[Basic concepts and future prospects of oncologic surgery].
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Combined Modality Therapy↗
Biomedical subjects
D Elias
Publications and source records attributed to D Elias.
[Role of imaging in abdominopelvic follow-up after resection of colorectal cancer].
The imaging techniques used to follow-up patients submitted to surgery for colorectal cancers are presented as are their advantages and disadvantages. The sensitivity of ultrasonography (US) for postoperative surveillance of the liver varies considerably according to whether the absence or presence of metastases is sought (83%) or their exact number (53-82%). US is recommended by French clinicians as the standard follow-up examination whereas, American clinicians tend to discuss CT-Scan or MRI for the same purpose. Some authors advocate Doppler ultrasonography for the detection of liver metastases. Spiral CT-Scan offers better results than conventional CT and is now considered second in rank to US for follow-up studies. Its sensitivity exceeds 90% for metastases greater than 1 cm. IRM and arterial CT-scan are not applicable for follow-up but are sometimes indicated for difficult cases before hepatectomy. US is also an appropriate technique for postoperative exploration of the abdominal cavity. When the CEA level and the US examination are normal, this technique is sufficient. However, in dubious clinical or biological cases, US should be associated with a spiral CT-Scan. Most clinicians recommend a reference CT-Scan, two to four months after the resection and every 6 months for 2 years and then annually. The same follow-up strategy is advocated after abdominoperineal resection and for surveillance of the pelvis. The sensitivity of CT-Scan is between 69 and 88% but it is unable to differentiate recurrence from fibrosis. IRM, with a sensitivity of 90%, is the best method for overcoming with problems related to the differential diagnosis and particularly novel fast acquisition imaging and contrast agents. Ultrasonoendoscopy, repeated every 4 to 6 months after anterior resection, is also a useful examination for surveillance of the pelvis. PET-Scan has produced encouraging results for the detection of metastases and for the differential diagnosis between local recurrence and fibrosis. When available, this technique could become the "gold standard" for the surveillance of patients following surgery for colorectal cancers.
Abdominal Neoplasms↗
[Pseudo-continent perineal colostomy. Results and techniques].
OBJECTIVE: This prospective study was conducted to assess functional results obtained after pseudo-continent perineal colostomy using the Schmidt procedure. METHODS: Functional outcome was assessed in 40 patients who had undergone amputation of the rectum for cancer and pseudo-continent perineal colostomy reconstruction between 1989 and 1995 in our institution. The cancer pathology, operative procedure and post-operative care were noted. Morbidity, functional outcome and degree of patient satisfaction were recorded. Mean follow-up was 45 months (18-87) in 100% of the patients. RESULTS: There were no operative deaths. Twenty patients had post-operative complications and 2 patients required early conversion to definitive abdominal colostomy due to severe perineal complications. Function outcome showed normal continence in 4 patients, air incontinence in 23, occasional minimal leakage in 9 and incontinence requiring iliac colostomy in 2. Eighty-six percent of the patients were highly satisfied or satisfied with their continence capacity. DISCUSSION: Pseudo-continent perineal colostomy is a reliable technique which can be proposed as an alternative to left iliac colostomy after amputation of the rectum for cancer if a rigorous procedure is applied: careful patient selection, informed consent, rigorous surgical procedure, daily life-long irrigation of the colon.
Adenocarcinoma↗
[Treatment of peritoneal carcinosis of colorectal origin].
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Antimetabolites, Antineoplastic↗
[Hepatic metastases of colorectal cancers: intra-arterial chemotherapy. Value and indications].
Intraarterial hepatic chemotherapy (IAHC) increases the tumoral exposure of the liver metastases to cytotoxic agents. IAHC may be used in case of non resectable and isolated liver metastases from colorectal origin. It gives a tumor response rate of about 50%. Seven phase III trials and a recent metaanalysis testing IAHC using FUDR demonstrated its superiority over systemic chemotherapy using FUDR or bolus 5FU in terms of response rate and an increase in survival compared to symptomatic treatment. IAHC drawbacks are the biliary toxicity observed with some protocols, the development of extrahepatic metastasis and its cost. The ongoing protocols aim to improve the IAHC efficacy and tolerance and are frequently associated to systemic chemotherapy. The discovery of new active products in colorectal cancer and the optimisations of combinations of 5FU and leucovorin in terms of efficacy stimulate research aimed at developing more active combinations of IAHC and active systemic chemotherapy. The best IAHC indications are presently unresectable hepatic metastases from colorectal cancer without extra-hépatic metastases, with less than 50% liver involvement, with a CEA level under 100 ng/ml.
Antineoplastic Agents↗
[Value of endorectal ultrasonography in the treatment of rectal tumors].
OBJECTIVES: To determine the diagnostic accuracy of endosonography and to appreciate its influence on the therapeutic strategy. METHODS: Sixty-two patients referred to the gastroenterology unit between April 1990 and February 1995 for a rectal tumor. Thirty-two patients did not receive any preoperative treatment (group A) and 30 were treated by radiotherapy or chemoradiotherapy before surgery (group B). Transrectal ultrasonography was performed with a Bruel and Kjaer device. RESULTS: Diagnostic accuracy for parietal infiltration was 84% for the entire series, 94% for group A and 73% for group B. Diagnostic accuracy of lymph node invasion was 71% for the entire series, 81% and 60% for groups A and B, respectively. It is highly probable that a histopathologic down-staging due to preoperative treatment explained the results in the group B. Using a pragmatic approach which combined the results for parietal infiltration and for lymph node invasion, transrectal ultrasonography would have correctly selected 20 among the 25 patients who could have been treated by local excision. The use of this same pragmatic approach in patients with high risk of local recurrence enabled correct selection of 26 among the 32 exposed patients. CONCLUSION: We conclude that transrectal ultrasonography: 1. is a reliable technique for the pretherapeutic staging of rectal cancer, especially for the assessment of parietal infiltration. Progress is needed for the diagnosis of lymph node invasion; 2. selects well the patients who can be treated by local excision; 3. is a reliable technique for the selection of patients who need preoperative treatment.
Evaluation Studies as Topic↗
[Blood transfusions in cancer patients].
In this review, we develop four topics on the relationship between blood transfusion and cancer. First, the rationale for not allowing blood donations from patients with infiltrating tumors is presented. Second, the different possibilities for autotransfusions in cancer patients are discussed. Predeposited autotransfusions are rarely possible in these patients, in addition to the high cost. The usefulness of another method, intraoperative autologous transfusion with blood saved from the surgical field, is not well established. Our third topic concerns the effect of transfusion on cancer induction. In some cases, the risk of cancer is higher after allogenic transfusion resulting from a mechanism involving alterations of the immune function. Finally, the relationship between transfusion and cancer recurrence is controversial. In spite of numerous studies attempting to elucidate this relationship, no final conclusion can be drawn at the present time. What is sure, is that patients requiring blood transfusion have a higher risk of recurrence than patients who do not need transfusion.
Blood Donors↗
A role of Hsp60 in autoimmune diabetes: analysis in a transgenic model.
A pathogenic role for self-reactive cells against the stress protein Hsp60 has been proposed as one of the events leading to autoimmune destruction of pancreatic beta cells in the diabetes of nonobese diabetic (NOD) mice. To examine this hypothesis, we generated transgenic NOD mice carrying a murine Hsp60 transgene driven by the H-2E alpha class II promoter. This would be expected to direct expression of the transgene to antigen-presenting cells including those in the thymus and so induce immunological tolerance by deletion. Detailed analysis of Hsp60 expression revealed that the endogenous gene is itself expressed strongly in thymic medullary epithelium (and weakly in cortex) yet fails to induce tolerance. Transgenic mice with retargeted Hsp60 showed overexpression of the gene in thymic cortical epithelium and in bone marrow-derived cells. Analysis of spontaneous T-cell responses to a panel of self and heterologous Hsp60 antigens showed that tolerance to the protein had not been induced, although responses to an immunodominant 437-460 epitope implicated in disease were suppressed, probably indicating an epitope shift. This correlated with changes in disease susceptibility: insulitis in transgenic mice was substantially reduced so that pathology rarely progressed beyond periislet infiltration. This was reflected in a substantial reduction in hyperglycemia and disease. These data indicate that T cells specific for some epitopes of murine Hsp60 are likely to be involved in the islet-cell destruction that occurs in NOD mice.
Animals↗
Prospective study of microscopic lymph node involvement of the hepatic pedicle during curative hepatectomy for colorectal metastases.
Extensive lymph node dissection of the hepatic pedicle was undertaken in 100 consecutive patients undergoing curative hepatectomy for colorectal liver metastases in whom lymph node involvement of the hepatic pedicle was not macroscopically detectable. Microscopic lymph node involvement was found in 14 patients, in very different lymph node sites, and was related only to the number of metastases, extent of liver involvement and carcinoembryonic antigen level (all P < 0.05).
Adult↗
Liver abscess formation after local treatment of liver tumors.
Our goal was to determine a subset of patients at high risk of developing liver abscesses after local treatment of liver tumors (LTLT) and establish guidelines for the conduct of LTLT in the safest conditions in such patients. Five hundred sixty-one LTLT, 489 transhepatic arterial chemoembolizations (TAC, 10 hepatic embolizations, and 62 percutaneous intratumor injections (PIT), were retrospectively reviewed for liver parenchyma necrosis and abscess formation. Four patients developed abscesses, three after TAC and one after PIT. Despite broad-spectrum antibiotherapy, percutaneous drainage, and surgery, two patients died. A left hepatectomy was required in the other two patients for cure. All four patients had a carcinoid or a neuroendocrine pancreatic tumor. Three out of four patients had bilioenteric anastomoses, and the fourth had recently undergone cholecystectomy and papillotomy. A Lipiodol/doxorubicin mixture without any particulate embolization was injected in the three patients who developed abscesses after TAC. LTLT in patients with bilio enteric anastomosis or papillotomy and/or neuroendocrine or carcinoid tumor should be performed with strict precautions during the procedure and for peri-procedural care.
Antineoplastic Agents↗
NOD mouse diabetes: the ubiquitous mouse hsp60 is a beta-cell target antigen of autoimmune T cells.
In the NOD mouse, the onset of beta-cell destruction is associated with spontaneous development of T-lymphocytes reactive to members of the 60 kDa heat shock protein (hsp60) family, including the Mycobacterial (MT) and the human (H) hsp60 molecules. Diabetes in the NOD mouse is a spontaneous tissue-specific autoimmune disease occurring without prior immunization. Therefore, it has been suggested that the anti-hsp60 T cells involved in the autoimmune diabetes of NOD mice might reflect molecular mimicry between MT-hsp60 and a beta-cell tissue specific molecule sharing similar T cell epitopes, the p277 peptide of hsp60 in particular. We cloned and expressed the mouse hsp60 cDNA from a beta-cell tumour. This mouse beta-cell hsp60 cDNA was found to be identical in sequence to the hsp60 of mouse fibroblasts. We further report that NOD spleen cells and an NOD diabetogenic T cell clone C9 responded to the recombinant mouse hsp60 and to its peptide M-p277 to the same extent as to H-hsp60 and H-p277. Splenocytes of mice of other strains did not respond to p277. Moreover, treatment of 3 month old NOD mice with the non-modified self M-p277 peptide was as efficient as H-p277, from which it differs in one amino acid, in halting progression of the disease. Thus, anti-H-p277 T cells modulating diabetes in the NOD mouse are autoreactive, and are targeted at the mouse beta-cell hsp60, which is not tissue specific. These findings raise the question of how a non-tissue specific molecule may be a target of a tissue-specific autoimmune disease.
Amino Acid Sequence↗
Preoperative portal vein embolization for extension of hepatectomy indications.
To render hepatectomy feasible in patients with an initially deficient volume of the future remnant liver (FRL), we redistributed portal blood flow rich in hepatotrophic substances toward the FRL. Redistribution was achieved with preoperative portal vein embolization (POPE) feeding the future resected liver. POPE was performed in 31 patients, under fluoroscopic guidance, via a percutaneous access. POPE was well tolerated and surgery was practicable in 24 patients without severe postoperative liver failure. Seven operations were cancelled, but only one due to insufficient hypertrophy of the FRL. FRL volume values were 90 to 560 mL (mean 260 mL) before POPE and 160-783 mL (mean 443 mL) after POPE, which represents a median increase of 79% +/- 50%. Hypertrophy of the FRL was 90% +/- 52% after 30 days with cyanoacrylate, 53% +/- 6% after 43 days with Gelfoam, and 44% +/- 30% after 35 days with coils. Slight shrinkage was obtained in the volume of the embolized liver, for which resection was planned. Overall survival was 2-62 months (mean 26 months), disease-free survival was 0-60 months (mean 19 months), and 7 patients are disease-free and alive 14 to 60 months (mean 43 months) after surgery. Although exclusively applicable in a limited subset of patients, POPE widens the possibilities of curative hepatectomies, because it induces sound hypertrophy of unembolized liver segments. Cyanoacrylate seems to ensure better and faster hypertrophy.
Adolescent↗
The hsp60 peptide p277 arrests the autoimmune diabetes induced by the toxin streptozotocin.
The development of autoimmune diabetes in the NOD strain of mice (H-2g7) is marked by the presence of T-cells reactive to the p277 peptide of the 6O-kDa heat shock protein (hsp60). We have found that the p277 peptide can be used as a therapeutic vaccine to arrest NOD diabetes. Recently, we found that T-cell autoimmunity to p277 also develops spontaneously in C57BL/KsJ mice (H-2d) during the induction of autoimmune diabetes by a very low dose of the beta-cell toxin streptozotocin (STZ). We now report the inhibition of STZ toxin-induced autoimmune diabetes by p277 peptide therapy. Administration of two doses each of 100 micrograms of peptide p277 in mineral oil given 1 week after toxin induction and 85 days later was most effective. The effect of p277 on STZ toxin-induced diabetes was marked by a shift in p277 autoimmunity from a T-cell proliferative response to the production of anti-p277 antibodies. The anti-p277 antibodies were predominantly of the IgG1 and IgG2b isotypes, known to be regulated by Th2 type cytokines; IgG2a antibody, known to be dependent on interferon (IFN)-gamma, was induced to a much lesser degree. Peptide p277 therapy was specific: treatment of the mice with an immunogenic peptide from the sequence of another antigen, GADp34, failed to prevent the development of diabetes. The GADp34 peptide induced lower titers of specific antibodies, and the antibodies were predominantly of the IgG2a class. Thus, p277 peptide therapy, marked by the induction of Th2-type antibodies, can be effective in toxin-induced autoimmune diabetes.
Amino Acid Sequence↗
[Tumor implantation in cicatrization sites following surgery for digestive cancers].
The natural history of surgically treated intraabdominal malignancy is such that a large proportion of patients present tumor recurrence at wound sites. Numerous factors operating within the wound environment are important determinants in tumor cells arrest or growth at these sites. This article describes the interactions between the traumatized tissues and tumor cells, and attempts to understand the important factors that may have an impact on implantation of cancer cells in wound sites. Modifications of these biologic factors may represent new perspectives for preventing tumor recurrence in intraabdominal wound sites.
Animals↗
[Management of disclosed hepatic metastases].
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Digestive System Neoplasms↗
[Major hepatectomy after intra-arterial chemotherapy for initially unresectable liver tumors. Frequency, technical problems, results and indications].
BACKGROUND: Major hepatectomy after prolonged intra-arterial hepatic chemotherapy (IAHC) is extremely rare, because IAHC usually fails to reduce the tumor volume sufficiently or obtain a long duration of response, or both, and because it impairs hepatic function. The present report was done to study the frequency, feasibility and the results of hepatectomy following IAHC. STUDY DESIGN: This retrospective study consisted of 14 patients treated with at least six courses of IAHC (mean of 17.6, median of 13, range of six to 48 courses) for hepatic tumors: colorectal metastases (n = 9), apudoma metastases (n = 4), and hepatoblastoma (n = 1). Systemic chemotherapy was associated in eight cases during (n = 5), or after (n = 3) IAHC. Initially, multiple hepatic tumors were unresectable in ten cases. They eventually became resecable, but were associated with extensive extrahepatic sites of involvement in four cases. All patients underwent curative major hepatectomy after a careful and specific morphologic and functional hepatic assessment. Right portal vein embolization was performed preoperatively upon three patients, resulting in 38, 44 and 77 percent hypertrophy of the left lobe before hepatectomy. Hepatectomy was also performed upon three patients with hepatic arterial thrombosis induced by IAHC, after a careful workup of the neoarteriovascularization of the liver. RESULTS: These 14 cases only represented 5.8 percent of the 239 patients in whom a catheter was inserted for IAHC, and 4.2 percent of the 335 patients who had hepatectomy for carcinoma. Postoperatively, there was no mortality and no clinical hepatic insufficiency. However, ten complications occurred in eight patients (three of them resulted in reoperation). Histologic examination revealed substantial modifications of the hepatic parenchyma because of IAHC. Results concerning survival were very encouraging: five of the nine patients with metastases of the colon and rectum are free of disease, with a mean follow-up period of 36 months after the beginning of IAHC. CONCLUSIONS: The decision to perform a major hepatectomy after prolonged IAHC is difficult and must be based on an output morphologic assessment with computed tomographic portography and a careful evaluation of functional liver impairment because of IAHC (the therapeutic strategy proposed by Makuuchi for hepatectomy in patients with cirrhosis, based on indocyanine green clearance and volume to resect, is very useful for this purpose). Hepatectomy is technically difficult to perform following IAHC because of a flabby parenchyma and unusually high pressure in the small central hepatic veins. This draw-back is circumvented by using techniques: such as preoperative hypertrophy of the future remaining liver, a transparenchymatous approach of vasculobiliary structures, and intermittent clamping of the hepatic pedicle or vascular isolation of the liver. Postoperative complications occurred more frequently than after major, hepatectomy in other clinical settings (p < 0.05). However, as this therapeutic approach greatly increases survival, it should not be neglected by clinicians, although indications for its use are very rare.
Adult↗
[Antineoplastic therapy and perioperative period in oncologic surgery].
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Adjuvants, Immunologic↗
Intermittent vascular exclusion of the liver (without vena cava clamping) during major hepatectomy.
Intermittent vascular exclusion of the liver (IVEL) combines clamping of the hepatic pedicle with clamping of the main hepatic veins without interruption of caval flow. In this retrospective study, eight cases of total IVEL and eight of partial IVEL were analysed (involving only the middle and left hepatic veins) during major hepatectomy for malignant tumours. Liver parenchyma was pathological in nine cases. IVEL was feasible in 16 of the 18 attempts and was efficient in reducing bleeding during hepatectomy in 15 cases. Mean duration of IVEL was 60.2 (range 37-140) min, mean blood loss was 1230 (range 300-2800) ml and there were no postoperative complications related to the procedure. The major advantages of this technique of liver vascular exclusion (good tolerance and possibility of long duration) merit its inclusion in the list of different clamping techniques available for use during hepatectomy.
Adult↗