Biomedical subjects
Publications and source records attributed to M Ducreux.
Explore the source record for details and available documents.
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.
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.
PURPOSE: To provide evidence for the therapeutic efficacy of oxaliplatin (Eloxatin) when given as a 2-6-hour i.v. infusion, alone or in combination with 5-fluorouracil/folinic acid (5-FU +/- FA) in patients with advanced colorectal carcinoma (ACRC) who have failed 5-FU-based therapy. To confirm the safety of the drug and its combination in an extended-access context. PATIENTS AND METHODS: Prescribing physicians were supplied oxaliplatin on a nominative compassionate-use basis, after obtaining informed consent. Europe-wide, 206 ACRC patients in 44 centers received 1168 cycles of chemotherapy with oxaliplatin (80-100 mg/m2 q 2 weeks or 100-135 mg/m2 q 3 weeks) delivered as a short (2-6 hours) i.v. infusion, 177 of them (1026 cycles) receiving oxaliplatin + 5-FU +/- FA. RESULTS: Oxaliplatin added to the 5-FU +/- FA regimens of 111 verified 5-FU-refractory patients (imaging and/or clinical proof of progression under prior 5-FU-based regimen), elicited objective responses in 25 of 98 evaluable patients, (ORR: 25.5%, 95% confidence interval (95% CI: 17-35). The median time to progression was 4.1 months (95% CI: 3.3-5.0) and the median overall survival was 9.6 months (95% CI: 8.2-10.9). Differences in the toxicity profile of the oxaliplatin + 5-FU +/- FA combination appear related to administration modality, dose and schedule of the 5-FU-based regimen. CONCLUSIONS: The addition of oxaliplatin (2-6-hour i.v. infusion) to 5-FU +/- FA regimens is active in ACRC patients with clinical resistance to fluoropyrimidines. The therapeutic index of oxaliplatin + 5-FU +/- FA combinations administered as salvage therapy compares favorably with those reported in recent phase II-III trials involving other new agents or combinations active in 5-FU-refractory ACRC patients.
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.
PURPOSE: To evaluate the efficacy and safety of intraarterial hepatic iodine 131 iodized oil for treatment of hepatocellular carcinoma in patients with impeded portal venous flow. MATERIALS AND METHODS: Twenty-four patients (mean age, 61 years) with hepatocellular carcinoma underwent 38 courses of 131I iodized oil (one to three per patient), with a mean dose of 2,146 MBq injected into the proper hepatic artery. Hepatocellular carcinoma manifested as single nodules (n = 8; mean, 7.75 cm), multiple nodules (n = 13; mean, 5.46 cm), or a mass (n = 3) occupying more than two hepatic segments. Portal venous thrombosis was complete (n = 10), right (n = 9), left (n = 2), or multisegmental (n = 1). Two patients had hepatofugal portal flow. RESULTS: Among the 23 patients with evaluable results, response to treatment was partial in three, and disease was stable in 12 and progressive in eight. Estimated actuarial survival rates were 70%, 33%, 12%, and 6% at 3, 6, 9, and 12 months, respectively, with two patients alive at 9 and 11 months. The median survival time was 147 days. Adverse events were the early death of one patient owing to hepatic failure and transient symptomatic hepatic failure after 12 courses in nine patients. CONCLUSION: In this preliminary experience, intraarterial hepatic 131I iodized oil did not demonstrate high efficacy in the treatment of hepatocellular carcinoma in patients with portal venous thrombosis, as side effects were not rare.
PURPOSE: To determine the maximum-tolerated dose (MTD) and recommended dose of irinotecan (CPT-11) in combination with fluorouracil (5-FU) and leucovorin (LV), using a biweekly LV5FU2 regimen and increasing doses of CPT-11, and to assess the efficacy of this combination in pretreated patients with colorectal cancer (CRC). PATIENTS AND METHODS: All patients had metastatic CRC and a World Health Organization performance status of 0 or 1. CPT-11 was administered over a 90-minute infusion every 2 weeks at a range of dose levels (100, 120, 150, 180, 200, 220, and 260 mg/m(2)). LV5FU2 was started 1 hour after the end of the biweekly CPT-11 infusion and was also administered on day 2. RESULTS: Fifty-five patients were entered onto this trial; 549 cycles were administered. The MTD was not reached at 260 mg/m(2), and a dose level of 300 mg/m(2) was added. The MTD as defined in the protocol was not reached at this dose level either, but all patients had cycles delayed and/or required a dose reduction. This dose was deemed to be the MTD. To take into account both the toxicity of and compliance with the biweekly schedule, the recommended CPT-11 dose was established at 180 to 200 mg/m(2). Antitumor activity was observed at almost all dose levels, with an objective response rate of 22%. Median time to progression was 6.3 months and overall survival was 15 months. CONCLUSION: The biweekly CPT-11/LV5FU2 combination is feasible and safe, without overlapping toxicity. CPT-11 at 180 to 200 mg/m(2) in combination with LV5FU2 has been selected as the recommended dose for further studies.
Screening was performed in 130 consecutive patients with apparently sporadic neuroendocrine tumors (NET) to assess the prevalence of multiple endocrine neoplasia type 1 (MEN1) and hormonal production. Screening for MEN1 included measurement of serum calcium and PTH [PTH-(1-84)], gastrin, PRL, and insulin-like growth factor type I (IGF-I) levels. MEN1 genetic testing was performed in patients with two components of the MEN1 syndrome. Screening for hormonal production included measurement of serum neuron-specific enolase (NSE), calcitonin (CT), glycoprotein alpha-subunit (GP alpha), hCG beta-subunit (free hCG beta), and somatostatin levels. Twenty-four-hour urinary free cortisol (UFC) and 5-hydroxyindolacetic acid (5-HIAA) determinations were also performed. Four patients had hyperparathyroidism, none of whom had pituitary or familial disease. Hyperprolactinemia was compatible with a pituitary disease in one patient. No acromegalic feature or any increase in IGF-I was found. Hypergastrinemia, compatible with an associated pancreatic NET, was found in one patient. Genetic screening of the MEN1 gene was performed in five of the six patients with two components of the MEN1 syndrome. A nonsense mutation (Arg108stop) was identified in the tumor of one patient. Elevated NSE, 5-HIAA, CT, GP alpha, free hCG beta, SMS, and nonsuppressible UFC were found in 47%, 46%, 14%, 19%, 12%, 3%, and 6% of NET patients, respectively. Production of CT, GP alpha, and free hCG beta was highly related to the primary site: all but two of these secretions originated in foregut NET. 5-HIAA secretion was found in 27% of foregut-derived and 85% of midgut-derived NET. In conclusion, MEN1 is a rare event in patients presenting with apparently sporadic NET. It occurred mainly in foregut NET and should be screened for by serum calcium and PTH-(1-84) measurements. Routine hormonal measurements should depend on the primary site. NSE, 5-HIAA, CT, and alphaGP should be routinely measured in foregut-derived NET; only serum NSE and 5-HIAA measurements are recommended in midgut-derived NET.
Neuroendocrine tumors (NET) of the thyroid gland are rare. Apart from medullary thyroid carcinoma (MTC), metastases of gastroenteropancreatic (GEP) NET may also occur. Features of six patients (five men, one female: age range, 39-67 years) with thyroid metastases from a GEP-NET are described. Thyroid metastases were bilateral in all patients and were associated with enlarged neck lymph nodes in five. In four cases, the thyroid tumor was either the first sign of the disease (n = 2) or was an isolated site of recurrence (n = 2). The tumors were well (n = 3) or poorly differentiated (n = 3). Five tumors for which the primary site could be determined corresponded to foregut-derived tumors (3 lungs, 1 thymus and 1 pancreatic NET). One tumor demonstrated calcitonin (CT) production as shown by immunohistochemistry and elevated plasma CT levels. However, the disease history and the clinical features strongly favored a metastasizing GEP-NET. No tumoral RET proto-oncogene mutation was found in this patient. The differential diagnosis between metastatic GEP-NET and MTC is crucial because prognosis, work-up, and treatment differ greatly.
OBJECTIVE: Amine precursor uptake and decarboxylation is a classical feature of gastroenteropancreatic (GEP) neuroendocrine tumors (NET). Production of catecholamines was studied in GEP NET and non-NET patients. DESIGN: A cross-sectional study was undertaken. METHODS: We studied catecholamine and metabolite secretion in 115 consecutive GEP NET patients and in 20 patients with non-NET. After specific extraction, vanilmandelic acid, homovanilic acid, catecholamines (norepinephrine, epinephrine, dopamine) and methoxylated derivates (metanephrine, normetanephrine, methoxytyramine) in urinary extracts were analyzed by high performance liquid chromatography. Results were indexed to the 24-h urinary creatinine levels. RESULTS: Among the 115 patients with NET, 9 (8%) had an increase of at least one urinary catecholamine or metabolite; in 7 out of the 9 the increase was slight being less than twice the upper value of the normal range. Elevated urinary dopamine (3 patients), methoxytyramine (6 patients), norepinephrine (2 patients) and normetanephrine (2 patients) were found. No increased urinary excretion of epinephrine nor metanephrine was observed. An adrenal mass existed in one of these nine patients but metaiodobenzylguanidine scintigraphy was negative as was immunohistochemistry for epithelial markers. None of the 20 patients with non-NET demonstrated an increased excretion of catecholamine or metabolites. No relationships were found between catecholamine and metabolite excretions and patients' tumor and treatment characteristics. CONCLUSION: Production of catecholamines and metabolites is a rare event in GEP NET patients. Histological results, including positive immunohistochemistry for epithelial markers may help to diagnose GEP NET.
131Iodine concentration has been described in several extra-thyroidal tissues. Recent evidence has shown that iodine uptake is achieved by the recently cloned human Na(+)/I(-) symporter (hNIS) gene. However, conflicting results were observed in the expression of hNIS transcripts in extra-thyroidal tissues. In order to document further the distribution of hNIS, we investigated its expression using an immunohistochemical method, based on a polyclonal antibody raised against a synthetic peptide. Various extra-thyroidal tissues were examined, particularly from the digestive tract. Our results confirm that the salivary glands and the stomach express hNIS protein significantly. In contrast, hNIS was undetectable in the colon but the rectal mucosa, which has never been examined, exhibited positive immunohistochemical staining. Other digestive tissues, including the oesophagus, small intestine and appendix, were negative. Weak staining was observed in the mammary gland, indicating that hNIS is expressed in this tissue. The pancreas, skin, ovaries, spleen and kidney showed no positive immunostaining.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Anal cancers (AC) represent rare gastrointestinal tumors and there are only a few studies dealing with the treatment of AC at the metastatic stage. We report here the results of one chemotherapy regimen based on the experience of the Gustave-Roussy Institute. Between 1985 and 1996, 19 patients: 3 males, 16 females, have been treated with a combination of 5-fluorouracil (5FU) and cisplatinum (CDDP) (FUP regimen). Their median age was 58, their performance status (WHO grade: G) was G0-1 in 68% and G2 in 32% of the cases. Metastasis were synchronous in 6 cases and metachronous in 13 cases. Metastatic sites were the liver (10 cases), the lymph nodes 11 cases (paraaortic 5, iliac 4 and inguinal 2) and pulmonary in 3 cases; in 9 cases the lymph nodes metastasis were isolated, in 7 cases the liver metastasis were isolated. One patient received FUP as an adjuvant treatment has been only considered for toxicity and survival. The FUP regimen combined an IV 5FU continuous infusion (1 g/m2/d (5 days) and a short infusion of CDDP (100 mg/m2) on day 2, every 4 weeks: 10 patients received further local treatment. According to WHO criteria, 18 patients were evaluable for the efficacy and 19 for the tolerance. The median number of cycles was 4. The response rate was 66% (standard error : 22%) with 1 complete response and 11 partial response; there were also 4 stabilisations and 2 progressions. Toxicity rate was neutropenia grade (G) 3-4 in 13% of the patients without febrile neutropenia, G3 nausea in 30%, no G2 or 3 mucositis or diarrhoea, and 2 patients experienced a nephrotoxicity G1-2. The actuarial survival was 62.2% at 1 year and 32.2% at 5 years and the median survival was 34.5 months. Three patients are still alive at 4, 5 and 7 years and benefited from additional local treatment (the patient treated with adjuvant chemotherapy after hepatic resection and 2 patients treated after response to the FUP regimen, by surgery or radiotherapy). The FUP combination gave a high response rate with an acceptable toxicity in patients with metastatic anal cancer. Combined with local treatment it does allow prolonged survivals for some patients.
The efficacy of chemotherapy on digestive neuro-endocrine tumours is not yet fully established and depends on the tumour type and on the differentiation of the neuro-endocrine tumours. Reports have indirectly suggested the superior activity of chemotherapy for pancreatic neuro-endocrine tumours than for metastatic carcinoid tumours (response rates around 60% vs 20%). Neuro-endocrine tumour differentiation is also a major factor and a higher chemotherapy efficacy (tumour responses: 69%) has been suggested in undifferentiated or poorly differentiated neuro-endocrine tumours which respond to chemotherapy, a little like small cell lung carcinomas. The efficacy of interferons has also been reported in phase II trials only, with symptomatic and biological responses in about 50% of the cases and tumour responses in 10 to 15%; some studies have suggested an interesting tumour growth control with prolonged survival but this efficacy has still to be investigated to clearly establish the best indications. The role of chemotherapy has to be discussed with surgeons and, in slowly progressing tumours, after the use of somatostatin analogues.
AIM: To evaluate the efficiency of percutaneous radiofrequency ablation in the treatment of liver metastases. METHODS: Eighteen patients with 31 liver metastases, mainly from colorectal cancer, 10 - 35 mm in diameter (m = 23), underwent 26 courses of percutaneous radiofrequency ablation. Fifteen patients had previously undergone hepatectomy, and 3 patients had contra-indications to surgery. Imaging guidance was ultrasound in 21 patients, CT in 4 (tumors not seen with ultrasound), and both in 1. A generator working at 450 KHz with a maximum output power of 150 W was used to treat each lesion for 18 - 20 min. Treatment was monitored with real time ultrasound. RESULTS: Among the 12 patients followed more than 3 months, only one of the 24 treated lesions recurred after a mean follow up of 259 ¿ 109 days. Liver disease was controlled in 8 of the 12 patients after 90 - 509 days (m = 306). Among these 8 patients, 3 were tumor free after 559, 378 and 90 days, respectively; 2 died tumor free of non-tumoral disease (pulmonary embolism, digestive bleeding); 3 developed lung metastases treated with chemotherapy (n = 2) or surgery (n = 1). Three of the 12 patients had widespread hepatic tumor occurrence, and one patient died of these metastases. Six patients experienced mild skin burns, but no major complication was observed. CONCLUSION: Radiofrequency ablation of hepatic metastases appears safe and promising in this preliminary experience. Further investigation is needed.
BACKGROUND AND OBJECTIVES: It is now established that liver resection is beneficial for metastases from colorectal cancer. Nevertheless, a surgical margin estimated at less than 10 mm at preoperative imaging is considered an absolute contraindication to surgery by some, and a relative contraindication by others. The true impact of the width of the margin on the prognosis is unclear. METHODS: From 1984 to 1996, 196 patients underwent curative hepatectomy for liver metastases and were studied prospectively. Surgery was to be curative (or a complete R0 resection) and mortality was to be avoided. Of these 196 patients, 136 had surgical margins of less than 10 mm. Sixty-eight percent had multiple liver metastases and 15% had extrahepatic metastatic lesions. Clinical and pathological factors were studied specifically and a multivariate analysis was carried out. RESULTS: Overall 5-year survival rate of these 136 patients (taking into account postoperative mortality which attained 1.5%) was 27.8% and the disease-free survival was 22.9%. The surgical margin was 0 mm in 30 cases. The sole prognostic factor was the discovery of unsuspected (resectable) extrahepatic lesions at laparotomy (P < 0.001) ; the width of the free margin had no significant effect. However, in the multivariate analysis of prognostic factors for the entire series (269 hepatectomies), three powerful parameters were identified : (1) the curative nature of resection (P = 0.0007), (2) less than 20% of liver involvement (P = 0.002), and (3) a free margin exceeding 9 mm (P = 0.02). A correlation was found between narrow margins and extensive disease (high number of metastases, bilateral sites, and extended hepatectomy). There was also a greater likelihood of microscopic satellite lesions within 10 mm around the metastases. CONCLUSIONS: The prognostic impact of the width of the surgical margin should not be overestimated. Hepatectomy for liver metastases can procure long-term survival, even in patients with supposedly poor prognostic factors. Resection is justified as long as it is complete and the risks are minimal.
BACKGROUND: Forty-nine cases of circumferential pharyngolaryngectomy with total esophagectomy (PLTE) done between 1982 and 1996 were studied retrospectively. These procedures were performed for advanced squamous cell tumors of the superior esophageal sphincter (n = 23), for hypopharyngeal tumors with synchronous esophageal carcinoma (n = 15), and for hypopharyngeal tumors extensively invading the cervical esophagus (n = 11). METHODS: Ninety-six percent of the patients had T3-4 lesions, and it was impossible to use a free jejunal graft reconstruction. Patients underwent primary surgery in 70% of the cases, and salvage surgery (after failure of chemoradiotherapy) in 30%. In most patients, esophagectomy was performed without thoracotomy (n = 45). Resection was curative (R0) in 70% of the cases, in spite of lymph node invasion in 94%. Reconstruction of the digestive tract was achieved with the stomach in 33 patients (67%) or with the colon in 16 patients (33%). RESULTS: Before 1989, postoperative mortality was high, was correlated with the high frequency of palliative surgery, and resulted in unsatisfactory survival results (overall 5-year survival rate of 7%). After 1989, as a result of better selection of patients and appropriate training of our team, postoperative mortality decreased from 33% to 10%, R1-2 resections decreased from 39% to 26%, and a 3-year overall survival rate of 28% was obtained for the last 25 patients, all of whom were able to eat without difficulty. These results are superior to the survival rates and functional results obtained with radiochemotherapy alone for such advanced tumors, even though the voice is preserved with radiochemotherapy alone. CONCLUSIONS: PLTE for advanced pharyngeal or cervical esophageal tumors is the best treatment currently available, but it is indicated only in very selected cases: when it is technically impossible to perform reconstruction with a free jejunal graft after circumferential pharyngolaryngectomy; as primary surgery, rather than as salvage surgery following chemoradiotherapy; after careful preoperative morphologic and endoscopic assessment of the extent of the tumor; and in patients able to tolerate a thoracotomy for an esophagectomy with lymphadenectomy. Selection according to these guidelines should improve results.