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To determine whether exotoxin A may affect the transport of fluid across the lung epithelium, two isogenic strains of Pseudomonas aeruginosa PA103 (10(8) colony-forming units), one (PA103 tox omega) with a structural gene mutation in exotoxin A, were instilled into the distal airspaces of anesthetized rats. PA103 parental strain, but not its mutant, stimulated the removal of fluid from the distal airspaces of the lung. Instillation of exotoxin A alone caused a dose-dependent increase in the fluid transport across the lung epithelium. Instillation of amiloride (10(-3) M) with exotoxin A demonstrated that this effect partially depended on increased uptake of sodium across the lung epithelium. The absence of stimulation after instillation of an exotoxin A mutant (PE delta Glu553) without ADP-ribosyltransferase activity demonstrated that the effect of exotoxin A depended on its ADP-ribosyltransferase activity. Finally, the instillation of exotoxin A in rats depleted of macrophages indicated that the effect of exotoxin A was not secondary to the activation of alveolar macrophages by this toxin. In conclusion, these results indicate that the in vivo release of exotoxin A by live airspace P. aeruginosa directly stimulates the fluid removal from the airspaces by the lung epithelium. This may alter the volume or composition of airway secretions, and may contribute to the lung disease in patients infected with P. aeruginosa.

Despite substantial advances in the management of such patients, the prognosis of ventilated neutropenic patients remains grim. The objective of our study was to evaluate the benefit of tracheotomy in this category of patients, in terms of mortality while they were in the intensive-care unit and nosocomial pneumonias. The charts of 53 consecutive, ventilated, neutropenic patients, or those destined to be imminently neutropenic, admitted to our intensive-care unit during a 4-year period, have been retrospectively reviewed. Tracheotomy was performed at the bedside or in the operating room: 20 patients underwent tracheotomy within 48 h of mechanical ventilation (ET group), while 33 were tracheotomized later or remained intubated (INT group). The two groups were comparable with regard to the underlying disease, respiratory failure, mechanical ventilation patterns and severity scores, but neutropenia was more profound in the ET group. Mortality while in the intensive-care unit was similar (ET: 70%; INT: 78.8%). However, the survival curves showed a trend towards longer survival in the ET group, even after adjustment for the degree of neutropenia (log-rank test: P = 0.07). The incidence of pneumonias was similar in both groups. No major complications of tracheotomy were reported. These findings suggest that a tracheotomy could be proposed for neutropenic patients requiring mechanical ventilation, in order to prolong their survival beyond the end of the neutropenic period. A prospective study is underway to confirm these preliminary results.

A high incidence of bacterial infections has been previously reported during interleukin-2 (IL-2) treatment, mainly due to catheter-related infections. Antibiotic prophylaxis has been successfully used to decrease such infections. The goal of this study was to evaluate an alternative way to reduce catheter-related infections in IL-2-treated patients by the use of totally implanted catheters. A total of 74 patients with metastatic renal cell carcinoma, referred to our institution to receive IL-2 from March 1989 to July 1991, were included in this prospective study. IL-2 was given on a 2-days-a-week schedule (24 x 10(6) IU m-2 day-1) either alone (41 patients) or in association with interferon gamma (33 patients). All these patients were prospectively evaluated for fever, bacteremia and line-site infection. Seven patients (9.5%) had one (2 patients) or more (5 patients) positive blood cultures with Staphylococcus aureus. Antibiotics were used only in 5 patients, and the catheter had to be removed in only 2 of these patients. In the other patients, no further infection developed despite the lack of antibiotics. Moreover, 9 patients had positive blood cultures with Staphylococcus epidermidis (1.9% of total number of blood cultures). In conclusion, a totally implanted catheter appears to reduce the incidence of infections in IL-2-treated patients, at least on a 2-days-a-week schedule.

Objective: To evaluate the safety of tracheotomy in neutropenic ventilated cancer patients, in terms of infectious and haemorrhagic complications., Design: Retrospective study., Setting: A medical-surgical intensive care unit in a Cancer-hospital., Patients and Participants: 26 consecutive patients undergoing a tracheotomy in neutropenic period, from 1987 to 1990., Interventions: Tracheotomy, performed at the bedside or in operating room., Measurements and Results: In all neutropenic patients undergoing a tracheotomy, the characteristics and duration of both neutropenia and mechanical ventilation have been recorded. Stomal bleeding and infection, and infectious pneumonias and alveolar haemorrhage have been carefully reviewed. Platelets were transfused in 23 of the 26 patients at the time of the procedure; no local haemorrhage was observed. Neither stomal nor pulmonary infections secondary to tracheotomy were noted. No respiratory worsening was attributable to the tracheotomy. Nineteen patients (73%) died in ICU, without direct link between tracheotomy and death., Conclusions: These findings suggest that a tracheotomy can be safely performed in neutropenic patients requiring mechanical ventilation.

Background: During severe sepsis, the existence of a pathologic oxygen supply dependency remains controversial., Study Objective: To evaluate the relationship between oxygen delivery (DO2) and oxygen consumption (VO2) during severe sepsis and to compare, in this respect, survivors and nonsurvivors and patients with normal or increased concentration of plasma lactate., Study Design: Cohort analytic study., Setting: Three European ICUs in university hospitals., Patients: Seventeen mechanically ventilated patients with severe sepsis (six with high blood lactate levels) studied within the first day of diagnosis., Interventions and Measurements: Pulmonary elimination of carbon dioxide, or carbon dioxide production (VCO2) and VO2 were measured by indirect calorimetry before and after two interventions designed to increase DO2 (calculated from the Fick equation): inflation of a military antishock trouser (MAST) and infusion of dobutamine., Results: During MAST inflation, DO2 increased by 19% in patients with a normal concentration of plasma lactate (p < 0.01), but remained unchanged in patients with high lactate levels. During dobutamine infusion, DO2 increased in both groups by 16% (p < 0.01) and 20% (p < 0.05), respectively. In both groups, we found that the VO2 and VCO2 were not affected by either the MAST or the dobutamine-induced increase in DO2. There was no difference between survivors and nonsurvivors., Conclusion: There was no evidence of a pathologic oxygen supply dependency in patients with severe sepsis, even in those who had an elevated concentration of plasma lactate and in those who ultimately died. These results do not favor the conclusion that maximizing DO2 is a primary therapeutic objective in such patients.

Four out of 23 consecutive patients treated with high-dose Ara-C for lymphomas in our institution developed a strikingly similar syndrome during the perfusion. It was characterized by the onset of fever, diarrhea, shock, pulmonary edema, acute renal failure, metabolic acidosis, weight gain and leukocytosis. Thorough bacteriological screening failed to provide evidence of infection. Sequential biological assays of IL-1, IL-2, TNF and PAF were performed during Ara-C infusion to ten patients, including the four who developed the syndrome. TNF and PAF activity was found in the serum of respectively two and four of the cases, but not in the six controls. As TNF and PAF are thought to be involved in the development of septic shock and adult respiratory distress syndrome, we hypothesize that high-dose Ara-C may be associated with cytokine release.

Adequate humidification of inspired gases with HMEs during long-term MV remains controversial. In this study, a comparison is made between tracheal secretions during long-term MV either with HME or conventional HH. Both the HME and HH groups were similar with respect to age, sex, diagnosis, duration of MV, SAPS and mortality. Temperature of gases in the tracheal tube was lower and the amount of tracheal instillations was greater in the HME group than in the HH group. Tracheal secretions became thicker between day 1 (control) and day 5, in the HME group than in the HH group. Four and two tube occlusions occurred in HME and HH groups, respectively. Tracheal bacterial colonization was similar in the two groups. Given the advantages of HME (reduced nurses' work and financial cost), HME could be routinely used under cautious surveillance and replaced by HH if difficulty in suctioning occurs.

Twenty-eight patients with synchronous esophageal and head and neck epidermoid cancers have been treated by a combined protocol including esophagectomy. Seventy-nine percent received pre-operative chemotherapy, 50% had resection of the head and neck lesion at the same time as the esophagectomy and 79% received post-operative irradiation. Two patients died during the post-operative period (7%), and 1, 2 and 3-yr survival rate (Kaplan-Meier) was respectively 64, 32 and 27%. Contrary to our initial assumption, there was no significant decrease in survival compared to patients operated on for an isolated esophageal cancer. The patients were divided into 4 very simple prognostic groups based on the T and N stages of the clinical pre-therapeutic TNM classification: T1 or T2 for esophageal lesions and different T or N stages according to the prognosis for head and neck lesions. A study of each group tended to show that esophagectomy was beneficial except in cases of synchronous T2 esophageal cancer and locally advanced head and neck cancer (there was 2-yr survival in this group). The 28 patients studied represent a particular population which presented 91 cancerous localisations during the duration of the study (mean: 3.25 localisations per patient).

A 35-year-old woman experienced diffuse intraalveolar haemorrhage with respiratory distress and acute renal failure. Renal histology and evolution confirmed Wegener's granulomatosis. Early use of immunosuppressive drugs allowed weaning from mechanical ventilation and temporary improvement of the renal failure. A review of the literature emphasizes the rarity of alveolar hemorrhage as an initial symptom of Wegener's granulomatosis and the necessity of aggressive management.

A 38-year-old man with a colonic carcinoma experienced cardiogenic shock during continuous intravenous treatment with 5-fluorouracil (5-FU), without clinical or electrical signs of coronary insufficiency and with a normal coronary angiogram. His symptoms resolved after eight days of inotropic and vasodilator therapy. Because of the severity of the shock, rechallenge was not performed. This is the first case of acute cardiac failure without coronary ischemia, associated with 5-FU monotherapy. Experimental studies suggest that this adverse effect could be due to myocardial accumulation of 5-FU leading to depletion of high energy phosphate compounds. This might also explain the more frequently seen acute coronary insufficiency due to 5-FU.

5-fluorouracil is a drug that is widely used in cancerology. Its cardiotoxicity must be known, as it is not exceptional and potentially dangerous. Two cases are reported in which the coronary insufficiency was documented and recurred when 5-fluorouracil was reintroduced. The mechanism of cardiac toxicity seems to be coronary spasm, as shown by exercise tests and the normal results of coronary arteriography. It seems preferable to refrain from using 5-fluorouracil after a recent myocardial infarction or in patients with unstable angina. Reintroduction of the drug is usually followed by recurrence of cardiotoxicity, even under coronary vasodilators.

Acute haemorrhagic pancreatitis developed in a 12 year old boy treated for lymphoblastic lymphoma. No etiological factor could be identified, except for asparaginase. Although the condition was initially severe, the patient recovered. Regular CT monitoring demonstrated the formation of a pseudocyst in the pancreatic tail which spontaneously regressed without complications.

In order to determine the usefulness of systematic radiological exploration after gastrectomy, 123 gastrectomies (39 total, 84 subtotal) performed over a 10-year period were reviewed. Control radiology had been carried out in 51% of the cases. Retrospectively, except for the lower percentage of total gastrectomies the two groups (with and without control radiology) were comparable. The overall incidence of fistula (9%) was similar to that found in the literature, bearing in mind that 90% of gastrectomies in this series were performed for cancer. The only two factors predictive of fistula were the presence of fever or of post-operative focal infection (P less than 0.001). It would appear that control radiology after gastrectomy is indicated only when post-operative fever is present. If this were done the number of useless examinations would be reduced and the cost-effectiveness ratio of radiology would be improved.

The authors report the case of a man of 62 who was admitted with a clinical and electrocardiographic picture of a posterior infarction which was very soon complicated by collapse and anuria. The findings on catheterisation of the right side of the heart were as expected. The cardiac index was very low, and the major abnormality was a type of adiastole with equal pressures in the right ventricle and the auricle of the right atrium. Despite an attempt to assist the circulation by an intra-aortic ballon, the patient died within a few hours. The postmortem examination confirmed the presence of a massive infarction of the left ventricle, but also of the right ventricle, together with rupture of the posterior papillary muscle of the mitral valve, and ischaemic rupture of one papillary muscle of the tricuspid valve.

Fifty operable epidermoid esophageal carcinomas were treated by combined chemotherapy, surgery and radiotherapy. The post-operative mortality was 5.4% and the severe post-operative morbidity was 29%. The vindesine-5FU-platinum association and the vindesine-endoxan-platinum association gave respectively 55% and 35% objective responses (OR) after two preoperative courses without increasing the operative mortality. The patients who showed an OR had a less important tumoral extension. Thus, an objective response to the pre-operative chemotherapy is in fact a new prognostic factor. Survival without recurrence seems to be increased when chemotherapy is efficient in the curative resection group. These findings incite to promote prospective randomized studies with this kind of combined therapy.

A preliminary study was conducted with early and continuous intraportal adjuvant chemotherapy (IPAC) after a curative hepatectomy for colorectal metastases. The IPAC consisted of 14 days of 5-FU infusion at the rate of 600 mg/m2/d. The ultimate aim of this study was to reduce the frequency of recurrences in the remaining liver after curative hepatectomy. Twelve patients were included. IPAC was initiated in nine of them, while three technical failures occurred. The 14-day course with continuous 5-FU was given five times. The treatment had to be ceased prematurely because one medical and three mechanical complications occurred during the infusion. Pains and vomiting were frequent, but were usually the result of mechanical complications. No important hepatotoxicity or haematological toxicity was observed. This study shows that a full course of chemotherapy could be administered in only 40% of the patients. Further pilot studies with the aim of improving feasibility should be undertaken. If the mechanical problems are improved and IPAC duration is reduced, then feasibility should be dramatically increased. Subsequently, only a prospective randomized study would confirm the efficiency of the method in minimizing liver recurrence.

In view of the frequency and the importance of denutrition in digestive cancer patients, continuous enteral nutrition (EN) might be an useful adjuvant treatment should these patients be able to receive an efficient anti-tumoral course of treatment. EN is as effective as total parenteral nutrition in undernourished patients and probably decreases the extent and the frequency of post-operative complications. In contrast, when considered as a complement to radiation therapy or chemotherapy, EN does not enhance tolerance of treatment, response rate nor survival even though it improves the patient's nutritional status. These results must be considered with caution as most of the randomized trials conducted have only included small groups of patients. Further randomized trials are required in homogenous populations of digestive cancer patients in a state of undernutrition and who are eligible candidates for curative treatment. Basic research projects aiming at a specific form of nutritional support for cancer patients are badly needed.

Five - Fluorouracil (5 FU) is widely used in oncology, especially in tumors of the gastrointestinal tract and in carcinoma of the breast. Its side effects (gastrointestinal, haematological, alopecia) are well known. However, its cardiac effects are not widely appreciated, despite an incidence similar to that observed with the anthracyclines (1.6% vs 2.2%) and a high mortality rate (12.5%). A new case of coronary insufficiency is reported illustrating the absence of a dose-effect relationship and the frequency of recurrence of symptoms when 5 FU is reintroduced even with coronary vasodilator therapy. The mechanism of cardiotoxicity in this case seems to be coronary spasm.

A surgical technique is described which has been adapted from the operation known as "total duodenal diversion", but which is suitable for the anatomical conditions resulting from an upper pole gastrectomy. The method was used successfully in two patients with severe esophagitis from bile reflux resistant to all medical treatment and resulting from upper pole gastrectomies.

Twenty cases of hypovolemic shock of various etiologies in which initial diagnosis was massive pulmonary embolism are analyzed. The error was due to intensity of respiratory failure symptoms and electrocardiographic changes suggesting acute cor pulmonale. However, although constant, hypoxemia was mild and easily corrected by oxygen administration. Hypovolemia was confirmed by low central venous pressure (CPV EQUALS 1, 3 cm H20); in 7 patients, right heart catheterism showed lowered cardiac output associated to low ventricular filling pressures (VFP). Rapid blood volume expansion simultaneously corrected in all cases both shock and clinical signs of "respiratory failure", while CVP increased only slightly. These findings suggest that CVP must be carefully checked when faced with a clinical picture of massive pulmonary embolism and if low, rapid blood volume expansion must be performed under CVP monitoring, in order to rule out hypovolemic shock.