Pierre-Philippe Massault

Temporary placement of partially covered self-expandable metal stents for anastomotic biliary strictures after liver transplantation: a prospective, multicenter study

BACKGROUND Management of anastomotic biliary strictures after liver transplantation deserves optimization. OBJECTIVE To evaluate placement and removal of partially covered self-expandable metal stents (PCSEMSs) in this setting. DESIGN Prospective, multicenter, uncontrolled study. SETTING Three French academic hospitals with liver transplantation units and tertiary referral endoscopy centers. PATIENTS Twenty-two patients (18 men, 4 women, aged 49.7 ± 12 years) with anastomotic biliary stricture. Seventeen (77.3%) presented stricture recurrence after plastic stenting. INTERVENTIONS PCSEMSs were placed across the stricture for 2 months and then removed. Patients were followed by clinical examination and liver function tests 1, 3, 6, 9, and 12 months after PCSEMS removal. MAIN OUTCOME MEASUREMENT The ability to remove PCSEMS. RESULTS PCSEMS placement was successful in all patients, after sphincterotomy in 21 patients. Stent-related complications included minor pancreatitis (3 patients), transient pain (1 patient), and cholangitis (1 patient). Stent removal was achieved in all patients but 2 whose stents had migrated distally. Partial stent dislocation was noted in 5 patients (upward in 4, downward in 1). Complications associated with stent removal were minor, including self-contained hemorrhage (1 patient) and fever (1 patient). The stricture persisted at the end of treatment in 3 patients (13.6%), all of whom had stent migration or dislocation. Recurrence of anastomotic stricture after initial success occurred in 9 of 19 patients (47.4%) within 3.5 ± 2.1 months. Sustained stricture resolution was observed in 10 of 19 patients (52.6%), 45.6% from an intent-to-treat perspective. LIMITATIONS Uncontrolled study with limited follow-up. CONCLUSIONS Temporary placement and removal of PCSEMSs in anastomotic biliary strictures after liver transplantation is feasible, although sometimes demanding. Stent migration may impair final outcome.

Hepatocellular carcinoma developed on compensated cirrhosis: Resection as a selection tool for liver transplantation

The objective of this study was to evaluate the histological profile obtained from primary resection of hepatocellular carcinoma (HCC) as a selection tool for liver transplantation (LT). The natural history of HCC depends on its histological features. The clinical effectiveness of resection as a selection tool for salvage or de principe LT has been previously advocated. Between 1987 and 2006, 20 patients underwent a resection prior to LT. Long‐term survival of these 20 patients was compared to that of 73 patients who underwent primary LT. Histological features of the resected specimen were compared to those of the recurrences. Feasibility, morbidity, and mortality of LT following primary resection were also analyzed. Mean follow‐up was 3.8 ± 4.4 and 2.7 ± 4.5 years from resection and LT, respectively; 6 patients died. The mean 1‐, 3‐, 5‐, and 10‐year overall survival rates were 71%, 61%, 55%, and 45% and 74%, 66%, 66%, and 40% after primary transplantation and primary resection, respectively (not significant). At LT, 14 patients had a recurrence, but histological study of the recurrence was not possible in 2 (complete necrosis). For 9 patients (75%), histological features of both primary and recurrent tumors were exactly the same. Four patients had recurrence following LT; in each case, primary and recurrent nodules shared the same histological markers of poor prognosis. De principe transplantation was proposed to 6 patients because of poor prognosis histological features on the resected specimen. All these patients are alive without recurrence with a mean follow‐up of 55 months. In conclusion, the natural history of HCC can be predicted on the basis of the histological profile of the resected specimen, which may be used as a selection tool for LT. De principe LT in patients within Milan criteria with poor prognosis histological features may be an optimal strategy. Liver Transpl 14:779–788, 2008.

Interleukin-4 induces the activation and collagen production of cultured human intrahepatic fibroblasts via the STAT-6 pathway

Interleukin-4 (IL-4) is overexpressed in liver grafts in a context of severe recurrent hepatitis C, during which the development of fibrosis is dramatically accelerated. In this study, we examined the effects of IL-4 on the activation and collagen production of cultured human intrahepatic (myo)fibroblasts (hIHFs), and investigated the underlying mechanisms. The myofibroblastic nature of cells was evaluated morphologically using activation markers (smooth muscle α-actin, vimentin and prolyl 4-hydroxylase). Quiescent hIHFs were obtained by cell incubation in serum-free medium or cell culture on Matrigel. We first analyzed IL-4 receptor expression, STAT-6 activation by IL-4, and STAT-6 inhibition by an anti-IL-4 antibody or by STAT-6 small-interfering RNA (siRNA) transfection. We then focused on collagen production, using quantitative real-time PCR to analyze the effect of IL-4 on the mRNA expression of collagens I, III and IV, and on collagen levels in supernatants of hIHFs, using the Sircol collagen assay. hIHFs cultured in plastic wells appeared to be morphologically activated. The expression of activation markers was reduced by serum deprivation or culture on Matrigel, and restored by IL-4 incubation. The IL-4 receptor was expressed by hIHFs, and STAT-6 was activated following incubation with IL-4. Both anti-IL-4 antibody and STAT-6 siRNA transfection inhibited this activation. The treatment of hIHFs with IL-4 increased the mRNA expression of collagens I, III and IV (P<0.05) and elevated collagen levels in supernatants (P=0.01 vs untreated cells). Therefore, IL-4 exerts profibrotic effects by activating hIHFs and inducing collagen production and secretion. This effect requires IL4-R binding and STAT-6 activation. IL-4 may thus be involved in accelerated course of fibrogenesis during recurrent hepatitis C.

Interleukin-4 induces human hepatocyte apoptosis through a Fas-independent pathway

IL‐4 is overexpressed in liver grafts during severe recurrent hepatitis C and rejection. Hepatocyte apoptosis is involved in both these phenomena. We therefore examined the proapoptotic effect of IL‐4 on HepG2 cells and human hepatocytes in vitro, together with the underlying mechanisms. We first measured IL‐4 receptor expression, STAT6 activation by IL‐4, and STAT6 inhibition by an anti‐IL‐4 antibody or by STAT6 siRNA transfection. We then focused on the pathways involved in IL‐4‐mediated apoptosis and the role of STAT6 activation in apoptosis initiation. The IL‐4 receptor was expressed on both cell types, and STAT6 was activated by IL‐4. Both anti‐IL‐4 and STAT‐6 siRNA inhibited this activation. IL‐4 induced apoptosis of both HepG2 cells (P= 0.008 vs. untreated control) and human hepatocytes (P<0.001 vs. untreated control). IL‐4 reduced the mitochondrial membrane potential, activated Bid and Bax, and augmented caspase 3, 8, and 9 activity. STAT6 blockade inhibited IL‐4‐induced apoptosis. Expression of Fas and Fas ligand was unaffected when HepG2 cells and hepatocytes were cultured with IL‐4, and Fas/FasL pathway blockade failed to inhibit IL‐4‐induced apoptosis. These results show that IL‐4 induces apoptosis of human hepatocytes through IL‐4 receptor binding, STAT6 activation, decreased mitochondrial membrane potential, and increased caspase activation, independently of the Fas pathway. IL‐4 might thus contribute to the progression of severe liver graft damage.—Aoudjehane, L., Podevin, P., Scatton, O., Jaffray, P., Dusanter‐Fourt, I., Feldmann, G., Massault, P. P., Grira, L., Bringuier, A., Dousset, B., Chouzenoux, S., Soubrane, O., Calmus, Y., Conti, F. Interleukin‐4 induces human hepatocyte apoptosis through a Fas‐independent pathway. FASEB J. 21, 1433–1444 (2007)

Pancreatic fistula after pancreaticoduodenectomy: the conservative treatment of choice

BACKGROUND A pancreatic fistula (PF) is the most common complication after pancreaticoduodenectomy (PD), and its reported incidence varies from 2% to 28%. The aim of the present study was to analyse the treatment of a complicated PF comparing the surgical approach with conservative techniques. METHODS From January 2000 through to August 2006, 121 patients were submitted for PD. The study consisted of 70 men and 47 women, with a median age of 60 years (SD +/- 12). The main indications for PD were pancreatic duct carcinoma in 52 patients (44.5%), ampullary carcinoma or adenoma in 18 (15.4%) and islet cell tumour in 11 (9.4%). Reconstruction by pancreatogastrostomy was performed in 65 patients (55.6%), and pancreatojejunostomy in 52 patients (44%). RESULTS Thirty-five patients (30%) developed a PF. Amongst these, 20 were managed conservatively and 14 were reoperated. These two groups of patients were compared with patients without a PF for analysis. There was no significant difference in the mean age, the gender ratio, American Society of Anesthesiologists (ASA) classification, surgical time and blood replacement, number of associated procedures, vascular resection and type of reconstruction between the three groups. There were five post-operative deaths (4.2%), three patients (21.4%) in the surgical treatment group (P < 0.01). Mean total number of complications (P= 0.02) and mean length of hospital stay (P < 0.001) were greater in the surgical group. The medium delay between the pancreatic resection and reoperation was 10 days (range, 3-32 days). Completion splenopancreatectomy was required in five patients whereas conservative treatment including debridement and drainage was applied in nine patients. CONCLUSION The surgical approach for a PF is associated with a higher mortality and morbidity. There is no advantage in performing completion pancreatectomy (CP) instead of extensive drainage as a result of the same mortality and morbidity rates and the risk of endocrine insufficiency. In cases of complicated PF, radiological or surgical conservative treatment is recommended.

Lessons Learned from the First 100 Laparoscopic Liver Resections: Not Delaying Conversion May Allow Reduced Blood Loss and Operative Time

BACKGROUND The laparoscopic approach to liver resective surgery is slowly spreading to specialized centers. Little is known about factors influencing the immediate postoperative outcome. STUDY DESIGN The purpose of the study was to evaluate the immediate outcome of laparoscopic liver resection (LLR), with particular emphasis on intraoperative bleeding and conversion. A retrospective analysis of demographic, clinical, and surgical data, including conversion, morbidity/mortality, and hospital stay, of the first 100 patients at our institution undergoing LLR from February 1997 through March 2007 was performed. RESULTS Indication for LLR was benign lesion in 28 patients, malignancy in 33, and living donation in 39. Seventy-five resections involved two or more segments. Mean blood loss was 120 ± 127.6 mL. One patient (1%) required transfusion. Mean operative time was 253 ± 91.6 minutes. No patient died. Postoperative complications occurred in 21 patients. The conversion rate was 17%. Variables related to conversion were American Society of Anesthesiologists Class II, body mass index, cirrhosis, necessity for the Pringle maneuver, and intraoperative blood loss. Conversion did not influence the operative time. Patients with conversion had more complications and a longer hospital stay. CONCLUSIONS Liver resection by laparoscopy is feasible and safe, implying low intraoperative blood loss. Not perfect physical conditions, cirrhosis, high body mass index, and, intraoperatively, blood loss and the necessity of a Pringle maneuver should be considered risk factors for conversion. A meticulous dissection by bipolar coagulation, Harmonic(®) (Ethicon) scalpel, and ultrasound dissector, other than the attitude not to delay conversion in difficult cases, may allow for low blood loss without prolongation of operative time, with a possible, slight increase of the conversion rate.

Median Arcuate Ligament in Orthotopic Liver Transplantation: Relevance to Arterial Reconstruction

Median arcuate ligament (MAL) syndrome results from luminal narrowing of the celiac artery by the insertion of the diaphragmatic muscle fibers or by fibrous bands of the celiac nervous plexus. In 10% to 50% of cases it is responsible for significant angiographic celiac trunk compression. In orthotopic liver transplantation (OLT), the presence of celiac compression by MAL is considered to be a risk factor for hepatic arterial thrombosis (HAT); it may lead to graft loss. Various surgical procedures have been proposed to overcome the impact of MAL in OLT, but their impact is still ill defined. The aim of our study was to compare standard hepatic artery reconstruction and graft reconstruction (aortohepatic bypass) in terms of HAT among patients with MAL undergoing OLT. We retrospectively reviewed 168 adult recipients of OLT performed from January 1991 to December 1998. Ten cases (5.6%) of celiac compression by MAL were identified after celiomesenteric arteriography. There was no significant difference in terms of HAT incidence when aortohepatic bypass was performed compared to a standard anastomosis; moreover, this was greater in the graft reconstruction group (25% vs 17%; P = .67). In our opinion, the presence of an arcuate ligament should not contraindicate a routine hepatic artery reconstruction.

The effect of erythropoietin on allogeneic blood requirement in patients undergoing elective liver resection: a model simulation.

We investigated whether recombinant human erythropoietin (rHuEPO) administration would reduce red blood cell (RBC) transfusion requirements in patients undergoing elective liver resection. We retrospectively investigated 200 patients undergoing elective liver resection. Factors likely to predict perioperative RBC transfusion were studied using a logistic regression analysis. A mathematical model was used to simulate RBC transfusion requirements if (a) transfusion thresholds had been predefined at a hemoglobin concentration of 7–8 g/dL, (b) preoperative hemoglobin concentrations had been increased to 15 g/dL by rHuEPO administration in patients with preoperative hemoglobin concentration in the range 10–13 g/dL, and (c) both interventions had been used. A cost/benefit evaluation of rHuEPO administration formed part of this simulation. RBC transfusion was correlated with major and median liver resection, total liver vascular exclusion, and a combined nonhepatic abdominal surgery but was not correlated with a preoperative hemoglobin concentration in the range 10–13 g/dL. Adherence to a small transfusion threshold or rHuEPO administration alone would have resulted in a slight reduction in transfusion requirements and transfusion rates for the whole population. However, the two interventions in combination would have significantly reduced both variables. One-hundred-eighteen patients undergoing median and major liver resection received 92% of RBC transfused. Sixty-six of these 118 patients had preoperative hemoglobin concentrations in the range 10–13 g/dL and could have received rHuEPO before surgery. rHuEPO alone would have avoided the transfusion of 63 RBC packs of 203 in this subgroup and 12 transfused patients of 31 (P = 0.02). rHuEPO administration to these 66 patients would have cost 186,000 Euro. The 63 RBC saved would have cost 10,710 Euro.

Best practices to optimize intraoperative photography.

BACKGROUND Intraoperative photography is used extensively for communication, research, or teaching. The objective of the present work was to define, using a standardized methodology and literature review, the best technical conditions for intraoperative photography. MATERIALS AND METHODS Using either a smartphone camera, a bridge camera, or a single-lens reflex (SLR) camera, photographs were taken under various standard conditions by a professional photographer. All images were independently assessed blinded to technical conditions to define the best shooting conditions and methods. RESULTS For better photographs, an SLR camera with manual settings should be used. Photographs should be centered and taken vertically and orthogonal to the surgical field with a linear scale to avoid error in perspective. The shooting distance should be about 75 cm using an 80-100-mm focal lens. Flash should be avoided and scialytic low-powered light should be used without focus. The operative field should be clean, wet surfaces should be avoided, and metal instruments should be hidden to avoid reflections. For SLR camera, International Organization for Standardization speed should be as low as possible, autofocus area selection mode should be on single point AF, shutter speed should be above 1/100 second, and aperture should be as narrow as possible, above f/8. For smartphone, use high dynamic range setting if available, use of flash, digital filter, effect apps, and digital zoom is not recommended. CONCLUSIONS If a few basic technical rules are known and applied, high-quality photographs can be taken by amateur photographers and fit the standards accepted in clinical practice, academic communication, and publications.

Common bile duct stenosis caused by chronic pancreatitis after liver transplantation for alcoholic cirrhosis.

BACKGROUND The prevalence of chronic pancreatitis in patients with alcoholic cirrhosis ranges from 7% to 11% and is not considered a contraindication for liver transplantation. METHODS Among 59 liver transplant recipients grafted for alcoholic cirrhosis, we report two observations of common bile duct stenosis due to chronic pancreatitis. RESULTS In both cases, pretransplant work-up disclosed no clinical or radiological evidence of chronic pancreatitis. The diagnosis of common bile duct stricture was made 6 and 60 months after liver transplantation. One patient was reoperated upon, and his choledochocholedochostomy was converted into a Rouxen-Y choledochojejunostomy. The second patient experienced metastatic laryngeal carcinoma and died before reoperation. CONCLUSIONS These observations suggest that common bile duct stricture caused by chronic pancreatitis may occur after liver transplantation for alcoholic cirrhosis, even after a long-standing history of abstinence.