Stéphane Koch

Experience of liver transplantation for incurable alveolar echinococcosis: a 45-case European collaborative report.

Background. Alveolar echinococcosis (AE) of the liver is a rare and severe parasitic disease. It behaves like a slow-growing liver cancer, and liver transplantation (LT) has been proposed in advanced cases since 1985. The aim of this retrospective study was to collect all AE transplant cases in Europe, analyze the results, and specify the usefulness of LT for this unusual indication. Methods. A questionnaire was sent to 83 LT centers from July 1996 to December 1999. Results. Sixty-five centers responded: 45 AE patients (mean age, 45.8 years) underwent an LT procedure at 16 LT centers. The mean interval between diagnosis and LT was 5 years. One patient died during the hepatectomy phase. Five-year survival was 71%. Five-year survival without recurrence was 58%. The nine early deaths were mostly related to bacterial or fungal infections, or both, in patients in bad condition when LT was performed. Six patients had a graft AE reinfection. Five late deaths were related directly to ongoing AE. In the other cases, benzimidazole (BZM) therapy seemed to stabilize AE residues. Conclusions. This unique experience indicates that LT is feasible for life-threatening AE. Specific management is needed to optimize the results: earlier decision for LT in incurable symptomatic biliary AE, pre- and post-LT BZM therapy, meticulous pre-LT evaluation to identify extrahepatic extension, and an immunosuppressive regimen kept to a minimum.

Indications and results of liver transplantation for Echinococcus alveolar infection: an overview.

BackgroundAlveolar echinococcosis (AE) of the liver, caused by the larval stage of the fox tapeworm Echinococcus multilocularis, has the characteristics of a slow-growing liver cancer. It is one of the rare parasitic diseases for which a parasitolytic drug is not yet available, and AE is lethal in the absence of appropriate therapeutic management. Complete surgical resection of the parasite at an early stage of infection provides favourable prospects for cure, but, due to a long clinical latency, many cases are diagnosed at an advanced stage, so that partial liver resection can be performed in only 35% of patients. Benzimidazole (BZM) treatment is given in inoperable cases but these compounds are only parasitostatic, and lifelong therapy is required. During the past 20 years some centres have considered liver transplantation (LT) for the treatment of incurable AE.MethodsOur review summarizes the results of this experience based on a series of 47 European patients who received transplants between 1985 and 2002, tries to specify the real place of LT for AE, and underlines the measures that could be undertaken in the future to improve the results.ResultsFive-year survival was 71%. Five-year survival without recurrence was 58%. Major technical difficulties related either to previous laparotomies or to the loco-regional involvement were observed. The nine early deaths concerned AE patients with a long past-history of symptomatic AE (iterative cholangitis, secondary biliary cirrhosis). Five late deaths were directly related to ongoing AE, located in the brain in three cases, a very rare AE location that was not investigated before LT in these patients.ConclusionsIn general, the pre-LT screening for distant AE metastases appeared insufficient in this series. Heavy immunosuppressive schemes, absence or delayed re-introduction of BZM after LT have clearly played a role in this unfavourable course. This unique experience indicates that, despite major technical difficulties, LT for incurable AE is feasible and could be discussed in very symptomatic cases. Before LT, interventional radiology should be preferred to repeated laparotomies. Pre-LT and post-LT BZM treatment is mandatory. A careful evaluation of possible distant metastases should be done before the decision for LT is made. After LT, the possibility of an ongoing AE must be permanently kept in mind. This could be reduced by lightening the immunosuppressants, carefully following the specific circulating antibodies, and applying a systematic radiological evaluation, not only to the graft but also to the lungs and the brain.

Core needle versus standard needle for endoscopic ultrasound-guided biopsy of solid pancreatic masses: a randomized crossover study

BACKGROUND AND STUDY AIMS A new core biopsy needle for endoscopic ultrasound (EUS)-guided sampling has recently been developed. The aim of this prospective multicenter study was to compare this needle with a standard needle in patients with solid pancreatic masses. PATIENTS AND METHODS Consecutive patients with solid pancreatic masses referred to 17 centers for EUS-guided sampling were included. Each patient had two passes with a standard 22G needle and a single pass with a 22G core needle performed in a randomized order. Samples from both needles were separately processed for liquid-based cytology and cell-block preparation and were assessed independently by two blinded expert pathologists. The primary endpoint was the accuracy of the detection of malignancy. The reference standard was based on further cytohistological analysis obtained under ultrasound or computed tomography scanning, endoscopic or surgical guidance, and/or by clinical follow-up with repeated imaging examinations for at least 12 months. The secondary endpoints were the rate of technical failure and the quality of the cytohistological samples obtained. RESULTS Of the 80 patients included (49 men; mean age 67.1 ± 11.1), 87.5 % had final malignant diagnoses (adenocarcinoma n = 62, 77.5 %). There was no difference between the needles in diagnostic accuracy (standard needle 92.5 % vs. core needle 90 %; P = 0.68) or technical failure. Both pathologists found the overall sample quality significantly better for the standard needle (expert 1, P = 0.009; expert 2, P = 0.002). CONCLUSIONS The diagnostic accuracy of EUS sampling for solid pancreatic masses using standard and core needles seems comparable but with a better overall histological sample quality for the former. ClinicalTrial.gov identifier: NCT01479803.

Treatment of ulcerative colitis refractory to steroid therapy by oral microemulsion cyclosporine (Neoral)

Background Intravenous cyclosporine is active in 60% to 80% of patients with ulcerative colitis (UC) who failed to respond to intravenous corticosteroids. Several studies have suggested that cyclosporine in microemulsion form (Neoral) has some efficacy in this setting, but the optimal dose, blood level, time to response, and remission need to be better defined. The aim of this study was to evaluate the response to Neoral and its toxicity in active corticosteroid‐refractory UC. Methods Between March 2002 and August 2005, 20 courses of Neoral [initial dose, 2.3 mg/kg (range, 1.8 to 2.8 mg/kg) every 12 hours] were prescribed in 19 consecutive patients for a UC attack that did not respond to intravenous methylprednisolone. All patients received prophylaxis against Pneumocystis carinii. Results Response was obtained in 17 of 20 attacks (85%) after 3.5 days (range, 1 to 7). Remission was obtained in 15 of 20 attacks (75%) after 13 days (range, 2 to 30 days). Four responders relapsed and underwent colectomy 21 to 900 days after the start of Neoral. Overall, 14 of 19 patients (74%) were colectomy free after a median follow‐up of 8 months (range, 1 to 41 months). Cyclosporine blood levels were measured at fasting (C0) and 2 hours after Neoral administration (C2) in a subgroup of 10 responders. The results were 103 ng/mL (range, 32 to 240 ng/mL) for C0 and 761 ng/mL (183 to 1390 ng/mL) for C2. One severe bedridden patient with neonatal encephalopathy died. Main side effects observed were mild transient renal impairment (n = 2), hypertension (n = 1), cytomegalovirus infection (n = 2), and esophageal candidiasis (n = 1). Conclusions In active corticosteroid‐refractory UC, Neoral seems to have the same efficacy and toxicity as the intravenous form. Trough target cyclosporine blood levels should not exceed 100 ng/mL for C0 and 700 ng/mL for C2.

Janus kinase inhibition with tofacitinib: changing the face of inflammatory bowel disease treatment.

The advent of anti-Tumor Necrosis Factor (TNF) therapy has changed the way of treating inflammatory bowel disease (IBD). However, primary and secondary failure are relatively frequent with all anti-TNF agents, which are available only as parenteral agents. Tofacitinib is an oral janus kinase (JAK) inhibitor that inhibits JAK family kinase members, in particular JAK1 and JAK3, achieving a broad limitation of inflammation by interfering with several cytokine receptors. It first proved its efficacy as an immunosuppressive regimen after renal transplantation, and was recently approved by the FDA for rheumatoid arthritis. First data in IBD are promising, especially in ulcerative colitis. Ongoing clinical trials in both UC and Crohns disease (CD) are needed to further explore its efficacy in CD and to better assess its safety profile.

Non-surgical and non-chemical attempts to treat echinococcosis: do they work?

Cystic echinococcosis (CE) and alveolar echinococcosis (AE) are chronic, complex and neglected diseases. Their treatment depends on a number of factors related to the lesion, setting and patient. We performed a literature review of curative or palliative non-surgical, non-chemical interventions in CE and AE. In CE, some of these techniques, like radiofrequency thermal ablation (RFA), were shelved after initial attempts, while others, such as High-Intensity Focused Ultrasound, appear promising but are still in a pre-clinical phase. In AE, RFA has never been tested, however, radiotherapy or heavy-ion therapies have been attempted in experimental models. Still, application to humans is questionable. In CE, although prospective clinical studies are still lacking, therapeutic, non-surgical drainage techniques, such as PAIR (puncture, aspiration, injection, re-aspiration) and its derivatives, are now considered a useful option in selected cases. Finally, palliative, non-surgical drainage techniques such as US- or CT-guided percutaneous biliary drainage, centro-parasitic abscesses drainage, or vascular stenting were performed successfully. Recently, endoscopic retrograde cholangiopancreatography (ERCP)-associated techniques have become increasingly used to manage biliary fistulas in CE and biliary obstructions in AE. Development of pre-clinical animal models would allow testing for AE techniques developed for other indications, e.g. cancer. Prospective trials are required to determine the best use of PAIR, and associated procedures, and the indications and techniques of palliative drainage.

Esophageal stents as a salvage therapy for non-malignant iatrogenic esophageal perforations.

BACKGROUND Esophageal non-malignant perforations are severe life-threatening conditions. The current treatment is either surgical or conservative. METHODS We report a case series of 3 consecutive patients (1 female, 2 male; 34-68 years) treated with expandable covered stents for non-malignant iatrogenic esophageal perforations. OBSERVATIONS In our series, 3 out of 3 patients sealed their perforations and resumed normal oral intake. Complications observed were 2 stent migrations, which occurred at 6 and 11 months after stent insertion, a stenosis due to acid reflux treated by another stent insertion above the first one. On the basis of the data available, it appears that esophageal stents was successful in 82% of the cases. The mortality and complication rates were of 7% and 32% respectively. The main complications observed were peptic stenosis above the stent and fistulas. CONCLUSION These results are promising but need to be confirmed in large-scale prospective studies. Mediastinal drainage remains mandatory when sepsis is present.

Spondyloarthritis and the gut: A new look

Joint Bone Spine - In Press.Proof corrected by the author Available online since mardi 6 janvier 2015

Improved survival of cirrhotic patients with variceal bleeding over the decade 2000–2010

BACKGROUND AND OBJECTIVE Advances in the management of variceal bleeding (VB) have been highlighted recently. We aimed at assessing whether changing the management of VB has improved the outcome (mortality and rebleeding rates). METHODS The files of two cohorts (n=57, 2000-2001 and n=64, 2008-2009) of patients referred to our university center were reviewed after a cross-searching using two coding systems. Data were recorded during the six months after VB. RESULTS As compared to 2000-2001, more use of general anesthesia (25.4% vs. 11.1%; P=0.049), band ligations (96.1% vs. 71.4%; P=0.001), octreotide (95.3% vs. 80.7%; P=0.012) and antibiotic prophylaxis (93.8% vs. 82.5%; P=0.09) were performed in 2008-2009, whereas the number of red-cell units transfused during the hospital stay (4.3 ± 3.2 vs. 7.1 ± 5.7; P=0.005) decreased. Surprisingly, more than 60% of patients reached the emergency department from home without medical assistance in both periods. In 2008-2009, patients had more comorbidities and no patients underwent early-TIPS but the 6-week mortality rate (24.6% vs.10.9%; P=0.048) was lower. The 6-week mortality was associated with high MELD score (HR=1.13; 95%CI: 1.08-1.18) and hypovolemic shock (HR=5.36; 95%CI: 1.96-14.67) at admission. In multivariate analysis adjusted on MELD and comorbidities, the 2008-2009 period (HR: 0.42; 95%CI: 0.20-0.87; P=0.02) was associated with a lower 6-month mortality rate. CONCLUSIONS Although cirrhotic patients with VB had more comorbidities in 2008-2009 and received no early-TIPS, their prognosis has improved during this last decade concomitantly to a more intensive care and a lower transfusion strategy.

The expansion of endoscopic submucosal dissection in France: A prospective nationwide survey

Introduction Early reports of endoscopic submucosal dissection (ESD) in Europe suggested high complication rates and disappointing outcomes compared to publications from Japan. Since 2008, we have been conducting a nationwide survey to monitor the outcomes and complications of ESD over time. Material and methods All consecutive ESD cases from 14 centers in France were prospectively included in the database. Demographic, procedural, outcome and follow-up data were recorded. The results obtained over three years were compared to previously published data covering the 2008–2010 period. Results Between November 2010 and June 2013, 319 ESD cases performed in 314 patients (62% male, mean (±SD) age 65.4 ± 12) were analyzed and compared to 188 ESD cases in 188 patients (61% male, mean (±SD) age 64.6 ± 13) performed between January 2008 and October 2010. The mean (±SD) lesion size was 39 ± 12 mm in 2010–2013 vs 32.1 ± 21 for 2008–2010 (p = 0.004). En bloc resection improved from 77.1% to 91.7% (p < 0.0001) while R0 en bloc resection remained stable from 72.9% to 71.9% (p = 0.8) over time. Complication rate dropped from 29.2% between 2008 and 2010 to 14.1% between 2010 and 2013 (p < 0.0001), with bleeding decreasing from 11.2% to 4.7% (p = 0.01) and perforations from 18.1% to 8.1% (p = 0.002) over time. No procedure-related mortality was recorded. Conclusions In this multicenter study, ESD achieved high rates of en bloc resection with a significant trend toward better outcomes over time. Improvements in lesion delineation and characterization are still needed to increase R0 resection rates.