In-Hospital Clinical Features, Morbidity, and Mortality of Patients with Neurofibromatosis 1 in France: A Nationwide, Population-Based Retrospective Cohort Study.

Neurofibromatosis 1 (NF1) is a multisystem disease that can affect nearly every organ system. The aim of our study was to describe the in-hospital population with NF1 in France. We conducted a nationwide retrospective cohort study using the French hospital administrative database. A total of 11,425 patients with NF1 (53.4% female, 19,080 person years) were identified from January 2013 to December 2019. A total of 23% had at least one diagnosis of a comorbidity or NF1-associated complication or disease, and it was highest in the age group of 10-15 years. A total of 2,601 (22.8%) had a diagnosis of cancer. There were 366 (3.2%) in-hospital deaths, and we observed a standardized mortality ratio of 4.14 (95% confidence interval = 3.71-4.56), with a higher standardized mortality ratio in women and in the age group of 10-15 years. The standardized incident ratio (SIR) of cancer was 10.3 (95% confidence interval = 9.6-11.1). We observed high SIR values for cancer in childhood, with a decrease toward that of the general population by age 70 years. We observed high SIRs for NF1-associated cancers: CNS SIR of 195.4 (95% confidence interval = 172.2-220.9) and small intestine SIR of 102.9 (95% confidence interval = 71.7-143.2). The study provides a better understanding of the prognosis in people living with NF1.

The 10-month mortality rate among older patients treated for digestive system cancer during the first wave of the COVID-19 pandemic: The CADIGCOVAGE multicentre cohort study.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic has had a dramatic impact on cancer diagnosis and care pathways. Here, we assessed the mid-term impact of the COVID-19 pandemic on older adults with cancer before, during and after the lockdown period in 2020. MATERIALS AND METHODS: We performed a retrospective, observational, multicentre cohort study of prospectively collected electronic health records. All adults aged 65 or over and having been newly treated for a digestive system cancer in our institution between January 2018 until August 2020 were enrolled. RESULTS: Data on 7,881 patients were analyzed. Although the overall 10-month mortality rate was similar in 2020 vs. 2018-2019, the mortality rate among for patients newly treated in the 2020 post-lockdown period was (after four months of follow-up) significantly higher. A subgroup analysis revealed higher mortality rates for (i) patients diagnosed in the emergency department during the pre-lockdown period, (ii) patients with small intestine cancer newly treated during the post-lockdown period, and (iii) patients having undergone surgery with curative intent during the post-lockdown period. However, when considering individuals newly treated during the lockdown period, we observed lower mortality rates for (i) patients aged 80 and over, (ii) patients with a biliary or pancreatic cancer, and (iii) patients diagnosed in the emergency department. DISCUSSION: There was no overall increase in mortality among patients newly treated in 2020 vs. 2018-2019. Longer follow-up is needed to assess the consequences of the pandemic. A subgroup analysis revealed significant intergroup differences in mortality.

Impact of two waves of Sars-Cov2 outbreak on the number, clinical presentation, care trajectories and survival of patients newly referred for a colorectal cancer: A French multicentric cohort study from a large group of university hospitals.

The SARS-Cov2 may have impaired care trajectories, patient overall survival (OS), tumor stage at initial presentation for new colorectal cancer (CRC) cases. This study aimed at assessing those indicators before and after the beginning of the pandemic in France. In this retrospective cohort study, we collected prospectively the clinical data of the 11.4 million of patients referred to the Greater Paris University Hospitals (AP-HP). We identified new CRC cases between 1 January 2018 and 31 December 2020, and compared indicators for 2018-2019 to 2020. pTNM tumor stage was extracted from postoperative pathology reports for localized colon cancer, and metastatic status was extracted from CT-scan baseline text reports. Between 2018 and 2020, 3602 and 1083 new colon and rectal cancers were referred to the AP-HP, respectively. The 1-year OS rates reached 94%, 93% and 76% for new CRC patients undergoing a resection of the primary tumor, in 2018-2019, in 2020 without any Sars-Cov2 infection and in 2020 with a Sars-Cov2 infection, respectively (HR 3.78, 95% CI 2.1-7.1). For patients undergoing other kind of anticancer treatment, the percentages are 64%, 66% and 27% (HR 2.1, 95% CI 1.4-3.3). Tumor stage at initial presentation, emergency level of primary tumor resection, delays between the first multidisciplinary meeting and the first anticancer treatment did not differ over time. The SARS-Cov2 pandemic has been associated with less newly diagnosed CRC patients and worse 1-year OS rates attributable to the infection itself rather than to its impact on hospital care delivery or tumor stage at initial presentation.

Effect of lockdown on digestive system cancer care amongst older patients during the first wave of COVID-19: The CADIGCOVAGE multicentre cohort study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has had a dramatic impact on cancer diagnosis and treatment. Most patients newly diagnosed with digestive system cancer are aged 65 and over. METHODS: We performed a retrospective, observational, multicentre cohort study based on prospectively collected electronic health records. All adults aged 65 or over and having been newly treated for a digestive system cancer between January 2018 until August 2020 were enroled. RESULTS: Data on 7882 patients were analysed. The first COVID-19 lockdown period led to a 42.4% decrease in newly treated digestive system cancers, and the post-lockdown period was associated with a 17% decrease. The decrease in newly treated digestive system cancer did not differ as a function of age, sex, comorbidities, primary tumour site, and disease stage. The proportion of patients admitted to an emergency department increased during the lockdown period. We do not observe a higher 3-month mortality rate in 2020, relative to the corresponding calendar periods in 2018 and 2019. CONCLUSION: To avoid a decrease in newly treated cancers during future lockdown periods, access to healthcare will have to be modified. Although 3-month mortality did not increase in any of the patient subgroups, the 2020 cohort must be followed up for long-term mortality.

Lymphoproliferative malignancies in patients with neurofibromatosis 1.

Neurofibromatosis 1 (NF1) is an inherited, autosomal-dominant, tumor predisposition syndrome with a birth incidence as high as 1:2000. A patient with NF1 is four to five times more likely to develop a malignancy as compared to the general population. The number of epidemiologic studies on lymphoproliferative malignancies in patients with NF1 is limited. The aim of this study was to determine the incidence rate of lymphoproliferative malignancies (lymphoma and leukemia) in NF1 patients followed in our referral center for neurofibromatoses. We used the Informatics for Integrated Biology and the Bedside (i2b2) platform to extract information from the hospital's electronic health records. We performed a keyword search on clinical notes generated between Jan/01/2014 and May/11/2020 for patients aged 18 years or older. A total of 1507 patients with confirmed NF1 patients aged 18 years and above were identified (mean age 39.2 years; 57% women). The total number of person-years in follow-up was 57,736 (men, 24,327 years; women, 33,409 years). Mean length of follow-up was 38.3 years (median, 36 years). A total of 13 patients had a medical history of either lymphoma or leukemia, yielding an overall incidence rate of 22.5 per 100,000 (0.000225, 95% confidence interval (CI) 0.000223-0.000227). This incidence is similar to that of the general population in France (standardized incidence ratio 1.07, 95% CI 0.60-1.79). Four patients had a medical history leukemia and 9 patients had a medical history of lymphoma of which 7 had non-Hodgkin lymphoma, and 2 had Hodgkin lymphoma. Our results show that adults with NF1 do not have an increased tendency to develop lymphoproliferative malignancies, in contrast to the general increased risk of malignancy. While our results are consistent with the recent population-based study in Finland, they are in contrast with the larger population-based study in England whereby NF1 individuals were found to be 3 times more likely to develop both non-Hodgkin lymphoma and lymphocytic leukemia. Large-scale epidemiological studies based on nationwide data sets are thus needed to confirm our findings.

Neurofibromatosis I and multiple sclerosis.

Neurofibromatosis 1 (NF1) is one of the most common autosomal dominant genetic disorders with a birth incidence as high as 1:2000. It is caused by mutations in the NF1 gene on chromosome 17 which encodes neurofibromin, a regulator of neuronal differentiation. While NF1 individuals are predisposed to develop benign and malignant nervous system tumors, various non-tumoral neurological conditions including multiple sclerosis (MS) have also been reported to occur more frequently in NF1. The number of epidemiologic studies on MS in NF1 individuals is very limited. The aim of this study was to determine the estimated population proportion of MS in NF1 patients followed in our Referral Centre for Neurofibromatosis using the Informatics for Integrated Biology and the Bedside (i2b2) platform to extract information from the hospital's electronic health records. We found a total 1507 patients with confirmed NF1, aged 18 years (y) and above (mean age 39.2y, range 18-88y; 57% women). Five NF1 individuals were found to have MS, yielding an estimated population proportion of 3.3 per 1000 (0.0033, 95% Confidence Interval 0.0014-0.0077). The median age at diagnosis was 45 y (range 28-49 y). Three patients had relapsing-remitting MS and two patients had secondary progressive MS. Patients with NF1 were found to be twice more likely to develop MS than the general population in France (odds ratio 2.2), however this result was not statistically significant (95% Confidence Interval 0.91-5.29). Our results show that patients with NF1 might have a slight increased tendency to develop MS; however, due to the small sample size of our study, the results may not be sufficiently powered to detect this rare association. Large-scale epidemiological studies based on nationwide datasets are needed to confirm our findings. These findings further emphasize the need for a focused follow-up of patients with NF1, as early detection and management of MS can prevent further neurological disability.

Clinical relevance and impact of Corynebacterium isolation in lower respiratory tract of critically ill patients requiring mechanical ventilation.

PURPOSE: Corynebacterium spp. (C. spp.) is commonly considered as a contaminant in respiratory specimens. No study has ever focused on its clinical relevance in the lower respiratory tract of patients admitted to the intensive care unit (ICU) and requiring mechanical ventilation. The aims were to describe the characteristics of ICU patients with a C. spp. positive deep respiratory specimen, to investigate the impact of C. spp. on the occurrence of pneumonia, and to evaluate the outcomes of these pneumonia. METHODS: We retrospectively included all adult patients admitted to ICU in a 1000-bed University Hospital (2007-2017) who had a C. spp. positive lower respiratory tract specimen at a significant quantitative level. We used clinical, radiological, and microbiological criteria to classify the likelihood of such pneumonia. RESULTS: Among the 31 patients included, acute respiratory failure and postoperative care after major surgery were the main reasons of admission. SAPS II was 47 [34-60]. C. spp. pneumonia was considered as probable, possible and unlikely in 10, 14, and 7 patients, respectively. Fifty-two and 94% of C. spp. strains were sensitive to amoxicillin, and vancomycin/linezolid, respectively. Seventeen patients had a complete course of antibiotic against C. spp. The overall ICU mortality was 58%. CONCLUSION: Corynebacterium spp seems to be responsible for authentic pneumonia in mechanically ventilated patients. It should be considered as clinically relevant when predominantly present in respiratory specimen from patients suspected with pneumonia in ICU, and empirically treated.

Safety of laparoscopic hepatectomy in patients with hepatocellular carcinoma and portal hypertension: interim analysis of an open prospective study.

BACKGROUND: The laparoscopic approach might increase the number of cirrhotic patients with hepatocellular carcinoma (HCC) indicated for liver resection, otherwise contraindicated due to portal hypertension. The goal of this study was to confirm the safety of laparoscopic liver resection (LLR) in patients with portal hypertension. METHODS: This prospective, single-center, open study (ClinicalTrials.gov ID: NCT02145013) included all consecutive cirrhotic patients who underwent LLR for HCC from 2014 to 2017. Short-term outcomes were compared between patients with and without clinically significant portal hypertension (CSPH, defined by hepatic venous pressure gradient ≥ 10 mmHg). RESULTS: The study population included 45 patients, comprising 27 patients (60%) in the no CSPH group and 18 patients (40%) in the CSPH group. All planned procedures could be performed. The two groups did not differ in the extent of resection, transfusion, duration of clamping, and need for conversion. Overall, the 90-day mortality and severe morbidity rates were nil. Moderate morbidity was significantly higher in the CSPH group (39 vs. 4%, p = 0.01); however, the two groups did not differ in the rate of unresolved liver decompensation. Intensive care unit and hospital stays were significantly longer in the CSPH group. At 2 years, overall survival was 77% in the no CSPH group and 100% in the CSPH group (p = 0.17), and recurrence-free survival was 55% in the no CSPH group and 79% in the CSPH group (p = 0.10). CONCLUSION: LLR is safe in BCLC 0-A patients with CSPH, with no mortality and good short-term outcomes. Re-evaluation of the BCLC guidelines is needed.

Economic burden of preemptive treatment of CMV infection after allogeneic stem cell transplantation: a retrospective study of 208 consecutive patients.

BACKGROUND: Cytomegalovirus (CMV) infection and disease (CMV episodes) are global concerns after allogeneic hematopoietic stem cell transplantation (HSCT). They affect survival, both by direct and indirect effects. Due to safety issues of current anti-CMV antivirals, long-term CMV prophylaxis is poorly tolerated and the most common strategy to decrease the incidence of CMV disease is preemptive. New, less toxic, molecules are currently being assessed for CMV prophylaxis which should replace or considerably decrease the preemptive approach. The aim of this study was to assess the economic burden of CMV episodes after HSCT with a preemptive approach. METHODS: We analyzed data from 208 consecutive adults transplanted in our institution, between 2008 and 2013. Hospital resource utilization was retrieved via the linked hospital admissions and Diagnostic Related Groups for the period of conditioning to 12 months after transplant. RESULTS: CMV episodes occurred in 70 patients (34%) over the first 12 months following HSCT, after a mean of 75 days (median: 46 (7-334)). The mean total length of stay was significantly associated with the occurrence of a CMV episode (113.9 vs. 87.5 days, p = 0.0002) but was associated neither with the pre-transplant CMV serology of donors/recipients nor with survival. The mean cost of transplant was €104,016 (SD = €37,281) after 12 months. Bivariate and multivariate analyses indicated that the occurrence of >1 CMV episode increased the costs of allogeneic HSCT by 25-30% (p < 0.0001). CONCLUSION: Our study, which is the largest, single-institution cost study of allogeneic HSCT in Europe, shows that two or more CMV episodes significantly increased the transplant cost. New prophylactic strategies to prevent CMV infection and disease should decrease transplant costs.

Patients' comorbidities reduce the clinical value of emergency colonoscopy: results of a retrospective cohort study.

BACKGROUND AND STUDY AIMS: Urgent endoscopy is often used to diagnose and sometimes treat acute upper gastrointestinal syndromes (hemorrhage, toxic ingestion, and occlusion). However, its suitability concerning the management of lower gastrointestinal conditions in emergency circumstances is controversial. PATIENTS AND METHODS: We studied the role of emergency colonoscopy in diagnosis and treatment of all consecutive patients presenting with acute lower gastrointestinal symptoms referred to our hospital on an emergency basis. All patients were first managed by physicians from the emergency room and/or the intensive care unit (ICU); the treatments included fluid resuscitation, blood transfusion, and antibiotic or cardiotonic as needed. Bowel cleansing was performed to purge the colon of clots, stool, and blood when clinically possible; alternatively, a bowel enema was used. Patients only underwent a computed tomography (CT) scan prior to the colonoscopy in clinically relevant situations. Colonoscopy was performed within 6 - 36 hours after hospitalization or the beginning of the clinical symptoms (hemorrhage, sepsis, colon distension) or occlusion, as assessed by abdominal CT scan. RESULTS: From 2010 to 2015, 603 patients underwent urgent colonoscopy; among them, 214 (36 %) presented with lower GI bleeding, while 264 (44 %) had symptoms suggestive of intestinal ischemia; almost half (49 %, n = 295) of the patients were hospitalized in the ICU. Patients received therapies, such as clips (15 %), epinephrine injections (5 %), bipolar coagulation (7 %), or devolvulation (3 %) using colonoscopy or antibiotic therapy when needed. No perforation was observed after colonoscopy and only three cases of hemorrhage recurrence were documented as complications after the procedure. Overall, 192 patients died within 1 month after colonoscopy due to four independent risk situations, as follows: septic shock, heart transplantation, multiorgan failure, and ischemic colitis. Only 67 (35 %) underwent urgent intestinal surgery when ischemic colitis was identified, and this did not have a significant effect on the mortality rate. CONCLUSIONS: Urgent bedside colonoscopy is feasible and safe for routine use. The highest advantage was observed in patients with red blood hemorrhage, diarrhea, and colon distension when symptoms were not associated with multiorgane failure, heart transplantation, or septic shock. As revealed by colonoscopy and pathological features, ischemic colitis is associated with a bad prognosis, and patients experience a higher rate of early mortality regardless of whether they undergo urgent colon surgery.

Low Rates of Blood Transfusion in Elective Resections of Neurofibromas in a Cohort Study: Neurofibroma Length as a Predictor of Transfusion Requirement.

BACKGROUND: Neurofibromas in neurofibromatosis type 1 induce aesthetic and functional morbidity. Perioperative bleeding has been reported as an obstacle to neurofibroma resections. The authors studied the requirement for blood transfusion during surgical treatment of neurofibromatosis type 1. METHODS: Six hundred twenty-two procedures performed on 390 neurofibromatosis type 1 patients at the national referral center from 1995 to 2011 were analyzed in two chronologic sets of patients: set 1 (February of 1995 to September of 2007), in which only one surgeon operated; and set 2 (October of 2007 to January of 2011), in which two additional surgeons were involved. Malignant peripheral nerve sheath tumors, reconstructive procedures, and spontaneous hemorrhages were excluded from the analysis. Age, sex, preoperative hemoglobin concentration, location, length, estimated volume and histologic features of the largest neurofibroma (cumulative values for multiple neurofibromas), and procedure duration were studied as potential predictors of blood transfusion that were measured in terms of units of packed red blood cells. RESULTS: Seventy reconstructive procedures, two cases of spontaneous hemorrhage, and 32 malignant peripheral nerve sheath tumor resections were excluded. Among 516 procedures (318 and 198 in sets 1 and 2, respectively), 17 (2.7 percent) required blood transfusions. The requirement for transfusion was associated with neurofibroma length in both sets, with an optimal cutoff value of 13 cm in both sets. CONCLUSIONS: Contrary to the literature, the requirement for blood transfusion was found to be low (2.7 percent of the cases) during elective resection of neurofibromas in neurofibromatosis type 1. Elective resections of benign neurofibromas less than 13 cm in length were not associated with a requirement for blood transfusion. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

One or two steps for laparoscopic conversion of failed adjustable gastric banding to sleeve gastrectomy: a nationwide French study on 3357 morbidly obese patients.

BACKGROUND: Adjustable gastric banding (AGB) has been a very common bariatric procedure, but long-term AGB related complications have led to an increased number of second procedures. Sleeve gastrectomy (SG) is one option and can be done as a 1- or 2-step procedure. OBJECTIVES: To compare the 1-step and 2-step approachs of conversion of AGB to SG with respect to postoperative mortality and morbidity. SETTING: Nationwide study, France. METHODS: All morbidly obese patients who underwent AGB followed by SG in France between 2007 and 2012 were included. Multivariate analyses were conducted using the French National Health Service Database data to ascertain predictive factors for 90-day postoperative mortality and morbidity. RESULTS: There were 2061 and 1296 patients in the 1-step and 2-step conversion groups, respectively. The readmission rate was 22.8% and 16.5% in the 1- and 2-step groups, respectively (P<.001). More patients required an intensive care unit stay in the 1-step group (11.7 % versus 6.7%; P<.001). The 90-day mortality was .1%, with no difference between the 2 groups (1% versus .08%). The complication rate was 14.7% (1-step 15.9% versus 2-step 12.7%; P = .009). The timing of AGB removal (P = .02), patient age 50-60 years (P = .004), hypertension (P = .01), surgical approach (P = .002), and hospital status (P = .015) were significantly associated with the complication rate. CONCLUSION: This study indicates that the 2-step conversion of failed AGB to SG results in a significantly reduced rate of postoperative staple line leaks, gastric tube stricture, respiratory complication, and need for intensive care unit stay.

Reduction in early mortality outcomes after bariatric surgery in France between 2007 and 2012: A nationwide study of 133,000 obese patients.

BACKGROUND: Early postoperative mortality after bariatric surgery has been reported in large national studies before sleeve gastrectomy (SG) was introduced as a stand-alone procedure. The aim of this study was to investigate the 90-day postoperative mortality rates after bariatric surgery in France on a nationwide basis. METHODS: All morbidly obese patients who underwent adjustable gastric banding (AGB), gastric bypass (GBP), or SG in France between 2007 and 2012 were included in this study. Multivariate analyses were conducted using the French National Health Service Database data to ascertain predictive factors for 90-day postoperative mortality. RESULTS: Data from 133,804 patients were analyzed. SG was performed in 36.5% of cases, GBP in 31.2%, AGB in 32.3%, and revisional surgery in 5.1%. The postoperative mortality rate (POM) for the 3 procedures was 0.12%. The rate of POM remained stable for AGB (0.01%), and it decreased from 0.25 to 0.08% and from 0.36 to 0.11% for SG and GBP, respectively. POM was greater among male patients and was associated with age, type-2 diabetes, high blood pressure, body mass index, open surgery, and hospital procedural volume. CONCLUSION: The rate of early mortality after bariatric surgery was low, and has decreased greatly during the past few years. AGB presents a mortality rate close to nil and SG has a risk of early mortality that is about half that of GBP.

Prognostic factors in necrotizing soft-tissue infections (NSTI): A cohort study.

BACKGROUND: Necrotizing soft-tissue infection (NSTI) is uncommon but life-threatening. A recent meta-analysis estimated the overall mortality at 23.5%. OBJECTIVE: We sought to identify risk factors associated with mortality in a cohort of patients with NSTI in a tertiary care center. METHODS: We identified 512 patients with NSTI between 1996 and 2012 in the national hospital database Program for Medicalization of Information Systems and examined risk factors of mortality with NSTI by univariate and multivariate analysis. RESULTS: We included 109 patients with a confirmed diagnosis of NSTI; 31 (28%) died at a median follow-up of 274 days (range 2-6135 days). On multivariate analysis, independent risk factors of mortality were age older than 75 years (hazard ratio [HR] 4.4, 95% confidence interval [CI] 1.8-10.3), multifocal NSTI (HR 5.9, 95% CI 1.9-18.5), severe peripheral vascular disease (HR 5.1, 95% CI 1.5-17.0), hospital-acquired infection (HR 3.9, 95% CI 1.4-10.7), severe sepsis (HR 7.4, 95% CI 1.7-33.1), and septic shock on hospital admission (HR 13.9, 95% CI 3.8-50.4). LIMITATIONS: This was a retrospective cohort, which disallows a precise record of the delay between diagnosis and surgery. CONCLUSION: Our findings for this robust cohort of patients with a definite diagnosis of NSTI could help clinicians stratify NSTI severity at clinical course onset.

Influence of atmospheric pressure on infrarenal abdominal aortic aneurysm rupture.

BACKGROUND: Meteorologic conditions have a significant impact on the occurrence of cardiovascular events. Previous studies have shown that abdominal aortic aneurysm rupture (AAAR) may be associated with atmospheric pressure, with conflicting results. Therefore, we aimed to further investigate the nature of the correlation between atmospheric pressure variations and AAAR. METHOD: Hospital admissions related to AAAR between 2005-2009 were assessed in 19 districts of metropolitan France and correlated with geographically and date-matched mean atmospheric pressures. In parallel and from 2005-2009, all fatal AAARs as reported by death certificates were assessed nationwide and correlated to local atmospheric pressures at the time of aortic rupture. RESULTS: Four hundred ninety-four hospital admissions related to AAAR and 6,358 deaths nationwide by AAAR were identified between 2005-2009. Both in-hospital ruptures and aneurysm-related mortality had seasonal variations, with peak/trough incidences in January and June, respectively. Atmospheric pressure peaks occurred during winter. Univariate analysis revealed a significant association (P < 0.001) of high mean atmospheric pressure values and AAAR. After multivariate analysis, mean maximum 1-month prerupture atmospheric pressure had a persistent correlation with both in-hospital relative risk (1.05 [95% confidence interval: 1.03-1.06]; P < 0.0001) and aneurysm rupture-related mortality relative risk (1.02 [95% confidence interval: 1.01-1.03]; P < 0.0001). CONCLUSION: The annual incidence of AAAR is nonhomogeneous with a peak incidence in winter, and is independently associated with mean maximum 1-month prerupture atmospheric pressure.

Rituximab and chlorambucil versus rituximab alone in gastric mucosa-associated lymphoid tissue lymphoma according to t(11;18) status: a monocentric non-randomized observational study.

Forty-nine patients, t(11;18)-positive (n = 31) and t(11;18)-negative (n = 18), were treated without randomization with rituximab-chlorambucil or rituximab alone. Evaluation was performed at week (W) 6, week (W) 25 and every 6 months (Wx). Comparing the rituximab-chlorambucil group to the rituximab-alone group, remission was obtained in 93% vs. 66% at W6 (p = 0.01), in 93% vs. 81% at W25 (p = 0.14) and in 93% vs. 76% at Wx (p = 0.07). Comparing the rituximab-chlorambucil group to the rituximab-alone group in t(11;18)-positive patients, remission was obtained in 100% vs. 45% at W6 (p = 0.0005), in 100% vs. 66% at W25 (p = 0.01) and in 96% vs. 55% at Wx (p = 0.01). Comparing the rituximab-chlorambucil group to the rituximab-alone group in t(11;18)-negative patients, remission was obtained in 66% vs. 83% at W6 (p = 0.32), in 66% vs. 92% at W25 (p = 0.22) and in 83% vs. 92% at Wx (p = 0.47). In conclusion, rituximab-chlorambucil is significantly more rapidly efficient than rituximab alone. In t(11;18)-positive patients, the combination is more efficient than rituximab alone. In t(11;18)-negative patients, rituximab alone is as efficient as rituximab-chlorambucil and may be an alternative treatment.

Face transplantation program in France: a cost analysis of five patients.

BACKGROUND: Among 18 face transplantations (FTs) performed worldwide, seven were performed at the Henri Mondor Hospital, Paris, France. Their feasibility and risk-benefit ratios have been reported, whereas this study analyzed the costs of FT for our first five patients. MATERIALS AND METHODS: The first five FT patients transplanted at the Henri Mondor Hospital presented disfigurements due to neurofibromatosis, severe burns, or ballistic trauma and had no relevant comorbidity. All were socially isolated and unemployed. We analyzed the costs of preoperative investigations, operative procedures, and hospitalization for each patient. A public research program (PHRC) financed the procedures, and the clinical research department refunded each FT's cost. To allow comparisons between health care systems, the cost of FT was compared with the mean costs of heart, liver, and kidney transplantations performed at the same institution. RESULTS: If all the five patients survived the FT procedure, one patient died during subsequent revisions procedures for sepsis. The overall costs for the operation and its subsequent hospitalization for each patient ranged from (20AC)103,108 to (20AC)170,071, depending on the transplant required, the technical pitfalls, the outcomes, and mainly postoperative intensive cares. CONCLUSIONS: In our institution, the transplantation of a face led to higher costs than heart or any other solid organ and represented twice the costs faced for a liver transplantation. FT is currently performed in a research setting, and cost might decrease with teams' experiences, which may shorten postoperative intensive care and overall hospital stays.

Respective prognostic values of germinal center phenotype and early (18)fluorodeoxyglucose-positron emission tomography scanning in previously untreated patients with diffuse large B-cell lymphoma.

BACKGROUND AND OBJECTIVES: Diffuse large B-cell lymphomas (DLBCL) have a variable outcome, and powerful methods of prognostication are needed in order to choose the best treatment for each patient. Immunophenotypic classification of the tumor as germinal center (GC) or non-germinal center-like (nGC) and early response evaluation with 18fluorodeoxyglucose positron emission tomography (18FDG-PET) scanning have been correlated with survival in DLBCL but the two methods have never been evaluated simultaneously in the same patient population. Our aim was to investigate their respective prognostic values in the same series of patients. DESIGN AND METHODS: We investigated the expression of CD10, Bcl-6, and MUM1 in 81 patients with DLBCL evaluated early with 18FDG-PET. The tumors were classified as GC or nGC using the algorithm of Hans et al. The results of both methods were correlated with the patients' characteristics and survival. RESULTS: CD10 was positive in 27/76 (36%), Bcl-6 in 43/74 (58%), and MUM1 in 33/73 (45%) interpretable cases. Thirty-eight (51%) were in the GC group, and 36 (49%) in the nGC group. With a median follow-up of 33 months, estimated 3-year event-free survival (EFS) of the whole population was 67%. There was no influence of GC/nGC phenotype on survival. Three-year EFS was 46% in the early PET-positive group versus 80% in the PET-negative group (p=0.0003). INTERPRETATION AND CONCLUSIONS: The prognostic value of GC/nGC phenotype is not confirmed in this heterogeneous series, whereas early PET findings are confirmed to be a powerful predictor of outcome. The impact of treatment decisions based on early PET results should be evaluated.

Prognostic value of translocation t(11;18) in tumoral response of low-grade gastric lymphoma of mucosa-associated lymphoid tissue type to oral chemotherapy.

PURPOSE: To determine the impact of translocation t(11;18) on response to oral alkylating agents in gastric mucosa-associated lymphoid tissue lymphoma (GML). PATIENTS AND METHODS: Fifty-three patients with a GML were studied. Helicobacter pylori-positive patients (n = 34) received anti-H pylori treatment and H pylori-negative patients (n = 19) or patients who failed to respond to anti-H pylori treatment received oral alkylating agents. t(11;18) was detected by reverse transcription polymerase chain reaction from frozen gastric biopsies. RESULTS: t(11;18) was detected in 32% of patients. It was more prevalent in H pylori-negative as compared with H pylori-positive patients (12 of 19 v five of 34 patients; P = .0005). Among 31 H pylori-eradicated patients, t(11;18) was detected in three patients, all of whom experienced treatment failure, and it was absent in 28 patients: 21 patients (75%) were in remission and seven patients (25%) experienced treatment failure (P = .03). Among 21 patients who received an alkylating agent, t(11;18) was detected in 12 patients: five patients (42%) were in remission and seven patients (58%) experienced treatment failure. t(11;18) was absent in nine patients: eight patients (89%) were in remission and one patient (11%) experienced treatment failure by the end of treatment. Four patients in remission relapsed during follow-up (median, 7 years): they all had t(11;18). Durable remission was obtained in eight (89%) of the nine patients without t(11;18) versus one of the 12 patients (8%) with t(11;18) (P = .0003). CONCLUSION: Presence of t(11;18) in GML is predictive of resistance to oral alkylating agents, with less than 10% of durable remission at long-term follow-up.

Health, economic, and quality-of-life effects of erythropoietin and granulocyte colony-stimulating factor for the treatment of myelodysplastic syndromes: a randomized, controlled trial.

In myelodysplastic syndromes (MDS), anemia responds to recombinant human erythropoietin (rHuEPO) alone and in combination with recombinant human granulocyte-colony-stimulating factor (rHuGCSF) in 10% to 20% and in 35% to 40% of patients, respectively. We randomly divided 60 patients with low-grade anemic MDS and serum EPO levels lower than 500 IU/L (500 mU/mL) into 2 groups: rHuEPO + rHuG-CSF (arm A) and supportive care (arm B). After 12 weeks, those who had erythroid responses were given rHuEPO alone for 40 additional weeks. They were also given rHuG-CSF if they had relapses. A response was considered major if the hemoglobin (Hb) level was 115 g/L (11.5 g/dL) or higher and minor Hb increase was 15 g/L (1.5 g/dL) or more or if it remained stable without transfusion. Ten of 24 patients responded in arm A, and 0 of 26 responded in arm B (P =.01). Eight patients in arm A continued rHuEPO therapy alone, and 6 had relapses. Responses were always restored when rHuG-CSF was reintroduced. Mean direct costs per patient were 26,723 euros (arm A) and 8,746 euros (arm B). Quality of life was assessed with a Functional Assessment of Cancer Therapy-Anemia (FACT-An) scale. Similar percentages of patients from both arms showed significant clinical improvement. rHuEPO plus rHuG-CSF led to responses in 41.7% of MDS patients. This treatment was expensive. No effect on quality of life was demonstrated.