Objective To provide a review of the world literature on laparoscopic liver resection. Summary background data Initially described for peripheral, benign tumors resected by nonanatomic wedge resections, minimally invasive liver resections are now being performed more frequently, even for larger, malignant tumors located in challenging locations. Although a few small review articles have been reported, a comprehensive review on laparoscopic liver resection has not been published. Methods We conducted a literature search using Pubmed, screening all English publications on laparoscopic liver resections. All data were analyzed and apparent case duplications in updated series were excluded from the total number of patients. Tumor type, operative characteristics, perioperative morbidity, and oncologic outcomes were tabulated. Results A total of 127 published articles of original series on laparoscopic liver resection were identified, and accounted for 2,804 reported minimally invasive liver resections. Fifty percent were for malignant tumors, 45% were for benign lesions, 1.7% were for live donor hepatectomies, and the rest were indeterminate. Of the resections, 75% were performed totally laparoscopically, 17% were hand-assisted, and 2% were laparoscopic-assisted open hepatic resection (hybrid) technique, with the remainder being other techniques or conversions to open hepatectomies. The most common laparoscopic liver resection was a wedge resection or segmentectomy (45%) followed by anatomic left lateral sectionectomy (20%), right hepatectomy (9%), and left hepatectomy (7%). Conversion from laparoscopy to open laparotomy and from laparoscopy to hand-assisted approach occurred in 4.1% and 0.7% of reported cases, respectively. Overall mortality was 9 of 2,804 patients (0.3%), and morbidity was 10.5%, with no intraoperative deaths reported. The most common cause of postoperative death was liver failure. Postoperative bile leak was observed in 1.5% of cases. For cancer resections, negative surgical margins were achieved in 82% to 100% of reported series. The 5-year overall and disease-free survival rates after laparoscopic liver resection for hepatocellular carcinoma were 50% to 75% and 31% to 38.2%, respectively. The 3-year overall and disease-free survival rates after laparoscopic liver resection for colorectal metastasis to the liver were 80% to 87% and 51%, respectively. Conclusion In experienced hands, laparoscopic liver resections are safe with acceptable morbidity and mortality for both minor and major hepatic resections. Oncologically, 3- and 5-year survival rates reported for hepatocellular carcinoma and colorectal cancer metastases are comparable to open hepatic resection, albeit in a selected group of patients.

World review of laparoscopic liver resection-2,804 patients.

Publisher Summary This chapter attempts to identify the principles and issues elucidated in animal models that may provide insights for the development of effective approaches to modulate T cell functions to promote the eradication of human tumors. The importance of T cells in surveillance against the outgrowth of tumor cells is probably best demonstrated with virally transformed tumors, such as EBV-induced B cell lymphomas, which occur with markedly increased frequency in transplant patients specifically depleted of T cells, and with UV-induced squamous cell cancers that occur with high frequency in renal transplant patients. Second, the reasons for the growth of presumably immunogenic tumors in immunocompetent hosts have become more apparent with an improved understanding of the function of T cell subsets and the requirements for the induction and expression of T cell responses. The earlier perceptions that cytotoxic T cells recognize foreign proteins integrally inserted in the cell membrane had focused efforts for more than a decade on the use of the powerful new monoclonal antibody technology combined with biochemical purification techniques to isolate tumor antigens expressed on the cell membrane. However, analyses of the requirements for recognition of virally infected cells by CD8 + cytotoxic T cells demonstrated that Class I-restricted T c do not recognize integral membrane proteins but rather recognize intracellular proteins that are synthesized in the cytoplasm. Tumors containing unique or mutated and potentially immunogenic cellular proteins may selectively or predominantly elicit only CD4 + or CD8 + T cell responses because the antigen is adequately presented in the context of only one MHC molecule, and in this setting only T cells from the subset restricted to that MHC molecule appear effective in tumor therapy.

Adoptive T cell therapy of tumors: mechanisms operative in the recognition and elimination of tumor cells.

Eukaryotic cells constantly form and internalize plasma membrane vesicles in a process known as endocytosis. Endocytosis serves a variety of housekeeping and specialized cellular functions, and it can be mediated by distinct molecular pathways. Among them, internalization via clathrin-coated pits, lipid raft/caveolae-mediated endocytosis and macropinocytosis/phagocytosis are the most extensively characterized. The major endocytic pathways are usually distinguished on the basis of their differential sensitivity to pharmacological/chemical inhibitors, although the possibility of nonspecific effects of such inhibitors is frequently overlooked. This review provides a critical evaluation of the selectivity of the most widely used pharmacological inhibitors of clathrin-mediated, lipid raft/caveolae-mediated endocytosis and macropinocytosis/phagocytosis. The mechanisms of actions of these agents are described with special emphasis on their reported side effects on the alternative internalization modes and the actin cytoskeleton. The most and the least-selective inhibitors of each major endocytic pathway are highlighted.

Pharmacological inhibition of endocytic pathways: is it specific enough to be useful?

Liver membranes from young beagle dogs were found to possess binding sites that resemble the low density lipo- protein (LDL) receptors originally described in cultured human fibroblasts. Treatment of the dogs with colestipol (a bile acid se- questrant) and mevinolin (a cholesterol synthesis inhibitor) pro- duced a 3-fold increase in LDL binding activity. This increase cor- related with a 2-fold increase in the fractional catabolic rate for intravenously administered human or canine "LI-labeled LDL, suggesting that the increased hepatic receptors were responsible for the enhanced clearance of LDL from plasma. The hepatic lipo- protein receptors of control and drug-treated dogs resembled hu- man fibroblast LDL receptors in that they bound apoprotein E- containing lipoproteins, such as very low density lipoproteins and a subfraction of high density lipoproteins (HDL ), with 10-fold higher affinity than the apoprotein B-containing lipoprotein LDL; failed to bind canine HDL and human HDL3 which are devoid of apoproteins B and E; failed to bind methylated LDL; required cal- cium; and were destroyed by Pronase. Treatment of dogs with mevinolin not only increased the fractional catabolic rate for LDL but also reduced the synthetic rate for the lipoprotein. The current data suggest that the liver of dogs contains functional LDL recep- tors that are susceptible to metabolic regulation and that a drug- induced increase in the activity of these receptors can contribute to a lowering of plasma levels of LDL-cholesterol.

Regulatory role for hepatic low density lipoprotein receptors in vivo in the dog (cholesterol synthesis inhibitor/mevinolin/bile acid sequestrant/colestipol/catabolism of plasma lipoproteins)

Spirulina is a species of filamentous cyanobacteria that has long been used as a food supplement. In particular, Spirulina platensis and Spirulina maxima are the most important. Thanks to a high protein and vitamin content, Spirulina is used as a nutraceutical food supplement, although its other potential health benefits have attracted much attention. Oxidative stress and dysfunctional immunity cause many diseases in humans, including atherosclerosis, cardiac hypertrophy, heart failure, and hypertension. Thus, the antioxidant, immunomodulatory, and anti-inflammatory activities of these microalgae may play an important role in human health. Here, we discuss the antioxidant, immunomodulatory, and anti-inflammatory activities of Spirulina in both animals and humans, along with the underlying mechanisms. In addition, its commercial and regulatory status in different countries is discussed as well. Spirulina activates cellular antioxidant enzymes, inhibits lipid peroxidation and DNA damage, scavenges free radicals, and increases the activity of superoxide dismutase and catalase. Notably, there appears to be a threshold level above which Spirulina will taper off the antioxidant activity. Clinical trials show that Spirulina prevents skeletal muscle damage under conditions of exercise-induced oxidative stress and can stimulate the production of antibodies and up- or downregulate the expression of cytokine-encoding genes to induce immunomodulatory and anti-inflammatory responses. The molecular mechanism(s) by which Spirulina induces these activities is unclear, but phycocyanin and β-carotene are important molecules. Moreover, Spirulina effectively regulates the ERK1/2, JNK, p38, and IκB pathways. This review provides new insight into the potential therapeutic applications of Spirulina and may provide new ideas for future studies.

The antioxidant, immunomodulatory, and anti-inflammatory activities of Spirulina: an overview

Background
Higher hospital and surgeon volumes have been associated with improved outcomes after hepatic resection. Subspecialty training has not previously been associated with improved outcomes after hepatic resection. The objective of this study was to determine what effects, if any, surgeon’s volume and training had on the outcomes after hepatic resection.

Impact of surgeon training on outcomes after resective hepatic surgery.

Percutaneously inserted indwelling subclavian vein silastic catheters have revolutionized the administration of chemotherapeutic agents. Complications associated with insertion of such lines have always included bleeding, pneumothorax, haemothorax, arterial cannulation, and catheter displacement. Recently a patient receiving 5-fluorouracil and folinic acid for 11 months for small bowel carcinoma experienced a catheter fracture with distal segment embolization in the right atrium. A literature survey revealed 13 cases where mechanical shearing forces on the catheter caused by compression of the catheter between the clavicle and first rib were thought to be the cause for this complication. Interestingly all cases involved patients receiving chemotherapy. Radiologically, potential candidates for catheter fracture can be identified by the pinched-off sign with bending and pinching of the catheter at the thoracic inlet. Recommendations are for more lateral insertions of such percutaneously placed catheters and if the pinched-off sign is seen, then said catheters should be followed radiologically and probably should not remain in situ for longer than 6 months.

Indwelling subclavian catheters and a visit with the "pinched-off sign".

A population-based study of the biology of the thin-level melanoma according to site, Breslow's thickness, and Clark's level was undertaken. Two hundred fifteen patients were studied with a mean follow-up of 41 months. Overall, 23 patients (10.7%) had recurrences, 8 locally, 9 regionally, and 6 systemically, despite an adequate local excision. A multivariate analysis was done. In the patients with thin lesions (less than 1 mm), increasing level (p

Influence of level and depth on recurrence rate in thin melanomas

Five cases of bloody nipple discharge during pregnancy without associated breast masses were seen over the past 3 years by the author. Because of the reported association of breast cancer with bloody nipple discharge, close follow-up of these women at monthly intervals during pregnancy and trimonthly during the postpartum period was carried out. In all instances, the discharge appeared late during the second trimester or during the third trimester of pregnancy. It was unilateral and spontaneous and arose from multiple ducts, and it was associated with an increase in breast size and always with the larger breast of the two. The discharge cytologic study done on all cases was negative for neoplastic cells and the discharges resolved spontaneously within 2 months of onset. Postpartum follow-up ranging from 6 months to 3 years has revealed no evidence of neoplastic changes thus far. Mammograms ordered before these patients were referred were not helpful due to the increase in density of the breast tissue secondary to the pregnancy. Because a few cases of breast cancer during pregnancy have presented solely with a bloody nipple discharge, I recommend extremely close follow-up of these women and no surgical intervention unless a mass is discovered or the nipple discharge cytology is either suspicious or positive at the initial visit or during follow-up.

Rene Lafreniere

Papers

Impact of surgeon training on outcomes after resective hepatic surgery.

Indwelling subclavian catheters and a visit with the "pinched-off sign".

Influence of level and depth on recurrence rate in thin melanomas

Bloody nipple discharge during pregnancy: A rationale for conservative treatment

The Modified Vaccination Technique.