Colectomy in patients with liver disease: albumin-bilirubin score accurately predicts outcomes.

BACKGROUND: Patients with liver disease undergoing colectomy have higher rates of complications and mortality. The Albumin-Bilirubin score is a recently developed system, established to predict outcomes after hepatectomy, that accounts for liver dysfunction. METHODS: All patients undergoing colectomy were identified in the 2015-2018 American College of Surgeons National Surgical Quality Improvement Program colectomy-targeted database. Demographics and outcomes were compared between patients with Albumin-Bilirubin Grade 1 vs. 2/3. Multivariable regression was performed for outcomes including colorectal-specific complications. Areas under the receiver operative characteristic curves were calculated to determine accuracy of the Albumin-Bilirubin score. RESULTS: Of 86,273 patients identified, 48% (N = 41,624) were Albumin-Bilirubin Grade 1, 45% (N = 38,370) Grade 2 and 7% (N = 6,279) Grade 3. Patents with Grade 2/3 compared to Grade 1 had significantly increased mortality (7.2% vs. 0.9%, p < 0.001) and serious morbidity (31% vs. 12%, p < 0.001). Colorectal-specific complications including anastomotic leak (3.7% vs. 2.8%, p < 0.001) and prolonged ileus (26% vs. 14%, p < 0.001) were higher in patients with Grade 2/3. Grade 2/3 had increased risk of mortality (odds ratio 3.07, p < 0.001) and serious morbidity (1.78, p < 0.001). Albumin-Bilirubin had excellent accuracy in predicting mortality (area under the curve 0.81, p < 0.001) and serious morbidity (0.70, p < 0.001). CONCLUSION: Albumin-Bilirubin is easily calculated using only serum albumin and total bilirubin values. Grade 2/3 is associated with increased rates of mortality and morbidity following colectomy. Albumin-Bilirubin can be applied to risk-stratify patients prior to colectomy.

Dosing strategies for de novo once-daily extended release tacrolimus in kidney transplant recipients based on CYP3A5 genotype.

BACKGROUND: Tacrolimus extended-release tablets have been Food and Drug Administration-approved for use in the de novo kidney transplant population. Dosing requi rements often vary for tacrolimus based on several factors including variation in metabolism based on CYP3A5 expression. Patients who express CYP3A5 often require higher dosing of immediate-release tacrolimus, but this has not been established for tacrolimus extended-release tablets in the de novo setting. AIM: To obtain target trough concentrations of extended-release tacrolimus in de novo kidney transplant recipients according to CYP3A5 genotype. METHODS: Single-arm, prospective, single-center, open-label, observational study (ClinicalTrials.gov: NCT037 13645). Life cycle pharma tacrolimus (LCPT) orally once daily at a starting dose of 0.13 mg/kg/day based on actual body weight. If weight is more than 120% of ideal body weight, an adjusted body weight was used. LCPT dose was adjusted to maintain tacrolimus trough concentrations of 8-10 ng/mL. Pharmacogenetic analysis of CYP3A5 genotype was performed at study conclusion. RESULTS: Mean time to therapeutic tacrolimus trough concentration was longer in CYP3A5 intermediate and extensive metabolizers vs CYP3A5 non-expressers (6 d vs 13.5 d vs 4.5 d; P = 0.025). Mean tacrolimus doses and weight-based doses to achieve therapeutic concentration were higher in CYP3A5 intermediate and extensive metabolizers vs CYP3A5 non-expressers (16 mg vs 16 mg vs 12 mg; P = 0.010) (0.20 mg/kg vs 0.19 mg/kg vs 0.13 mg/kg; P = 0.018). CYP3A5 extensive metabolizers experienced lower mean tacrolimus trough concentrations throughout the study period compared to CYP3A5 intermediate metabolizers and non-expressers (7.98 ng/mL vs 9.18 ng/mL vs 10.78 ng/mL; P = 0 0.008). No differences were identified with regards to kidney graft function at 30-d post-transplant. Serious adverse events were reported for 13 (36%) patients. CONCLUSION: Expression of CYP3A5 leads to higher starting doses and incremental dosage titration of extended-release tacro limus to achieve target trough concentrations. We suggest a higher starting dose of 0.2 mg/kg/d for CYP3A5 expressers.

Simple Prediction Score for Developing Surgical Site Infection after Clean Neck Operation.

Background: Clean neck operations (thyroidectomies, parathyroidectomies, and lymph node resection) are among the most common procedures performed in the United States. Surgical site infections (SSIs) after clean neck operations are rare, but the consequences are devastating and often life-threatening. The aim of this study was to develop a score that will identify patients at high risk for developing a SSI after a clean neck procedure. Materials and Methods: Patients with either thyroidectomies, parathyroidectomies, or lymph node resection of the neck were identified from the 2016 and 2017 databases of the American College of Surgeons National Surgical Quality Improvement Program and were used for this analysis. Our primary goal was to build a scoring system with which we will be able to identify patients at high risk for SSI after a clean neck operation. Results: Of a total of 99,877 patients, 72,719 patients had a thyroidectomy, 22,043 patients had parathyroidectomy, and 5,115 patients had lymph node resection of the neck. Multivariable logistic regression identified the following independent risk factors associated with post-operative SSI: male gender (adjusted odds ratio [aOR], 1.25; 95% confidence interval [CI], 1.03-1.51), diabetes mellitus (aOR, 1.34; 95% CI, 1.07-1.67), smoking (aOR, 1.66; 95% CI, 1.36-2.04), pre-operative steroid use (aOR, 1.75; 95% CI, 1.21-2.53), cancer diagnosis (aOR, 1.44; 95% CI, 1.17-1.77), radical lymphadenectomies (aOR, 2.94; 95% CI, 2.16-4), and total operative time ≥198 minutes (aOR, 2.25; 95% CI, 1.82-2.78). Afterward, we developed a prognostic score for calculating the odds of having post-operative SSI. One point was allotted for each of the aforementioned factors, except lymphadenectomies where two points were allotted, and operative time was excluded. Our score was associated with a stepwise higher risk of post-operative SSI after a clean neck operation. Conclusions: Pre-operative and intra-operative factors can predict which patients undergoing a clean neck surgery may develop SSI. Our prognostic score may help guide surgeons identify patients at high-risk for SSI after clean neck surgery and these patients might benefit from prophylactic use of antibiotic agents.

Perioperative Blood Transfusions or Operative Time: Which Drives Post-Hepatectomy Outcomes?

BACKGROUND: Perioperative blood transfusions and operative time are surgical quality indicators. The aim of this analysis is to determine which of these variables drives post-hepatectomy outcomes. METHODS: Patients undergoing major or partial hepatectomy were identified in the 2014-2018 American College of Surgeons National Surgical Quality Improvement Program hepatectomy targeted database. Prolonged operative time was defined as ≥ 240 minutes. Multivariable logistic regressions were performed for multiple postoperative outcomes. RESULTS: Of 20 521 hepatectomies, 18% of patients received a perioperative transfusion, and the median operative time was 218 minutes. Patients receiving a transfusion had a significant (P < .001) increase in mortality (5.1% vs. .7%) and serious morbidity (43% vs. 16%). Prolonged operative time was associated with significantly (P < .001) increased mortality (2.4% vs. .8%) and serious morbidity (29% vs. 14%). Those with primary hepatobiliary cancer had the highest rates of postoperative morbidity and mortality compared to patients with metastatic and benign disease when a transfusion occurred. On multivariable regression analyses, perioperative transfusions conferred a higher risk (P < .001) than prolonged operative time for mortality (OR 5.02 vs. 1.47) and serious morbidity (OR 2.56 vs. 1.50). CONCLUSIONS: Perioperative blood transfusions are a more robust predictor of post-hepatectomy outcomes than increased operative time, especially in patients with primary hepatobiliary cancer.

Recent Improvements in Racial Disparity in the Treatment of Hepatocellular Carcinoma: How Times Have Changed.

BACKGROUND: Race has been shown to impact receipt of and outcomes following hepatobiliary surgery. We sought to determine if racial disparities in the management of hepatocellular carcinoma persist. METHODS: Information on patients with hepatocellular carcinoma diagnosed between 2012 and 2016 was obtained from the Surveillance, Epidemiology, and End Results database. The sample was stratified by race/ethnicity, and associations between tumor characteristics, treatment, and survival were assessed. RESULTS: Of 33,672 patients, the mean age was 65 years, and 77% were male. By race, 17,150 (51%) were white, 4755 (14%) black, 6850 (20%) Hispanic, and 4917 (15%) Asian. When assessing the likelihood of treatment versus no treatment for tumors less than 5 cm, no difference was observed between whites and blacks in any year, but Hispanics were less likely than whites to receive treatment in most years. Asians were more likely to receive treatment every year. When assessing the likelihood of transplant versus surgical resection, blacks were less likely than whites to undergo transplant in all years except 2016. Hispanics were equally likely, while Asians were less likely to undergo transplant in all years. For years 2012 to 2016 collectively, Asians had better 5-year survival rates than other races after undergoing ablation and resection. No difference in the risk of death was observed among blacks, whites, or Hispanics after undergoing ablation, resection, or transplant. CONCLUSION: Racial disparities for blacks and Hispanics have improved. Although Asians were less likely to undergo transplant, they had better survival after undergoing resection or ablation.

Predicting Operative Outcomes in Patients with Liver Disease: Albumin-Bilirubin Score vs Model for End-Stage Liver Disease-Sodium Score.

BACKGROUND: The albumin-bilirubin score (ALBI) has recently been shown to have increased accuracy in predicting post-hepatectomy liver failure and mortality compared with the Model for End-Stage Liver Disease (MELD). However, the use of ALBI as a predictor of postoperative mortality for other surgical procedures has not been analyzed. The aim of this study was to measure the predictive power of ALBI compared with MELD-sodium (MELD-Na) across a wide range of surgical procedures. STUDY DESIGN: Patients undergoing cardiac, pulmonary, esophageal, gastric, gallbladder, pancreatic, splenic, appendix, colorectal, adrenal, renal, hernia, and aortic operations were identified in the 2015-2018 American College of Surgeons NSQIP database. Patients with missing laboratory data were excluded. Univariable analysis and receiver operator characteristic curves were performed for 30-day mortality and morbidity. Areas under the curves were calculated to validate and compare the predictive abilities of ALBI and MELD-Na. RESULTS: Of 258,658 patients, the distribution of ALBI grades 1, 2, 3 were 51%, 42%, and 7%, respectively. Median MELD-Na was 7.50 (interquartile range 6.43 to 9.43). Overall 30-day mortality rate was 2.7% and overall morbidity was 28.6%. Increasing ALBI grade was significantly associated with mortality (ALBI grade 2: odds ratio [OR] 5.24; p < 0.001; ALBI grade 3: OR 25.6; p < 0.001) and morbidity (ALBI grade 2: OR 2.15; p < 0.001; ALBI grade 3: OR 6.12; p < 0.001). On receiver operator characteristic analysis, ALBI outperformed MELD-Na with increased accuracy in several operations. CONCLUSIONS: ALBI score predicts mortality and morbidity across a wide spectrum of surgical procedures. When compared with MELD-Na, ALBI more accurately predicts outcomes in patients undergoing pulmonary, elective colorectal, and adrenal operations.

Fatty liver: The metabolic syndrome increases major hepatectomy mortality.

BACKGROUND: As the obesity epidemic worsens, the prevalence of fatty liver disease has increased. However, minimal data exist on the impact of combined fatty liver and metabolic syndrome on hepatectomy outcomes. Therefore, the aim of this analysis is to measure the outcomes of patients who do and do not have a fatty liver undergoing hepatectomy in the presence and absence of the metabolic syndrome. METHODS: Patients with fatty and normal livers undergoing major hepatectomy (≥3 segments) were identified in the 2014 to 2018 American College of Surgeon National Surgical Quality Improvement Program database. Patients undergoing partial hepatectomy and those with missing liver texture data were excluded. Propensity matching was used and adjusted for multiple variables. A subgroup analysis stratified by the metabolic syndrome (body mass index ≥30 kg/m2, hypertension and diabetes) was performed. Demographics and outcomes were compared by χ2 and Mann-Whitney tests. RESULTS: Of 2,927 hepatectomies, 30% of patients (N = 863) had a fatty liver. The median body mass index was 28.6, and the metabolic syndrome was present in 6.3% of patients (N = 184). After propensity matching, 863 patients with fatty and 863 with normal livers were compared. Multiple outcomes were significantly worse in patients with fatty livers (P <.05), including serious morbidity (32% vs 24%), postoperative invasive biliary procedures (15% vs 10%), organ space infections (11% vs 7.8%), and pulmonary complications. Patients with fatty livers and the metabolic syndrome had significantly increased postoperative cardiac arrests, pulmonary embolisms, and mortality (P < .05). CONCLUSION: Fatty liver disease is associated with significantly worse outcomes after major hepatectomy. The metabolic syndrome confers an increased risk of postoperative mortality.

Minimally Invasive Hepatectomy in North America: Laparoscopic Versus Robotic.

BACKGROUND: Minimally invasive hepatectomy has been shown to be associated with improved outcomes when compared with open surgery. However, data comparing laparoscopic and robotic hepatectomy is lacking and limited to single-center studies. METHODS: Patients undergoing major (≥ 3 segments) or partial (≤ 2 segments) hepatectomy were identified in the 2014-2017 ACS-NSQIP hepatectomy targeted database. Patients undergoing laparoscopic and robotic approaches were compared, and propensity score matching was utilized to adjust for bias. RESULTS: Of 3152 minimally invasive hepatectomies (MIHs), 86% (N = 2706) were partial and 14% (N = 446) were major. The laparoscopic approach was utilized in 92% of patients (N = 2905) and 8% were performed robotically (N = 247). The percentage of MIHs increased over time (p < 0.01). After matching, 240 were identified in each cohort. Compared with the robotic approach, patients undergoing laparoscopic hepatectomy had a significantly higher conversion rate (23% vs. 7.4%) but had shorter operative time (159 vs. 204 min) (p < 0.001). Laparoscopic cases undergoing an unplanned conversion to open were associated with increased morbidity (p < 0.001), but this difference was not observed in robotic cases. Both MIH approaches had low mortality (1.0%, p = 1.00), overall morbidity (17%, p = 0.47), and very short length of stay (3 days, p = 0.80). CONCLUSION: Minimally invasive hepatectomy is performed primarily for partial hepatectomies. Laparoscopic hepatectomy is associated with a significantly higher conversion rate, and converted cases have worse outcomes. Both minimally invasive approaches are safe with similar mortality, morbidity, and a very short length of stay. Graphical Abstract.

When does a Pringle Maneuver cause harm?

BACKGROUND: The Pringle Maneuver (PM) is considered to be safe and effective. However, data regarding perioperative outcomes after a PM are conflicting. Therefore, the aim of this analysis is to compare the outcomes of patients who have and have not undergone a PM in North America. METHODS: Patients undergoing major (≥3 segments) or partial hepatectomy (≤2 segments) were identified in the 2014-17 ACS-NSQIP hepatectomy database. Patients with and without a PM were compared. Propensity matching was utilized, and subgroup analyses by liver texture, hepatectomy extent and pathology were performed. RESULTS: Prior to matching, 3706 (24%) of 15,748 hepatectomy patients underwent a PM. The PM was utilized in 1445 (27%) of major and 2261 (22%) of partial hepatectomies. After matching, 3295 patients with and 3295 without a PM were compared. Operative time was significantly increased for patients undergoing a PM (246 vs. 225 min, p < 0.001). Subgroup analyses revealed post-hepatectomy liver failure and septic shock to be significantly increased (both p < 0.05) for patients undergoing a PM during a partial hepatectomy or in patients with metastatic disease. CONCLUSION: Patients undergoing a partial hepatectomy and those with metastatic disease have worse outcomes when a Pringle Maneuver is performed.

Frailty Predicts Morbidity and Mortality After Laparoscopic Cholecystectomy for Acute Cholecystitis: An ACS-NSQIP Cohort Analysis.

BACKGROUND: Current guidelines recommend laparoscopic cholecystectomy be offered for patients with acute cholecystitis except those deemed as high risk. Few studies have examined the impact of frailty on outcomes for patients undergoing laparoscopic cholecystectomy. Therefore, the aim of this study was to determine the association of frailty with postoperative morbidity and mortality in patients undergoing laparoscopic cholecystectomy for acute cholecystitis. METHODS: Patients undergoing laparoscopic cholecystectomy for acute cholecystectomy were identified from 2005 to 2010 in the American College of Surgeons National Surgical Quality Improvement Project (NSQIP). The Modified Frailty Index (mFI) was used a surrogate for frailty, and patients were stratified as non-frail (mFI 0), low frailty (mFI 1-2), intermediate frailty (mFI 3-4) and high frailty (mFI ≥ 5). Univariable and multivariable analyses were performed. Receiver operator curves (ROC) and an area under the curve (AUC) were generated to determine accuracy of mFI in predicting postoperative morbidity and mortality. RESULTS: Of the 6898 patients undergoing laparoscopic cholecystectomy, 3245 (47%) patients were non-frail. There were 2913 (42%) patients with low-frailty, 649 (9%) patients with intermediate frailty, and 91 (2%) with high frailty. Clavien IV complications were higher for intermediate frail patients (OR 1.81, 95% CI 1.00-3.28, p = 0.050) and high-frail patients (OR 4.59, 95% CI 1.98-10.7, p < 0.001). Additionally, mortality was higher for patients with intermediate frailty (OR 4.69, 95% CI 1.37-16.0, p = 0.014) and high frailty (OR 12.2, 95% CI 2.67-55.5, p = 0.001). The mFI had excellent accuracy for mortality (AUC = 0.83) and Clavien IV complications (AUC = 0.73). CONCLUSION: Frailty is associated with postoperative morbidity and mortality in patients undergoing laparoscopic cholecystectomy for acute cholecystitis.

Liver Ischemia Reperfusion Injury, Enhanced by Trained Immunity, Is Attenuated in Caspase 1/Caspase 11 Double Gene Knockout Mice.

Ischemia reperfusion injury (IRI) during liver transplantation increases morbidity and contributes to allograft dysfunction. There are no therapeutic strategies to mitigate IRI. We examined a novel hypothesis: caspase 1 and caspase 11 serve as danger-associated molecular pattern (DAMPs) sensors in IRI. By performing microarray analysis and using caspase 1/caspase 11 double-knockout (Casp DKO) mice, we show that the canonical and non-canonical inflammasome regulators are upregulated in mouse liver IRI. Ischemic pre (IPC)- and post-conditioning (IPO) induce upregulation of the canonical and non-canonical inflammasome regulators. Trained immunity (TI) regulators are upregulated in IPC and IPO. Furthermore, caspase 1 is activated during liver IRI, and Casp DKO attenuates liver IRI. Casp DKO maintained normal liver histology via decreased DNA damage. Finally, the decreased TUNEL assay-detected DNA damage is the underlying histopathological and molecular mechanisms of attenuated liver pyroptosis and IRI. In summary, liver IRI induces the upregulation of canonical and non-canonical inflammasomes and TI enzyme pathways. Casp DKO attenuate liver IRI. Development of novel therapeutics targeting caspase 1/caspase 11 and TI may help mitigate injury secondary to IRI. Our findings have provided novel insights on the roles of caspase 1, caspase 11, and inflammasome in sensing IRI derived DAMPs and TI-promoted IRI-induced liver injury.

Albumin-Bilirubin Score vs Model for End-Stage Liver Disease in Predicting Post-Hepatectomy Outcomes.

BACKGROUND: The Albumin-Bilirubin score (ALBI) has been established to predict outcomes after hepatectomy. However, the relative value of ALBI and Model for End-Stage Liver Disease (MELD) in predicting post-hepatectomy liver failure and mortality has not been adequately evaluated. Therefore, the aim of this study was to validate and compare ALBI and MELD with respect to post-hepatectomy liver failure and mortality. STUDY DESIGN: Patients undergoing major hepatectomy (≥3 segments) or partial hepatectomy (≤2 segments) were identified in the 2014 to 2017 American College of Surgeons NSQIP Procedure Targeted Participant Use File. Univariable and multivariable analyses were performed for 30-day post-hepatectomy liver failure (PHLF) and mortality. Predictive accuracy was assessed using a receiver operator characteristic curve and calculating the area under the curve (AUC). RESULTS: For 13,783 patients, median ALBI was -2.6, and median MELD score was 6.9. Severe PHLF (grade B to C) and mortality rates were 2.9% and 1.8%, respectively. Multivariable analyses revealed ALBI grade 2/3 to be a stronger predictor than MELD ≥10 with respect to severe PHLF (odds ratio [OR] 2.30; 95% CI, 1.95 to 2.73; p < 0.001 vs OR 1.00; 95% CI, 0.78 to 1.23; p = 0.99) and mortality (OR 3.35; 95% CI, 2.49 to 4.52; p < 0.001 vs OR 1.73; 95% CI, 1.36 to 2.20; p < 0.001). ALBI also had better discrimination compared with MELD for severe PHLF (AUC 0.67 vs AUC 0.60) and mortality (AUC 0.70 vs AUC 0.58) in patients with hepatocellular carcinoma. CONCLUSIONS: ALBI is a powerful predictor of PHLF and mortality. Compared with MELD, ALBI is more accurate, especially in patients with hepatocellular carcinoma.

Impact of Donor Specific HLA Antibody Monitoring After Kidney Transplantation.

Kidney transplantation (KT) recipients with donor specific HLA antibodies (DSA) encounter higher rates of acute rejection and inferior allograft survival. We report our single center experience with prospective DSA monitoring and provide details of treatments utilized to overcome the potential impact of DSA in a cohort of predominantly African American adult KT recipients. Seventy-five flow crossmatch negative KT recipients underwent periodic screening for DSA utilizing the single antigen bead assay at 3, 6, 9, and 12 months post-transplant. Allograft biopsies were performed in the presence of DSA and/or evidence of graft dysfunction. The incidence of DSA was 23%, with a predominance of Class II antibodies. The rate of rejection was 6 times higher in DSA positive KT recipients compared to DSA negative patients (41% versus 7%, p = 0.004). In the DSA positive group, rejections occurred exclusively in the presence of de novo DSA and were predominantly antibody-mediated or mixed rejections. Despite a higher incidence of rejection in KT recipients with DSA, there were no significant differences in serum creatinine, graft survival, and patient survival between DSA positive and negative recipients at median follow-up of 18 months. DSA positive patients had significantly higher proteinuria compared to DSA negative recipients at 6 months, 1 year, and 3 years of follow-up. In conclusion, the detrimental effects of DSA on allograft function could be mitigated by serial DSA surveillance, protocol biopsies, and alterations in immunosuppression. With these measures, the improvement in graft survival in DSA positive KT recipients, at least at short-term, is encouraging.

Evaluation of composite mesh for ventral hernia repair.

INTRODUCTION: Composite mesh prostheses incorporate the properties of multiple materials for ventral hernia repair. This study evaluated a polypropylene/ePTFE composite mesh with a novel internal polydioxanone (PDO) absorbable ring. METHODS: Composite mesh was placed intraperitoneally in 16 pigs through an open laparotomy and explanted at 2, 4, 8, and 12 weeks. Intraabdominal adhesions were measured laparoscopically. Host tissue in-growth was assessed histologically and tensiometrically. Degradation of the internal PDO ring component was also measured tensiometrically. Appropriate statistical tests were used, and P ≤.05 indicated significance. RESULTS: No adhesions were formed in 50% of the grafts explanted at 8 weeks and 25% of grafts explanted at 12 weeks. There were significantly more vascular structures at 8 weeks, 73.5 ± 28, compared with 2 weeks, 6.75 ± 2 (P ≤.01). The T-peel force at the mesh-host tissue interface was not significantly different among time points. The absorbable PDO ring underwent complete degradation by 12 weeks. CONCLUSIONS: This composite mesh was associated with minimal intraabdominal adhesions, progressive in-growth of host tissues, and complete degradation of a novel internal PDO ring that aided mesh positioning. This composite hernia mesh showed a favorable performance in a porcine model of open ventral hernia repair.

International multicentre prospective study on microwave ablation of liver tumours: preliminary results.

BACKGROUND: Microwave ablation (MWA) is increasingly utilized in the treatment of hepatic tumours. Promising single-centre reports have demonstrated its safety and efficacy, but this modality has not been studied in a prospective, multicentre study. METHODS: Eighteen international centres recorded operative and perioperative data for patients undergoing MWA for tumours of any origin in a voluntary Internet-based database. All patients underwent operative MWA using a 2.45-GHz generator with a 5-mm antenna. RESULTS: Of the 140 patients, 114 (81.4%) were treated with MWA alone and 26 (18.6%) were treated with MWA combined with resection. Multiple tumours were treated with MWA in 40.0% of patients. A total of 299 tumours were treated in these 140 patients. The median size of ablated lesions was 2.5 cm (range: 0.5-9.5 cm). Tumours were treated with a median of one application (range: 1-6 applications) for a median of 4 min (range: 0.5-30.0 min). A power setting of 100 W was used in 78.9% of cases. Major morbidity was 8.3% and in-hospital mortality was 1.9%. CONCLUSIONS: These multi-institution data demonstrate rapid ablation time and low morbidity and mortality rates in patients undergoing operative MWA with a high rate of multiple ablations and concomitant hepatic resection. Longterm follow-up will be required to determine the efficacy of MWA relative to other forms of ablative therapy.

Hepatic tumor ablation: application in a community hospital setting.

Primary liver tumors are a common clinical problem in the United States and worldwide. Resection has historically been used to treat liver lesions. Commonly used liver-directed therapies include transarterial chemoembolization, selective internal radiation therapy, and ablative therapy. Only ablative therapy can cause direct destruction of the targeted tissue. The commercially available modalities in the United States are all based on thermoablative technology. This article examines the various ablative technologies and their application, as well as how these procedures can be performed safely and with optimal outcomes, in a community cancer center.

Pancreatic resection in a large tertiary care community-based hospital: building a successful pancreatic surgery program.

Pancreatic resection can be performed safely in the community-based hospital setting only when appropriate systems are in place for patient selection and preoperative, operative, and postoperative care. Pancreatic surgery cannot be performed optimally without considerable investment in, and coordination of, multiple departments. Delivery of high-quality pancreatic cancer care demands a rigorous assessment of the hospital structure and the processes through which this care is delivered; however, when a hospital makes the considerable effort to establish the necessary systems required for delivery of quality pancreatic cancer care, the community and hospital will benefit substantially.

Leptin inhibits hepatocellular carcinoma proliferation via p38-MAPK-dependent signalling.

OBJECTIVES: Obesity is a significant risk factor for many liver diseases, including hepatocellular carcinoma (HCC). Leptin has been identified as a central mediator of factors that regulate energy intake and expenditure, including appetite, metabolism and fat storage. The role of leptin in the initiation, development and progression of HCC remains poorly understood. The aims of this study were to determine the effect(s) of leptin on HCC cell proliferation and to identify potential signalling mechanism(s) by which leptin exerts these effects. METHODS: Rat H4IIE HCC cells and H4IIE-derived HCC tumours were analysed for leptin receptor (LR) expression. H4IIE cells were treated with leptin (0-100 ng/ml) in the absence or presence of pharmacological inhibitors of p42/p44 mitogen-activated protein kinase (MAPK) (PD98059), p38-MAPK (SB202190) or Janus kinase-signal transducers and activators of transcription (JAK-STAT) (AG490; 10 µM) signalling. Cell proliferation was determined and signal pathway activity analysed. RESULTS: Immunohistochemistry identified increased LR expression in HCC in human tissue. Leptin did not significantly affect H4IIE cell numbers in serum-depleted (0.1% [v/v] foetal bovine serum [FBS]) medium. However, leptin significantly inhibited serum-stimulated (1.0% [v/v] FBS) H4IIE proliferation. Immunoblot analysis demonstrated that leptin significantly activated p42/p44-MAPK, p38-MAPK and STAT3 signalling in a time-dependent manner. Pretreatment of H4IIE cells with SB202190 abrogated leptin-dependent inhibition of H4IIE proliferation, an effect not observed in cells pretreated with PD98059 or AG490. CONCLUSIONS: Leptin inhibits HCC cell growth in vitro via a p38-MAPK-dependent signalling pathway. Identifying similar effects on tumour growth in vivo may provide an attractive therapeutic target for slowing HCC progression.

Real-time three-dimensional guided ultrasound targeting system for microwave ablation of liver tumours: a human pilot study.

OBJECTIVES: This study aimed to evaluate a novel three-dimensional ultrasound (US) guidance system for use in hepatic microwave ablation (MWA). METHODS: An in vitro assessment was performed in which users with different degrees of experience were evaluated for accuracy in targeting phantom lesions embedded in agar using US alone, or US in conjunction with the InVision™ System (IVS). An eight-patient pilot trial of the IVS was then performed in the setting of open hepatic MWA, in which lesions would otherwise have been targeted with conventional US. RESULTS: In vitro studies demonstrated that the IVS significantly improved targeting accuracy at all levels of operator experience (novice, beginner and expert). In the human trial, a total of 31 tumours were targeted and all lesions were hit in one pass, as assessed by independent US image observations. There were no adverse operative events; however, there was minor line-of-sight interference with the infra-red tracking mechanism when some lesions high on the dome of the liver were targeted. CONCLUSIONS: The IVS significantly increased the accuracy of complex targeting procedures of phantom lesions and enhanced targeting in an eight-patient clinical pilot study. During the accrual phase of this pilot study, the development of improved non-optical tracking hardware obviated the requirement to maintain a direct line of sight. The trial was then halted prematurely in order to focus on the application of the IVS utilizing this non-optical modality.

Hepatic tumor ablation.

Ablation of liver tumors is part of a multimodality liver-directed strategy in the treatment of various tumors. The goal of ablation is complete tumor destruction, and ultimately improvement of quality and quantity of life for the patient. Technology is evolving rapidly, with important improvements in efficacy. The current state of ablation technology and indications for ablation are described in this review.