Panagiotis Lainas

Laparoscopic major hepatectomy: an evolution in standard of care.

Objective:To analyze the results of 6 international surgical centers performing laparoscopic major liver resections. Summary Background Data:The safety and feasibility of laparoscopy for minor liver resections has been previously demonstrated. Major anatomic liver resections, initially considered to be unsuitable for laparoscopy, are increasingly reported by several centers worldwide. Methods:Prospective databases of 3 European, 2 U.S., and 1 Australian centers were combined. Between 1997 and 2008, 210 major liver resections were performed: 136 right and 74 left hepatectomies. Results and differences in surgical techniques between the 6 centers are outlined. Results:Surgical duration was 250 minutes (range: 90–655 minutes). Operative blood loss was 300 mL (range: 20–2500 mL). Thirty patients (14.3%) received blood transfusion. Conversion to open surgery was required in 26 patients (12.4%). Portal triad clamping was performed in 24 patients (11.4%). Median tumor size was 5.4 cm (range: 1–25 cm) and surgical margin was 10.5 mm (range: 0–70 mm). Two patients died during the postoperative period from pulmonary embolism and urosepsis. Liver-specific and general complications occurred in 17 (8.1%) and 29 patients (13.8%), respectively. Hospital length of stay was 6 days (range: 1–34 days). A further analysis of early (n = 90) and late (n = 120) experience showed improved surgical and postoperative results in the latter group. Conclusions:This multicenter study demonstrates that laparoscopic major liver resections are feasible in selected patients and results improve with experience. However, proficiency in both open liver surgery and advanced laparoscopy is compulsory and surgeons must begin with minor laparoscopic resections.

Minimally Invasive Liver Resection for Metastatic Colorectal Cancer: A Multi-Institutional, International Report of Safety, Feasibility, and Early Outcomes

Objective:To evaluate a multicenter, international series on minimally invasive liver resection for colorectal carcinoma (CRC) metastasis. Summary Background Data:Multiple single series have been reported on laparoscopic liver resection for CRC metastasis. We report the first collaborative multicenter, international series to evaluate the safety, feasibility, and oncologic integrity of laparoscopic liver resection for CRC metastasis. Methods:We retrospectively reviewed all patients who underwent minimally invasive liver resection for CRC metastasis from February 2000 to September 2008 from multiple medical centers from the United States and Europe. The multicenter series of patients were accumulated into a single database. Patient demographics, preoperative, operative, and postoperative characteristics were analyzed. Actuarial overall survival was calculated with Kaplan-Meier analysis. Results:A total of 109 patients underwent minimally invasive liver resection for CRC metastasis. The median age was 63 years (range, 32–88 years) with 51% females. The most common sites of primary colon cancer were sigmoid/rectum (51%), right colon (25%), and left colon (13%). Synchronous liver lesions were present in 11% of patients. For those with metachronous lesions liver lesions, the median time interval from primary colon cancer surgery to liver metastasectomy was 12 months. Preoperative chemotherapy was administered in 68% of cases prior to liver resection. The majority of patients underwent prior abdominal operations (95%). Minimally invasive approaches included totally laparoscopic (56%) and hand-assisted laparoscopic (41%), the latter of which was employed more frequently in the US medical centers (85%) compared with European centers (13%) (P = 0.001). There were 4 conversions to open surgery (3.7%), all due to bleeding. Extents of resection include wedge/segmentectomy (34%), left lateral sectionectomy (27%), right hepatectomy (28%), left hepatectomy (9%), extended right hepatectomy (0.9%), and caudate lobectomy (0.9%). Major liver resections (≥3 segments) were performed in 45% of patients. Median OR time was 234 minutes (range, 60–555 minutes) and blood loss was 200 mL (range, 20–2500 mL) with 10% receiving a blood transfusion. There were no reported perioperative deaths and a 12% complication rate. Median length of hospital stay for the entire series was 4 days (range, 1–22 days) with a shorter stay in medical centers in the United States (3 days) versus that seen in Europe (6 days) (P = 0.001). Negative margins were achieved in 94.4% of patients. Actuarial overall survivals at 1-, 3-, and 5-year for the entire series were 88%, 69%, and 50%, respectively. Disease-free survivals at 1-, 3-, and 5-year were 65%, 43%, and 43%, respectively. Conclusions:Minimally invasive liver resection for colorectal metastasis is safe, feasible, and oncologically comparable to open liver resection for both minor and major liver resections, even with prior intra-abdominal operations, in selected patients and when performed by experienced surgeons.

Laparoscopic versus open right hepatectomy: a comparative study

BACKGROUND The safety of laparoscopic major liver resections is still uncertain. The aim of this study was to compare our results for laparoscopic right hepatectomy (LRH) with those for open right hepatectomy (ORH). METHODS Patients undergoing LRH were compared with retrospectively selected patients from our ORH database. The 2 groups were well matched for sex, age, American Society of Anesthesiologists score, body mass index, liver disease, and tumor size. Surgical and postsurgical outcomes were compared. RESULTS Seventy-two patients were analyzed: 22 in the LRH group and 50 in the ORH group. Operating time was similar. Blood loss was significantly less in laparoscopic resections (P = .038). Specific morbidity rates were not different, general morbidity was lower after laparoscopy (P = .04), and the severity of postsurgical complications was not different. Mean hospital stay was significantly shorter after laparoscopy (P = .009). COMMENTS Laparoscopy improved surgical and postsurgical outcomes for ORH in selected patients. This is the first comparative study to demonstrate an advantage of laparoscopy for a major liver resection. Prospective randomized studies with a greater number of cases are needed to confirm the role of laparoscopy in major liver resections.

Laparoscopic Hepatectomy for Hepatocellular Carcinoma: A European Experience

BACKGROUND Some series have suggested that laparoscopy is beneficial for resection of hepatocellular carcinoma. This has to be confirmed in larger series. The aim of this study was to analyze the results of 3 European surgical centers on laparoscopic liver resections for hepatocellular carcinoma. STUDY DESIGN Prospective databases of 3 European centers involved in the development of laparoscopic liver surgery were combined. Between 1998 and 2008, 163 liver resections for hepatocellular carcinoma were performed. Liver parenchyma was cirrhotic in 120 (73.6%) patients. Liver resection was anatomic in 107 (65.6%) patients and was a major resection (>or=3 segments) in 16 (9.8%). A totally laparoscopic approach was used in 155 (95.1%) patients. RESULTS Median surgical duration was 180 minutes. Median operative blood loss was 250 mL, and 16 (9.8%) patients received blood transfusion. Conversion to open surgery was required in 15 (9.2%) patients. Median tumor size was 3.6 cm and median surgical margin was 12 mm. Liver-specific and general complications occurred in 19 (11.6%) and 17 (10.4%) patients, respectively. Hospital length of stay was 7 days. A further analysis of early (n = 75) and recent (n = 88) experiences showed improved results in the latter group. Overall and recurrence-free survival rates at 1, 3, and 5 years were 92.6%, 68.7%, 64.9%, and 77.5%, 47.1%, 32.2%, respectively. CONCLUSIONS This study demonstrates that laparoscopic resection for hepatocellular carcinoma is feasible in selected patients, with good operative and oncologic results. Laparoscopy should be routinely considered in centers experienced in liver surgery and advanced laparoscopy.

Efficient hepatocyte engraftment and long‐term transgene expression after reversible portal embolization in nonhuman primates

The feasibility of ex vivo gene therapy as an alternative to liver transplantation for the treatment of liver metabolic diseases needs to be analyzed in large animal models. This approach requires appropriate gene transfer vectors and effective hepatocyte engraftment. Lentiviral vectors have the ability to transduce nondividing differentiated cells, such as hepatocytes, and portal vein occlusion increases hepatocyte engraftment. We investigated whether reversible portal vein embolization combined with ex vivo lentivirus‐mediated gene transfer is an effective approach for successful hepatocyte engraftment in nonhuman primates and whether the transgene remains expressed in the long term in transplanted hepatocytes in situ. Simian hepatocytes were isolated after left lobe resection, and the left and right anterior portal branches of animals were embolized with absorbable material. Isolated hepatocytes were labeled with Hoechst dye or transduced in suspension with lentiviruses expressing green fluorescent protein under the control of the human apolipoprotein A‐II promoter and transplanted via the inferior mesenteric vein. The whole procedure was well tolerated. The embolized liver was revascularized within 2 weeks. The volume of nonembolized liver increased from 38.7% ± 0.8% before embolization to 55.9% ± 1% after embolization and hepatocytes significantly proliferated (10.5% ± 0.4% on day 3 after embolization). Liver repopulation after transplantation with Hoechst‐labeled hepatocytes was 7.4% ± 1.2%. Liver repopulation was 2.1% ± 0.2% with transduced hepatocytes, a proportion similar to that obtained with Hoechst‐labeled cells, given that the mean transduction efficacy of simian hepatocyte population was 34%. Transgene expression persisted at 16 weeks after transplantation. Conclusion: We have developed a new approach to improve hepatocyte engraftment and to express a transgene in the long term in nonhuman primates. This strategy could be suitable for clinical applications. (HEPATOLOGY 2009.)

Liver regeneration and recanalization time course following reversible portal vein embolization

BACKGROUND/AIMS Permanent portal vein embolization (PVE) is a widely practised technique. The use of an absorbable material would be safer in clinical situations in which the embolized liver is not resected. We evaluated the efficiency of reversible PVE in terms of liver regeneration and analyzed the precise time course of portal recanalization. METHODS Nine monkeys underwent PVE of the left and right anterior portal branches using powdered absorbable material. Repeated portograms were carried out until complete revascularization of the embolized liver. Hepatocyte proliferation rates were assessed by BrdU incorporation. Liver segment volumes were determined by CT scans performed before embolization, then 1 month and 1 year after embolization. RESULTS Reversible PVE induced significant hepatocyte proliferation in the non-embolized segments (13.5+/-1.0%, 10.5+/-0.8% and 9.1+/-2.0% of cells on days 3, 5 and 7, respectively). One month after the embolization, the non-embolized liver volume had increased from 38.4+/-1.3% to 54.8+/-0.5% of total liver volume. Proximal and complete revascularization occurred 6-8 and 12-16 days, respectively. CONCLUSIONS Reversible PVE efficiently induces liver regeneration. The use of absorbable material avoids long-term liver scarring. Such material may be suitable for several clinical indications, including cell transplantation.

Laparoscopic major hepatectomy can be safely performed with colorectal surgery for synchronous colorectal liver metastasis

BACKGROUND The optimal strategy for resectable synchronous colorectal liver metastases remains controversial. Although some authors advocate a staged treatment, an increasing number of studies have reported that combined colorectal and liver resection is safe. Laparoscopic combined resection in primary colorectal cancer with synchronous liver metastases has been reported but there are no specific data for major liver resections. In the present study, we evaluated the feasibility of a simultaneous entirely laparoscopic procedure, in the light of the benefits of laparoscopy in both colon and liver surgery, and discussed the benefits of this strategy. METHODS Two cases are presented of totally laparoscopic major liver resections associated with laparoscopic colorectal resections for synchronous liver metastases with the emphasis on the technical aspects. Duration of surgery, blood loss and post-operative outcome were evaluated. RESULTS   Laparoscopic right hepatectomy or left hepatectomy with simultaneous colon resection for liver metastasis was feasible and safe with only one suprapubic 5-mm trocar added to the usual trocar sites. The mean duration of surgery was 327 min with a mean estimated blood loss of 200 ml. The post-operative course was uneventful. DISCUSSION In selected patients, laparoscopic major hepatectomies for unilobular synchronous metastases can be safely performed simultaneously with colorectal surgery.

Bleeding control during laparoscopic liver resection: a review of literature

Despite the established advantages of laparoscopy, bleeding control during laparoscopic liver resection (LLR) is a liver‐specific improvement. The 2nd International Consensus Conference on Laparoscopic Liver Resection was held in October 2014 at Morioka, Japan. One of the most capital questions was: What is essential in bleeding control during LLR? In order to correctly address this question, we conducted a comprehensive review of the literature. Essential points based on personal experience of the expert panel are also discussed. A total of 54 publications were identified. Based on this analysis, the working group built these recommendations: (1) a pneumoperitoneum of 10–14 mmHg should be used as it allows a good control of the bleeding without significant modifications of hemodynamics; (2) a low central venous pressure (<5 mmHg) should be used; (3) laparoscopy facilitates inflow and outflow control; and (4) surgeons should be experienced with the use of all surgical devices for liver transection and should master laparoscopic suture before starting LLR. Precoagulation with radiofrequency can be useful, particularly in cases of atypical resection. These recommendations are mostly based on experts’ opinions and on B or C quality of evidence grade studies. More prospective data are required to confirm these results.

Ex vivo liver-directed gene therapy for the treatment of metabolic diseases: advances in hepatocyte transplantation and retroviral vectors.

Transplantation of hepatocytes, whether genetically modified or not, has become an alternative to orthotopic liver transplantation for the treatment of patients with metabolic disease. However, more than ten years after the first clinical trial of ex vivo gene therapy to treat patients with Familial Hypercholesterolemia, there are still a number of impediments to these approaches. Numerous animal models are still being developed on the one hand to improve hepatocyte integration within hepatic parenchyma and function, and on the other hand to develop vectors that drive long-term transgene expression in situ. These include large animal models such as non-human primates, which have recently led to significant progress in hepatocyte transplantation. Simultaneous development of lentiviral vectors from different lentivirus species has permitted the transfer of genes into mitotically-quiescent primary cells including differentiated hepatocytes. Particularly third generation vectors derived from HIV-1 lentivirus are the most widely used and have significantly improved the safety and efficiency of these vectors. Given the shortage of organs and problems related to immunosuppression on one hand, and recent progresses in hepatocyte transduction and transplantation on the other hand, ex vivo approach is becoming a real alternative to allogeneic hepatocyte transplantation. We review the present progresses and limits of the ex vivo liver gene therapy approach in different animal models, emphasizing clinically relevant procedures.

Laparoscopic liver resection with selective prior vascular control.

BACKGROUND Selective control of vascular inflow can reduce blood loss and transfusion rates and may be particularly efficient in laparoscopic liver resection (LLR). The aim of this study was to evaluate the efficacy of selective prior vascular control (PVC) in patients undergoing laparoscopic or open liver resections (OLR). METHODS Between 1999 and 2008, 52 patients underwent LLR with PVC with prospective data collection and were compared with patients undergoing OLR with PVC. RESULTS There was no difference in the operative time between the 2 groups. Blood loss and transfusion rates were lower in patients who underwent LLR (367 vs 589 mL, P = .001; 3.8% vs 17.3%, P = .05, respectively). Morbidity did not differ significantly between the 2 groups. Hospital stay was longer in the OLR group (11.0 vs 7.4 days, P = .001). CONCLUSIONS PVC during LLR was feasible and improved intraoperative and postoperative results. Selective PVC should be obtained in LLR whenever possible.