Gemcitabine-oxaliplatin combination for ovarian cancer resistant to taxane-platinum treatment: a phase II study from the GINECO group.

Advanced ovarian carcinoma in early progression (<6 months) (AOCEP) is considered resistant to most cytotoxic drugs. Gemcitabine (GE) and oxaliplatin (OXA) have shown single-agent activity in relapsed ovarian cancer. Their combination was tested in patients with AOCEP in phase II study. Fifty patients pre-treated with platinum-taxane received q3w administration of OXA (100 mg m(-2), d1) and GE (1000 mg m(-2), d1, d8, 100-min infusion). Patient characteristics were a : median age 64 years (range 46-79),and 1 (84%) or 2 (16%) earlier lines of treatment. Haematological toxicity included grade 3-4 neutropaenia (33%), anaemia (8%), and thrombocytopaenia (19%). Febrile neutropaenia occurred in 3%. Non-haematological toxicity included grade 2-3 nausea or vomiting (34%), grade 3 fatigue (25%),and grade 2 alopecia (24%). Eighteen (37%) patients experienced response. Median progression-free (PF) and overall survivals (OS) were 4.6 and 11.4 months, respectively. The OXA-GE combination has high activity and acceptable toxicity in AOCEP patients. A comparison of the doublet OXA-GE with single-agent treatment is warranted.

Single photon emission computerized tomography (SPECT) for monitoring regeneration of the human liver after partial hepatectomy for secondary tumours.

In 18 patients, the liver volume during regeneration after partial hepatectomy for secondary tumours was estimated by single photon emission computerized tomography (SPECT). Hepatic weight index (HWI) was subsequently calculated to follow evolution of the regeneration as a function of postoperative complications over a 30-day period. In patients with postoperative complications the HWI curves initially rose progressively and either reached a plateau or declined thereafter. The same pattern of HWI evolution was observed in patients with tumour recurrence, which was diagnosed later. On the other hand, in patients without postoperative complications the HWI curves rose continuously. These findings showed that a regenerative response was not the same in patients with or without postoperative complications; whereas in patients with tumour recurrence it could additionally provide prognostic information.

Plasma and jejunal glutamine levels after extensive small bowel resection in dogs.

Recent studies have demonstrated that glutamine may be required for mucosal growth and that it is widely utilised by the intestinal tract after surgery. This study has evaluated the effect of massive small bowel resection on plasma and jejunal glutamine and related amino-acids level evolution after surgery. Transection was performed in 6 dogs (control group) and enterectomy in 10 dogs leaving 25cm of jejunum, associated with colectomy (group 1). Plasma glutamine levels decreased on D2 (p = 0.03) in the resected group while a significant decrease of plasma alanine levels was observed on D2 (p = 0.002), D4, D6 and D8 (p < 0.001). Intestinal mucosa glutamic acid content was increased on D8 in this group (p < 0.001). No changes were observed in the control group. These results suggest that glutamine is a required substrate after massive small bowel resection which could improve the intestinal adaptation encountered after enterectomy.

Influence of N-acetylglutamine or glutamine infusion on plasma amino acid concentrations during the early phase of small-bowel adaptation in the dog.

Glutamine is a nonessential neutral amino acid that is widely consumed by the intestinal tract in catabolic states. We have followed up the plasma amino acid profile after extensive small-bowel resection in dogs receiving total parenteral nutrition (TPN) with or without glutamine (GLN) or N-acetylglutamine (aGLN) supplementation. Animals were divided into four groups according to the type of surgery (enterectomy or transection) and nutrition (TPN, TPN with aGLN, or TPN with GLN). Plasma GLN levels decreased in group I (enterectomy and TPN) on day 2 (p = .03) and significantly increased on postoperative days in groups III (enterectomy and TPN with aGLN) and IV (enterectomy and TPN with GLN). A significant increase of plasma GLN was observed in groups III and IV compared with group I on days 6 and 8 (p = .03 and p = .01). Plasma alanine decreased in groups with bowel resection, whereas no change was observed in the control group (transection) and the decrease of plasma alanine was significantly less pronounced in groups III and IV compared with group I. The increase of crypt depth and villous height was more pronounced in groups III and IV. These results suggest that GLN is a required substrate for mucosal growth and function, which could improve the intestinal adaptation encountered after enterectomy.

Ambulatory home total parenteral nutrition.

Ambulatory total parenteral nutrition (TPN) at home was used in 85 patients within a 6-yr period. Indications include severe malabsorption, fistulas, anorexia nervosa, and malignancies. The median duration of home TPN (HPN) was 67 days (range: 30-4,155 days). HPN duration for patients with benign diseases was longer [357.12 days (range: 30-4,155 days)] than for cancer patients [93.54 days (range: 30-421 days)]. Under HPN, patients gained a good nutritional status with an increase of total protein (p less than 0.001) and serum albumin levels (p less than 0.001). Weight gain was also significant (p less than 0.001). The rehospitalization rate was low (7.8%), but it was higher when HPN lasted for more than 3 months (10.87% +/- 1.58%) compared with short-term HPN (5.69% +/- 1.25%). Metabolic complications were unusual, and rehospitalization was related to the oncological treatment and/or infectious complications. Therefore, ambulatory HPN is a nutritional support that can significantly improve the life of patients with alimentary failure. Moreover, HPN allows significant cost savings compared to the alternative of prolonged hospitalization.

Assessment of tumour response to chemotherapy for metastatic colorectal cancer: accuracy of the RECIST criteria.

Evaluation of tumour size modifications in response to treatment is a critical issue in the management of advanced malignancies. In 1981, the World Health Organization (WHO) established guidelines for tumour response assessment. These WHO1981 criteria were recently simplified in a revised version, named RECIST (Response Evaluation Criteria in Solid Tumours), which uses unidimensional instead of bidimensional measurements, a reduced number of measured lesions, withdrawal of the progression criteria based on isolated increase of a single lesion, and different shrinkage threshold for definitions of tumour response and progression. In order to validate these new guidelines, we have compared results obtained with both classifications in a prospective series of 91 patients receiving chemotherapy for metastatic colorectal cancer. Data from iterative tomographic measurements were fully recorded and reviewed by an expert panel. The overall response and progression rates according to the WHO1981 criteria were 19% and 58%, respectively. Using RECIST criteria, 16 patients were reclassified in a more favourable subgroup, the overall response rate being 28% and the progression rate 45% (non-weighted kappa concordance test 0.72). When isolated increase of a single measurable lesion is not taken into account for progression with the WHO1981 criteria, only 7 patients were reclassified and the kappa test was satisfying, i.e. > or =0.75, for the whole population as well as for each of the responding and progressive subgroups. Since it provides concordant results with a simplified method, the use of RECIST criteria is recommended for evaluation of treatment efficacy in clinical trials and routine practice.

Any clinical benefit from the use of oncofoetal markers in the management of chemotherapy for patients with metastatic colorectal carcinomas?

AIMS: Computed tomography (CT) is the reference technique for evaluating response to chemotherapy. The potential helpfulness of tumour markers is debated. MATERIALS AND METHODS: From March 1997 to January 1999, 91 consecutive patients receiving chemotherapy for metastatic colorectal carcinoma underwent whole-body spiral CT, estimates of anti-carcinoembryonic antigen (CEA) and CA19-9 every 8 weeks. RESULTS: CEA and CA19-9 levels were above normal in 78 (85.7%) and 61 (67.5%) patients, respectively. Tumour response evaluation according to the RECIST criteria was obtained at 8-week evaluation in 83 (91%) patients. The positive predictive values (PPV) for response of a decrease of the marker levels were 53.8 for CEA and 41.7 for CA19-9 using a 30% decrease threshold, and 60/52.2, respectively, using a 50% decrease threshold. Meaningful PPV values (> 90%) for progression of an increase of the marker levels were only obtained using the 200% increase threshold for CEA alone or a combination of CEA and CA 19-9. A 100% CEA increase between baseline and the 8-week evaluation was correlated to overall survival (P = 0.0023). The need for a radiological confirmation of tumour progression could be avoided by the systematic dosage of tumour markers at baseline and after 8 weeks of treatment only in a sub-population of 13% of the patients with a 200% increase of CEA or CA 19-9 at 8 weeks. CONCLUSIONS: CEA, CA 19-9, or both should be used with caution for tumour response evaluation to chemotherapy in addition to CT in metastatic colorectal carcinoma.

[Parenteral feeding at home. 100 cases]. / L'assistance nutritive parentérale à domicile. Cent observations.

Between 1979 and 1986, 100 patients underwent parenteral nutrition at home on account of malnutrition consecutive to digestive insufficiency or heavy anti-cancer chemotherapy. Parenteral feeding was performed through a buried catheter for a mean period of 74 days (range 30 to 430 days). The patients' nutritional status was improved, with a significant increase in weight, total plasma proteins and serum albumin (P less than 0.001). The principal complication observed was infection, and few patients (10.61%) were rehospitalized. Home parenteral nutrition may be regarded as "the artificial bowel" for chronic malnutrition patients. It increases the duration and quality of life without prolonging the time spent in hospital, and it reduces health expenses by 50 to 70%.

[Home parenteral nutrition for adults. Results of a multicenter survey in France]. / Nutrition parentérale à domicile chez l'adulte. Résultats d'une enquête multicentrique en France.

Home parenteral nutrition (HPN) is a growing therapy in North America and Europe. This first multicenter retrospective study of HPN in France has collected data on 81 patients sent home before December 31st, 1985. Intestinal failure, secondary to short bowel syndrome, small bowel stenosis or fistula, was the main indication for HPN. In 95 p. 100 of the cases, the clinical nutritional status during HPN was either normal or subnormal. The annual incidence of catheter change for technical complication was 0.78 and the mortality rate was 1.2 p. 100. Social rehabilitation was recovered during HPN in 60 p. 100 of patients. Thirty percent of the patients died of their primary disease during HPN but 43 p. 100 were off treatment, and 27 p. 100 were on HPN at the end of the study. The cost of HPN was reduced by 64 p. 100 in comparison with the cost of parenteral nutrition carried out in hospital.

[Treatment of epithelial cancer of the ovary. In favor of primary radical and regional surgery before chemotherapy and radiotherapy]. / Traitement du cancer épithélial de l'ovaire. Pour une chirurgie radicale et régionale premiére avant chimiothérapie et radiothérapie

The treatment of epithelial carcinoma of the ovary (90% of malignant ovarian tumours) has largely benefited from chemotherapy, notably since the advent of cisplatinum. Radiotherapy may be an important adjuvant treatment to sterilize the pelvis. Both chemo- and radiotherapy are effective mainly on small residual diseases, hence the importance of initial surgery with maximal cell reduction, notably in carcinomas classified as stage III according to the International Gynaecology and Obstetrics Federation system. Regional surgery of the ovary must be pelvic and abdominal: from Douglas' pouch to the diaphragmatic domes. This therapeutic approach requires the resolution of two problems: intensive care and post-operative feeding. It has 2 major advantages: it avoids second-look operations or reduces their number, and it increases the survival rate at 5 years.

[Total and prolonged parenteral nutrition at the hospital and at the patient's home: its socio-economic importance]. / La nutrition parentérale totale et prolongée à l'hôpital et au domicile du malade: son intérêt socio-économique.

Total parenteral nutrition with "All in one" nutritive mixtures is used in France from 1970. These advances ensure a more simple treatment for intensive care units. Nutritive mixtures provide the caloric and nitrogen daily requirements added with micronutrients (electrolytes, trace elements and vitamins) and this technique allows home parenteral nutrition. "All in one" nutritive mixtures have reduced the infectious complications and the industrial quality control during parenteral solutes admixing has decreased again this infectious risk. So, nutritive mixtures result in sparing of nurse time, material for preparation and antibiotic costs. Moreover, although the costs of home parenteral nutrition are considerable, this technique still reduces annual costs by 50% to 70%, avoids prolonged hospitalization and allows the patients to resume a more normal existence at home. Development of new technologies and nutritive mixtures for specific malnutrition are now required to improve treatment of these patients with insufficiency digestive tract.

Clinical, biological, and histological follow-up during intestinal adaptation after small-bowel resection in the dog.

Massive resections of the intestine including the ileocecal valve are associated with a high mortality. This model of short bowel in the dog consists of an extensive small-bowel resection (remaining jejunum 25 cm) associated with colectomy. Small-bowel adaptation is evidenced by increases of crypt depth (p = 0.02) and villus height (p = 0.001) in animals fed per os. Plasma glutamine levels decrease after surgery, while there is a significant decrease of plasma alanine levels (p less than 0.001). This model should allow to pursue investigations on the importance of glutamine as an essential fuel for intestinal mucosa regeneration.

Total parenteral nutrition needs in different types of short bowel syndrome.

Thirty-nine patients with short bowel syndrome after extensive small bowel resection, with or without associated partial or total colectomy, received continuous total parenteral nutrition followed by discontinuous parenteral nutrition. Home parenteral nutrition was introduced in 16 of these patients; in eight it was permanent. The assessment of nutritional status included body weight; standard urinary and blood studies; albumin, prealbumin, and transferrin serum levels; and both urinary and fecal nitrogen. A statistically significant correlation (P less than 0.001) was observed between the length of the remaining small bowel and the necessary duration of nutritional support. Multivariate analysis allowed us to classify patients into three groups as a function of remaining gut length and the duration of required nutritional support. This study should help to define the best nutritional support protocol for patients with various short bowel syndromes in order to ensure the best possible intestinal adaptation and to improve their quality of life.

Calcium absorption following small bowel resection in man. Evidence for an adaptive response.

Seventeen patients who had undergone extensive small bowel resection were studied for calcium absorption (FACa) and plasma vitamin D metabolites. FACa was measured by a double radio-tracer technique and expressed as percentage of total oral dose. FACa was decreased compared with controls (34%, range: 3-46 v 65%, range: 57-73, P less than 0.01). A positive correlation (r = 0.49, P = 0.05) was found between FACa and the remaining length of small bowel (SBL). As wide variations in both SBL and duration after surgery were observed among the seventeen investigated patients, we were led to individualize less heterogeneous subgroups of patients. Better correlations were found when the patients were divided into two subgroups according to whether the time interval between the resection and the investigation was shorter (r = 0.75, n = 11, P less than 0.02) or longer (r = 0.89, n = 6, P = 0.05) than 2 years. In thirteen patients who had a SBL shorter than 100 cm, a positive correlation was observed between FACa and the time interval after surgery (months): r = 0.65, P less than 0.05. Plasma 1,25 (OH)2D was markedly reduced in the whole group (31 pmol l-1, range: 8-108) compared with controls (103 pmol-1, range: 59-134, P less than 0.01). The present study shows that in extensively small bowel resected patients, calcium absorption is reduced, the alteration being dependent both on the length of the remnant small bowel and on the time after surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

[Short bowel syndromes in adults. Prognostic factors. Evaluation and treatment. Retrospective study. Apropos of 80 cases]. / Les syndromes de l'intestin grêle court de l'adulte. Facteurs pronostics. Evaluation et traitement. Etude rétrospective. A propos de 80 cas.

Since 1981, a consensus is appeared in order to define and to precise the natural evolution of short bowel with a maximal remaining small bowel of 150 cm. The phenomenon of intestinal adaptation which are better known in animals than in humans, are on the dependence of luminal, hormonal and humoral factors (epidermal growth factor, polyamines). The knowledge of prognostical factors and the anatomical and functional evaluation of remaining small bowel allow to "measure" the improvement of digestive absorption and to decide the duration of nutritional support. An experience in 80 cases of short bowel syndrome is reported. A significant correlation exists between the duration of parenteral nutrition support and the length of the remaining gut (p < 0.001) and multifactorial analysis differentiates 3 groups of short bowel characterized by their length and parenteral support duration.

Experimental model of extended repeated partial hepatectomy in the dog.

The model of extended repeated partial hepatectomy without vascular shunt in dogs is presented. It consisted of 65% initial hepatectomy and after liver regeneration (6-10 weeks) repeated hepatectomy. Finally, only the papillary process of the caudate lobe (PPC), which constitutes 5% of the initial hepatic mass, was left intact. The most important finding was an ability of PPC to reconstitute the liver mass which enabled survival without the vascular shunt. After repeated hepatectomy the need for artificial hepatic assistance (parenteral nutritional support with frozen plasma) was imperative to offset the effects of acute hepatic failure and to support PPC regeneration.

[Serum marker of the functional hepatic mass after extensive hepatectomy. The branched/aromatic amino acid ratio. Experimental and clinical studies]. / Un marqueur sérique de la masse hépatique fonctionelle après hépatectomie élargie. Le rapport des acides aminés ramifiés (AAR) sur les aromatiques (AAA). Etudes expérimentales et cliniques.

During severe hepatic insufficiency, serum amino acid profile is modified with an increase of aromatic amino acids (AAA) (Tyrosine and Phenylalanine) and methionine concentrations and a decreased value of 3 branched chain amino acids (BCAA) (leucine, isoleucine and valine). These observations have been confirmed after hepatic surgery in experimental and clinical studies. In experimental models, after 10, 32, 68, 77 or 90% hepatectomy in Wistar rats, the BCAA/AAA ratio (R) is correlated with the extent of hepatectomy: r = 0.74, p < 0.001; with the post-operative interval time (8, 24, 32, 48, 168 or 240 hours): r = 0.60, p < 0.001 and with the liver weight when animals are sacrificed: r = 0.64, p < 0.001. In clinical studies, 26 patients have undergone 60 to 80% hepatectomy for primary or secondary tumors of the liver and R is determined on the immediate post-operative day and every day during the first post-operative week. Liver regeneration is followed by single photon emission computerized tomoscintigraphy on days 0, 7 and 30 with assessment of hepatic growth index (HGI) estimated by the ratio: liver mass on day 7 or 30/remnant liver mass on day 0. On post-operative day 7, R is 1.61 +/- 0.3 (normal: 3.5 +/- 0.51). Mean liver volume is 60 +/- 11% and HGI is 1.9 +/- 0.3. On this day, a correlation is found between R and HGI (r = 0.76). On post-operative day 30, HGI is 2.34 +/- 0.50, mean liver volume is 89.6 +/- 0.9% and R is 2.02 +/- 0.65.(ABSTRACT TRUNCATED AT 250 WORDS)