Paolo Strignano

The first one thousand liver transplants in Turin: a single-center experience in Italy

The first Italian liver transplant center to reach the goal of 1000 procedures was Turin. The paper reports this single‐center experience, highlighting the main changes that have occurred over time. From 1990 to 2002, 1000 consecutive liver transplants were performed in 910 patients, mainly cirrhotics. Surgical technique was based on the preservation of the retrohepatic vena cava of the recipient. The veno‐venous bypass was used in 30 cases only and abandoned since 1997. Operating time, warm ischemia time and length of hospital stay significantly decreased over the years, while operating room extubation became routine. Immunosuppression pivoted on cyclosporine A. Management of retransplantations, marginal grafts, and of HCV‐positive, HBV‐positive and hepatocellular carcinoma recipients were optimized. Median follow‐up of the patients was 41 months. Overall survival rates at 1, 5 and 10 years were 87%, 78% and 72% respectively. Survival rates obtained in the second half of the cases (1999–2002 period) were significantly better than those obtained in the first half (1990–1998 period) (90% vs. 83% at 1 year and 81% vs. 76% at 5 years respectively). Increasing experience in liver transplant surgery and postoperative care allowed standardization of the procedure and expansion of the activity, with parallel improvement of the results.

Endoscopic retrograde cholangiopancreatography in patients with biliary complications after orthotopic liver transplantation: outcomes and complications.

Biliary complications after orthotopic liver transplantation (OLT) still remain a major cause of morbidity and mortality. The most frequent complications are strictures and leakages in OLT cases with duct-to-duct biliary reconstruction (D-D), which can be treated with dilatation or stent placement during endoscopic retrograde cholangiopancreatography (ERCP), although this procedure is burdened with potentially severe complications, such as retroperitoneal perforation, acute pancreatitis, septic cholangitis, bleeding, recurrence of stones, strictures due to healing process. The aim of the study was to analyze the outcome of this treatment and the complications related to the procedure. Among 1634 adult OLTs, we compared postprocedural complications and mortality rates with a group of 5852 nontransplanted patients (n-OLTs) who underwent ERCP. Of 472 (28,8%) post-OLT biliary complications, 319 (67.6%) occurred in D-D biliary anstomosis cases and 94 (29.5%) patients underwent 150 ERCP sessions. Among 49/80 patients (61.2%) who completed the procedure, ERCP treatment was successful. Overall complication rate was 10.7% in OLT and 12.8% in n-OLT (P = NS). Compared with the n-OLT group, post-ERCP bleeding was more frequent in OLT (5.3% vs 1.3%, P = .0001), while the incidence of pancreatitis was lower (4.7% vs 9.6%, P = .04). Procedure-related mortality rate was 0% in OLT and 0.1% in n-OLT (P = NS). ERCP is a safe procedure for post-OLT biliary complications in the presence of a D-D anastomosis. Morbidity and mortality related with this procedure are acceptable and similar to those among nontransplanted population.

Duodenal Switch Operation for Pathologic Transpyloric Duodenogastric Reflux

Objective:To assess the long-term results of the duodenal switch operation made for pathologic transpyloric duodenogastric reflux (DGR). Summary Background Data:DGR symptoms and lesions are poorly responsive to medical treatment. Methods:A duodenal switch operation was made on 48 patients suffering from pathologic transpyloric DGR either unrelated (n = 28) or secondary (n = 20) to previous upper gastrointestinal (GI) surgery, including cholecystectomy or vagotomy. The diagnosis was based on the combination of several objective arguments: a long history of gastric symptoms (ie, nausea, epigastric pain, and/or bilious vomiting) poorly responsive to medical treatment (48 of 48), gastroesophageal reflux symptoms unresponsive to proton-pump inhibitors (PPI) (23 of 29), gastritis on upper GI endoscopy (37 of 48) and/or at histology (28 of 41), presence of a bilious gastric lake at >1 upper GI endoscopy (30 of 48), DGR at diisopropyl iminodiacetic acid (DISIDA) scintigraphy scanning (7 of 13), pathologic 24-hour intragastric bile monitoring with the Bilitec device (40 of 41), and absence of Helicobacter pylori antral infection (39 of 41). Results:At follow-up (median, 81 months), gastric symptoms were nil, had improved, and remained unchanged in 29 (60.4%), 16 (33.3%), and 2(4.2%) patients, respectively, and 1 patient experienced symptomatic recurrence after a 92-month symptom-free period (2.1%). Among the 44 patients who had postoperative upper GI endoscopy, 42 (95.5%) had no gastritis whereas 5 (11.3%) had an ulcer at the duodenojejunostomy. Gastric exposure to bile at postoperative 24-hour intragastric Bilitec test in 36 patients was nil, within the normal range, and still slightly pathologic in 15 (41.7%), 19 (52.8%), and 2 (5.5%), respectively. Conclusions:The duodenal switch operation made on patients in whom diagnosis of pathologic transpyloric DGR is supported by several objective arguments provides most of them with symptomatic and endoscopic improvement parallel to abolishment or normalization of gastric exposure to bile. Postoperative PPI therapy during a 2-month period is to be recommended to prevent the development of an anastomotic ulcer.

Development and validation of a questionnaire evaluating the impact of hepatitis B immune globulin prophylaxis on the quality of life of liver transplant recipients.

To date, there is still a lack of instruments for specifically assessing the impact of anti–hepatitis B virus prophylaxis after liver transplantation (LT) on health‐related quality of life (HRQOL) and treatment satisfaction. Focusing on the use of hepatitis B immune globulin (HBIG), we developed and validated the Immunoglobulin Therapy After Liver Transplantation Questionnaire (ITaLi‐Q), which includes 41 items and covers 5 domains (side effects, positive and negative feelings, impact on the flexibility of daily activities, support, and satisfaction). The questionnaire was tested by 177 consecutive LT patients [71.8% were male, 38.4% were more than 60 years old, 58.8% were on intramuscular (IM) HBIG, and 41.2% were on intravenous (IV) HBIG]. A factor analysis confirmed the hypothesized structure, and a multitrait, multi‐item analysis showed favorable psychometric characteristics for ITaLi‐Q: item‐scale correlations > 0.40 for all items but 1, high scaling success rates (>90% for all scales but 1), excellent internal consistency (Cronbachs α ≥ 0.8 for all scales), and good reproducibility (test‐retest coefficient > 0.70 for all scales but 2). ITaLi‐Q was able to discriminate between subgroups of patients according to their clinical and sociodemographic characteristics. In comparison with patients on IV HBIG, patients on IM HBIG reported significantly better HRQOL scores on the Flexibility (81.5 ± 21.4 versus 73.1 ± 24.2, P = 0.01) and Negative Feelings scales (90.1 ± 17.3 versus 85.4 ± 20.7, P = 0.04), but they reported worse HRQOL scores on the Side Effects scale (81.8 ± 22.8 versus 95.6 ± 7.4, P < 0.001). No differences were found between the route of HBIG administration and the Satisfaction, Positive Feelings, Impact, and Support scales. In conclusion, ITaLi‐Q showed adequate psychometric characteristics and revealed that the route of HBIG administration has a significant impact on specific HRQOL domains beyond a patients satisfaction. Liver Transpl 18:332–339, 2012.

Negativization of viremia prior to liver transplant reduces early allograft dysfunction in hepatitis C–positive recipients

Although early allograft dysfunction (EAD) negatively impacts survival from the first months following liver transplantation (LT), direct‐acting antiviral agents (DAAs) have revolutionized hepatitis C virus (HCV) therapy. We investigated the EAD definition best predicting 90‐day graft loss and identified EAD risk factors in HCV‐positive recipients. From November 2002 to June 2016, 603 HCV‐positive patients (hepatocellular carcinoma, 53.4%) underwent a first LT with HCV‐negative donors. The median recipient Model for End‐Stage Liver Disease (MELD) score was 15, and the median donor age was 63 years. At LT, 77 (12.8%) patients were HCV RNA negative; negativization was achieved and maintained by pre‐LT antiviral therapy (61 patients) or pre‐LT plus a pre‐emptive post‐LT course (16 patients); 60 (77.9%) patients received DAAs and 17 (22.1%) interferon. We compared 3 different EAD definitions: (1) bilirubin ≥ 10 mg/dL or international normalized ratio ≥ 1.6 on day 7 after LT or aspartate aminotransferase or alanine aminotransferase > 2000 IU/L within 7 days of LT; (2) bilirubin > 10 mg/dL on days 2‐7 after LT; and (3) MELD ≥ 19 on day 5 after LT. EAD defined by MELD ≥ 19 on day 5 after LT had the lowest negative (0.1) and the highest positive (1.9) likelihood ratio to predict 90‐day graft loss. At 90 days after LT, 9.2% of recipients with EAD lost their graft as opposed to 0.7% of those without EAD (P < 0.001). At multivariate analysis, considering variables available at LT, MELD at LT of >25 (OR = 7.4) or 15‐25 (OR = 3.2), graft macrovesicular steatosis ≥ 30% (OR = 6.7), HCV RNA positive at LT (OR = 2.7), donor age > 70 years (OR = 2.0), earlier LT era (OR = 1.8), and cold ischemia time ≥ 8 hours (OR = 1.8) were significant risk factors for EAD. In conclusion, in HCV‐positive patients, MELD ≥ 19 on day 5 after LT best predicts 90‐day graft loss. Preventing graft infection by pre‐/peri‐LT antiviral therapy reduces EAD incidence and could be most beneficial in high‐MELD patients and recipients of suboptimal grafts. Liver Transplantation 23 915–924 2017 AASLD.

Herniation of an abdominal antireflux fundoplication into the chest: what does it mean?

OBJECTIVES The specific contribution of the herniation of an abdominal antireflux fundoplication into the chest to symptomatic and therefore surgical failure remains unclear. METHODS The study was conducted in 189 consecutive fundoplication patients, categorized as patients reoperated on for chest herniation of either an abdominal 360° (Group 1; n = 95) or a partial (Group 2; n = 10) fundoplication, and patients having undergone an intrathoracic 360° fundoplication for short oesophagus (Group 3; n = 84; reference group). There were four subgroups in Group 1: 1A: wrap still complete and perioesophageal; 1B: wrap still complete but perigastric; 1C: wrap still perioesophageal but partially disrupted and 1D: wrap perigastric and partially disrupted. RESULTS The prevalence of defective symptoms (heartburn and regurgitation) was significantly lower (P < 0.0001) in Group 3 (0.0%) and Subgroup 1A (3.7%) than in Subgroups 1B (84.4%), 1C (86.7%) and 1D (100%) and Group 2 (100%). The prevalence of obstructive symptoms (dysphagia, chest pain, necrosis and perforation) was significantly higher (P < 0.0001) in Subgroup 1A (100%) than in Subgroups 1B (57.8%), 1C (60.0%) and 1D (25.0%). The prevalence of a short oesophagus, an abdominal wall hernia repair and high abdominal pressure episodes in reoperated patients were 13.7, 36.2 and 67.2%, respectively. CONCLUSIONS Unlike perigastric or partial fundoplication, a 360° perioesophageal abdominal fundoplication, when herniated into the chest, is still effective against reflux. Obstructive symptoms are due to either diaphragmatic strangulation or perigastric migration of the wrap (slipknot effect). Short oesophagus, weakness of the abdominal wall and high abdominal pressure episodes favour the herniation process.

External Biliary Fistula in Orthotopic Liver Transplantation

During orthotopic liver transplantation (OLT), various situations may occur in which biliary reconstruction is neither technically feasible nor recommended. One bridge to a delayed anastomosis can be an external biliary fistula (EBF). This procedure allows the surgeon to execute hemostatic maneuvers, such as abdominal packing; therefore, biliary reconstruction can be subsequently performed in a bloodless operative field without edematous tissues. EBF can be made by placing in the donor biliary tract a cannula that is fixed to the bile duct using 2-0 silk ties and secured outside the abdominal wall. The biliary anastomosis will be performed within 2 days after the OLT. The aim of this study was to examine the safety of EBF in terms of the incidence of biliary complications compared with a direct anastomosis. Among 1,634 adult OLTs performed in 17 years in our center, 1,322 were carried out with termino-terminal hepaticocholedochostomy (HC-TT); two with side-to-side hepaticocholedochostomy; 208 with hepaticojejunostomy (HJ); 31 with EBF and delayed HC-TT, and 71 with EBF and delayed HJ. Biliary complication rates in the EBF group were 24.5%, including 23.9% in the delayed HJ and 25.8% in the delayed HC-TT. Biliary complication incidence among all OLTs was 24.6% (P = NS). No complications related to the procedure were observed. Therefore, EBF is a safe technique without a higher biliary complication rate. It may be useful when a direct biliary anastomosis is dangerous.

Peri-hepatic gauze packing for the control of haemorrhage during liver transplantation: A retrospective study

BACKGROUND Albeit accepted in the trauma setting, use of peri-hepatic gauze packing has been rarely reported during liver transplantation. AIMS To assess the results of packing in liver transplantation. METHODS We reviewed clinical characteristics, intraoperative events and postoperative outcome of consecutive adult liver transplantation recipients between 2003 and 2013. Patients treated with packing were compared to no-packing patients and to matched controls selected using a propensity score. RESULTS Of 1396 recipients, 107 were treated with packing for peri-hepatic bleeding (76.6%), allograft damage (12.1%) or partial outflow obstruction (11.2%). Urgent reoperation for ongoing haemorrhage was required in 6 (5.6%). Correction of haemodynamic and coagulation parameters was constantly achieved. Overall, patient (90% vs. 98%, p<0.001) and graft (83.2% vs. 94.7%, p<0.001) 3-month survival was significantly reduced in packing patients. However, after matching, no significant difference was observed in patient (89.3% vs. 95.2%, p=0.12) and graft (83.5% vs. 92.2%, p=0.06) 3-month survival. Patient survival was associated with recipient age (HR 2.59; p=0.04) and donor age × recipient MELD (HR 2.04; p=0.02), but not with packing (HR 1.81; p=0.29). CONCLUSIONS In our experience, packing was a valuable adjunct to conventional means of haemostasis during liver transplantation and, after accounting for confounding covariates, was not associated with inferior outcomes.

Pre-operative treatments for adenocarcinoma of the lower oesophagus and gastro-oesophageal junction: a review of the current evidence from randomized trials

Adenocarcinomas of the lower oesophagus and gastro-oesophageal junction are a complex clinico-pathological setting. Multimodality therapy is considered mandatory in most disease presentations. Nevertheless, the most appropriate treatment package has yet to be established. We herein summarize the evidence derived from randomized phase III trials on pre-operative treatments in this oncological scenario.

Transthoracic open window hepatostomy: A salvage approach to right lobe abscesses after liver transplantation

Pyogenic abscesses in grafts after liver transplantation (LT) are observed in 0.5% to 1% of patients, with mortality rates up to 45%. Predisposing factors are hepatic artery thrombosis, presence of hepaticojejunostomy, biliary obstruction, ascendant cholangitis, bacteremia, and percutaneous procedures (liver biopsy and biliary drainage). Therapeutic options include antibiotics, immunosuppression withdrawal, percutaneous or surgical drainage, liver resection, and retransplantation. However, in extreme situations, treatments can fail and retransplantation can be contraindicated because of sepsis, a complex surgical history, or both. In this setting, a salvage approach to abscesses located in the right hepatic area was devised, inspired by the open window thoracostomy described by Clagett in 1963 for postpneumonectomy empyema. Similar to the Clagett procedure, the so-called open window hepatostomy (OWH) is based on transthoracic surgical drainage of the septic cavity and secondary wound healing. With over 1820 consecutive LT procedures performed from 1990 to 2008, the technique was applied in only 3 cases (0.2%), always resulting in control of infection and preservation of life. Repeated dressings and further interventions were needed without exception because an external biliary fistula invariably appeared. Complete skin closure was obtained in 2 cases in 12 years and 7 months, respectively. The most recent patient, whose case is illustrated here, is now at an advanced stage of the healing process. CASE REPORT