Overall survival with adjuvant atezolizumab after chemotherapy in resected stage II-IIIA non-small-cell lung cancer (IMpower010): a randomised, multicentre, open-label, phase III trial.

BACKGROUND: IMpower010 (NCT02486718) demonstrated significantly improved disease-free survival (DFS) with adjuvant atezolizumab versus best supportive care (BSC) following platinum-based chemotherapy in the programmed death-ligand 1 (PD-L1)-positive and all stage II-IIIA non-small-cell lung cancer (NSCLC) populations, at the DFS interim analysis. Results of the first interim analysis of overall survival (OS) are reported here. PATIENT AND METHODS: The design, participants, and primary-endpoint DFS outcomes have been reported for this phase III, open-label, 1 : 1 randomised study of atezolizumab (1200 mg q3w; 16 cycles) versus BSC after adjuvant platinum-based chemotherapy (1-4 cycles) in adults with completely resected stage IB (≥4 cm)-IIIA NSCLC (per the Union Internationale Contre le Cancer and American Joint Committee on Cancer staging system, 7th edition). Key secondary endpoints included OS in the stage IB-IIIA intent-to-treat (ITT) population and safety in randomised treated patients. The first pre-specified interim analysis of OS was conducted after 251 deaths in the ITT population. Exploratory analyses included OS by baseline PD-L1 expression level (SP263 assay). RESULTS: At a median of 45.3 months' follow-up on 18 April 2022, 127 of 507 patients (25%) in the atezolizumab arm and 124 of 498 (24.9%) in the BSC arm had died. The median OS in the ITT population was not estimable; the stratified hazard ratio (HR) was 0.995 [95% confidence interval (CI) 0.78-1.28]. The stratified OS HRs (95% CI) were 0.95 (0.74-1.24) in the stage II-IIIA (n = 882), 0.71 (0.49-1.03) in the stage II-IIIA PD-L1 tumour cell (TC) ≥1% (n = 476), and 0.43 (95% CI 0.24-0.78) in the stage II-IIIA PD-L1 TC ≥50% (n = 229) populations. Atezolizumab-related adverse event incidences remained unchanged since the previous analysis [grade 3/4 in 53 (10.7%) and grade 5 in 4 (0.8%) of 495 patients, respectively]. CONCLUSIONS: Although OS remains immature for the ITT population, these data indicate a positive trend favouring atezolizumab in PD-L1 subgroup analyses, primarily driven by the PD-L1 TC ≥50% stage II-IIIA subgroup. No new safety signals were observed after 13 months' additional follow-up. Together, these findings support the positive benefit-risk profile of adjuvant atezolizumab in this setting.

[Antibiotic consumption and bacterial sensitivity in a teaching hospital: A 5-year study]. / Profil de consommation et de sensibilité aux antibiotiques utilisés dans un centre hospitalier universitaire : étude rétrospective sur cinq ans.

INTRODUCTION: To reduce risks of antibiotic resistance, governmental and learned societies decreed the optimal use of antibiotics. The relation between antibiotic consumption and bacterial resistance increase has been clearly demonstrated over the last several years. Antibiotic consumption data and bacterial sensitivity data are regularly published, but very few publications have searched for a correlation between these two variables. This study focused on antibiotic use and consumption as well as bacterial sensitivity to these antibiotics. OBJECTIVES: The main objective was to describe the changes in antibiotic consumption and bacterial sensitivity in a mother-child teaching hospital. The secondary objectives were to explore whether antibiotic use and bacterial sensitivity were correlated and to comment on the usefulness of these data for clinicians. METHODS: This was a 5-year retrospective, descriptive, cross-sectional study. All samples from usually sterile biologic liquids of hospitalized pediatric patients were included in the study. The samples from outpatient clinics were excluded. All types of bacteria identified in more than 30 isolates were included in the study. The antibiotics usually used to treat these bacteria were included. To assess antibiotic consumption, we calculated the number of days of therapy per 1000 patient-days for hospitalized pediatric patients and we calculated the Pearson correlation coefficient between antibiotic consumption and sensitivity rates to these antibiotics. Two scenarios were explored: one with correlation by year and one with the next year for bacterial sensitivity. RESULTS: During the study period (2010-2011 to 2014-2015), overall antibiotics consumption remained relatively stable. Concerning bacterial sensitivity, we noted important changes (sensitivity rates increased for 12 antibiotic-bacteria pairs, remained stable for five, and decreased for 15). We found three significant correlations for the first scenario: Pseudomonas aeruginos-ceftazidime (P=0.01), P. aeruginosa-ciprofloxacin and fluoroquinolone consumption (P=0.02), Enterococcus sp-ampicillin and penicillin consumption (P=0.04). For the second scenario, we found only two significant correlations: coagulase-negative Staphylococcus-oxacilline and penicillin consumption (P=0.02), P. aeruginosa/piperacillin (P=0.04). CONCLUSION: This exploratory study allowed us to describe antibiotic consumption and bacterial sensitivity progression. To our knowledge, this is the first study exploring the correlation between antibiotic consumption and the bacterial sensitivity rate in pediatrics in Canada. It remains very difficult to show this correlation between these two variables because of the multiple sources of bacterial resistance. These data are particularly useful for the antimicrobial stewardship programs and for clinicians.

Interferon treatment of multiple pulmonary malignancies associated with papilloma virus.

Over a period of four years, beginning in spring 1988, a previously healthy man developed a primary squamous cell carcinoma of the tonsil, treated with radiotherapy, followed by 10 distinct, primary bronchial squamous cell carcinomas. Four of the cancers were surgically resected, all of which were positive by hybridization for human papilloma virus (type 16). Following the institution of alpha interferon, three smaller lesions disappeared and a larger one shrank in size, facilitating surgical resection. Over the following seven years no new ones have appeared. The finding of papilloma virus in malignancies should prompt consideration of antiviral therapy.

Endoscopic upper thoracic sympathectomy.

Thoracoscopic sympathectomy provides a superb surgical option for the many patients with incapacitating essential hyperhidrosis. Whether one thoracoscopic approach to sympathectomy is ever likely to prevail is doubtful, as the results of the various reported techniques seem to be quite similar. There are definite advantages to the single-port approaches, which are faster and usually do not require repositioning of the patient to do both sides. In the rare instances where dense apical adhesions are encountered or when significant bleeding is encountered from one of the intercostal vessels, the two- or three-port approaches definitely provide better control (see commentary in article by Kohno and Takamoto). Surgeon preference probably dictates which approach is used at the different centers. Compensatory sweating remains a frequent and sometimes serious complication of the procedure, particularly in individuals living in hot climates. An understanding of its mechanisms needs improvement, with the hope of preventing its occurrence in the future. In the meantime, patients have to be informed of its frequency, and operations could probably be tailored to the patients' needs and their local climate.

Role of bronchoscopy in massive hemoptysis.

Airway hemorrhage is a potentially rapidly fatal condition. Death may occur within minutes from asphyxiation before control can be achieved. The primary prognostic factors are the rate of bleeding and the underlying cardiopulmonary status of the patient. Bronchoscopy is central in management, but the goals differ, depending on circumstances. In stable patients who have minimal hemoptysis, bronchoscopy can diagnose the cause specifically and be used as the primary treatment modality. In the setting of massive or life-threatening bleeding, bronchoscopy primarily is performed to maintain ventilation and to direct endobronchial blockade. Although flexible bronchoscopy is an acceptable mode initially, there should be no delay in performing rigid bronchoscopy when it becomes apparent that bleeding is too vigorous to permit [figure: see text] successful airway exploration with the smaller flexible instrument. Once isolation of bleeding has been achieved, the choice must be made between embolization, surgical resection, or both of these procedures.

Surgical management of lung gangrene.

OBJECTIVE: To review the outcomes of five cases of pulmonary resection for lung gangrene. DESIGN: A retrospective chart review. SETTING: A tertiary referral centre. POPULATION STUDIED: Five patients who underwent pulmonary resection for lung gangrene between April and December 1999. MAIN RESULTS: Pathological confirmation of lung gangrene was obtained in all cases. Three patients were ventilator dependent. All five patients had ongoing sepsis despite antibiotic therapy. Additional indications for resection included bronchopleural fistula (two patients), empyema (three patients) and hemoptysis (one patient). In two cases, there was evidence of bilateral, diffuse necrotizing pneumonia, while in three cases the process was localized to one side. Computed tomography revealed cavitation in four cases and the absence of blood supply to the affected lung in one case. Surgical resection included wedge resection (one patient), lobectomy (two patients), bilobectomy (one patient) and pneumonectomy (one patient). In all cases, the bronchial stump was reinforced with an intercostal flap. Postoperative empyema occurred in two cases, one treated by thoracoscopic decortication, the other by percutaneous drainage. There were no instances of stump leak and no deaths. One patient remains ventilator dependent. CONCLUSIONS: Resection for lung gangrene is possible even in the setting of diffuse parenchymal changes and ventilator dependency. A computed tomography scan of the chest is important to make the diagnosis of lung gangrene and to plan operative management. Reinforcement of the bronchial stump is critical.

Reconstruction of irradiated postpneumonectomy empyema cavity with chain-link coupled microsurgical omental and TRAM flaps.

We present the first case of complete hemithoracic reconstruction of an irradiated postpneumonectomy recurrent empyema cavity that was unresponsive to multiple conventional treatments. The procedure described used a chain-link of two coupled free flaps consisting of an omental and TRAM flap. A single abdominal donor site and single operative position are other advantages of this technique that provides sufficient volume to obviate the need for thoracoplasty even in the largest wounds.

Descending necrotizing mediastinitis: An analysis of the effects of serial surgical debridement on patient mortality.

OBJECTIVES: Descending necrotizing mediastinitis is a polymicrobial infection originating in the oropharynx with previously reported mortality rates of 25% to 40%. This investigation reviews the effects of serial surgical drainage and debridement on the survival of patients with descending necrotizing mediastinitis. METHODS: A retrospective review of patients from 1980 through 1998 with a diagnosis of descending necrotizing mediastinitis was performed. Their records were abstracted for personal demographics, hospital course, morbidity, and mortality. Also abstracted were all reports of patients with descending necrotizing mediastinitis published in English between 1970 and 1999. RESULTS: We treated 10 patients in whom descending necrotizing mediastinitis was identified. The mean age of the patients was 38 years. They underwent a mean of 6 +/- 4 computed tomographic imaging studies, 4 +/- 1 transcervical drainage procedures, and 2 +/- 1 transthoracic drainage procedures. Three patients required abdominal exploration and 4 underwent tracheostomy. No deaths occurred. In contrast, 96 patients with descending necrotizing mediastinitis were identified from the literature with a mean age of 38 years. They underwent a mean of 2 +/- 1 computed tomographic imaging studies, 2 +/- 1 transcervical drainage procedures, and 0.7 + 0.3 transthoracic drainage procedures. Sixteen (17%) patients required abdominal exploration and 34 (35%) underwent tracheostomy. Twenty-eight (29%) patients from the literature cohort died during their treatment. CONCLUSION: Descending necrotizing mediastinitis remains a life-threatening infection. On the basis of experience accrued in treating these patients, an algorithm incorporating computed tomographic imaging for diagnosis and surveillance and serial transcervical and transthoracic operative drainage is outlined in the hope of reducing the excessive mortality of descending necrotizing mediastinitis.

Early complications. Chylothorax.

Postpneumonectomy chylothorax is a very common but serious complication. Drainage of the pneumonectomy space, metabolic and nutritional support with TPN, and absolute enteral rest may lead to control of the leak. Failure of these measures to obtain a rapid resolution of the chyle losses should be followed by early surgical intervention in most instances in an effort to alleviate the chronic metabolic, nutritional, and immunological consequences of prolonged chyle losses.

Bronchial-atrial fistula after lung transplant resulting in fatal air embolism.

We describe a rare case of fatal air embolism in a patient in whom a left atrial-bronchial fistula developed 1 month after single lung transplant. The cause was a combination of mediastinal infection and bronchial necrosis.

Percutaneous placement of tracheal T tube.

Tracheal T tubes provide effective palliation of unresectable benign and malignant tracheal obstruction, but placement may be difficult when previous operation, radiation, or tumor limits surgical exposure of the cervical trachea. Percutaneous placement using commercially available percutaneous tracheostomy kits may provide an alternative approach in these cases.

A comparison of rigid -v- video thoracoscopy in the management of chest trauma.

Between December 1, 1994 and April 1,1998, 44 thoracoscopic procedures were performed in 42 patients following chest injuries. Indications included exploration in 15, retained haemothorax in 10, continued bleeding after chest tube placement in 3, air leak in 5 and empyema in 11. Video thoracoscopy was used in 24 cases and rigid thoracoscopy in 20, including 14 patients in whom video thoracoscopy was contraindicated. There was no difference in the operative times, length of stay or incidence of complications. Two formal and 3 "mini" thoracotomies were used in the video thoracoscopy group. Three "mini" thoracotomies were required in the rigid thoracoscopy group. Rigid thoracoscopy is an effective tool that, in selected cases, increases the utility of thoracoscopy in the management of chest trauma and its complications.

Tracheobronchial resection and reconstruction.

OBJECTIVE: To assess the indications and results of airway resection and how frequently airway reconstructive options changed proposed therapy. DESIGN: A retrospective survey of patients undergoing major airway resection. SETTING: University of Washington-affiliated hospitals, Seattle, May 1992 through December 1996. PATIENTS: Fifty consecutive patients with resectable benign and malignant tracheal or main bronchial disease undergoing tracheobronchial resections. INTERVENTIONS: Patients underwent major airway resection as follows: tracheal or laryngotracheal resection, 23 patients; carinal resection, 6; and bronchial sleeve resection with or without pulmonary resection, 21. Indications for surgery were non-small cell lung cancer in 19 patients, primary airway tumor in 12, thyroid carcinoma in 1, and tracheal or bronchial stenosis in 18. MAIN OUTCOME MEASURES: Change in prereferral planned therapy from palliative to definitive or to pulmonary-sparing procedure, morbidity and mortality, relief of symptoms, and survival. RESULTS: Mortality was 0%, and morbidity, 32% (15/50). Airway reconstruction changed the proposed therapy in 42 patients (84%). Functional results were good to excellent in 17 (94%) of 18 patients with benign disease. Patients with malignant disease had a 1-year survival of 93% (27/29) and a 2-year survival of 67% (12/18). CONCLUSIONS: Airway resection and reconstruction provide reliable relief of benign and malignant tracheobronchial disease with minimal morbidity and mortality. Airway reconstruction frequently changed prereferral planned therapy and provided definitive and parenchymal-sparing procedures to patients with complex airway lesions.

Optimal treatment of descending necrotising mediastinitis.

BACKGROUND: Descending necrotising mediastinitis is caused by downward spread of neck infection and has a high fatality rate of 31%. The seriousness of this infection is caused by the absence of barriers in the contiguous fascial planes of neck and mediastinum. METHODS: The recent successful treatment of seven adult patients with descending necrotising mediastinitis emphasises the importance of optimal early drainage of both neck and mediastinum and prolonged antibiotic therapy. The case is also presented of a child with descending necrotising mediastinitis, demonstrating the rapidity with which the infection can develop and lead to death. Twenty four case reports and 12 series of adult patients with descending necrotising mediastinitis published since 1970 were reviewed with meta-analysis. In each case of confirmed descending necrotising mediastinitis the method of surgical drainage (cervical, mediastinal, or none) and the survival outcome (discharge home or death) were noted. The chi 2 test of statistical significance was used to detect a difference between cases treated with cervical drainage alone and cases where mediastinal drainage was added. RESULTS: Cervical drainage alone was often insufficient to control the infection with a fatality rate of 47% compared with 19% when mediastinal drainage was added (p < 0.05). CONCLUSIONS: Early combined drainage with neck and chest incisions, together with broad spectrum intravenous antibiotics, should be considered standard care for this disease.

Cell kinetics analysis of surgically resected non-small cell carcinoma of the lung using the AgNOR silver stain.

Cell kinetics analysis of lung carcinoma using DNA flow cytometry has shown a significant correlation with the biological behavior of these neoplasms. Ploidy has shown a more significant association with aggressive behavior. The method may however not be available in all centers. Two counts of the AgNOR silver stain have been correlated with ploidy and proliferative activity (PA). The first count, which is the mean number of AgNOR granules (mAgNOR), correlates with ploidy. The second count is the percentage of cells with > 5 AgNORs/nucleus (pAgNOR), reflects PA. We performed the AgNOR silver stain using the two above-mentioned counts in 41 cases of surgically resected nonâsmall cell carcinoma of the lung. The cases included 14 adenocarcinomas, 24 squamous cell carcinomas, and three undifferentiated nonâsmall cell carcinomas. Follow-up data were available on 36 of the patients, ranging from 10 to 31 months (median 18 months). Thirteen of these patients (36%) developed progressive disease. Adenocarcinomas showed mAgNOR counts suggestive of aneuploidy (> 2.4) in nine of the 14 patients (64%) and 16 of the 24 squamous carcinomas (66%). The adenocarcinomas showed high pAgNOR counts (> 8%) in eight of the 14 cases (57%), in contrast to 15 of the 24 squamous carcinomas (62%). The AgNOR counts did not show any statistically significant correlation with tumor type, grade or stage of disease. The mAgNOR counts were aneuploid in all 13 progressive cases and in only 10 of the 23 stable cases (43%)(P=0.001). The pAgNOR counts were high in 12 of the 13 cases that progressed (92%), in contrast to 10 of the 23 stable cases (43%)(P=0.01). There is no significant evidence that squamous carcinoma of the lung may have a higher incidence of aneuploidy and high PA than adenocarcinoma. Our data also confirm previous data showing that aneuploid lung carcinomas have more aggressive behavior than diploid ones. This study also indicates that, despite the short-term follow-up data, the use of the AgNOR silver stain for cell kinetics analysis of nonâsmall cell carcinoma of the lung may potentially provide useful predictive information on the biologic behavior of lung carcinoma. Long-term follow-up may provide more significant information.