Reduced infections with perioperative immunonutrition in head and neck cancer: exploratory results of a multicenter, prospective, randomized, double-blind study.

BACKGROUND & AIMS: Head and neck cancer surgery is affected by complications in 20-60% of cases, with risk factors being malnutrition, alcoholism and immunosuppression due to cancer. The aim of the study was to investigate whether preoperative or perioperative immunonutrition could reduce postoperative infectious complications (IC) and surgical-site infections (SSI) in this population. METHODS: This was a multicenter, prospective, randomized, double-blind study. Patients with oropharyngeal and pharyngolaryngeal tumour were randomly allocated to three groups: a) perioperative formula of Impact(®) without immune nutrients, named "reference diet" (group A, control); b) preoperative Impact(®) and "reference diet" postoperatively (group B); c) Impact(®) perioperatively (group C). Products were available in oral and enteral formula and were given 7 days before surgery and for 7-15 days postoperatively. The primary and secondary endpoints were the incidence of IC and SSI, respectively. RESULTS: Of 312 randomized patients, 205 were evaluable for ITT analysis. There was no significant difference in IC and SSI. However out of this population, only 64 patients had taken at least 75% of the theoretical intake from surgery to day 10 (per-protocol population). In this condition, a significant difference in IC (OR = 0.24, p = 0.05), SSI (OR = 0.17, p = 0.04) and also in the median length of postoperative stay (18 vs. 25 days, p = 0.05) was demonstrated between groups A and C. CONCLUSIONS: In the ITT population, no significant difference in IC, SSI and LOS was demonstrated. Positive exploratory results on the perioperative Impact(®) per-protocol population, encourage further study in head and neck cancer patients. Registered under ClinicalTrials.gov Identifier no. NCT00765440.

Prevalence, risk factors and clinical implications of malnutrition in French Comprehensive Cancer Centres.

BACKGROUND: This epidemiological observational study aimed at determining the prevalence of malnutrition in non-selected adults with cancer, to identify risk factors of malnutrition and correlate the results with length of stay and 2-month mortality. METHODS: This prospective multicentre 1-day study conducted in 17 French Comprehensive Cancer Centres included 1545 patients. Body mass index (BMI), weight loss (WL) in the past 6 months and age were routinely recorded according to the French national recommendations for hospitalised patients; malnutrition was rated as absent, moderate or severe according to the level of WL and BMI. Age, sex, tumour site, type of hospitalisation and treatment, disease stage, World Health Organisation performance status (PS) and antibiotic therapy were the potential malnutrition risk factors tested. Follow-up at 2 months allowed to determine the correlation with length of stay and mortality. RESULTS: Malnutrition was reported in 30.9% of patients, and was rated as severe in 12.2%. In multivariate analysis, only pre-existing obesity (BMI> or =30), PS > or =2 and head-and-neck or upper digestive cancers were associated with increased risk of malnutrition. Antibiotics use was significantly higher in malnourished patients (35.5 vs 22.8%; P<0.001). Severe malnutrition was independently associated with mortality. The median length of stay was 19.3+/-19.4 days for malnourished patients vs 13.3+/-19.4 days for others (P<0.0001). CONCLUSION: In French Comprehensive Cancer Centres, one out of three cancer patients are malnourished and this was associated with a longer length of stay. Pre-existing obesity could be identified as a new risk factor for malnutrition in our cancer patient population perhaps because of a misidentification or a delay in nutrition support in this category of patients.

[Concomitant bifractionated radiotherapy and chemotherapy with cisplatin and 5-fluorouracil in locally progressive, non-resectable epidermoid carcinomas of the pharynx: ten years experience at the Antoine Lacassagne center]. / Radiothérapie bifractionnée et chimiothérapie par cisplatine et 5-fluoro-uracile concomitantes dans les carcinomes épidermoïdes localement évolués non résécables du pharynx: dix ans d'expérience au centre Antoine Lacassagne.

PURPOSE: Patients suffering from locally advanced unresectable squamous cell carcinoma of the oropharynx and hypopharynx treated with radiotherapy alone have a poor prognosis. More than 70% of patients die within 5 years mainly due to local recurrences. The aim of this study was to evaluate retrospectively the Antoine Lacassagne Cancer Center's experience in a treatment by concomitant bid radiotherapy and chemotherapy. Evaluation was based on analysis of the toxicity, the response rates, the survival, and the clinical prognostic factors. PATIENTS AND METHODS: From 1992 to 2000, 92 consecutive patients were treated in our single institution. All of them had stage IV, unresectable squamous cell carcinoma of the pharynx and they received continuous bid radiotherapy (two daily fractions of 1.2 Gy, 5 days a week, with a 6-h minimal interval between fractions). Total radiotherapy dose was 80.4 Gy on the oropharynx and 75.6 Gy on the hypopharynx. Two or three chemotherapy courses of cisplatin (CP)-5-fluorouracil (5FU) were given during radiotherapy at 21-day intervals (third not delivered after the end of the radiotherapy). CP dose was 100 mg/m2 (day 1) and 5-FU was given as 5-day continuous infusion (750 mg/m2/day at 1st course; 430 mg/m2/day at 2nd and 3rd courses). Special attention was paid to supportive care, particularly in terms of enteral nutrition and mucositis prevention by low-level laser energy. RESULTS: Acute toxicity was marked and included WHO grade III/IV mucositis (89%, 16% of them being grade IV), WHO grade III dermatitis (72%) and grade III/IV neutropenia (61%). This toxicity was significant but manageable with optimised supportive care, and never led to interruption of treatment for more than 1 week, although there were two toxic deaths. Complete global response rate at 6 months was 74%. Overall global survival at 1 and 2 years was 72% and 50% respectively, with a median follow-up of 17 months. Prognostic factors for overall survival were the Karnofsky index (71% survival at 3 years for patients with a Karnofsky index of 90-100% versus 30% for patients with a Karnofsky index of 80% versus 0% for patients with a Karnofsky index of 60-70%, p = 0.0001) and tumor location (55% at 3 years for oropharynx versus 37% for panpharynx versus 28% for hypopharynx, p = 0.009). CONCLUSION: These results confirm the efficacy of concomitant bid radiotherapy and chemotherapy in advanced unresectable tumor of the pharynx. The improvement in results will essentially depend on our capacity to restore in a good nutritional status the patients before beginning this heavy treatment.

Comparison between nasogastric tube feeding and percutaneous fluoroscopic gastrostomy in advanced head and neck cancer patients.

Wasting is a major complication of advanced head and neck cancer and the aim of this study was to compare nasogastric tube feeding (NG) and percutaneous fluoroscopic gastrostomy (PFG) in these patients. The goal of these two methods of nutritional support was to improve or maintain the initial nutritional status during treatment. A total of 90 patients, all stage IV oropharynx or hypopharynx tumor, were reviewed from a prospective databank. All these patients were treated by concomitant chemotherapy and twice-daily continuous radiotherapy with no acceleration. Fifty patients were managed by PFG, and the rest by NG. Mechanical failure, duration of feeding, complications, nutritional evaluation and quality of life were analysed. Mechanical failure occurred in 32 of the 40 NG patients and in seven of the gastrostomy group. In the PFG group, 80% of patients conserved their nutritional support after the end of the radiotherapy, none patient in the NG group. In the PFG group, two presented a wound infection and six had aspiration pneumonia while in the NG group, 21 had aspiration pneumonia probably due to the NG tube (gastroesophageal reflux). The feeding methods were found to be equally effective at maintaining body weight and body mass index at time 1 (3 weeks) and at time 2 (6 weeks). Advantages were associated with PFG cosmesis, mobility and quality of life. PFG is a safe and effective method of providing enteral nutrition during treatment to patients with advanced head and neck cancer and offers important advantages over NG.

Systematic percutaneous fluoroscopic gastrostomy for concomitant radiochemotherapy of advanced head and neck cancer: optimization of therapy.

Wasting is a major complication of advanced head and neck cancer. Concomitant chemotherapy and twice-daily continuous radiotherapy with no acceleration represents a promising treatment modality for these tumors, but increases the risk of mucositis. This report describes the results achieved with percutaneous fluoroscopic gastrostomy (PFG) and its impact on the quality of life of patients with head and neck cancer in terms of their nutritional status. A total of 50 stage IV tumors of the oropharynx and hypopharynx recorded in a prospective database were reviewed retrospectively. All patients were managed by PFG, which was found to be a safe and effective technique with no technical failures. PFG feeding resulted in a mean increase in body weight of 2.5 kg within 3 weeks. The body mass index (BMI) was maintained at 3 and 6 weeks. Minor complications occurred, but no major complications were noted. The overall procedure-related mortality rate was nil. Further prospective investigations are necessary to determine whether treatment of wasting improves patient survival.

Cost-benefit analysis of percutaneous interventional radiological procedures in cancer patients.

The goal of this work was to evaluate the costs and benefits of percutaneous interventional radiological procedures (PIRP) in terminal cancer patients, from the perspective of the Radiodiagnostics Department. The subjects were 225 patients who underwent different kinds of treatments, such as placement of endovenous or urinary stents, percutaneous gastrostomy, alcoholization of metastatic disease, celiac plexus block, tumor embolization, and inferior vena caval filter. We retrospectively analyzed the consequences in terms of survival, quality of life and cost ratios and found that this study fully justifies the use of interventional radiology in palliative oncology: 60% and 40% of the patients, respectively, were still alive at 1 month and 3 months; the additional cost of PIRP procedures is low (< 12%) compared with the total cost of hospitalization.

[Thoughts on the role of celiosurgery in patients with major obesity]. / Réflexions sur la place de la coelio-chirurgie chez les obèses majeurs.

Is coelioscopic surgery an interesting way in massive obese patients? This is well established concerning the post-operative benefit, with a decreased risk of pulmonary and thrombo-embolic complications. But technical difficulties are not well described, whereas we encountered some: incomplete retraction of intra-abdominal organs, weakness and hemorrhagic tendency of the tissues, and most of all an insufficient pneumoperitoneum in all patients preventing sometime the surgical procedure. We analyse those obstacles to propose solutions when the laparoscopic way seems better regarding to the post-operative risk. We study their predictive factors, the best one being the thickness of the abdominal anterior wall, whereas the body weigh is an inadequate factor.

[Intra-arterial chemotherapy of ORL cancer. Value of an implantable infusion system and scintigraphic monitoring]. / Chimiothérapie intra-artérielle des cancers ORL. Apports d'un système d'infusion implantable et de la surveillance scintigraphique.

The technical difficulties and complications related to arterial catheterisation have inhibited the development of regional chemotherapy in ENT oncology despite the numerous theoretical advantages associated with this method. We report our recent experience with a completely implantable infusion system; 12 systems were inserted, 11 unilateral and 1 bilateral. Treatment was carried out in 8 patients and the perfect biocompatibility of the material was confirmed. Good distribution of the infusion to the tumor zone and lack of cerebral diffusion were confirmed before treatment using an infusion of free Technetium.

Liver, spleen, and vessels: preliminary clinical results of CT with perfluorooctylbromide.

This phase 1-2 trial investigated the use of a 100% wt/vol emulsion of perfluorooctylbromide (PFOB) in computed tomography (CT) of 30 patients with metastatic cancer. Injection of 3 g/kg (maximum dose administered to these patients) provided an average liver enhancement of +31 HU on CT scans obtained after 48 hours. Maximum splenic opacification occurred immediately after injection; 1 g/kg, which allowed an immediate enhancement of +35 HU, appeared sufficient for the diagnosis of splenic conditions. Vascular opacification was insufficient for diagnostic purposes. In four patients with metastases, more lesions were seen with the use of PFOB with CT than with conventional CT. Adverse effects included five cases of low back pain that were reversible when the infusion rate was reduced. Fever and trembling were also noted 6 hours after injection in five patients. In all patients, symptoms regressed spontaneously within several hours. Clinically inapparent and dose-independent splenomegaly (volume increase of at least 20% on CT examinations) was noted in eight patients.

[Induction chemotherapy with Cis DDP-5FU in cancers of the upper respiratory and digestive tract after 70 years of age]. / Chimiothérapie première Cis DDP-5 FU des cancers des voies aéro-digestives supérieures après 70 ans.

Sixty one aged patients with advanced squamous cell carcinoma of the upper aerodigestive tract were given a chemotherapy Cis DDP-5 FU before any local treatment. The objective response rate was 77% which included 46% of complete response. Toxic manifestations were more severe than those observed in the general population with the same protocol (nine deaths during the course of the treatment). A few appropriate measures may contribute for the improvement of the therapeutic index: consideration of nutritional and cardiac status, reduction of doses according to age, pharmacokinetic monitoring of 5 FU. An acceptable level of toxicity will be necessary in the design of future, intensive induction trials. The possibility of conservative treatment with a high level of reliability would justify the use of induction chemotherapy in the aged subjects.

Perfluoroctylbromide and hepatosplenic computed tomography. Preliminary clinical study.

The preliminary results of perfluorocytlbromide (PFOB) emulsion when used as an intravenous contrast agent for hepatosplenic CT imaging in humans are reported. Ten patients were examined using dosages ranging from 1 to 2 g/kg. There was good clinical and biochemical tolerance. Diagnostic dose for liver enhancement seems to be at least 2 g/kg, whereas 1 g/kg was sufficient for splenic enhancement.

[Cardiotoxicity of 5-fluorouracil. Spasm or direct myocardial toxicity?]. / Cardiotoxicité du 5 fluoro-uracile. Spasme ou toxicité myocardique directe?

The authors report on a case of cardiotoxicity observed during a protocol including a 5-day continuous infusion of 5-fluorouracil; anginal manifestations recurred during a second treatment course. Coronary angiography, thallium scintigraphy and methergine test were all normal. An attempt to prevent the recurrence of such manifestations using a calcium inhibitor and nitroderivatives was unsuccessful. In connection with this case, six other with anginal manifestation and four sudden deaths under the same protocol, a review of the relevant literature is included in the discussion on the factors that may favor cardiotoxicity and the different etiopathogenic hypothesis. The generally accepted hypothesis is a coronary spasm but a direct cardiotoxicity of 5-FU cannot be. The only therapeutic possibility appears to be the definitive halt of 5-FU after the onset of such manifestations.

[Implantation of permanent cardiac pacing electrodes by the retropectoral transvenous approach. Results of a series of 152 cases]. / Mise en place des sondes de stimulation cardiaque permanente par les veines rétro-pectorales. Résultats d'une série de 152 cas.

When the cephalic vein is unsuitable for the introduction of pacing electrodes, the retropectoral veins near the external border of pectoralis major near its subclavian attachment, approached through the same incision, may provide a suitable alternative. It was not possible to catheterise the cephalic vein in 23,8% of 756 consecutive implantations of endocavitary pacing electrodes. The retropectoral veins were looked for in 172 cases and found and used in 159 cases (92,4%). This percentage of success increased to 97,6% in the latter 83 attempts. These veins are usually very distensible. No complications or accidents were recorded. The only disadvantage was the relatively long dissection time. The stability of the pacing electrodes with this approach was excellent as reoperation was only required in 3% of cases (2 displacements and 3 exit blocks or pericardial migrations). This approach is therefore practicable in the large majority of cases in which the cephalic vein cannot be used. The multiplicity of the retropectoral veins should allow the introduction of two electrodes if sequential atrioventricular pacing were to be chosen. In addition, this approach would be useful when an atrial pacing electrode is to be added to a preexisting ventricular pacing electrode and one hesitates to puncture the subclavian vein because of the risk of damaging the electrode already in place. When direct subclavian puncture is the technique of choice of the operator, the retropectoral veins may be used when the subclavian approach is contraindicated or impossible. In any case, denudation of the retropectoral veins leads to fewer incidents than when the latter approach is used.