Laparoscopic Versus Open Hemihepatectomy: The ORANGE II PLUS Multicenter Randomized Controlled Trial.

PURPOSE: To compare outcomes after laparoscopic versus open major liver resection (hemihepatectomy) mainly for primary or metastatic cancer. The primary outcome measure was time to functional recovery. Secondary outcomes included morbidity, quality of life (QoL), and for those with cancer, resection margin status and time to adjuvant systemic therapy. PATIENTS AND METHODS: This was a multicenter, randomized controlled, patient-blinded, superiority trial on adult patients undergoing hemihepatectomy. Patients were recruited from 16 hospitals in Europe between November 2013 and December 2018. RESULTS: Of the 352 randomly assigned patients, 332 patients (94.3%) underwent surgery (laparoscopic, n = 166 and open, n = 166) and comprised the analysis population. The median time to functional recovery was 4 days (IQR, 3-5; range, 1-30) for laparoscopic hemihepatectomy versus 5 days (IQR, 4-6; range, 1-33) for open hemihepatectomy (difference, -17.5% [96% CI, -25.6 to -8.4]; P < .001). There was no difference in major complications (laparoscopic 24/166 [14.5%] v open 28/166 [16.9%]; odds ratio [OR], 0.84; P = .58). Regarding QoL, both global health status (difference, 3.2 points; P < .001) and body image (difference, 0.9 points; P < .001) scored significantly higher in the laparoscopic group. For the 281 (84.6%) patients with cancer, R0 resection margin status was similar (laparoscopic 106 [77.9%] v open 122 patients [84.1%], OR, 0.60; P = .14) with a shorter time to adjuvant systemic therapy in the laparoscopic group (46.5 days v 62.8 days, hazard ratio, 2.20; P = .009). CONCLUSION: Among patients undergoing hemihepatectomy, the laparoscopic approach resulted in a shorter time to functional recovery compared with open surgery. In addition, it was associated with a better QoL, and in patients with cancer, a shorter time to adjuvant systemic therapy with no adverse impact on cancer outcomes observed.

Long-term oncological outcomes after laparoscopic parenchyma-sparing redo liver resections for patients with metastatic colorectal cancer: a European multi-center study.

BACKGROUND: Laparoscopic redo resections for colorectal metastases are poorly investigated. This study aims to explore long-term results after second, third, and fourth resections. MATERIAL AND METHODS: Prospectively updated databases of primary and redo laparoscopic liver resections in six European HPB centers were analyzed. Procedure-related overall survival after first, second, third, and fourth resections were evaluated. Furthermore, patients without liver recurrence after first liver resection were compared to those with one redo, two or three redo, and patients with palliative treatment for liver recurrence after first laparoscopic liver surgery. Survival was calculated both from the date of the first liver resection and from the date of the actual liver resection. In total, 837 laparoscopic primary and redo liver resections performed in 762 patients were included (630 primary, 172 first redo, 29 second redo, and 6 third redo). Patients were bunched into four groups: Group 1-without hepatic recurrence after primary liver resection (n = 441); Group 2-with liver recurrence who underwent only one laparoscopic redo resection (n = 154); Group 3-with liver recurrence who underwent two laparoscopic redo resections (n = 29); Group 4-with liver recurrence who have not been found suitable for redo resections (n = 138). RESULTS: No significant difference has been found between the groups in terms of baseline characteristics and surgical outcomes. Rate of positive resection margin was higher in the group with palliative recurrence (group 4). Five-year survival calculated from the first liver resection was 67%, 62%, 84%, and 7% for group 1, 2, 3, and 4, respectively. Procedure-specific 5-year overall survival was 50% after primary laparoscopic liver resection, 52% after the 1st reoperation, 52% after the 2nd, and 40% after the 3rd reoperation made laparoscopic. CONCLUSIONS: Multiple redo recurrences can be performed laparoscopically with good long-term results. Liver recurrence does not aggravate prognosis as long as the patient is suitable for reoperation.

Laparoscopic Liver Surgery Training Course on Thiel-Embalmed Human Cadavers: Program Evaluation, Trainer's Long-Term Feedback and Steps Forward.

OBJECTIVES: The purpose of this study was to evaluate the feedback of participants upon laparoscopic liver surgery (LLS) course on Thiel-embalmed human bodies. METHODS: From 2010 to 2017, ten LLS masterclasses have been organized by the Department of Hepatobiliary Surgery at Ghent University Hospital. A 23-question anonymous survey was electronically sent to 119 participants between November 2017 and January 2018, exploring their characteristics and asking for evaluation of the course. The obstacles for implementing LLS in their centers have been assessed. RESULTS: Sixty-four surgeons (53.8%) responded to the survey; 42 (65.6%) were employed at a university hospital; and 39 (60.9%) were in the first decade of their practice as a consultant surgeon. Forty-three (67.2%) surgeons reported an increased percentage of LLS cases afterward. Training on Thiel cadavers was considered superior (49.2%) to other training options including proctoring in the operating room (34.9%), virtual reality (6.3%), video training (4.8%) and practicing on pigs (4.8%). Obstacles identified contained inadequate training, patient's referral pattern, financial issues, lack of dedicated surgical team and time constrains. CONCLUSIONS: This survey revealed that a structured short-time program incorporating interactive discussion, live operations and hands-on training on human bodies under proctorship may enhance efficient training in laparoscopic liver surgery. In a step forward for upcoming courses, the importance of team building has to be addressed.

Laparoscopic liver resections for hepatocellular carcinoma. Can we extend the surgical indication in cirrhotic patients?

BACKGROUND: Evidence on the value of laparoscopic liver resections (LLR) for hepatocellular carcinoma (HCC) and severe cirrhosis is still lacking. The aim of this study is to assess surgical and oncological outcomes of LLR in cirrhotic HCC patients. METHODS: The analysis included 403 LLR for HCC from seven European centres. 333 cirrhotic and 70 non-cirrhotic patients were compared. A matched comparison was performed between 100 Child-Pugh A and 25 Child-Pugh B patients. RESULTS: There was no difference in blood loss (250 vs. 250 mL, p 0.465) and morbidity (28.6 vs. 26.4%, p 0.473) between cirrhotics and non-cirrhotics, and liver-specific complications were similar (12.8 vs. 12%, p 0.924). The sub-analysis revealed similar perioperative outcomes in either Child-Pugh A or B patients. Noteworthy, ascitis (11 vs. 12%, p 0.562) and liver failure (3 vs. 4%, p 0.595) were not different. ASA score (OR 1.76, p 0.034) and conversion (OR 2.99, p 0.019) were risk factors for major morbidity. Despite lower recurrence-free survival in cirrhotics (43 vs. 55 months, p 0.034), overall survival was similar to non-cirrhotic patients (84 vs. 76.5, p 0.598). CONCLUSION: LLR for HCC appear equally safe in cirrhotic and non-cirrhotic patients, and the advantages can be witnessed in those with advanced cirrhosis. Severe comorbidities and conversion should be considered risk factors for complications-rather than the severity of cirrhosis and portal hypertension-when liver resection is performed laparoscopically. Such results may be of great interest to liver surgeons and hepatologists when deciding on the management of HCC within cirrhosis.

Long-term survival after multimodality therapy including surgery for metastatic esophageal cancer.

BACKGROUND AND OBJECTIVES: Esophageal cancer (EC) remains an aggressive disease with a poor survival. Management of metastatic EC is limited to palliative chemotherapy (CT). Scientific contributions regarding the role of surgery are scarce and controversial. We analysed outcome of surgically treated metastatic EC patients. METHODS: We retrospectively identified surgically treated metastatic EC patients from our esophagectomy database. The aim of this study was to evaluate surgical complications, pathological response, oncological outcome and mean survival of these aggressively treated stage IV cancer patients. RESULTS: Twelve stage IV patients with disease presentation limited to outfield lymph node (LN) and/or liver metastasis were treated with an aggressive multimodality treatment including surgery. Mean age was 58 years (75% male, 75% Adenocarcinomas). Median postoperative hospital stay was 15 d. Radiological anastomotic leakage occurred in one patient. In hospital, mortality was nil. Complete resection was achieved in all but one. Metastatic recurrence occurred in 64% of R0 resected patients. At date of censoring, after a median follow-up of 22 months, 50% of the surgical resected patients are still alive and 33% are free of disease recurrence. Kaplan-Meier curves show a possibility to long-term survival after aggressive multimodality therapy including surgery. CONCLUSIONS: In selected metastatic EC patients, multimodality treatment including surgery has an acceptable surgical outcome with a potentially long-term survival.

Gallstone ileus: monocentric experience looking for the adequate approach.

Common complications of biliary lithiasis are cholecystitis, bile duct lithiasis, and acute biliary pancreatitis. Gallstone ileus is uncommon complications often requiring surgical approach. It is a mechanical bowel obstruction caused by a biliary calculus usually originating from a bilioenteric fistula. Because of the limited number of reported cases, the optimal surgical method of treatment has been the subject of ongoing debate. A retrospective, observational, descriptive study was conduct on patients diagnosed with non-neoplastic bowel occlusion. For each case of gallstone ileus, the following variables were revised: personal and clinical data, mean time of onset of symptoms, length of pre- and postoperative stay, imaging studies, biochemical tests, site of the bilioenteric fistula and occlusion, surgical strategy, postoperative course, follow-up, and mortality. Of the 290 cases of non-neoplastic bowel obstruction from 2008 to 2015, 11 (3.7%) were due to gallstone ileus. The majority of patients were elderly women (F 9/M 2) with high average age (82.4; 76-88) and significant comorbidities. Five cases of small-bowel occlusions were treated with solely enterolithotomy. For the remaining six cases, digestive resection and cholecystectomy were performed. Complications rate (20 vs. 80%) and postoperative stay (12.4 vs. 25.3 days) were lower in the group of enterolithotomy with respect to the group treated with other procedures. In-hospital mortality was nil. Gallstone ileus is an uncommon bowel occlusion affecting mainly the elderly female population. Enterotomy with stone extraction alone is associated with better outcomes than more invasive techniques.

The practice of laparoscopic liver surgery in Belgium: a national survey.

BACKGROUND: Laparoscopic liver surgery (LLS) gained popularity bringing several advantages including decreased morbidity and reduction of length of hospital stay compared to open. METHODS: To understand practice and evolution of LLS in Belgium, a 20-questions survey was sent to all members of the Royal Belgian Society for Surgery, the Belgian Section of Hepato-Pancreatic and Biliary Surgery and the Belgian Group for Endoscopic Surgery. RESULTS: Thirty-seven surgical units representing 61 surgeons performing LLS in Belgium responded: 50% from regional hospitals, 28% from university and 22% from peripheral hospitals. Replies from high volume centers (>50 liver-surgery/year) were 19%. More than 25% of liver procedures were performed laparoscopically in 35% of centers. LLS is adopted since more than 15-years in 14.5% of centers with an increasing rate reported in 59%. Low relevance of LLS in the hospital organization (26.5%) and lack of time in surgical schedules (12%) or of specific training (9%) are the main barriers for further diffusion. More than 80% of the responders agreed to participate to a national prospective registry. CONCLUSION: LLS is mainly performed in experienced HPB units with an increasing interest in peripheral centers. A prospective national registry will be useful by providing real data in terms of indications, morbidity and overall evolution.

The single surgeon learning curve of laparoscopic liver resection: A continuous evolving process through stepwise difficulties.

The aim of the study was to evaluate the single-surgeon learning curve (SSLC) in laparoscopic liver surgery over an 11-year period with risk-adjusted (RA) cumulative sum control chart analysis.Laparoscopic liver resection (LLR) is a challenging and highly demanding procedure. No specific data are available for defining the feasibility and reproducibility of the SSLC regarding a consistent and consecutive caseload volume over a specified time period.A total of 319 LLR performed by a single surgeon between June 2003 and May 2014 were retrospectively analyzed. A difficulty scale (DS) ranging from 1 to 10 was created to rate the technical difficulty of each LLR. The risk-adjusted cumulative sum control chart (RA-CUSUM) analysis evaluated conversion rate (CR), operative time (OT) and blood loss (BL). Perioperative morbidity and mortality were also analyzed.The RA-CUSUM analysis of the DS identified 3 different periods: P1 (n = 91 cases), with a mean DS of 3.8; P2 (cases 92-159), with a mean DS of 5.3; and P3 (cases 160-319), with a mean DS of 4.7. P2 presented the highest conversion and morbidity rates with a longer OT, whereas P3 showed the best results (P < 0.001). Fifty cases were needed to achieve a significant decrease in BL. The overall morbidity rate was 13.8%; no perioperative mortality was observed.According to our analysis, at least 160 cases (P3) are needed to complete the SSLC performing safely different types of LLR. A minimum of 50 cases can provide a significant decrease in BL. Based on these findings, a longer learning curve should be anticipated to broaden the indications for LLR.

Liver transplantation for adenomatosis: European experience.

The aim of this study was to collect data from patients who underwent liver transplantation (LT) for adenomatosis; to analyze the symptoms, the characteristics of the disease, and the recipient outcomes; and to better define the role of LT in this rare indication. This retrospective multicenter study, based on data from the European Liver Transplant Registry, encompassed patients who underwent LT for adenomatosis between January 1, 1986, and July 15, 2013, in Europe. Patients with glycogen storage disease (GSD) type IA were not excluded. This study included 49 patients. Sixteen patients had GSD, and 7 had liver vascular abnormalities. The main indications for transplantation were either a suspicion of hepatocellular carcinoma (HCC; 15 patients) or a histologically proven HCC (16 patients), but only 17 had actual malignant transformation (MT) of adenomas. GSD status was similar for the 2 groups, except for age and the presence of HCC on explants (P = 0.030). Three patients with HCC on explant developed recurrence after transplantation. We obtained and studied the pathomolecular characteristics for 23 patients. In conclusion, LT should remain an extremely rare treatment for adenomatosis. Indications for transplantation primarily concern the MT of adenomas. The decision should rely on morphological data and histological evidence of MT. Additional indications should be discussed on a case-by-case basis. In this report, we propose a simplified approach to this decision-making process.

Robotic versus laparoscopic resections of posterosuperior segments of the liver: a propensity score-matched comparison.

BACKGROUND: Open parenchymal-preserving resection is the current standard of care for lesions in the posterosuperior liver segments. Laparoscopy and robot-assisted surgery are emergent surgical approaches for liver resections, even in posteriorly located lesions. The objective of this study was to compare robot-assisted to laparoscopic parenchymal-preserving liver resections for lesions located in segments 7, 8, 4a, and 1. METHODS: Demographics, comorbidities, clinicopathologic characteristics, surgical treatments, and outcomes from patients who underwent laparoscopic and robot-assisted liver resection in two centers for lesions in the posterosuperior segments between June 2008 and February 2014 were reviewed. A 1:2 matched propensity score analysis was performed by individually matching patients in the robotic cohort to patients in the laparoscopic cohort based on demographics, comorbidities, performance status, tumor stage, location, and type of resection. RESULTS: Thirty-six patients who underwent robot-assisted liver resection were matched with 72 patients undergoing laparoscopic liver resection. Matched patients displayed no significant differences in postoperative outcomes as measured by blood loss, hospital stay, R0 negative margin rate, and mortality. The overall morbidity according to the comprehensive complication index was also similar (34.6 ± 33 vs. 18.4 ± 11.3, respectively, for robotic and laparoscopic approach, p = 0.11). Patients undergoing robotic liver surgery had significantly longer inflow occlusion time (77 vs. 25 min, p = 0.001) as compared with their laparoscopic counterparts. CONCLUSIONS: Although number and severity of complications in the robotic group appears to be higher, robotic and laparoscopic parenchymal-preserving liver resections in the posterosuperior segments display similar safety and feasibility.

Tissue management with tri-staple technology in major and minor laparoscopic liver resections.

One of the most relevant technologic advancements in laparoscopic liver resection (LLR) is owing to the improved ability to safely secure and divide vascular and biliary structures and the liver parenchyma by the use of endostaplers. We compared, retrospectively, 35 LLRs with the Tri-Staple technology versus 57 LLRs without, during a 14-month period. Colorectal liver metastases were overall the main indication for LLR. Neither major hepatectomy nor left lateral sectionectomy was done in the nonstapled group. Mean surgical time and blood loss were similar, whereas the tumor number and size were significantly larger in the stapled group (P ≤ 0.01). The conversion rate was 0% and 3.5% (n = 2); and the morbidity rate was 9% (n = 3) and 12% (n = 7), respectively, in the stapled and nonstapled group (P = 0.8). No overall 3-month mortality was recorded. Endo GIA Reloads with Tri-Staple technology allow a proper division of the intrahepatic vessels and biliary structure. These devices in LLRs are safe and feasible, allowing major hepatectomy and complex cases as 2-staged procedures and laparoscopic living donor liver resections.

Biliverdin protects against liver ischemia reperfusion injury in swine.

Ischemia reperfusion injury (IRI) in organ transplantation remains a serious and unsolved problem. Organs that undergo significant damage during IRI, function less well immediately after reperfusion and tend to have more problems at later times when rejection can occur. Biliverdin has emerged as an agent that potently suppress IRI in rodent models. Since the use of biliverdin is being developed as a potential therapeutic modality for humans, we tested the efficacy for its effects on IRI of the liver in swine, an accepted and relevant pre-clinical animal model. Administration of biliverdin resulted in rapid appearance of bilirubin in the serum and significantly suppressed IRI-induced liver dysfunction as measured by multiple parameters including urea and ammonia clearance, neutrophil infiltration and tissue histopathology including hepatocyte cell death. Taken together, our findings, in a large animal model, provide strong support for the continued evaluation of biliverdin as a potential therapeutic in the clinical setting of transplantation of the liver and perhaps other organs.

Laparoscopic splenectomy: a single center experience. Unusual cases and expanded inclusion criteria for laparoscopic approach.

Laparoscopic splenectomy (LS) is nowadays considered as the gold standard for most hematological diseases where splenectomy is necessary, but many questions still remain. The aim of this study was to analyze our 5-years experiences consisting of 48 consecutive LS cases in order to assess the optimal approach and the feasibility of the procedure also in malignant diseases and unusual cases such as a primary spleen lymphoma, a big splenic artery aneurism, or a spleen infarct due to a huge pancreatic pseudo-cyst. Forty-eight consecutive patients underwent LS from January 2006 to January 2011 with at least 1-year follow-up. Clinical data and immediate outcome were retrospectively recorded; age, diagnosis, operation time, perioperative transfusion requirement, conversion rate, accessory incision, hospital stay, and complications were analyzed. We had 14 cases of malignant splenic disease, the most frequent malignant diagnosis was non-Hodgkin's lymphoma (12/14, 85.7 %). Splenomegaly (interpole diameter (ID) >20 cm) was observed in 12 cases (25 %) and massive splenomegaly (ID >25 cm) in 3 cases (6.25 %). Conversion to laparotomy occurred in two patients (4.16 %), both associated to uncontrollable bleeding in patients with splenomegaly. Mean operative time was 138 ± 22 min. Mean hospital stay was 4.5 days. Postoperative morbidity rate was 8.8 % for the benign group and 35.7 % in the malignant group. Mortality occurred in 1/48 patients (2.08 %), as a result of overwhelming post-splenectomy infection (OPSI). LS can be performed safely for malignant splenic disease and splenomegaly without any statistically significant increase of morbidity and mortality rate. Conversion rate is increased for massive splenomegaly. LS should be considered as the preferential approach even in patients with malignant disease, splenomegaly, or unusual cases. Massive splenomegaly should be considered as relative contraindication to LS even at experienced centers.

Liver resection for hepatocellular carcinoma ≤3 cm: results of an Italian multicenter study on 588 patients.

BACKGROUND: The best treatment for patients with small hepatocellular carcinoma (S-HCC) is still controversial. The aim of this study was to evaluate operative and long-term results after liver resection (LR) for S-HCC, defined as tumor ≤3 cm. STUDY DESIGN: Retrospective multicenter study of 588 LRs for S-HCC from 8 Italian hepatobiliary surgery units (years 1992 to 2008). Primary outcomes included operative risk. Logistic regression analysis was used to evaluate risk factors for postoperative mortality. Secondary outcomes were overall survival (OS) and disease-free survival (DFS), estimated by the Kaplan-Meier method. RESULTS: Postoperative mortality was 1.9%, morbidity was 35.7% (major morbidity 7.3%), and blood transfusion rate was 13.8%. Child-Pugh class B and blood transfusions were associated with higher postoperative mortality. Rates of microvascular invasion and microsatellite nodules were 37.0% and 23.1%. After a median follow-up of 38.4 months, 5- and 10-year OS rates were 52.8% and 20.3%, with DFS of 32.4% and 21.7%. Local recurrence rate was 1.4%. Between the years 2000 and 2008, 5-year OS was significantly higher than that between the years 1992 and 1999 (61.9% vs 42.6%; p < 0.001). In multivariable analysis, Child-Pugh class B, portal hypertension, and microsatellite lesions were independently associated with poor OS. Microsatellite lesion was the only variable independently associated with poor DFS. CONCLUSIONS: Liver resection for S-HCC has improved over the years, with decreased operative risk. Long-term survival after LR has increased. Despite small tumor size, rates of microsatellite nodules and microvascular invasion are not negligible. Presence of microsatellite lesions was the only variable identified as being associated with poor both OS and DFS.

Improvement in perioperative and long-term outcome after surgical treatment of hilar cholangiocarcinoma: results of an Italian multicenter analysis of 440 patients.

OBJECTIVE: To evaluate improvements in operative and long-term results following surgery for hilar cholangiocarcinoma. DESIGN: Retrospective multicenter study including 17 Italian hepatobiliary surgery units. PATIENTS: A total of 440 patients who underwent resection for hilar cholangiocarcinoma from January 1, 1992, through December 31, 2007. MAIN OUTCOME MEASURES: Postoperative mortality, morbidity, overall survival, and disease-free survival. RESULTS: Postoperative mortality and morbidity after liver resection were 10.1% and 47.6%, respectively. At multivariate logistic regression, extent of resection (right or right extended hepatectomy) and intraoperative blood transfusion were independent predictors of postoperative mortality (P = .03 and P = .006, respectively); in patients with jaundice, mortality was also higher without preoperative biliary drainage than with biliary drainage (14.3% vs 10.7%). During the study period, there was an increasingly aggressive approach, with more frequent caudate lobectomies, vascular resections, and resections for advanced tumors (T stage of 3 or greater and tumors with poor differentiation). Despite the aggressive approach, the blood transfusion rate decreased from 81.0% to 53.2%, and mortality slightly decreased from 13.6% to 10.8%. Median overall survival significantly increased from 16 to 30 months (P = .05). At multivariate analysis, R1 resection, lymph node metastases, and T stage of 3 or greater independently predicted overall and disease-free survival. CONCLUSIONS: Surgery for hilar cholangiocarcinoma has improved with decreased operative risk despite a more aggressive surgical policy. Long-term survival after liver resection has also increased, despite the inclusion of cases with more advanced hilar cholangiocarcinoma. Preoperative biliary drainage was a safe strategy before right or right extended hepatectomy in patients with jaundice. Pathologic factors independently predicted overall and disease-free survival at multivariate analysis.

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 (Cronbach's 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 patient's satisfaction.

Recurrent adenoid cystic carcinoma in the liver: a repeated laparoscopic surgical approach.

Adenoid cystic carcinoma (ACC) is characterized by a particularly aggressive behavior even many years after resection of primary tumor. The evolution of metastasis dramatically affects the final outcome but resection should always be evaluated. Herein is described a case of aggressive ACC of the parotid gland in a 30-year-old female. She developed local recurrence and lung metastases; then, she also developed two liver metastasis 112 and 132 months after the resection of the primitive cancer of the parotid gland. Both lesions were successfully managed by a laparoscopic approach. Intra-abdominal adhesions after the first surgery were mild, allowing an easier access for the second laparoscopic liver resection. At 1 year follow-up, the patient is liver disease free with a stable lung disease. To our knowledge, this is the first report of a double laparoscopic liver resection for parotid gland's ACC metachronous metastases. Patients with resected ACC need a strict and lifelong follow-up after the resection of the primitive cancer. Also for ACC, a laparoscopic approach to liver metastasis should always be considered as a viable alternative to open surgery. In our experience of over 90 cases, laparoscopic surgery causes less adhesions, allowing an easier approach for repeated resections.

Long-term absence of porcine endogenous retrovirus infection in chronically immunosuppressed patients after treatment with the porcine cell-based Academic Medical Center bioartificial liver.

BACKGROUND: Clinical use of porcine cell-based bioartificial liver (BAL) support in acute liver failure as bridging therapy for liver transplantation exposes the patient to the risk of transmission of porcine endogenous retroviruses (PERVs) to human. This risk may be enhanced when patients receive liver transplant and are subsequently immunosuppressed. As further follow-up of previously reported patients (Di Nicuolo et al. 2005), an assessment of PERV infection was made in the same patient population pharmacologically immunosuppressed for several years after BAL treatment and in healthcare workers (HCWs) involved in the clinical trial at that time. METHODS: Plasma and peripheral blood mononuclear cells (PBMCs) from eight patients treated with the Academic Medical Center-BAL (AMC-BAL), who survived to transplant, and 13 HCWs, who were involved in the trial, were assessed to detect PERV infection. A novel quantitative real-time polymerase chain reaction assay has been used. RESULTS: Eight patients who received a liver transplant after AMC-BAL treatment are still alive under long-term pharmacological immunosuppression. The current clinical follow-up ranges from 5.6 to 8.7 yr after BAL treatment. A new q-real-time PCR assay has been developed and validated to detect PERV infection. The limit of quantification of PERV DNA was ≥ 5 copies per 1 × 10(5) PBMCs. The linear dynamic range was from 5 × 10(0) to 5 × 10(6) copies. In both patients and HCWs, neither PERV DNA in PBMCs nor PERV RNA in plasma and PBMC samples have been found. CONCLUSION: Up to 8.7 yr after exposure to treatment with porcine liver cell-based BAL, no PERV infection has been found in long-term immunosuppressed patients and in HCWs by a new highly sensitive and specific q-real-time PCR assay.

Wide gene expression profiling of ischemia-reperfusion injury in human liver transplantation.

Ischemia-reperfusion injury (IRI) causes up to 10% of early liver failures in humans and can lead to a higher incidence of acute and chronic rejection. So far, very few studies have investigated wide gene expression profiles associated with the IRI process. The discovery of novel genes activated by IRI might lead to the identification of potential target genes for the prevention or treatment of the injury. In our study, we compared gene expression levels in reperfused livers (RL group) vs. the basal values before retrieval from the donor (basal liver [BL] group) using oligonucleotide array technology. We examined 10 biopsies from 5 livers, analyzing approximately 33,000 genes represented on the Affymetrix HG-U133APlus 2.0 oligonucleotide arrays (Affymetrix, Santa Clara, CA). About 13,000 individual genes were considered expressed in at least 1 condition. A total of 795 genes whose expression is significantly modified by ischemia-reperfusion in human liver transplantation were identified in this study. Some of them are likely to be completely activated by IRI, as they are not expressed in basal livers. The supervised gene expression analysis revealed that at least 12% of the genes involved in the apoptotic process, 12.5% of the genes involved in inflammatory processes, and 22.5% of the genes encoding for heat shock proteins are differentially expressed in RL samples vs. BL samples. Furthermore, IRI induces the upregulation of some genes' coding for adhesion molecules and integrins. In conclusion, we have identified a relevant amount of early genes regulated in the human liver after 7-9 hours of cold ischemia and 2 hours from reperfusion, many of them not having been described before in this process. Their analyses may help us to better understand the pathophysiology of IRI and to characterize potential target genes for the prevention or treatment of the liver injury in order to increase the number of patients that successfully undergo transplantation.

No evidence of in vitro and in vivo porcine endogenous retrovirus infection after plasmapheresis through the AMC-bioartificial liver.

BACKGROUND: Currently a number of bioartificial livers (BAL) based on porcine liver cells have been developed as a treatment to bridge acute liver failure patients to orthotopic liver transplantation or liver regeneration. These xenotransplantation related treatments hold the risk of infection of treated patients by porcine endogenous retrovirus (PERV) released from the porcine cells, as in vitro infection experiments and transplantations in immunocompromised mice have shown that PERV is able to infect human cells. The Academic Medical Center (AMC)-BAL, unlike other BALs, is characterized by direct contact between porcine liver cells and human plasma, and might therefore be permissive for PERV transfer. METHODS: Prior to a clinical phase I trial, human plasma perfused through the AMC-BAL was investigated for PERV DNA and RNA. Moreover productive infectivity was analyzed by exposing the plasma to HEK-293 cells that were subsequently tested for PERV DNA, PERV RNA and reverse transcriptase activity. RESULTS: Although PERV DNA was detected in the perfused plasma, no productive infectivity was detected. Consequently fourteen patients were treated with the AMC-BAL and monitored for PERV transmission. Immediately after treatment the plasma of the patients was positive for PERV DNA, most probably due to porcine liver cell lysis. The PERV DNA was cleared within 2 weeks post-treatment and no PERV RNA was detected. No productive infectivity in human embryonic kidney (HEK)-293 cells exposed to plasma of treated patients was detectable. CONCLUSION: To conclude, no release of infective PERV particles from the AMC-BAL was observed. Therefore we consider the AMC-BAL as safe, however careful surveillance of patients will be continued.