Ravi S. Chari

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.

Preoperative radiation and chemotherapy in the treatment of adenocarcinoma of the rectum

ObjectiveIn this study, the impact of preoperative chemotherapy and radiation on the histopathology of a subgroup of patients with rectal adenocarcinoma was examined. As well, survival, disease-free survival and pelvic recurrence rates were examined, and compared with a concurrent control group. Summary Background DataThe optimal treatment of large rectal carcinomas remains controversial; current therapy usually involves abdominoperineal resection plus postoperative chemoradiation; the combination can be associated with significant postoperative morbidity. In spite of these measures, local recurrences and distant metastases continue as serious problems. MethodsFluorouracil, cisplatin, and 4500 cGy were administered preoperatively over a 5-week period, before definitive surgical resection in 43 patients. In this group of patients, all 43 had biopsyproven lesions >3 cm (median diameter), involving the entire rectal wall (as determined by sigmoidoscopy and computed tomography scan), with no evidence of extrapelvic disease. The patients ranged from 31 to 81 years of age (median 61 years), with a male:female ratio of 3:1. A concurrent control group consisting of 56 patients (median: 62 years, male:female ration of 3:2) with T2 and T3 lesions was used to compare survival, disease-free survival, and pelvic recurrence rates. ResultsThe preoperative chemoradiation therapy was well tolerated, with no major complications. All patients underwent repeat sigmoidoscopy before surgery; none of the lesions progressed while patients underwent therapy, and 22 (51%) were determined to have complete clinical response. At the time of resection, 21 patients (49%) had gross disease, 9 (22%) patients had only residual microscopic disease, and 11 (27%) had sterile specimens. Of the 30 patients with evidence of residual disease, 4 had positive lymph nodes. In follow-up, 39 of the 43 remain alive (median follow-up = 25 months), and only 1 of the 11 patients with complete histologic response developed recurrent disease. Six of the 32 patients with residual disease (2 with positive nodes) have developed metastatic disease in follow-up (median time to diagnosis 10 months, range 3–15 months). Three of these patients with metastases have died (median survival after diagnosis of

Fluorodeoxyglucose PET imaging in the evaluation of gallbladder carcinoma and cholangiocarcinoma

Our goal was to evaluate fluorodeoxyglucose (FDG) positron emission tomography (PET) in staging patients with biliary tract cancers. Fifty consecutive patients who underwent FDG-PET for suspected cholangiocarcinoma (n = 36) or gallbladder carcinoma (n = 14) were reviewed. Patients with cholangiocarcinoma were divided into two groups: group 1 had nodular type (mass > 1 cm) (n = 22) and group 2 had inflltrating type (n = 14) cholangiocarcinoma. Thirty-one of 36 patients evaluated for cholangiocarcinoma had cholangiocarcinoma and five did not. Sensitivity was 85% for nodular morphology but only 18% for inflltrating morphology. Sensitivity for metastases was 65% but false negative for carcinomatosis in three of three patients. One false positive result occurred in a patient with primary sclerosing cholangitis who had acute cholangitis. Seven (58%) of 12 patients had FDG uptake along the tract of a biliary stent. FDG-PET led to a change in surgical management in 30% (11 of 36) of patients evaluated for cholangiocarcinoma because of detection of unsuspected metastases. Eleven of 14 patients with gallbladder carcinoma were newly diagnosed by cholecystectomy or another type of exploratory procedure, whereas three patients were undergoing follow-up. Nine had residual gallbladder carcinoma at the time of PET. Sensitivity for gallbladder carcinoma was 78%. Sensitivity for extrahepatic metastases was 50% in eight patients; six of them had carcinomatosis. These data suggest that PET is accurate in predicting the presence of nodular cholangiocarcinoma (mass > 1cm) but was not helpful for the inflltrating type. PET was also helpful for detecting residual gallbladder carcinoma following cholecystectomy, but was not helpful in patients with carcinomatosis. Although FDG-PET led to a change in management in 30% of patients with cholangiocarcinoma, it must be interpreted with caution in patients with primary sclerosing cholangitis and with stents in place, as well as in those with known granulomatous disease.

Complications of Laparoscopic Cholecystectomy

Laparoscopic cholecystectomy is a safe and effective treatment of cholelithiasis in experienced hands. Mortality is rare. The Southern Surgeons Club data and several other recent large series indicate that major complications occur in less than 3% of patients. The most significant common complication is injury to the bile duct, for which the greatest risk factor is inexperience. Major biliary injury usually requires reoperations. Roux-en-Y hepaticojejunostomies, often multiple, are usually necessary for repair. The popularity of this technique continues, and further efforts should be focused on elimination of the learning curve for major biliary injury. If injuries do occur, they should be recognized early, and patients should be referred to centers experienced in their treatment.

Effective treatment of biliary cystadenoma.

Objective:Evaluate experience over 15 years with treatment of this lesion. Summary Background Data:Biliary cystadenoma, a benign hepatic tumor arising from Von Meyenberg complexes, usually present as septated intrahepatic cystic lesions. Methods:Data were collected concurrently and retrospectively on patients identified from hospital medical records reviewed for pertinent International Classification of Diseases, Ninth Revision, Clinical Modification and CPT codes, pathology logs, and from operative case logs. Pathology specimens were rereviewed to confirm the diagnosis of biliary cystadenoma or biliary cystadenocarcinoma by 2 GI pathologists. Results:From October 1989 to April 2004 at our institution, 19 (18F:1M) patients had pathologically confirmed biliary cystadenomas, including one with a biliary cystadenocarcinoma. The mean age was 48 ± 15 years at initial evaluation. Complaints included abdominal pain in 74%, abdominal distension in 26%, and nausea/vomiting in 11%. Only 1 patient presented with an incidental finding. Symptoms had been present for 3 ± 5 years, with 1 to 4 different surgeons and many other physicians involved in the diagnosis or treatment prior to definitive ablation. Eight patients had undergone 20 previous treatments, including multiple percutaneous aspirations in 4 and 11 operative procedures. CT or US was diagnostic in 95%, with internal septations present in the hepatic cysts. Definitive operative intervention consisted of hepatic resection in 12 patients, enucleation in 6 patients, and fenestration and complete fulguration in 1 patient. There were no perioperative deaths. No recurrences were observed after definitive therapy, with follow-up of 4 ± 4 years. Conclusions:Biliary cystadenoma must be recognized and treated differently than most hepatic cysts. There remains a need for education about the imaging findings for biliary cystadenoma to reduce the demonstrated delay in appropriate treatment. Traditional treatment of simple cysts such as aspiration, drainage, and marsupialization results in near universal recurrence and occasional malignant degeneration. This experience demonstrates effective options include total ablation by standard hepatic resection and cyst enucleation.

Mechanisms Of Injury In Porcine Livers Perfused With Blood Of Patients With Fulminant Hepatic Failure

Hyperacute rejection of renal and cardiac xenografts is initiated by the reaction of recipient natural antibodies and complement with endothelial cell antigens of the donor organ. The liver is thought to be less susceptible to this form of rejection; however, the mechanisms underlying its decreased susceptibility are not known. We investigated the organ injury occurring in porcine livers perfused with blood from 4 human subjects with fulminant hepatic failure. Nine porcine livers were perfused via an extracorporeal circuit in order to provide temporary metabolic support. Each porcine liver exhibited metabolic function, and the duration of xenoperfusion ranged from 2 to 5 hr. Histologic examination of the xenoperfused livers revealed focal hepatocellular necrosis, prominent infiltration of neutrophils, and, in 7 of 9 cases, periportal and centrilobular hemorrhage and thrombosis. Immunopathology demonstrated minimal or no human IgM and IgG along the small vessels and sinusoidal surfaces. Trace deposits of human IgM were observed along the luminal surfaces of large blood vessels in most cases. Trace deposits of C3 were noted in 2 of 9 livers; however, C4, iC3b, C5b, properdin, and the membrane attack complex were not detected. Human anti-porcine natural antibody titers decreased less than expected during the perfusions. Serum CH50, C3, and C4 levels were low before each procedure and decreased slightly with perfusion. One patient perfused 2 porcine livers and a human liver. The human liver

Transforming growth factor-beta receptors and mannose 6-phosphate/insulin-like growth factor-II receptor expression in human hepatocellular carcinoma.

ObjectiveThe authors examined the expression of transforming growth factor-beta receptor (TGF-βr) types I and II and the mannose 6-phosphate/insulin-like growth factor-II receptor (M6-P/IGF-IIr) in human hepatocellular carcinoma (HCC). Summary Background DataTransforming growth factor-beta (TGF-β) is part of a superfamily of peptide-signaling molecules that play an important role in modulating cell growth. It is secreted as a latent complex and therefore, must be activated to elicit a biological response. Bioactivaton of the TGF-β complex is facilitated by binding to the M6-P/IGF-IIr. Once activated, TGF-β exerts its effects by binding to specific cell membrane TGF-β receptors. The loss of responsiveness of hepatocytes to TGF-β has been implicated in hepatocarcinogenesis and could result from a loss in the expression of either the TGF-β receptors or the M6-P/IGF-IIr. MethodsHuman hepatocellular carcinomas and surrounding normal tissue were collected from operating room samples and snap-frozen in liquid nitrogen (n = 13). Tissues from two tumors were fixed in Omni-fix for sectioning and immunohistochemistry staining for the M6-P/IGF-IIr and TGF-β1. RNA was extracted from both normal and malignant liver tissue and analyzed using an RNase protection assay. SDS-PAGE of purified membrane hybridized with 125I-IGF-β1 and 125I-IGF-II was used to determine the TGF-β type I (TGF-βrl) and type II (TGF-βrll) receptors and M6-P/IGF-IIr protein levels, respectively. Gels were quantitated by phosphorimager, and a paired t test was used for statistical analysis. ResultsIn HCC, a 60% (p < 0.01) and 49% (p < 0.02) reduction in the mRNA levels for Tβrl and Tβrll, respectively, relative to the receptor levels in surrounding normal liver, was shown. A similar decrease in the receptor protein levels also was observed. The M6-P/IGF-IIr mRNA and protein

Management of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the most common tumors globally, with varying prevalence based on endemic risk factors. In high-risk populations, including those with hepatitis B or C or with cirrhosis, serum α-fetoprotein (AFP) and screening ultrasound have improved detection of resectable HCC. Treatment options, including surgical resection, for patients with HCC must be selected based on the number and size of hepatic tumors, underlying hepatic function, patient condition, and available resources. An approach, which has been summarized shows the corresponding treatment choices under given clinical circumstances. For cirrhotic patients with less than three tumor nodules of a size less than 3 cm or a solitary HCC less than 5 cm, liver transplantation offers long-term survival similar to that observed in patients transplanted for nonmalignant disease. Ablative treatment using either chemical or thermal techniques provides locally effective tumor destruction. Transcatheter arterial chemoembolization (TACE) is commonly used for palliation of unresectable tumors as well as an adjunct to surgical resection, treatment of tumors before transplant, and in conjunction with other ablative therapies in a multimodality approach. Regional approaches to chemotherapy have produced more encouraging results than systemic chemotherapy, although both remain ineffective for long-term tumor control. Several newer treatment modalities are under investigation, including gene therapy, tagged antibodies, isolated perfusion, and novel radiotherapy techniques.

Protection of the liver during hepatic surgery

Very few areas in medicine have seen as many controversies as the evaluation and treatment of patients with liver diseases. Many novel therapies, often marketed before conclusive demonstration of their efficacy, have been developed to enable selective destruction of liver tumors to minimize the risk of liver failure associated with major surgery. Whether these techniques are effective and result in lesser complications often remains speculative. Persisting challenges in selecting the optimal therapy are the evaluation of the risk of surgery in patients with normal or diseased liver and the preparation for surgery. A panel of hepato-biliary surgeons experienced in the management of complex cases convened at the annual meeting of the American Hepato-Pancreato-Biliary Association in Boston, MA, to address the rapidly evolving field of protective strategies for hepatic surgery.

Venovenous Bypass in Adult Orthotopic Liver Transplantation: Routine or Selective Use?

BACKGROUND The role of venovenous bypass (VVB) during orthotopic liver transplantation (OLT) remains controversial. The aims of this study were to evaluate the current role of VVB at all major centers in North America, to examine the results of OLT and complications of VVB between two periods with a strict policy for routine versus selective use of VVB, and to review the literature. STUDY DESIGN A survey of 50 major liver transplant centers was conducted using mailed questionnaires. A retrospective chart review was performed for 547 OLT patients having transplantation during two distinct periods with a strict policy for routine versus selective use of VVB at the University of Toronto, Canada, and at Duke University Medical Center, Durham, North Carolina. The literature was reviewed with a focus on the benefits and indications for routine versus selective use of VVB. RESULTS Thirty-eight (76%) of 50 centers responded. Sixteen (42%) of them used VVB routinely, with a reported complication rate of 10-30%. Lymphocele and hematoma were the most common complications, but patients having major vascular injury, air embolism, and death were reported. A recent change to selective use of VVB was reported in 30% of the centers (11 of 38). In the Duke-Toronto series, the complication rates were similar between the two periods, at 13.4% and 18.8%, respectively. The outcome of OLT was not influenced by the policy of routine or selective use of VVB. CONCLUSIONS There is a trend away from the routine use of VVB during OLT. Intraoperative hemodynamic instability during the hepatectomy and a failed trial of hepatic venous occlusion were the most important criteria for using VVB. We conclude that VVB should be used selectively to avoid associated complications and to decrease operative time and costs.