Geographical Disparities of Outcomes of Hepatocellular Carcinoma in France: The Heavier Burden of Alcohol Compared to Hepatitis C.

BACKGROUND: Data on alcohol-related HCC are limited. AIMS: Our aim was to describe the incidence, management, and prognosis of alcohol compared to Hepatitis C (HCV)-related HCC at a national level. METHODS: Incident cases of HCC were identified in French healthcare databases between 2009 and 2012 and analyzed retrospectively. Demographic data, type, location, and annual HCC-caseload of the hospitals where patients were first managed were retrieved. Survival of incident cases was computed from the time of diagnosis and adjusted for potential confounding variables. RESULTS: The study population included 14,060 incident cases of alcohol and 2581 HCV-related HCC. Alcohol-related HCC was more frequent than HCV-related HCC (29.37 and 5.39/100,000 adults/year, respectively) with an heterogeneous distribution on the French territory. The optimal treatment was less frequently curative (20.5% vs 35.9%; p < 0.001), and survival was significantly shorter (9.5 [9.0-10.0] versus 16.8 [15.5-18.7] months p < 0.001) in alcohol compared to HCV-related HCC, with marked variations between regions for a given risk factor. In multivariable analysis in the whole study population, curative treatment was a strong predictor of survival (adjusted HR 0.28 [0.27-0.30] months p < 0.001). Being managed at least once in a teaching hospital during follow-up was independently associated with receiving a curative treatment and survival. CONCLUSION: In France, incidence of alcohol-related HCC is high and prognosis is poor compared to HCV-related HCC, with marked variations between regions. These results should guide future health policy initiatives pertaining to HCC care. Importantly, increasing patient' referral in expert centers could increase chances to receive curative treatment and improve outcomes.

The epidemiology of Budd-Chiari syndrome in France.

INTRODUCTION: Epidemiological data is lacking on primary Budd-Chiari syndrome (BCS) in France. METHODS: Two approaches were used: (1) A nationwide survey in specialized liver units for French adults. (2) A query of the French database of discharge diagnoses screening to identify incident cases in adults. BCS associated with cancer, alcoholic/viral cirrhosis, or occurring after liver transplantation were classified as secondary. RESULTS: Approach (1) 178 primary BCS were identified (prevalence 4.04 per million inhabitants (pmi)), of which 30 were incident (incidence 0.68 pmi). Mean age was 40 ±â€¯14 yrs. Risk factors included myeloproliferative neoplasms (MPN) (48%), oral contraceptives (35%) and factor V Leiden (16%). None were identified in 21% of patients, ≥2 risk factors in 25%. BMI was higher in the group without any risk factor (25.7 kg/m2 vs 23.7 kg/m2, p < 0.001). Approach (2) 110 incident primary BCS were admitted to French hospitals (incidence 2.17 pmi). MPN was less common (30%) and inflammatory local factors predominated (39%). CONCLUSION: The entity of primary BCS as recorded in French liver units is 3 times less common than the entity recorded as nonmalignant hepatic vein obstruction in the hospital discharge database. The former entity is mostly related to MPN whereas the latter with abdominal inflammatory diseases.

The Theory and Practice of Pancreatic Surgery in France.

OBJECTIVE: Measure the caseload of pancreatectomies that influences their short-term outcome, at a national level, and assess the applicability of a centralization policy. BACKGROUND: There is agreement that pancreatectomies should be centralized. However, previous studies have failed to accurately define a "high-volume" center. METHODS: French healthcare databases were screened to identify all adult patients who had elective pancreatectomies between 2007 and 2012. The patients' age, comorbidities, indication, and extent of surgery, and also the hospital administrative-type and location were retrieved. The annual-caseload of pancreatectomy was calculated for each hospital facility. The primary endpoint was 90-day mortality. Spline modeling was used to identify the different annual-caseload that influenced mortality. Logistic regressions were performed to assess if their influence was independent of confounders, and the accuracy of the model calculated. RESULTS: Overall, 22,366 patients underwent a pancreatectomy and the mortality was 8.1%. Two cut-offs were identified (25 and 65 per year): compared with centers performing >65 resections per year, the adjusted OR of mortality was 1.865 (1.529-2.276) in centers performing ≤25 resections per year and 1.234 (1.031-1.478) in those performing 26 to 65 resections per year. The average number of facilities performing ≤25, 26 to 65, and >65 pancreatectomies per year was 456, 20, and 9, respectively. The percentage of patients operated in these facilities was 56.6%, 19.9%, and 23.3%, respectively.For pancreaticoduodenectomies (12,670 patients; mortality 9.2%), there were 2 cut-offs (16 and 40 pancreaticoduodenectomies per year), and both were independent predictors of mortality (adjusted OR of 1.979 and 1.333). For distal pancreatectomies (7085 patients; 6.2% mortality), there were 2 cut-offs (13 and 25 distal pancreatectomies per year), but neither was an independent predictor of outcome (area under the receiver-operating characteristic curve of the model = 0.778). CONCLUSIONS: Centralization of pancreatic surgery is theoretically justified, but currently unrealizable. As the incidence of pancreatic cancer increases, there is an urgent need to improve the training of surgeons and develop both intermediate and high-volume centers.

Geographical variations in incidence, management and survival of hepatocellular carcinoma in a Western country.

BACKGROUND & AIMS: Information on the incidence, management, and prognosis of hepatocellular carcinoma (HCC) is derived from population samples, regional data, or registries. Comprehensive national evaluations within a given country are lacking. This study aimed to investigate regional variations in HCC care within France. METHODS: This observational study analysed data from French administrative databases for more than 30,000 patients with HCC diagnosed between 2009 and 2012, and followed-up until 2013. The incidence of HCC, access to surgery, and survival, at both the national level and two geographical levels (the 21 French regions and 95 French departments into which France is divided administratively), were determined. The influence on outcome of the structure of the hospital where HCC was first managed was assessed. RESULTS: At the national level, the median survival was 9.4months and only 22.8% of patients had curative treatment. There were marked variations between regions and departments in incidence, access to curative treatment (range 1.3-28.8% and 8.1-32.3% respectively), and in median survival (range 5.7-12.1 and 4.3-16.5months respectively). The administrative type and annual HCC-caseload of the hospital where patients were first admitted also had an independent influence on treatment and survival. CONCLUSION: Despite full insurance coverage for all citizens, national measures to reduce inequities in the management of cancer patients, standardised recommendations for HCC surveillance and management, the percentage of patients undergoing curative treatment and their survival may vary four-fold depending on their postcode. The hospital in which patients are first managed has a clear influence on accessibility to both good care and survival. LAY SUMMARY: Population-based studies have highlighted large and sometimes unexpected differences between countries in the survival of patients with malignancy. As these differences are considered to indicate the overall effectiveness of health systems, in addition to the incidence of the cancer or quality of registration, variations within a given country should be minimal. However, similar to between countries differences, this study shows differences within the same country in the incidence, curative treatment rate, and survival of patients with HCC. Evidence that access to care and survival varies within a country can strengthen the impetus for government and clinicians to address these disparities.

Laparoscopic left lateral sectionectomy: a population-based study.

BACKGROUND: Laparoscopic left lateral sectionectomy (LLS) has now become standard practice. However, published series are small and retrospective. The aim was to compare at a national level the use and short-term outcome of laparoscopic and open LLS. METHODS: National hospital discharge databases were screened to identify all adult patients who had undergone elective LLS in France between 2007 and 2012. Outcome measurements included blood transfusion, severe morbidity, mortality and length of hospital stay. The independent influence of the laparoscopic approach on these outcomes was tested overall and after stratifying for the indication (benign condition, primary malignancy, liver metastasis). RESULTS: Over the 6-year study period, 2198 patients underwent LLS, accounting for 6.9% of all elective liver resections. Some 28.5% of LLS procedures were performed laparoscopically. Among hospitals in which LLS was carried out, 33.2% of procedures were done laparoscopically (median 2 laparoscopic LLS resections per year). The laparoscopic approach was independently associated with a shorter length of hospital stay irrespective of the indication, and a lower transfusion rate in patients with benign condition or primary malignancy. CONCLUSION: LLS is seldom performed and the laparoscopic approach has not been adopted widely. The potential benefit of laparoscopic LLS varies according to the indication.

Laparoscopic Distal Pancreatectomy for Pancreatic Ductal Adenocarcinoma: Time for a Randomized Controlled Trial? Results of an All-inclusive National Observational Study.

OBJECTIVES: The aim of this study is to compare at a national level, the early and long-term outcome of distal pancreatectomy (DP) performed by laparoscopy (LapDP) or open surgery (OpenDP) for pancreatic ductal adenocarcinoma (PDAC). BACKGROUND DATA: LapDP is feasible and safe for benign conditions but its use for PDAC is controversial. METHODS: French healthcare databases were screened to identify all patients who had undergone LapDP or OpenDP for PDAC between 2007 and 2012. Endpoints were (i) 90-day mortality, (ii) morbidity, (iii) transfusion rate, (iv) length of hospital stay (LOS), and (v) long-term survival. Logistic regression and adjusted Cox models were used to compare LapDP and OpenDP with regard to these outcomes. Confounders included (i) patients' characteristics; (ii) associated surgical procedures; and (iii) characteristics of the hospital. Performance of the resulting models was determined by the area under the receiver operating characteristic (ROC) curve. RESULTS: Over the 6-year period, there were 2753 operations for PDAC: 2406 OpenDP and 347 LapDP (12.6%). The overall 90-day mortality rate was 5.2%; median LOS was 15 days, and median survival was 38 months. LapDP was not correlated with 90-day mortality but was associated with reduced pleuropulmonary morbidity (odds ratio (OR) 0.73, P = 0.028), blood transfusion (OR 0.44, P = 0.001), and LOS (P = 0.042), and was associated with increased survival (P = 0.0007). CONCLUSIONS: LapDP has not been adopted widely for PDAC. The early and long-term results of LapDP as currently practiced are as good as those of OpenDP. The next step in the evaluation of LapDP should be a randomized controlled trial (RCT), but such a trial is likely to suffer from insufficient recruitment.

How surgical technology translates into practice: the model of laparoscopic liver resections performed in France.

OBJECTIVES: Analyze, at a national level, the adoption and practice of laparoscopic liver resections (LAP), compared to open resections (OPEN). BACKGROUND: LAP initiated 20 years ago, has been described for all hepatectomies, and is considered as the reference technique for some resections. There are, however, no data on its adoption outside selected specialty centers. METHODS: French Healthcare databases were screened to identify all patients who underwent an elective LAP or OPEN between 2007 and 2012. Patients' demographics, associated conditions, indication for surgery, hepatectomy performed, and hospital type and hepatectomy caseload were retrieved. Patients who had possible overcoding of biopsies as wedge resections were identified to select REAL resections. Time trend analyses were performed using a piecewise linear regression and the average annual percent change (AAPC) calculated. RESULTS: There were 7881 (17.8%) LAP and 36,359 (82.2%) OPEN performed in an average of 483 hospitals. Of these, biopsies accounted for 29.9% of the LAP (7.3% of the OPEN, P<0.0001) and the incidence of LAP biopsies increased after 2009. The AAPC of the incidence of real LAP increased more than that of real OPEN (7.0% vs 1.3%) but most were minor resections (61.1% vs 28.9% for OPEN, P<0.0001), only 15% of patients were operated by LAP and intermediate (or major) resections were performed in 19.5% (or 4.8%) of hospitals performing liver resections. The proportion of resections performed by LAP was inversely related to annual caseload. The overall incidence of resections performed for benign conditions did not increase. CONCLUSIONS: LAP is not developing, has not been adopted for intermediate/major resections, does not result in overuse for benign indications and some of the 2009 -consensus statements are not applied.

The use of DRG for identifying clinical trials centers with high recruitment potential: a feasability study.

Recruitment of large samples of patients is crucial for evidence level and efficacy of clinical trials (CT). Clinical Trial Recruitment Support Systems (CTRSS) used to estimate patient recruitment are generally specific to Hospital Information Systems and few were evaluated on a large number of trials. Our aim was to assess, on a large number of CT, the usefulness of commonly available data as Diagnosis Related Groups (DRG) databases in order to estimate potential recruitment. We used the DRG database of a large French multicenter medical institution (1.2 million inpatient stays and 400 new trials each year). Eligibility criteria of protocols were broken down into in atomic entities (diagnosis, procedures, treatments...) then translated into codes and operators recorded in a standardized form. A program parsed the forms and generated requests on the DRG database. A large majority of selection criteria could be coded and final estimations of number of eligible patients were close to observed ones (median difference = 25). Such a system could be part of the feasability evaluation and center selection process before the start of the clinical trial.

Diabetes mellitus is an independent prognostic factor for major liver-related outcomes in patients with cirrhosis and chronic hepatitis C.

UNLABELLED: In patients with chronic hepatitis C (CHC), cirrhosis is associated with age, gender, diabetes, alcohol abuse, and coinfection with human immunodeficiency virus (HIV) or hepatitis B virus (HBV). The effect of these factors on the outcome of cirrhosis is unknown. This study in CHC patients with cirrhosis aimed to assess the influence of these factors on decompensation, liver transplantation, and death. Consecutive patients with CHC and cirrhosis hospitalized between January 1, 2006 and December 31, 2008 were followed up until death, transplantation, or study closure in March 2013. Gender, age, Model for End-Stage Liver Disease (MELD) score, diabetes, alcohol abuse, HIV, or HBV coinfection were collected at inclusion. The complications of cirrhosis, death, and liver transplantation were recorded at inclusion and during follow-up. The association between baseline factors and liver-related outcomes at inclusion and during follow-up were tested using logistic regression and Cox's model, respectively. A total of 348 patients with CHC and cirrhosis (68% men; median age: 59 years; median MELD: 10) were included. At baseline, 40% of the patients had diabetes, 29% alcohol abuse, and 6% HIV or HBV coinfection. Baseline MELD≥10 (P<0.001), diabetes (P=0.027), and HBV coinfection (P=0.001) were independently associated with transplantation-free survival. Baseline diabetes was independently associated with ascites (P=0.05), bacterial infections (P=0.001), and encephalopathy (P<0.001) at inclusion. Baseline diabetes was independently associated with development of ascites (P=0.057), renal dysfunction (P=0.004), bacterial infections (P=0.007), and hepatocellular carcinoma (P=0.016) during the follow-up. CONCLUSION: In patients with CHC and cirrhosis, diabetes is an independent prognostic factor. Improving diabetes control may improve the outcome of cirrhosis.

Incidence and risks of liver resection: an all-inclusive French nationwide study.

OBJECTIVE: To evaluate at a national level the incidence of liver resection, postoperative mortality, and variables that predict this outcome. BACKGROUND: Data on indications of and results of liver resection are mainly derived from high-volume centers. Nationwide data are lacking. METHODS: French health care databases were screened to identify all patients who had undergone elective hepatectomy between 2007 and 2010. The patients' age, address, associated conditions, indication and extent of hepatic (or extrahepatic) surgery and the hospital type, location, and hepatectomy caseload were retrieved. Logistic regression was used to measure the influence of these parameters on in-hospital and 90-day mortality rates. The model, created using patients operated on in 2007 and 2009, was tested in those operated on in 2008 and 2010. RESULTS: Overall, 28,708 hepatectomies were performed. The annual incidence (13.2 per 10 adult inhabitants) varied between regions, but the extremal quotient was limited to 2.2 because 15% of the operations took place outside the patients' home region. Hospitals performed a median of 4 resections per year but 53% of all resections were performed in institutions with a volume of more than 50 per year. Treatment for primary tumors and major resections correlated with hepatectomy caseload. In-hospital and 90-day mortality were 3.4% and 5.8%, respectively. The area under the receiver operating characteristic curve of the prognostic model was 0.78/0.77 in the training and validation sample. CONCLUSIONS: There were significant disparities in practice. In-hospital mortality underestimated true, postoperative mortality by more than 50%. The model created may be useful for more efficient regionalization of care and patient counseling.

Evaluation of the management of postoperative aseptic meningitis.

BACKGROUND: A consensus conference recommended empirical antibiotic therapy for all patients with postoperative meningitis and treatment withdrawal after 48 or 72 h if cerebrospinal fluid culture results are negative. However, this approach is not universally accepted and has not been assessed in clinical trials. METHODS: We performed a cohort study of all patients who received a diagnosis of postoperative meningitis from January 1998 through May 2005 in a teaching hospital. From January 1998 through September 2003 (control period), guidelines were lacking or were not implemented. From October 2003 through May 2005 (interventional period), all patients received a predefined intravenous antibiotic therapy that was discontinued on the third day if the meningitis was considered aseptic. Clinical outcome and duration of antibiotic therapy were analyzed for each patient. RESULTS: Seventy-five episodes of postoperative meningitis (21 cases of bacterial meningitis and 54 cases of aseptic meningitis) were investigated. Patients with aseptic meningitis received antibiotic treatment for a mean +/- standard deviation duration of 11+/-5 days during the control period and 3.5+/-2 days during the intervention period (P=.001). The duration of antibiotic treatment for bacterial meningitis was not significantly different between the 2 periods. All episodes of bacterial and aseptic meningitis were cured, and complications were rare during both periods. CONCLUSIONS: Stopping antibiotic treatment after 3 days is effective and safe for patients with postoperative meningitis whose cerebrospinal fluid culture results are negative.