The APSY-SED study: protocol of an observational, longitudinal, mixed methods and multicenter study exploring the psychological adjustment of relatives and healthcare providers of patients with cancer with continuous deep sedation until death.

BACKGROUND: Since 2016, France is the only country in the World where continuous deep sedation until death (CDSUD) is regulated by law. CDSUD serves as a response to refractory suffering in palliative situations where the patients' death is expected to occur in the following hours or days. Little is known on the psychological adjustment surrounding a CDSUD procedure for healthcare providers (HCPs) and relatives. Our study aims to gather qualitative and quantitative data on the specific processes behind the psychological adjustment of both relatives and HCPs, after the administration of CDSUD for patients with cancer. METHODS: The APSY-SED study is a prospective, longitudinal, mixed-methods and multicenter study. Recruitment will involve any French-speaking adult cancer patient for who a CDSUD is discussed, their relatives and HCPs. We plan to include 150 patients, 150 relatives, and 50 HCPs. The evaluation criteria of this research are: 1/ Primary criterion: Psychological adjustment of relatives and HCPs 6 and 13 months after the death of the patient with cancer (psychological adjustment = intensity of anxiety, depression and grief reactions, CDSUD-related distress, job satisfaction, Professional Stress and Professional experience). Secondary criteria: a)occurrence of wish for a CDSUD in patients in palliative phase; b)occurrence of wish for hastened death in patients in palliative phase; c)potential predictors of adjustment assessed after the discussion concerning CDSUD as an option and before the setting of the CDSUD; d) Thematic analysis and narrative account of meaning-making process concerning the grief experience. DISCUSSION: The APSY-SED study will be the first to investigate the psychological adjustment of HCPs and relatives in the context of a CDSUD procedure implemented according to French law. Gathering data on the grief process for relatives can help understand bereavement after CDSUD, and participate in the elaboration of specific tailored interventions to support HCPs and relatives. Empirical findings on CDSUD among patients with cancer in France could be compared with existing data in other countries and with results related to other medical fields where CDSUD is also conducted. TRIAL REGISTRATION: This protocol received the National Registration Number: ID-RCB2021-A03042-39 on 14/12/2021.

Ventilator-associated pneumonia and bloodstream infections in intensive care unit cancer patients: a retrospective 12-year study on 3388 prospectively monitored patients.

PURPOSE: Some publications suggest high rates of healthcare-associated infections (HAIs) and of nosocomial pneumonia portending a poor prognosis in ICU cancer patients. A better understanding of the epidemiology of HAIs in these patients is needed. METHODS: A retrospective analysis of all the patients hospitalized for ≥ 48 h during a 12-year period in the 12-bed ICU of the Gustave Roussy hospital, monitored prospectively for ventilator-associated pneumonia (VAP) and bloodstream infection (BSI) and for use of medical devices. RESULTS: During 3388 first stays in the ICU, 198 cases of VAP and 103 primary, 213 secondary, and 77 catheter-related BSIs were recorded. The VAP rate was 24.5/1000 ventilator days (95% confidence interval [CI] 21.2-28.0); the catheter-related BSI rate was 2.3/1000 catheter days (95% CI 1.8-2.8). The cumulative incidence during the first 25 days of exposure was 58.8% (95% CI 49.1-66.6%) for VAP, 8.9% (95% CI, 6.2-11.5%) for primary, 15.1% (95% CI 11.6-18.5%) for secondary and 5.0% (95% CI 3.2-6.8%) for catheter-related BSIs. VAP or BSIs were not associated with a higher risk of ICU mortality. CONCLUSIONS: This is the first study to report HAI rates in a large cohort of critically ill cancer patients. Although both the incidence of VAP and the rate of BSI are higher than in general ICU populations, this does not impact patient outcomes. The occurrence of device-associated infections is essentially due to severe medical conditions in patients and to the characteristics of malignancy.

Intensive care in patients with lung cancer: a multinational study.

BACKGROUND: Detailed information about lung cancer patients requiring admission to intensive care units (ICUs) is mostly restricted to single-center studies. Our aim was to evaluate the clinical characteristics and outcomes of lung cancer patients admitted to ICUs. PATIENTS AND METHODS: Prospective multicenter study in 449 patients with lung cancer (small cell, n = 55; non-small cell, n = 394) admitted to 22 ICUs in six countries in Europe and South America during 2011. Multivariate Cox proportional hazards frailty models were built to identify characteristics associated with 30-day and 6-month mortality. RESULTS: Most of the patients (71%) had newly diagnosed cancer. Cancer-related complications occurred in 56% of patients; the most common was tumoral airway involvement (26%). Ventilatory support was required in 53% of patients. Overall hospital, 30-day, and 6-month mortality rates were 39%, 41%, and 55%, respectively. After adjustment for type of admission and early treatment-limitation decisions, determinants of mortality were organ dysfunction severity, poor performance status (PS), recurrent/progressive cancer, and cancer-related complications. Mortality rates were far lower in the patient subset with nonrecurrent/progressive cancer and a good PS, even those with sepsis, multiple organ dysfunctions, and need for ventilatory support. Mortality was also lower in high-volume centers. Poor PS predicted failure to receive the initially planned cancer treatment after hospital discharge. CONCLUSIONS: ICU admission was associated with meaningful survival in lung cancer patients with good PS and non-recurrent/progressive disease. Conversely, mortality rates were very high in patients not fit for anticancer treatment and poor PS. In this subgroup, palliative care may be the best option.

[Treatment of infected breast implant in reconstructive surgery]. / Complication infectieuse sur prothèse en chirurgie reconstructrice mammaire : quelle attitude thérapeutique adopter ?

OBJECTIVE OF THE STUDY: Immediate failure in breast surgery with implant is a serious medical complication with negative ramifications for both the patient and the health care system. The classical treatment is removal of the breast implant and delay reconstruction. Our objective is to show that this standard treatment is not the good one in many cases, and abundant irrigation with implant salvage is a sure and effective alternative. PATIENTS AND METHODS: Between January 2001 and December 2009, among the 680 patients who had a breast reconstruction, 18 were operated using the same protocol treatment by the same surgeon: implant removal, irrigation, implant replacement, antibiotic treatment. RESULTS: After a median month follow-up period of 30 months, definitive conservation of the breast implant was obtained in all of the cases. CONCLUSION: This preliminary study provides encouraging results in a selected patient population improving the possibility of a conservative treatment according to a precise and rigourous protocol.

Poor prognosis nonseminomatous germ-cell tumours (NSGCTs): should chemotherapy doses be reduced at first cycle to prevent acute respiratory distress syndrome in patients with multiple lung metastases?

BACKGROUND: Patients with extensive lung metastases from nonseminomatous germ-cell tumours (NSGCTs) and dyspnoea at presentation are at high risk of acute respiratory distress syndrome (ARDS) and death within the first weeks after chemotherapy induction. This syndrome is linked to acute intra-alveolar haemorrhage related to early tumour necrosis, which in turn, can be complicated by pulmonary infection promoted by neutropenia. The management of these patients was modified at Institut Gustave Roussy in 1997 to try to avoid this complication. PATIENTS AND METHODS: Data concerning all patients with lung metastases from NSGCT and dyspnoea or a partial pressure of oxygen (pO(2)) <80 mmHg treated from 1980 to 2006 in our institution were collected. Patients were treated in a specialised intensive care unit. From 1980 to 1997, the first chemotherapy cycle consisted in a full-dose regimen. After 1997, a 3-day reduced induction regimen of EP (cisplatin 20 mg/m(2)/day and etoposide 100 mg/m(2)/day) was used, with bleomycin and two additional days of EP being postponed to day 15, with the regular BEP regimen being started at day 21. RESULTS: Twenty-five patients with poor-risk disseminated NSGCT according to the International Germ Cell Consensus Classification Group had extensive lung metastases plus dyspnoea at presentation (n = 6), a pO(2) <80 mmHg (n = 2), or both criteria (n = 17). Median human chorionic gonadotrophin was 200 000 UI (range 11-8 920 000), and 18 of 25 (72%) patients also had nonpulmonary visceral metastases. During the 1980-1997 period, 13 of 15 patients (87%) developed ARDS, 10 of whom died, and only 4 of 15 (27%) patients were long-term survivors. In contrast, during the 1997-2006 period, only 3 of 10 patients (30%) developed ARDS (P = 0.01), 2 of whom died, and 4 of 10 (40%) eventually survived. CONCLUSION: Initial reduction of chemotherapy doses during the first cycle of chemotherapy for poor prognosis NSGCT with extensive lung metastases seems to prevent the risk of early death due to ARDS.

Differential time to positivity of central and peripheral blood cultures is inaccurate for the diagnosis of Staphylococcus aureus long-term catheter-related sepsis.

OBJECTIVES: Differential time to positivity of cultures of blood drawn simultaneously from central venous catheter and peripheral sites is widely used to diagnose catheter-related bloodstream infections without removing the catheter. However, the accuracy of this technique for some pathogens, such as Staphylococcus aureus, is debated in routine practice. METHODS: In a 320-bed reference cancer centre, the charts of patients with at least one blood culture positive for S. aureus among paired blood cultures drawn over a six-year period were studied retrospectively. Microbiological data were extracted from the prospectively compiled database of the microbiology unit. Data concerning the 149 patients included were reviewed retrospectively by independent physicians blinded to the absolute and differential times to positivity, in order to establish or refute the diagnosis of catheter-related sepsis. Due to missing data, 48 charts were excluded, so 101 cases were actually analysed. The diagnosis was established in 62 cases, refuted in 15 cases and inconclusive in the remaining 24 cases. RESULTS: For the 64 patients with both central and peripheral positive blood cultures, the differential positivity time was significantly greater for patients with catheter-related bloodstream infections due to S. aureus (P<0.02). However, because of the high number of false-negative cases, the classic cut-off limit of 120 min showed 100% specificity but only 42% sensitivity for the diagnosis of catheter-related bloodstream infection due to S. aureus. CONCLUSIONS: These results strongly suggest that despite its high specificity, the differential time to positivity may not be reliable to rule out catheter-related bloodstream infection due to S. aureus.

Characteristics and outcome of patients with newly diagnosed advanced or metastatic lung cancer admitted to intensive care units (ICUs).

BACKGROUND: Although patients with advanced or metastatic lung cancer have poor prognosis, admission to the ICU for management of life-threatening complications has increased over the years. Patients with newly diagnosed lung cancer appear as good candidates for ICU admission, but more robust information to assist decisions is lacking. The aim of our study was to evaluate the prognosis of newly diagnosed unresectable lung cancer patients. METHODS: A retrospective multicentric study analyzed the outcome of patients admitted to the ICU with a newly diagnosed lung cancer (diagnosis within the month) between 2010 and 2013. RESULTS: Out of the 100 patients, 30 had small cell lung cancer (SCLC) and 70 had non-small cell lung cancer. (Thirty patients had already been treated with oncologic treatments.) Mechanical ventilation (MV) was performed for 81 patients. Seventeen patients received emergency chemotherapy during their ICU stay. ICU, hospital, 3- and 6-month mortality were, respectively, 47, 60, 67 and 71%. Hospital mortality was 60% when invasive MV was used alone, 71% when MV and vasopressors were needed and 83% when MV, vasopressors and hemodialysis were required. In multivariate analysis, hospital mortality was associated with metastatic disease (OR 4.22 [1.4-12.4]; p = 0.008), need for invasive MV (OR 4.20 [1.11-16.2]; p = 0.030), while chemotherapy in ICU was associated with survival (OR 0.23, [0.07-0.81]; p = 0.020). CONCLUSION: This study shows that ICU management can be appropriate for selected newly diagnosed patients with advanced lung cancer, and chemotherapy might improve outcome for patients with SCLC admitted for cancer-related complications. Nevertheless, tumors' characteristics, numbers and types of organ dysfunction should be taken into account in the decisional process before admitting these patients in ICU.

Changes in intensive care for allogeneic hematopoietic stem cell transplant recipients.

Intensive care unit (ICU) admission is associated with high mortality in allogeneic hematopoietic stem cell transplant (HSCT) recipients. Whether mortality has decreased recently is unknown. The 497 adult allogeneic HSCT recipients admitted to three ICUs between 1997 and 2011 were evaluated retrospectively. Two hundred and nine patients admitted between 1997 and 2003 were compared with the 288 patients admitted from 2004 to 2011. Factors associated with 90-day mortality were identified. The recent cohort was characterized by older age, lower conditioning intensity, and greater use of peripheral blood or unrelated-donor graft. In the recent cohort, ICU was used more often for patients in hematological remission (67% vs 44%; P<0.0001) and without GVHD (73% vs 48%; P<0.0001) or invasive fungal infection (85% vs 73%; P=0.0003) despite a stable admission rate (21.7%). These changes were associated with significantly better 90-day survival (49% vs 31%). Independent predictors of hospital mortality were GVHD, mechanical ventilation (MV) and renal replacement therapy (RRT). Among patients who required MV or RRT, survival was 29% and 18%, respectively, but dropped to 18% and 6% in those with GVHD. The use of ICU admission has changed and translated into improved survival, but advanced life support in patients with GVHD usually provides no benefits.

Prognostic factors for neutropenic patients in an intensive care unit: respective roles of underlying malignancies and acute organ failures.

The admission of neutropenic patients to an intensive care unit (ICU) is still controversial, especially if mechanical ventilation is required. To avoid useless stays in ICU, the evaluation of the respective role of the underlying malignancy and acute organ failures might be useful for better definition of the categories of patients who could benefit from aggressive ICU support. For this purpose, we carried out a retrospective study of the charts of 107 consecutive neutropenic patients admitted to an ICU in a comprehensive cancer centre over a four-year period. The following characteristics were recorded within 24 h of admission: patient data, characteristics of neutropenia and the underlying malignancy, the type and number of organ system failures (OSFs) and simplified acute physiological scores (SAPS and SAPS II). The impact of each variable on outcome in the ICU was studied by univariate and multivariate (logistic regression) analysis. 59 patients died in the ICU (mortality rate: 55%). Patients with a haematological malignancy (n = 57, 53%) were more likely to experience respiratory failure, an underlying malignancy deemed rapidly fatal, and to have longer lasting neutropenia than patients with a solid tumour (n = 50, 47%). However, the mortality rate did not differ in the two groups (haematological malignancy 61% versus solid tumour 48%, p = 0.16). Respiratory and cardiovascular organ failure (p < 0.001 for both) correlated with mortality in the ICU. In the multiple logistic regression model, only the number of organ system failures and respiratory failure remained predictive of ICU mortality. In conclusion, the characteristics of the underlying malignancy are not relevant when deciding whether or not neutropenic patients should be admitted to an ICU. The main risk factors for death in an ICU are the number of organ failures on admission, and among them the presence of respiratory failure.

Nebulized cyclosporine in the rat: assessment of regional lung and extrapulmonary deposition.

BACKGROUND: Nebulized cyclosporine (CsA) has been shown to limit lung allograft rejection as well as intramuscular (IM) CsA, with limited blood diffusion. The present study determined the pharmacokinetic parameters of nebulized CsA, by the assessment of regional lung deposition and extrapulmonary diffusion of CsA. METHODS: CsA was given either by IM injection (10 mg/kg) or by aerosol (at 10 and 25 mg/kg doses); 70 rats were killed at 25 and 50 min, and at 2, 4, 6, 8, 12, 24, or 48 hr after CsA administration. CsA levels were measured in the whole lung, in central and peripheral parts of the lung, in whole blood, kidney, and heart. The areas under the concentration time curves (AUCs) were determined. RESULTS: In blood, kidney, and heart, CsA levels were significantly higher for IM than for aerosol administrations at 10 and 25 mg/kg doses. In the whole lung, the AUC was greater for the aerosol route at 25 mg/kg doses (588 ng x hr/mg) than for the low-dose (200 ng x hr/mg) or IM administration (200 ng x hr/mg). The central to peripheral index of CsA (ratio of AUC central/peripheral part of the lung) was not significantly different for both aerosol administrations (0.63 and 0.69, respectively) and for the IM route (0.81). CONCLUSIONS: Nebulized CsA allows better pulmonary concentration than IM administration, with equivalent central and peripheral deposition whatever the mode of administration, and results in lower levels in blood, kidney, and heart.

Diagnosis of nosocomial pneumonia in cancer patients undergoing mechanical ventilation: a prospective comparison of the plugged telescoping catheter with the protected specimen brush.

STUDY OBJECTIVES: Quantitative culture of protected samples of lower respiratory tract secretions obtained by a fiberoptic protected specimen brush (PSB) is widely accepted for the diagnosis of ventilator-associated pneumonia (VAP), but this diagnostic procedure is time consuming, expensive, and may give rise to iatrogenic complications, especially in cancer patients who often present with thrombocytopenia. The plugged telescoping catheter (PTC) could be a satisfactory alternative to the PSB in this setting. The aim of the present study was to evaluate the interest of the PTC to diagnose VAP in ventilated cancer patients. DESIGN: A prospective observational study. SETTING: A 15-bed medical-surgical ICU in a comprehensive cancer center. PATIENTS AND INTERVENTIONS: Over a 9-month period, 42 patients suspected of having bacterial VAP during mechanical ventilation underwent 69 bronchial samplings: a blinded PTC and a fiberoptic PSB were performed successively in each case. A positive culture for both sampling procedures was defined as the recovery of > or = 10(3) cfu/mL of at least one potential pathogen. The PSB result was taken as the reference standard. MEASUREMENTS AND RESULTS: The overall agreement between the techniques was 87% (60/69). PTC had a sensitivity of 67%, a specificity of 93%, a positive predictive value of 71%, and a negative predictive value of 91%. CONCLUSIONS: We conclude that the accuracy of the blinded PTC compares well with that of the PSB for the diagnosis of VAP in cancer patients. The sensitivity of the PTC observed herein, which is slightly lower than that described in previous studies, may be due to the blinded nature of the method: the indications for initial or secondary coupling with a directed sampling method in patients with suspicion of localized pneumonia remain to be determined.

Nebulized cyclosporine for prevention of acute pulmonary allograft rejection in the rat: pharmacokinetic and histologic study.

BACKGROUND: With regard to limiting the systemic effects of cyclosporine A and obtaining better control of acute pulmonary allograft rejection, local immunosuppressive therapy with aerosolized cyclosporine A seems of interest. Given the in situ immunologic mechanisms of acute rejection, as well as the anatomic structure of the lung, this therapy is feasible as previously described by others. The aim of our study is to determine the pharmacokinetic parameters of nebulized cyclosporine A and the best modalities of administration. METHODS: In a pharmacokinetic study, the cyclosporine A was given either by intramuscular injection (10 mg/kg) or by aerosol at 10 and 25 mg/kg doses; 70 rats were killed at 25 and 50 minutes and 2, 4, 6, 8, 12, 24, or 48 hours after cyclosporine A administration. Cyclosporine A levels were measured in whole blood and in the lung. The areas under the concentration time curves were determined. Twenty-four lung transplantations were then performed. The rats were killed on postoperative day 9. Acute rejection was scored on a scale of 0 to 4, and cyclosporine A trough levels were measured in the lung and in the blood. RESULTS: With a jet nebulizer, the mass median aerodynamic diameter was 2.5 microns, with a standard geometric deviation of 2.3. In blood, the area under the concentration curve was greater for intramuscular (80.6 ng.hr/ml) than for aerosol administrations at 10 (15.1 ng.hr/ml) and 25 mg/kg (41.0 ng.hr/ml) doses. In the lungs, the area under the concentration curve was greater for the aerosol route at 25 mg/kg doses (588 ng.hr/mg) than for the low-dose (200 ng.hr/mg) or intramuscular administration (200 ng.hr/mg). The lung targeting index of cyclosporine A (ratio area under the concentration curve-lungs/area under the concentration curve-blood) was greater for both aerosol administrations than for the intramuscular route. In the study of the prevention of acute rejection, rats without immunosuppression (n = 6), rats receiving daily doses of cyclosporine A intramuscularly (10 mg/kg), and rats with aerosolized cyclosporine A daily (10 and 25 mg/kg/day) showed mean grades of acute rejection of, respectively, 4, 2.03 +/- 0.27, 2.33 +/- 0.52, and 2.17 +/- 0.46. The deposition of nebulized cyclosporine A was lower in transplanted than in native lung. CONCLUSIONS: Nebulized cyclosporine A allows better pulmonary concentration than intramuscular administration, and results in lower systemic levels. Prevention of acute rejection is as good with aerosolized cyclosporine A as with intramuscular cyclosporine A. This first pharmacokinetic study of nebulized cyclosporine A could lead to clinical applications.

Accuracy of totally implanted ports, tunnelled, single- and multiple-lumen central venous catheters for measurement of central venous pressure.

OBJECTIVE: To verify the accuracy of totally implanted ports, tunnelled central venous catheters (CVC), widely used in cancer patients, and multi-lumen catheters, used in intensive care units (ICUs), in measuring central venous pressure (CVP), using right atrial pressure (RAP) measured in a Swan-Ganz catheter as the reference standard. DESIGN: A prospective study, over a 10-month period. SETTING: A medical-surgical ICU in a comprehensive cancer centre. PATIENTS AND PARTICIPANTS: Patients who had both (1) a Swan-Ganz catheter and (2) either a tunnelled catheter, a single or a multi-lumen catheter, or a totally implanted port. INTERVENTIONS: RAP and CVP were measured simultaneously in each patient. MEASUREMENTS AND RESULTS: Fifty-six pairs of RAP-CVP measurements were performed in 35 patients: 6 tunnelled catheters, 6 non-tunnelled single-lumen catheters, 26 multiple-lumen catheters and 18 totally implanted ports were studied. RAP measured in the Swan-Ganz catheter and CVP measured in the CVC were strongly correlated (r = 0.94, p < 0.01), whatever the type of catheter studied. The mean difference between RAP and CVP was -0.39 +/- 1.73 (SD) mmHg. In 51 cases (91%), the difference was within the limits of agreement (-3.78 to 3.00 mmHg, Bland and Altman method). For the five cases with a difference of 4 mmHg (three totally implanted ports, one double- and one triple-lumen catheter), CVP was greater than RAP. CONCLUSIONS: CVP can be accurately measured in totally implanted ports, tunnelled or non-tunnelled single-lumen and multiple-lumen catheters. When the difference exceeds the limit of agreement, the discrepancy between the two measurements has limited significance in most cases.

Safety of tracheotomy in neutropenic patients: a retrospective study of 26 consecutive cases.

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.

Isospora belli infection in a patient with non-Hodgkin's lymphoma.

Isospora belli infection is frequent in patients with acquired immunodeficiency syndrome in tropical areas. It has also been reported in other immunodepressive diseases, such as lymphoblastic leukemia, adult T-cell leukemia, and Hodgkin's disease. To date, no case of non-Hodgkin's lymphoma-related isosporiasis has been reported in a non-HIV-infected patient. We describe a case of non-Hodgkin's lymphoma with chronic diarrhea due to I. belli. In Europe, I. belli can cause severe chronic diarrhea in patients with malignancies whose country of origin is in an endemic area. Trimethoprim-sulfamethoxazole can provide rapid and prolonged clinical and parasitologic cure.

Successful rescue in a patient with high dose methotrexate-induced nephrotoxicity and acute renal failure.

We describe the case of a 35-year old male who developed acute renal failure following high dose methotrexate therapy for Burkitt's non Hodgkin lymphoma. Serum methotrexate levels reached 37 micromol/l, and remained higher than 1 micromol/l for more than a week. Folinic acid rescue was intensified to 200-400 mg intravenously every 4 hours. As methotrexate binds markedly to proteins, plasma exchange was initially chosen, 4 sessions being performed from day 2 to day 4. The methotrexate pharmacokinetic profile was not significantly modified during plasma exchange, and serum drug level was 3 micromol/l. Continuous veno-venous hemodiafiltration was therefore performed from day 5 to day 10. This procedure also seemed ineffective, with evidence of low ultrafiltrate clearance. No extrarenal toxicity was observed in our patient. Thus, conventional extrarenal procedures appear to have a limited role in the setting of overexposure to methotrexate. The use of very high doses of folinic acid in our case probably played a major role in the eventual favorable outcome.

Mechanisms and risk factors for infection of pulmonary artery catheters and introducer sheaths in cancer patients admitted to an intensive care unit.

Pulmonary artery catheters (PACs) are typically inserted for short periods, and the extra-luminal route is assumed to be the overriding source of contamination and/or infection. Our aim was to assess the incidence of PAC and introducer colonization in cancer patients, and to study the mechanisms and risk factors for infection. Patients with a Swan-Ganz catheter admitted to an intensive care unit were prospectively analyzed over 14 months. As soon they were no longer necessary, PACs and introducer sheaths were removed and cultured. We recorded the mean duration of placement, the number of times PACs were handled and the site of insertion. Seventy-nine catheters were inserted in 68 patients. The median (range) duration was three days (0-10) for PACs, and 3.6 days (0-18) for introducers. PAC and/or percutaneous introducer sheath colonization was diagnosed in seven patients (8.9%), but in only one case were both colonized. Colonization rates were 15.5 per 1000 days for PACs and 14.1 per 1000 days for introducers. Introducers were mainly colonized before the 5th day, while PACs were mainly colonized after the 5th day. No PAC or introducer-related local infection or bacteraemia was diagnosed. Colonization was more frequent on catheters inserted into the internal jugular vein. The colonization rate was 5% for PACs and introducers. Our findings suggest that contamination of introducers and PACs may be dissociated and could result from either extraluminal or endoluminal colonization. As three of four PAC colonizations occurred after 5 days, the duration of catheter placement should be considered important. There was little clinical impact of microbial colonization.

Peritoneal carcinomatosis treatment with curative intent: the Institut Gustave-Roussy experience.

The prognosis of peritoneal carcinomatosis (PC), classically treated with intravenous chemotherapy, is very poor (mean survival of 6 months). The aim of this study is to report the results of a phase II study in which PC was treated with complete cytoreductive surgery, with the residual microscopic disease treated by immediate intraperitoneal post-operative chemotherapy (IIPC) for 5 days (mitomycin with fluorouracil or Adriamycin with Platinol. Fifty-four patients with PC from miscellaneous origins were treated between January 1993 and April 1996. The PC was important (clinically evident) but with no extraperitoneal localization in 29 cases. The PC was moderate or minor in 25 cases having been fortuitously discovered during a laparotomy for extraperitoneal cancer localization. Operating time was 7:21 h, associated frequently with extensive peritonectomies, and with resection of invaded organs (four organs per patient). IIPC was complete (5 days) in 91 per cent of patients. Three post-operative deaths (5.5%) occurred. Morbidity was present in 61 per cent of patients, and was related to surgical extension (P < 0.001). A 2-year survival of 50% was mainly correlated with the importance of the PC (P < 0.01), and was the same for both groups of patients (isolated major PC vs moderate (or minor) PC associated with extraperitoneal localization). PC recurrence rates were 30 per cent at 2 years. Complete cytoreductive surgery associated with IIPC is a logical and promising treatment of moderate and minor PC. However, it appears that it is a heavy treatment for patients (and physicians), and its efficacy will be proved only after a randomized study for survival, quality of life, and cost (currently ongoing).

Comparison of jet and ultrasonic nebulizers for alveolar targeting of methylprednisolone.

The secondary systemic effects of oral corticosteroid therapy in chronic lung disease indicate the possible benefits of local therapy. The aim of this study was to show if alveolar targeting of a corticosteroid, methylprednisolone (MP), is possible, and to determine which type of nebulizer allows the most selective deposition into the alveoli. A jet nebulizer (Respirgard II) with 2 ml volume fill (R2), and an ultrasonic nebulizer (Ultraneb 99) with 4 ml volume fill (U4), were compared using a 40-mg dose of MP labelled 99Tcm human serum albumin. Particle size and MP-to-albumin binding were measured in the aerosol cloud. Each nebulizer was used in random order in five healthy volunteers. A dynamic posterior scan of 68 images of 15 s each was performed with a Gammatome II gamma camera during inhalation. Peripheral and central regions of interest were automatically defined with reproducible methods, and the peripheral-to-central ratio was used as a penetration index. Stomach and oropharynx activities were estimated on static anterior and static left lateral views, respectively, at the end of the examination. The mass median aerodynamic diameter (MMAD) was lower for R2 when unlabelled MP was used. The MMAD of MP+HSA was compatible with alveolar targeting. In the aerosol cloud, MP-albumin binding was 75% for R2 and 79% for U4. Peripheral and central activities at equilibrium (13-16 min) were higher with U4, but the penetration index was significantly higher with R2. Moreover, the stomach and oropharynx activities were significantly lower with R2.(ABSTRACT TRUNCATED AT 250 WORDS)

[Complications and tolerance of heated intraperitoneal chemotherapy and cytoreductive surgery for peritoneal carcinomatosis: results of a phase I-II study of peritoneal carcinomatosis from different sources]. / Complications et tolérance de la chimio-hyperthermie intrapéritonéale (CHIP) après exérèse chirurgicale des carcinoses péritonéales (CP): résultats d'une étude de phase I-II portant sur des CP de différentes origines.

Peritoneal carcinomatosis represents the terminal stage of adenocarcinomas of the gastrointestinal tract. A new treatment combining cytoreductive surgery and intraperitoneal chemotherapy-hyperthermia has been used with encouraging results. The purpose of this study was to report the complications associated with this treatment. Fourty procedures were carry out in 37 patients. Death occurred in 3 patients. Major medical complications were 13 pulmonary infections, 11 acute renal failure (with only 3 who needed dialysis) and 10 patients with neutropenia grade 3 and 4 toxicity. Intra-abdominal complications occurred in 16 patients (there were 11 anastomotic leak and/or bowel perforation, and 12 intra-abdominal infections). Some complications like secretory diarrhea or tubulopathia which were related to these treatment need further investigations. Six procedures were without any complications, 6 presented minor ones and 22 major complications. Adverse effects were relatively important with this new treatment strategy. This was maybe due to a learning process; there is no death and only one anastomotic leak in our last study including 30 patients with cytoreductive surgery and intraperitoneal chemotherapy-hyperthermia.