Ibrahim Dagher

The International Position on Laparoscopic Liver Surgery: The Louisville Statement, 2008

Objective:To summarize the current world position on laparoscopic liver surgery. Summary Background Data:Multiple series have reported on the safety and efficacy of laparoscopic liver surgery. Small and medium sized procedures have become commonplace in many centers, while major laparoscopic liver resections have been performed with efficacy and safety equaling open surgery in highly specialized centers. Although the field has begun to expand rapidly, no consensus meeting has been convened to discuss the evolving field of laparoscopic liver surgery. Methods:On November 7 to 8, 2008, 45 experts in hepatobiliary surgery were invited to participate in a consensus conference convened in Louisville, KY, US. In addition, over 300 attendees were present from 5 continents. The conference was divided into sessions, with 2 moderators assigned to each, so as to stimulate discussion and highlight controversies. The format of the meeting varied from formal presentation of experiential data to expert opinion debates. Written and video records of the presentations were produced. Specific areas of discussion included indications for surgery, patient selection, surgical techniques, complications, patient safety, and surgeon training. Results:The consensus conference used the terms pure laparoscopy, hand-assisted laparoscopy, and the hybrid technique to define laparoscopic liver procedures. Currently acceptable indications for laparoscopic liver resection are patients with solitary lesions, 5 cm or less, located in liver segments 2 to 6. The laparoscopic approach to left lateral sectionectomy should be considered standard practice. Although all types of liver resection can be performed laparoscopically, major liver resections (eg, right or left hepatectomies) should be reserved for experienced surgeons facile with more advanced laparoscopic hepatic resections. Conversion should be performed for difficult resections requiring extended operating times, and for patient safety, and should be considered prudent surgical practice rather than failure. In emergent situations, efforts should be made to control bleeding before converting to a formal open approach. Utilization of a hand assist or hybrid technique may be faster, safer, and more efficacious. Indications for surgery for benign hepatic lesions should not be widened simply because the surgery can be done laparoscopically. Although data presented on colorectal metastases did not reveal an adverse effect of the laparoscopic approach on oncological outcomes in terms of margins or survival, adequacy of margins and ability to detect occult lesions are concerns. The pure laparoscopic technique of left lateral sectionectomy was used for adult to child donation while the hybrid approach has been the only one reported to date in the case of adult to adult right lobe donation. Laparoscopic liver surgery has not been tested by controlled trials for efficacy or safety. A prospective randomized trial appears to be logistically prohibitive; however, an international registry should be initiated to document the role and safety of laparoscopic liver resection. Conclusions:Laparoscopic liver surgery is a safe and effective approach to the management of surgical liver disease in the hands of trained surgeons with experience in hepatobiliary and laparoscopic surgery. National and international societies, as well as governing boards, should become involved in the goal of establishing training standards and credentialing, to ensure consistent standards and clinical outcomes.

Recommendations for laparoscopic liver resection: a report from the second international consensus conference held in Morioka.

OBJECTIVE This review aims to assess the impact of implementing dedicated emergency surgical services, in particular acute care surgery, on clinical outcomes. BACKGROUND The optimal model for delivering high-quality emergency surgical care remains unknown. Acute Care Surgery (ACS) is a health care model combining emergency general surgery, trauma, and critical care. It has been adopted across the United States in the management of surgical emergencies. METHOD A systematic review was performed after PRISMA recommendations using the MEDLINE, Embase, and Psych-Info databases. Studies assessing different care models and institutional factors affecting the delivery of emergency general surgery were included. RESULTS Twenty-seven studies comprising 744,238 patients were included in this review. In studies comparing ACS with traditional practice, mortality and morbidity were improved. Moreover, time to senior review, delays to operating theater, and financial expenditure were often reduced. The elements of ACS models varied but included senior clinicians present onsite during office hours and dedicated to emergency care while on-call. Referrals were made to specialist centers with primary surgical assessments taking place on surgical admissions units rather than in the emergency department. Twenty-four-hour access to dedicated emergency operating rooms was also described. CONCLUSIONS ACS models as well as centralized units and hospitals with dedicated emergency operating rooms, access to radiology and intensive care facilities (ITU) are all factors associated with improved clinical and financial outcomes in the delivery of emergency general surgery. There is, however, no consensus on the elements that constitute an ideal ACS model and how it can be implemented into current surgical practice.

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.

Improving the techniques for human hepatocyte transplantation: Report from a consensus meeting in London

On September 6 and 7, 2009 a meeting was held in London to identify and discuss what are perceived to be current roadblocks to effective hepatocyte transplantation as it is currently practiced in the clinics and, where possible, to offer suggestions to overcome the blocks and improve the outcomes for this cellular therapy. Present were representatives of most of the active clinical hepatocyte transplant programs along with other scientists who have contributed substantial basic research to this field. Over the 2-day sessions based on the experience of the participants, numerous roadblocks or challenges were identified, including the source of cells for the transplants and problems with tracking cells following transplantation. Much of the discussion was focused on methods to improve engraftment and proliferation of donor cells posttransplantation. The group concluded that, for now, parenchymal hepatocytes isolated from donor livers remain the best cell source for transplantation. It was reported that investigations with other cell sources, including stem cells, were at the preclinical and early clinical stages. Numerous methods to modulate the immune reaction and vascular changes that accompany hepatocyte transplantation were proposed. It was agreed that, to obtain sufficient levels of repopulation of liver with donor cells in patients with metabolic liver disease, some form of liver preconditioning would likely be required to enhance the engraftment and/or proliferation of donor cells. It was reported that clinical protocols for preconditioning by hepatic irradiation, portal vein embolization, and surgical resection had been developed and that clinical studies using these protocols would be initiated in the near future. Participants concluded that sharing information between the groups, including standard information concerning the quality and function of the transplanted cells prior to transplantation, clinical information on outcomes, and standard preconditioning protocols, would help move the field forward and was encouraged.

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.

International experience for laparoscopic major liver resection

Although minor laparoscopic liver resections (LLRs) appear as standardized procedures, major LLRs are still limited to few expert teams. The aim of this study was to report the combined data of 18 international centers performing major LLR. Variables evaluated were number and type of LLR, surgical indications, number of synchronous colorectal resections, details on technical points, conversion rates, operative time, blood loss and surgical margins. From 1996 to 2014, a total of 5388 LLR were carried out including 1184 major LLRs. The most frequent indication for laparoscopic right hepatectomy (LRH) was colorectal liver metastases (37.0%). Seven centers used hand assistance or hybrid approach selectively for LRH mostly at the beginning of their experience. Seven centers apply Pringles maneuver routinely. The conversion rate for all major LLRs was 10% and mean operative time was 291 min. Mean estimated blood loss for all major LLR was 327 ml and negative surgical margin rate was 96.5%. Major LLRs still remain challenging procedures requiring important experience in both laparoscopy and liver surgery. Stimulating the younger generation to learn and accomplish these techniques is the better way to guarantee further development of this surgical field.

Laparoscopic resection of hepatocellular carcinoma: a French survey in 351 patients.

OBJECTIVES Current clinical studies report the results of laparoscopic resection of hepatocellular carcinoma (HCC) obtained in small cohorts of patients. Because France was involved in the very early development of laparoscopic surgery, the present study was conducted in order to report the results of a large, multicentre experience. METHODS A total of 351 patients underwent laparoscopic liver resection for HCC during the period from 1998 to 2010 in nine French tertiary centres. Patient characteristics, postoperative mortality and morbidity, and longterm survival were retrospectively reviewed. RESULTS Overall, 85% of the study patients had underlying liver disease. Types of resection included wedge resection (41%), left lateral sectionectomy (27%), segmentectomy (24%), and major hepatectomy (11%). Median operative time was 180 min. Conversion to laparotomy occurred in 13% of surgeries and intraoperative blood transfusion was necessary in 5% of patients. The overall morbidity rate was 22%. The 30-day postoperative mortality rate was 2%. Negative resection (R0) margins were achieved in 92% of patients. Rates of overall and progression-free survival at 1, 3 and 5 years were 90.3%, 70.1% and 65.9%, and 85.2%, 55.9% and 40.4%, respectively. CONCLUSIONS This multicentre, large-cohort study confirms that laparoscopic liver resection for HCC is a safe and efficient approach to treatment and can be proposed as a first-line treatment in patients with resectable HCC.

Immortalization of a primate bipotent epithelial liver stem cell

Liver regeneration after partial hepatectomy results primarily from the simple division of mature hepatocytes. However, during embryonic and fetal development or in circumstances under which postnatal hepatocytes are injured, organ regeneration is believed to occur from a compartment of epithelial liver stem or progenitor cells with biliary and hepatocytic bipotentiality. The ability to identify, isolate, and transplant epithelial liver stem cells from fetal liver would greatly facilitate the treatment of hepatic diseases currently requiring orthotopic liver transplantation. Here we report the identification and immortalization by retrovirus-mediated transfer of the simian virus 40 large T antigen gene of primate fetal epithelial liver cells with a dual hepatocytic biliary phenotype. These cells grow indefinitely in vitro and express the liver epithelial cell markers cytokeratins 8/18, the hepatocyte-specific markers albumin and α-fetoprotein, and the biliary-specific markers cytokeratins 7 and 19. Bipotentiality of gene expression was confirmed by clonal analysis initiated from single cells. Endogenous telomerase also is expressed constitutively. After orthotopic transplantation via the portal vein, ≈50% of the injected cells integrated into the liver parenchyma of athymic mice without tumorigenicity. Three weeks after transplantation, cells having seeded in the liver parenchyma expressed both albumin and α-fetoprotein but had lost expression of cytokeratin 19. These results provide strong evidence for the existence of a bipotent epithelial liver stem cell in nonhuman primates. This unlimited source of donor cells also should enable the establishment of a model of allogenic liver cell transplantation in a large animal closely related to humans and shed light on important questions related to liver organogenesis and differentiation.