilateral character of the pheochromocytoma, and in one case the associated pancreatic neuroendocrine tumor led to the diagnosis of VHL. Systematic biological surveillance gave the diagnosis of contralateral pheochromocytoma in two cases. Search for associated tumoral lesions led to the diagnosis of hemangioblastoma of the cerebellum in two patients and pancreatic cyst in the third. No renal or retinal lesions were observed. Molecular study of the VHL gene evidenced point nonsense mutation of the gene in all three patients, involving codon 184 in two and codon 167 in the third (identical to the proband case). Systematic investigations in the families of the two other patients remains to be completed. CONCLUSION: The diagnosis of HVL disease should be suggested in case of familial pheochromocytoma and/or bilateral localizations, but also in case of neuroendocrine tumors of the pancreas associated with another cardinal lesion of the disease. Early screening and treatment of this potentially fatal disease is essential.
Adolescent↗
The 60-kDa heat shock protein modulates allograft rejection.
Allograft rejection is a process of immune reactivity triggered by foreign transplantation antigens. We now demonstrate that the 60-kDa heat shock protein (hsp60), a molecule that is identical in the donor and the recipient, can regulate allograft immunity. In wild-type mice, hsp60 expression was greatly enhanced in allografts being rejected. By using MHC class II (Ealpha) promoter hsp60 transgenic mice either as donors of skin with enhanced expression of hsp60, or as allograft recipients with decreased hsp60 autoimmunity, we found that augmented expression of mouse hsp60 in the allograft accelerated its rejection, whereas reduced autoimmunity to mouse hsp60 in graft recipients delayed the process. Moreover, in nontransgenic mice, therapeutic administration of hsp60 or hsp60 peptides, known to modulate naturally occurring hsp60 autoimmunity, led to delayed allograft rejection. Thus, we demonstrate that hsp60 expression and hsp60 autoimmunity can influence and modify the immune response to foreign antigens. Hence, autoimmunity to self-hsp60 epitopes is not necessarily an aberration, but may serve physiologically and therapeutically to modulate foreign immunity.
Animals↗
Decrease in hepatic cytochrome P450 after interleukin-2 immunotherapy.
Interleukin-2 (IL-2) has been shown to decrease cytochrome P450 (CYP) mRNAs and proteins in cultured rat hepatocytes, and IL-2 administration decreases CYPs in rats. Although high doses of IL-2 are administered to cancer patients, the effect on human CYPs has not yet been determined. Patients with hepatic metastases from colon or rectum carcinomas were randomly allocated to various daily doses of human recombinant IL-2 (from 0 to 12.10(6) units/m(2)). IL-2 was infused from day 7 to day 3 before hepatectomy and the conservation of a non-tumorous liver fragment in liquid nitrogen. Hepatic CYPs and monooxygenase activities were not significantly decreased in 5 patients receiving daily doses of 3 or 6 10(6) IL-2 units/m2, compared to 7 patients who did not receive IL-2. In contrast, in 6 patients receiving daily doses of 9 or 12 x 10(6) IL-2 units/m2, the mean values for immunoreactive CYP1A2, CYP2C, CYP2E1, and CYP3A4 were 37, 45, 60 and 39%, respectively, of those in controls; total CYP was significantly decreased by 34%, methoxyresorufin O-demethylation by 62%, and erythromycin N-demethylation by 50%. These observations suggest that high doses of IL-2 may decrease total CYP and monooxygenase activities in man.
Adenocarcinoma↗
Reflections and proposals for the worldwide standardization of lymphadenectomy for gastric carcinoma.
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Clinical Trials as Topic↗
T cell proliferative responses of type 1 diabetes patients and healthy individuals to human hsp60 and its peptides.
T cell responses to peptide epitopes of the 60 kDa heat shock protein (hsp60) have been shown to play a role in the pathogenesis of type 1 insulin-dependent diabetes mellitus (IDDM) in mice. To test whether hsp60 autoimmunity might be involved in human type 1 diabetes, we studied T cell proliferative responses (stimulation index; SI) to intact human hsp60, to hsp60 peptides and to a recall antigen (tetanus toxoid) in 25 newly diagnosed type 1 diabetes patients, in 22 type 2 (non-insulin-dependent diabetes mellitus, NIDDM) patients, and in 25 healthy blood donors. There were no significant differences between the T cell responses of the three groups to tetanus toxoid. However, the responses to hsp60 of the type 1 diabetes group (median SI=5) were significantly greater (P<0. 01) than those of the type 2 group (median SI=1.67) and of the blood donors (median SI=1.7). Epitope mapping revealed significant responses to at least seven different peptides, with prevalent responses to the p277 peptide previously mapped in NOD mice and to peptide p32. Thus, newly diagnosed type 1 diabetes patients, similar to prediabetic and newly diabetic NOD mice, show heightened autoimmunity to hsp60 and hsp60 peptides.
Adolescent↗
Inhibition of diabetes in NOD mice by idiotypic induction of SLE.
The present study was undertaken to investigate whether active induction of systemic lupus erythematosus (SLE) in non-obese diabetic (NOD) mice could affect their development of insulin-dependent diabetes mellitus (IDDM). NOD mice were immunized with a human IgM mAb carrying the 16/6 idiotype (MIV-7) or with control human IgM. The mice were bled monthly and tested for SLE-associated autoantibodies in the serum and for the presence of leukopenia, thrombocytopenia, proteinuria and immunoglobulin deposits in the kidneys. The development of diabetes was determined by a blood glucose level exceeding 15 mM on two consecutive weekly determinations and by the presence of insulitis in the pancreas. The NOD mice immunized with MIV-7 developed high and persistent levels of autoantibodies, including anti-DNA, anti-histones and anti-cardiolipin, untreated mice and those immunized with normal human IgM did not produce these autoantibodies. The MIV-7-immunized mice also manifested an elevated erythrocyte sedimentation rate, leukopenia, thrombocytopenia and significant proteinuria, as well as deposits of Ig in their kidney glomeruli. Thus, NOD mice immunized with MIV-7 developed both autoantibodies and clinical features of SLE. The MIV-7-treated mice, however, showed a significantly lower incidence of IDDM (25%vs. 90%, P<0.003), accompanied by amelioration of the insulitis. The present study indicates that the induction of SLE by idiotypic immunization can protect NOD mice from developing IDDM, pointing to the importance of immune dysregulation in shift from one autoimmune disease to another.
Animals↗
Acceleration of autoimmune diabetes by cyclophosphamide is associated with an enhanced IFN-gamma secretion pathway.
Cyclophosphamide (CY), an alkylating cytostatic drug, is known for its ability to accelerate a number of experimental autoimmune diseases including spontaneous diabetes in NOD mice. The mechanism(s) by which CY renders autoreactive lymphocytes more pathogenic is largely unknown, but it has been postulated that the drug preferentially depletes regulatory (suppressor) T cells. It has been suggested that in cell-mediated autoimmune diseases, Th2-like lymphocytes secreting IL-4 and/or IL-10 provide protection, while Th1-like cells secreting IFN-gamma are pathogenic. In this study, we analysed the effects of CY on autoimmune diabetes and cytokines in two mouse models: the spontaneous diabetes of NOD mice and the diabetes induced in C57BL/KsJ mice by multiple injections of low dose streptozotocin (LD-STZ). In both models, CY induced severe lymphopenia and accelerated the progression to hyperglycemia. This was associated with changes in splenic cytokine patterns indicating a shift towards the IFN-gamma-secreting phenotype. We provide here evidence that IFN-gamma producers are relatively resistant to depletion by CY and that Th0 clones can be shifted towards Th1. However, direct exposure of T lymphocytes to CY may not be a necessary condition for exacerbation of diabetes; NOD.scid mice treated with CY before adoptive transfer of NOD splenocytes developed diabetes at a higher rate than did controls. Thus, the acceleration of diabetes by CY seems to be a complex event, which includes the relatively high resistance of IFN-gamma producers to the drug, their rapid reconstitution, and a Th1 shift of surviving T cell clones.
Animals↗
[Treatment of peritoneal carcinomatosis using complete excision and intraperitoneal chemohyperthermia. A phase I-II study defining the best technical procedures].
OBJECTIVES: The complete or quasi complete resection of peritoneal carcinomatosis (PC) followed with IPCH is potentially able to cure some patients with a disease confined to the peritoneum. The aim of this prospective phase I-II study was to elaborate an efficient IPCH procedure with a good thermal homogeneity and a good spatial diffusion, which should be reproductible (and so standardizable and exportable), and to appreciate its tolerance and its carcinologic impact. PATIENTS AND METHODS: Seven IPCH procedures were successively tested in 32 patients (for a total of 35 IPCH); each of these were tested in at least four patients before being modified for technical or tolerance reason. Five of them were followed with an immediate postoperative intraperitoneal chemotherapy (IPIC) lasting four days. Thermal homogeneity was measured with six thermal probes situated in different places inside the abdominal cavity. Spatial diffusion was studied in the last patients by adding methylene blue in the IPCH liquid. The precise extent of the PC was reported, for each intra-abdominal region, and scored with a peritoneal index (ranging from 1 to 39). The mean follow-up was 23.85 months for the series. RESULTS: Procedures with the closure of the abdomen were not efficient: thermal homogeneity was almost satisfactory when only the skin was closed, but these 'closed' procedures did not permit the treatment of all the risky surfaces. The peritoneal cavity 'expander' did not permit the treatment of the parietal wound, and an undetermined amount of the perfusion oozed out at its periphery. The open technique by tracking the skin upwards was the best one. Death occurred in three patients (9.4%), and complications occurred in 24 patients (75%) during the postoperative course. Intra-abdominal complications were significantly correlated (P = 0.02) with the peritoneal index (scoring the extent of the PC). The two year survival rate was 60%, and PC did not recur in 50% of the patients. CONCLUSION: An efficient and reproducible procedure for IPCH was defined: an open procedure with an upwards traction of the skin. The post-IPCH IPIC was abandoned because it did not treat all the risky peritoneal surfaces. Patients with an extended PC and with extraperitoneal localization did not seem to have benefited from this therapeutic approach. Progress is needed in the chemotherapeutical procedure and indications must be more finely defined.
Adolescent↗
[Total pelvic exenteration and rectal cancer. Apropos of 20 cases].
STUDY AIM: The report of a series of 20 patients with the aim of trying to specify the implications of pelvic exenteration for rectal cancer. PATIENTS AND METHODS: From 1986 to 1996, 20 total pelvic exenterations were performed for rectal adenocarcinoma. This retrospective study included locally extended carcinomas (n = 10), and recurrences (n = 10) after anterior resection (n = 7), and after abdominoperineal resection (n = 3). The subjects included 13 men and seven women with a mean age of 54 years (34-74 years). Complaints were major and serious: pain (n = 20), rectal syndrome (n = 17), recto-vesical fistula (n = 5) recto-vaginal fistula (n = 5), urinary infection (n = 13), and hematuria (n = 6). Preoperative radiotherapy was performed in 11 patients and preoperative radio chemotherapy in six. The surgical procedure included a total pelvic exenteration with perinectomy in 12 patients, and a total pelvic exenteration with preservation of levator ani and perineum in eight, associated in two cases with a partial resection of the sacrum, and in two other cases with partial hepatectomy for a single liver metastasis. Urinary diversion was a trans ileal ureterostomy in 17 patients and a direct double ureterostomy in three. RESULTS: The mean duration of surgery was 6 h. The mean preoperative blood loss was 1,200 L. Nine patients received blood transfusion. There was no postoperative mortality but in contrast, the morbidity rate was high with mainly urinary and digestive complications, pelvic sepsis and thromboembolic complications. After pathological examination, tumoral resections were classified R0 in 19 cases, and R1 in one. All tumors were T4 with tumoral invasion of the bladder (n = 15), prostate (n = 6), seminal vesicles (n = 4), ureter (n = 3), vagina (n = 7), urethra (n = 1), and sacrum (n = 1). Lymph node involvement was present in four patients. The 3 and 5 year actuarial survival rate was respectively 47 and 18%. Thirteen patients died of their cancer, nine from metastases, and four from local recurrence with a mean survival of 29 and 32 months respectively. Seven patients were alive at the time of this study, six without actual recurrence. CONCLUSIONS: In spite of its aggressive aspect, total pelvic exenteration seems justified in rectal carcinoma when extended to the urinary tract, when it causes major functional disorders, when there are no detectable metastases, and when the tumor has no posterior or lateral fixation. Local tumoral evolution can usually be controlled by pelvic exenteration but prolongation of survival is not demonstrated.
Adenocarcinoma↗
Treatment of poorly differentiated neuroendocrine tumours with etoposide and cisplatin.
The purpose of this study was to evaluate by a retrospective analysis of 53 patients the efficacy of chemotherapy combining etoposide and cisplatin in the treatment of neuroendocrine tumours. The regimen was a combination of etoposide 100 mg m(-2) day(-1) for 3 days and cisplatin 100 mg m(-2) on day 1, given by 2-h intravenous infusion, administered every 21 days. Twelve patients had a well-differentiated and 41 a poorly differentiated neuroendocrine tumour. Toxicity of treatment was assessed in 50 patients and efficacy in 52 patients. Among the 11 patients with a well-differentiated tumour evaluable for tumoural response, only one (9.4%) had a partial response for 8.5 months. Forty-one patients with a poorly differentiated tumour showed an objective response rate of 41.5% (four complete and 13 partial responses); the median duration of response was 9.2 months, the median overall survival 15 months and the median progression-free survival 8.9 months. Haematological grade 3-4 toxicity was observed in 60% of the cases with one treatment-related death, digestive grade 3-4 toxicity in 40% and grade 3 alopecia was constant. No severe renal, hearing and neurological toxicities were observed (grade 1 in 6%, 14%, 72% respectively and no grade >1). We confirm that poorly differentiated neuroendocrine tumours are chemosensitive to the etoposide plus cisplatin combination. However, the prognosis remains poor with a 2-year survival lower than 20% confirming that new therapeutic strategies have to be developed.
Adult↗
During liver regeneration following right portal embolization the growth rate of liver metastases is more rapid than that of the liver parenchyma.
BACKGROUND: The relative growth rates of human liver metastases are not known. The aim of this study was to determine in humans the growth rate of liver parenchyma during regeneration and the growth rate of liver metastases during the same process. METHODS: Among 556 patients hepatectomized for a malignant lesion, 48 underwent preoperative selective right portal vein embolization to induce hypertrophy of the left lobe. Five cases were selected because a liver metastasis was present inside the regenerating left lobe. The volumes of the liver metastasis and left lobe were measured with a three-dimensional technique on pre-embolization and postembolization computed tomography (CT) or CT arterial portography. The median interval between the two measurements was 34 (range 28-40) days. RESULTS: An increase occurred in the volume of the liver metastasis and the left lobe in the four patients with functionally intact liver parenchyma, but not in the patient with an impaired parenchyma. The volumetric increase of the normal liver varied from 59 to 127 per cent, compared with 60 to 970 per cent for the liver metastases. The ratio between the growth rate of the left lobe and the liver metastasis varied from 1.0 to 15.6. The growth rates of two metastases in the left lobe of a single patient were different. CONCLUSION: In functionally intact liver parenchyma, during hepatic regeneration or hypertrophy, the growth rate of metastases is more rapid that that of the liver parenchyma. However, a wide variation in growth rate is observed between patients and between metastases.
Aged↗