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C Bognel

Publications and source records attributed to C Bognel.

At least 37 records · Page 2Linked to original sources
PubMed1993

Pharmacokinetic and pharmacodynamic advantages of pirarubicin over adriamycin after intraarterial hepatic administration in the rabbit VX2 tumor model.

Intraarterial chemotherapy with Adriamycin (ADM) has shown limited advantages over i.v. administration, with no reduction in systemic toxicities and modest decrease in peripheral plasma levels. In an effort to improve the selectivity of i.a. anthracycline chemotherapy, we compared pirarubicin (4'-O-tetrahydropyranyladriamycin, THP) and ADM in the surgically implanted VX2 rabbit tumor model. Both drugs were administered at the same dose (0.5 mg/kg) either by the intraarterial hepatic route (i.a.h.) or by the i.v. route. Anthracycline plasma and tissue levels were determined by high-performance liquid chromatography with fluorescence detection. ADM peak plasma concentration and area under the curve were not significantly reduced after i.a.h. administration compared to the i.v. route; however, ADM tumor concentration was 1.9-fold higher following i.a.h. administration compared to the i.v. infusion. After THP administration by the i.a.h. route, systemic exposure (area under the curve) was markedly reduced (8-fold) compared to the same dose administered i.v. These findings correlated well with the very low concentration of the drug in heart tissue following i.a.h. infusion. After i.a.h. administration, tumor THP concentrations were 10.5 times higher compared to the i.v. route. The pharmacokinetic advantage of i.a.h. administration of THP also led to a better antitumoral effect, as shown by a significantly lower tumor growth rate [3 +/- 2% (SD)] in the i.a.h.-treated animals compared to the i.v.-treated groups (58 +/- 9%). Administration of ADM by the i.a.h. route was also inferior to i.a.h. THP. Taken together, our results suggest a clear-cut advantage of THP over ADM for i.a.h. locoregional chemotherapy, because of higher local tumor concentrations, greater antitumoral effect, and lower systemic exposure following the i.a.h. administration of THP. This anthracycline analogue could also be of therapeutic advantage in tumors partially resistant to anthracyclines that would become vulnerable to the high local concentrations achieved with i.a.h. administration. Based on these encouraging results, clinical trials using THP administered by the i.a.h. route were initiated.

Animals↗
PubMed1993

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↗
PubMed1993

Pharmacology and antitumour effects of intraportal pirarubicin on experimental liver metastases.

Early liver metastases have a predominant portal blood supply. Intraportal (i.port.) vein administration of cytotoxics could theoretically achieve enhanced drug concentrations in tumour cells and be effective as adjuvant therapy after resection of colorectal carcinoma. Pirarubicin (which has a higher hepatic extraction than doxorubicin) was investigated on liver metastases of the VX2 rabbit tumour, which were of less than 2 mm in diameter 7 days after cells injection into the portal vein. To evaluate antitumour activity, 24 rabbits were randomised into three groups 7 days after implantation: (a) control, (b) i.v. pirarubicin, (c) i.port. pirarubicin at doses of 2 mg kg-1 in both groups. Portal infusions led to no hematological or hepatic toxicity. Pharmacokinetic parameters showed a significantly reduced systemic exposure after i.port. administration. Fourteen days after treatment, livers and lungs were analysed. The mean number (+/- s.d.) of tumour foci was (a) 8.62 (+/- 5.4), (b) 4.62 (+/- 3.2), (c) 2.25 (+/- 1.4) (P < 0.05 a vs c). The mean tumour area was (a) 6.31 (+/- 6.1), (b) 1.31 (+/- 2.2), (c) 0.43 (+/- 0.4 cm2) (P < 0.05 a vs c) and the percentage (95% C.I.) of rabbits with lung metastasis was: (a) 87.5% (47-99%), (b) 75% (35-97%), (c) 12.5% (3-52%) (P < 0.02 b vs c). Intraportal pirarubicin seems to be well tolerated and more efficient than i.v. administration, particularly in preventing extrahepatic dissemination.

Animals↗
PubMed1993

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↗
PubMed1993

[Benign glandular inclusions in inguinal and abdominopelvic lymph nodes in gynecologic pathology].

From 4 cases recently seen at the Institut Gustave-Roussy, this report describes the pathological and evolutive features of benign glandular inclusions in inguinal, pelvic or abdominal lymph nodes. These lesions are defined by the presence of tubular formations in lymph nodes, lined by a single layer of epithelium which is cuboidal or columnar and resembled that of tubal epithelium with ciliated, secretory and intercalary cells. In most cases, benign glandular inclusions in lymph nodes still quiescent. In rare instances, they may proliferate and become papillary. The association of proliferating glandular inclusions in lymph nodes with borderline tumor of the ovary raises the problem of their primary or metastatic origin. However, their pathological features argues for a primary origin in lymph nodes. Thus, we think that a metastatic potential of borderline tumors of the ovary is not supported by any convincing argument.

Abdomen↗
PubMed1993

[Single and multifactorial prognostic study of 400 operated rectal adenocarcinomas].

From 1976 to 1988, 496 patients with rectal adenocarcinoma have been treated at Gustave-Roussy Institute. There were 258 men (52%) and 238 women (48) with a median age of 61 years. Sixty pts (12%) had local treatment (contact-therapy or electro-resection). Thirty six pts (8.25%) had a simple exploration with colostomy. Four hundred pts had a resection: 202 abdomino-perineal resection, 7 perineal resection, 167 anterior resection, and 24 Hartmann's technique. Post-operative mortality was 1% (4 pts). Among these 400 pts, 208 had no complementary treatment, 134 had pre +/- post-operative radiotherapy and 58 had post-operative radiotherapy. Sixty one pts had palliative resection. The actuarial survival of the 400 pts at 3, 5 and 10 years are respectively 65%, 51% and 37.5%. The number of lost to follow-up patients was 11 (2.5%) at 5 years and 24 (5.5%) at 10 years. A retrospective uni and multifactorial analysis of the clinical, biological and histopathological data of the 400 pts was done, 18 factors were studied. Our judgement criterion was 5 year survival. The uni-factorial analysis showed 7 variables which had great influence on survival: age > 60 (p = 0.001), signs of severe illness (p < 0.0001), curative or palliative criterion of the surgery (p = 0.0001), depth of invasion (p = 0.0001), lymph node invasion (p = 0.0001), neural invasion (p = 0.0001) and positive emboli (p = 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗
PubMed1992

Nucleolar organizer regions in ovarian tumors: discrimination between carcinoma and borderline tumor.

Nonhistone nucleoproteins associated with the nucleolar organizer region (NOR) can be visualized by a silver-staining technique on paraffin-embedded tissues. The number of black dots (Ag NORs) appearing on the nuclei are thought to reflect cell differentiation of certain tumors and can be used as an adjunct in predicting their evolution. We applied this method to determine if Ag NORs counts could be used as a diagnostic aid in borderline tumors of the ovary. Thirty-two cases of adenocarcinomas, 25 cases of borderline tumors, and 14 cases of adenomas were selected from Bouin-fixed archival material after histological examination. Both mean values of Ag NORs counts demonstrated a progressive increase from adenomas to borderline tumors and to carcinomas; the differences were statistically significant. Using discriminant analysis, all cases of benign and malignant tumors except one adenoma and one carcinoma were discriminated as belonging to an individualized group. No difference was found between borderline tumor with peritoneal implants and those without peritoneal implants. The results indicate that the Ag NORs counting procedure may be useful in distinguishing borderline tumors from carcinomas and adenomas. Ag NORs counts cannot, however, predict the clinical behavior of borderline tumors of the ovary.

Adenocarcinoma↗
PubMed1992

[Gastric metastases. Apropos of 17 cases].

Seventeen cases of gastric metastases are reported; some of them appeared after a long latency period. Two cancers prevail from an aetiological standpoint: melanoma (7 cases) and breast cancer (4 cases). Endoscopic appearance is often typical in melanoma, but suggests a primary carcinoma or radiation-induced lesions in breast cancer. Surgery is reserved to located lesions, but seems to have no incidence on prognosis. Overall mean survival is 11 months with a range of 3 months to 5 years.

Adult↗
PubMed1991

[Is the aggressive treatment of locoregional recurrences of colorectal cancers justified?].

Fifty-two local recurrences (LR) of colonic (n = 31) or rectal (n = 21) cancers, with synchronous metastases in 19 cases, were treated aggressively between 1981 and 1989. Treatment consisted of extended surgical resection combined with transcutaneous radiation therapy. Intravenous chemotherapy (5 fluorouracil and folinic acid) was delivered to the last 42 patients. The synchronous metastases were resected in all cases, except one. A sufficient high-dose radiation therapy (45 Gy after complete excision and 60 Gy after incomplete excision) was performed in 23 cases only. The majority (29 cases) of the patients underwent a second operation, and some 3, 4, or 5 operations. Global survival and survival without recurrence were 60 percent and 42 percent at 3 years. These good results were not stable and decreased progressively with time. The excision required usually surgery of large magnitude. Postoperative mortality was null but morbidity and functional disorders were important. After complete excision of the LR, radiation therapy doubled the rate of local control when it was greater than 45 Gy. The benefit of radiation therapy was doubtful after incomplete excision, even with high-dose irradiation. The role of systemic chemotherapy could not be analyzed in this study. Study of prognostic factors showed that resectable synchronous metastases and rectal or colonic location of primary tumors were not correlated with survival, Survival was correlated with the local control of LR (P = 0.012) and the presence of invaded neighbouring organs (P = 0.006) which reflected the tumor volume. In conclusion, it was difficult to conclude if aggressive treatment of LR should be mandatory or not.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Intra-arterial hepatic chemotherapy with pirarubicin. Preclinical and clinical studies.

Intra-arterial hepatic chemotherapy (IAHC) with adriamycin (ADM) has not increased its therapeutic index. For our preclinical studies, we selected pirarubicin (THP), an ADM derivative with faster cellular uptake. In rabbits with VX2 tumor in the liver we compared plasmatic and cellular pharmacokinetics of ADM and THP after i.v. and IAH therapy. For ADM, there were no differences in plasma and heart concentrations, with only a slight increase in tumoral levels after IAH compared to i.v. administration; on the other hand, with IAH THP, there was important reduction in systemic exposure with a major increase in tumoral drug distribution. In the phase I study, involving nine patients with implanted catheters, the starting dose of THP was 30 mg/m2 with a 10 mg/m2 intrapatient escalation every 3 weeks in the absence of toxicity. Pharmacokinetics were compared for i.v. and IAH administration in seven patients. The limiting toxicity was neutropenia and the maximal tolerated dose (MTD) ranged from 50 to 110 mg/m2. Moderate nausea-vomiting (grade 1-2) and alopecia (grade 1) occurred at the MTD. No arterial occlusion, gastroduodenal ulcer, hepatitis, or sclerosing cholangitis were seen. In the phase II study, in colorectal cancer patients (CRC) with metastasis confined to the liver, patients were enrolled until June 1990. THP (40 min infusion every 3 weeks) was initiated at 60 mg/m2 with 10 mg/m2 increment until grade 2 hematotoxicity. The median MTD was 85 mg/m2 (range of 60-120 mg/m2), and the median number of cycles was 7 (range of 2-11) with cumulated doses from 180 to 1,030 mg/m2. Grade 2-4 neutropenia was reached in 15 patients. Other toxicities included two arterial occlusions, one episode of gastritis, but no hepatic toxicity and no heart failure. Antitumor effect (in 18 patients) included 1 CR, 5 PR, 3 MR, 6 NC, and 3 PD. The median survival was 18+ months and 1-year survival was 73% +/- 12%. Seven patients had extrahepatic progression at this time. In conclusion, besides 5-FU or Fudr, THP is active in IAHC (probably in relation with high local extraction) on CRC liver metastases usually unresponsive to ADM. It can be given in an outpatient setting with minimal toxicity.

Animals↗
PubMed1990

[Primitive digestive localizations of malignant non-Hodgkin's lymphoma. Prognostic factors of locally advanced disease: stage II. Report of 67 cases].

Sixty-seven patients with non-Hodgkin's lymphoma of the digestive tract with locally advanced disease (stage II) were analyzed to determine the main factors influencing survival. There were 19 patients with stage II E1 and 48 with stage II E2 disease (Musshoff classification). According to the Kiel classification, 46 percent were low grade, 46 percent were high grade, and 8 percent were unclassified. The principal sites involved included the stomach: 11 cases, small intestine: 21 cases, colon: 12 cases, and mesentery: 11 cases. Lymphoma was unique in 45 cases (67 percent). Treatment consisted of laparotomy in 61 of 67 cases: partial resection was achieved in 21 cases, complete resection in 27 cases, and exploration only in 13 cases. Chemotherapy, according to histopathological subtypes, was employed in 90 percent of cases. Radiation therapy was applied in 25 patients (37 percent), essentially when there was residual disease after surgery (17 patients). Therapeutic indications were dependent on histological subtype, extension, and the therapy regimen in use at the time of treatment. Five patients were treated by surgery only, 2 by surgery and radiation therapy, 37 by surgery followed by chemotherapy, and 23 by all three treatment modalities. Overall survival was 62 percent at 5 years. Univariate analysis showed that 5-year survival rates were not influenced by sex, age, histopathological subtype (low grade: 69 percent; high grade: 59 percent; NS) or local extension (stage II E1: 76 percent vs stage II E2: 59 percent; NS). In contrast, complete surgical excision (p = 0.06) and radiation therapy in case of local residual disease (p = 0.02) seemed to improve survival. The main prognostic factor was the achievement of a complete therapeutic response (CR) (p = 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

[Anatomo-pathologic ovarian cancers].

Ovarian cancers constitute a group of tumours characterized by a variety of histological patterns. The classification used is that of the W.H.O. Common épithelial account for two-thirds of all ovarian cancers. In this group, tumours of borderline malignancy should be distinguished from adenocarcinomas. Since these lesions are associated with an unusually good prognosis, it is of major importance to rule out an infiltration of the ovarian stroma. Extra-ovarian spread of borderline tumours probably results from a multifocal process which is not associated with the poor prognosis of metastatic involvement. Tumours of the mesenchyma and sex cords are less frequent, as are germ cell tumours. For the latter, preoperative assays of serum markers can be of help in the diagnosis and management of the cases.

Adenocarcinoma↗
PubMed1989

Prognostic factors in primary gastrointestinal non-Hodgkin's lymphoma. A multivariate analysis, report of 106 cases, and review of the literature.

The authors have reviewed 106 cases of primary gastrointestinal non-Hodgkin's lymphoma (GI-NHL) treated at the Institut Gustave-Roussy (IGR), France, between 1975 and 1986. The occurrence was 55 in the stomach, 26 in the small intestine, ten ileocecal, seven in the large intestine, and eight patients had multiple involvement. Patients were clinically staged according to the Ann Arbor staging system using the modification of Musshoff for Stage IIE. All histologic material of the 106 patients were reviewed and graded according to the Working Formulation (WF) and the Kiel classifications. Most patients received combination chemotherapy as part or all of their primary treatment program (95 patients, 90%). Seventy five patients (71%) had a multimodality treatment. The overall 5-year survival rate was 60%. Sixteen variables were tested by univariate analyses for prognostic influence on survival. Of these, only clinical stage (P less than 0.001), the achievement of initial complete remission (CR) (P less than 0.001), erythrocyte sedimentation rate (ESR) (P = 0.01), mesenteric involvement (P = 0.03), and serosal infiltration (P = 0.05) were significant prognostic factors. Important variables were tested by a multivariate analysis using the Cox model taking into account different treatment modalities. Only three variables entered the regression analysis at a significant level: clinical stage (P = 0.02), surgical resection (P = 0.03), and histologic grade (Kiel) (P = 0.04). When the achievement of initial CR was introduced into the model, it was the most significant variable (P less than 0.001) whereas all other variables became nonsignificant except for the histologic grade (Kiel) (P = 0.004). Based on results of the multivariate analyses we propose two prognostic classifications of patients: one at the initial evaluation depending on clinical stage, surgical resectability, and histologic grade (Kiel); the other at the end of primary treatment depending on the achievement or not of CR and the histologic grade.

Adolescent↗
PubMed1989

[Neoadjuvant chemotherapy in locally advanced gastric adenocarcinoma. Preliminary results].

Gastric adenocarcinoma locally advanced or located at the cardia, or of large size or with local lymphadenopathies are of bad prognosis. To improve the surgical results we have tested the feasibility and tumoral efficacity of pre-operative (neoadjuvant) chemotherapy. Twenty patients have been included between 6/87 and 12/88. Median age was 63 years (36-74); all patients were in good general condition (OMS 0-1). The tumors were located at the cardia in 50%. The tumor median size was 10 cm (6-19), pathological lymph nodes were seem at CAT. Scan in 10/20. The neoadjuvant chemotherapy was continuous IV, 5 FU 1 g/m2/day for 5 days + CDDP 100 mg/m2, day 1. The cycles were repeated every 4 weeks. The median number of cycles prior surgery was 2 (1-4) and depended of tolerance and efficacy. We have observed (WHO criteria). 1 CR, 12 PR (Responsible rate: 65%). 6 MR or S. One patient was non evaluable because coronary insufficiency complicating the first cycle. The neoadjuvant chemotherapy toxicity was mainly hematological. The surgical procedure was curative in 15/20 patients; palliative 4 and non feasible for progression 1. Normal rate of post-operative complications was encountered: 2 subphrenic abscess, 1 pneumopathy, 1 stercoral peritonitis. At this date 3/20 patients died (17 patients are still alive, among them 14 are NED (the overall median survival is more than 10 months). This study demonstrated the feasibility and high response rate of neoadjuvant chemotherapy in patients with locally advanced gastric carcinomas. A randomized trial is warranted to demonstrate the survival benefit.

Adenocarcinoma↗