Overexpression of Galectin-1 and Galectin-3 in hepatocellular carcinoma.

Galectins (Gals) are evolutionarily conserved proteins that bind to ß-galactoside containing glycans. Abnormal expression of Gals is associated with the development, progression, and metastasis of different types of cancer. Among the 11 Gals identified in humans, the roles of Gal-1 and Gal-3 have been extensively investigated in various tumors. Here, we summarize the roles of overly expressed Gal-1 and Gal-3 in the pathogenesis of hepatocellular carcinoma (HCC). The overexpression of Gal-1 and Gal-3 correlates with tumor growth, HCC cell migration and invasion, tumor aggressiveness, metastasis, and poor prognosis. A potentially promising future treatment strategy for HCC may include the combination of immunotherapy with Gal-1 inhibition. Additional research is warranted to investigate targeting Gal-1 and Gal-3 for HCC treatment.

Hepaticojejunostomy using short-limb Roux-en-Y reconstruction.

IMPORTANCE: When performing biliary reconstruction, one of the long-standing tenets of surgery is that Roux-en-Y (RY) reconstruction should use a long hepatic limb to decrease the risk for postoperative cholangitis. However, this practice is not well supported and may also make postoperative biliary endoscopy difficult. While some authors recommend Roux limbs of up to 75 cm, we have routinely used a Roux length of 20 cm to facilitate possible postoperative endoscopic access. OBJECTIVE: To review our experience with short-limb RY hepaticojejunostomy (HJ) and examine the short-term and long-term outcomes following this procedure, as well as the success of future biliary interventions. DESIGN: Retrospective medical record review of all patients who underwent short-limb RYHJ by 2 surgeons (N.N.N. and S.D.C.). SETTING: Tertiary care, university-affiliated teaching hospital. PARTICIPANTS: One hundred patients who underwent RYHJ were identified, with 30 of those patients being excluded owing to creation of an RYHJ to intrahepatic bile ducts with concomitant liver resection. MAIN OUTCOMES AND MEASURES: Patient records were reviewed to determine the incidence of postoperative cholangitis and biliary stricture. Secondary outcomes were the need for postoperative biliary endoscopy and success rates for endoscopic biliary interventions. RESULTS Seventy patients underwent short-limb RYHJ over an 11-year period (2001-2012). Indications included benign stricture (n = 18), malignant stricture (n = 12), choledochal cyst (n = 5), choledocholithiasis (n = 3), idiopathic cholangitis (n = 2), and deceased donor or live donor liver transplant (n = 30). Seven patients, including 4 liver transplant patients, developed clinical or radiographic evidence of postoperative biliary stricture, and all patients underwent successful endoscopic cholangiography. Four of these patients required dilation and/or stone extraction, which were accomplished endoscopically in all cases. CONCLUSIONS AND RELEVANCE: Short-limb RYHJ is safe and associated with a low incidence of postoperative complications. In addition, biliary intervention, when indicated, can be performed endoscopically with a high degree of success. In the absence of any evidence demonstrating longer limbs to be superior, we recommend using short-limb RY reconstruction for HJ.

Universal multifunctional HD video system for minimally invasive, [corrected] open and microsurgery.

BACKGROUND: Laparoscopy has familiarized most surgeons with the benefits of a surgical video system, including the ability to magnify fine structures, to display the operative field on a monitor for improved intraoperative communication, and to capture video footage for documentation and education. Use of intraoperative video systems during open surgery is far less common and the potential benefits of this have not been well explored. In this report we describe a simple video system that is applicable to both laparoscopic and open surgery. METHODS: We employed a standard laparoscopic HD camera (1080p) and telescope for initial laparoscopy. In cases requiring laparotomy, a mechanical arm is attached to the operating table and the camera is mounted without the telescope; this provides video display of the open surgical field. In cases requiring dissection or anastomosis of minute structures, a prototype telescope made for open cases is attached to the same camera; this provides improved magnification and illumination for the surgeon. Microsurgical components can then proceed with the surgeon working off the video monitor at a more convenient posture and with the benefits of video display. RESULTS: This multifunctional HD video system for open abdominal surgery has been utilized in 98 complex hepatopancreaticobiliary surgeries. Clear benefits include (1) improved intraoperative communication, (2) improved teaching of bystanders, (3) improved visualization of minute structures, and (4) improved capture and utilization of surgical video and images for education. In an analysis of patients who underwent pancreaticoduodenectomy (PD) with this system, there was a trend toward fewer pancreatic leaks and shorter length of stay but slightly longer operative time compared to PD prior to implementation of this system. CONCLUSIONS: This system can be employed with little added cost over a standard laparoscopy setup and has the potential to be widely utilized in surgical education programs.

Milan Criteria and UCSF Criteria: A Preliminary Comparative Study of Liver Transplantation Outcomes in the United States.

The application of orthotopic liver transplantation (OLT) for patients with hepatocellular cancer (HCC) necessitates highly selective criteria to maximize survival and to optimize allocation of a scarce resource. The objective of this study was to compare the outcomes of OLT for HCC in patients transplanted under Milan and UCSF criteria. The United Network of Organ Sharing (UNOS) database was queried for patients who had undergone OLT for HCC from 2002 to 2007, and 1,972 patients (Milan criteria, n = 1, 913; UCSF criteria, n = 59) were identified. Patients were stratified by pretransplant criteria (Milan versus UCSF), and clinical and pathologic factors and overall survival were compared. There were no differences in age, gender, diabetes mellitus, body mass index, and hepatitis B, or C status between the two groups. Overall survival was similar between the Milan and UCSF cohorts (1-, 2-, 3-, and 4-year survival rates: 88%, 81%, 76%, and 72% versus 91%, 80%, 68% and 51%, respectively, P = 0.21). Although the number of patients within UCSF criteria was small, our results nevertheless suggest that patients with HCC may have equivalent survival when transplanted under Milan and UCSF criteria. Long-term followup may better determine whether UCSF criteria should be widely adopted.

Ki-67 proliferative index predicts progression-free survival of patients with well-differentiated ileal neuroendocrine tumors.

Ki-67 proliferative index (Ki-67 index) is suggested to be an important prognostic variable and is included as one of the grading parameters for neuroendocrine tumors. The present study was undertaken to determine the usefulness of the Ki-67 index and the corresponding tumor grade in predicting progression-free survival (PFS) of patients with ileal well-differentiated neuroendocrine tumors (wNETs). Tumors from 57 patients with ileal wNETs were studied. Immunohistochemical staining for Ki-67 was performed on the primary as well as selected metastatic tumors and quantitated by computer-assisted image analysis using the Ariol system. The tumors were graded based on mitotic activity and Ki-67 index. Clinical and pathological variables affecting the PFS were analyzed. There were 29 women and 28 men, with a mean age of 59 years. At the time of initial presentation, 8 patients (14%) had localized disease (stages I and II), 29 patients (51%) had regional (nodal/mesenteric) spread (stage III), and 20 patients (35%) had distant metastasis (stage IV). Twelve patients experienced disease progression during subsequent follow-up. Patients with initial stage IV disease were more likely to experience disease progression (P = .005). Additionally, higher histological grade (as determined by Ki-67 index >2%) was associated with a decreased PFS (P = .001). Ki-67 index greater than 2% at either the primary site or the metastatic site was found to be the only significant predictor of PFS after consideration of all other variables in an adjusted analysis. In conclusion, the Ki-67 index predicts PFS of patients with ileal wNETs.

Recurrent hepatocellular carcinoma after liver transplant: identifying the high-risk patient.

BACKGROUND: Recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) is rarely curable. However, in view of the advent of new treatments, it is critical that patients at high risk for recurrence are identified. METHODS: Patients undergoing LT for HCC at a single centre between 2002 and 2010 were reviewed and data on clinical parameters and explant pathology were analysed to determine factors associated with HCC recurrence. All necrotic and viable tumour nodules were included in explant staging. All patients underwent LT according to the United Network for Organ Sharing (UNOS) Model for End-stage Liver Disease (MELD) tumour exception policies. RESULTS: Liver transplantation was performed in 122 patients with HCC during this period. Rates of recurrence-free survival in the entire cohort at 1 year and 3 years were 95% and 89%, respectively. Thirteen patients developed HCC recurrence at a median of 14 months post-LT. In univariate analysis the factors associated with HCC recurrence were bilobar tumours, vascular invasion, and stage exceeding either Milan or University of California San Francisco (UCSF) Criteria. Multivariate analysis showed pathology outside UCSF Criteria was the major predictor of recurrence; when pathology outside UCSF Criteria was found in combination with vascular invasion, the predicted 3-year recurrence-free survival was only 26%. CONCLUSIONS: Explant pathology can be used to predict the risk for recurrent HCC after LT, which may allow for improved adjuvant and management strategies.

Evaluation of absolute serum α-fetoprotein levels in liver transplant for hepatocellular cancer.

HYPOTHESIS: An elevated serum α-fetoprotein (AFP) level before orthotopic liver transplant (OLT) is predictive of mortality after OLT for hepatocellular carcinoma (HCC). DESIGN: Retrospective analysis of a population-based cohort. SETTING: United Network for Organ Sharing registry (2003-2008). PATIENTS: We identified 2253 patients who underwent OLT for HCC with available pre-OLT serum AFP values. METHODS: Patients were stratified by AFP levels into low (<20 ng/mL), medium (20-399 ng/mL), or high (≥400 ng/mL) groups. Clinical and pathological characteristics were compared among groups. Survival curves were constructed by the Kaplan-Meier method, and univariate and multivariate Cox-regression analysis was performed. RESULTS: Of the 2253 patients, 1210 (53.7%), 805 (35.7%), and 238 (10.6%) were in the low, medium, and high AFP groups, respectively. On univariate analysis, the low AFP group demonstrated the best 4-year survival (76%) compared with the medium (65%; P = .001) and high (57%; P < .001) AFP groups. When AFP levels in patients with only stage II HCC underwent assessment, improved survival in the low AFP group was still observed (P < .001). On multivariate analysis, the medium and high AFP groups were associated with higher mortality (hazard ratios, 1.50 [95% confidence interval, 1.19-1.89; P = .001] and 2.11 [1.55-2.88; P < .001], respectively). CONCLUSIONS: Serum AFP level is an independent prognostic predictor of outcome after OLT for HCC. The association between serum AFP value and post-OLT survival warrants further investigation to potentially better allocate donor allografts for HCC.

Race, ethnicity, and socioeconomic status influence the survival of patients with hepatocellular carcinoma in the United States.

BACKGROUND: Racial, ethnic, and socioeconomic disparities in the survival of patients with hepatocellular carcinoma (HCC) continue to exist. The authors of this report hypothesized that these differences result from inequities in access to care and in response to therapy. METHODS: Patients with HCC (n = 20,920) were identified from the Surveillance, Epidemiology, and End Results (SEER) database, and patients who underwent liver transplantation for HCC (n = 4735) were identified from the United Network for Organ Sharing (UNOS) database. Clinical and pathologic factors were compared after patients were stratified by race and ethnicity. RESULTS: The survival of patients with HCC improved over time for all racial, ethnic, and income groups (P < .001). Black and low income individuals had the poorest long-term survival (P < .001). On multivariate analysis, black race was predictive of the poorest survival (hazard ratio [HR], 1.15; 95% confidence interval [CI], 1.09-1.22; P < .001), whereas Asian race was associated with the best survival (HR, 0.87; 95% CI, 0.83-0.91; P < .001). After liver transplantation, black patients had the worst graft survival and overall survival (median survival [MS], 30.5 months and 39.7 months, respectively; P < .001), whereas Hispanics had the best survival (MS, 83.4 months and 86.6 months, respectively; P < .001). In a multivariate analysis of transplantation patients, race and ethnicity were associated significantly with outcome. CONCLUSIONS: Significant racial and ethnic disparities in the outcome of patients with HCC persist despite the receipt of comparable treatment. The authors concluded that further investigations are warranted to identify the reasons for the stark disparity in outcomes between black patients and Hispanic patients after liver transplantation for HCC.

Pancreatic neuroendocrine tumors: presentation, management, and outcomes.

Pancreatic neuroendocrine tumors (pNETs) are an uncommon pancreatic neoplasm. We reviewed the presentation, management, and outcome of patients with pNETs treated at a single center by a multidisciplinary approach between 2004 and 2008. Over this time period, 154 patients with carcinoid and neuroendocrine tumors were treated, which included 46 patients (30% of total) with pNETs. The most common presentations included abdominal pain (20 of 46 [43%]), systemic symptoms such as hypoglycemia (15 of 46 [33%]), and incidental mass (7 of 46 [15%]). Fourteen patients had functional tumors. At the time of diagnosis, 22 patients (48%) presented without metastases and 24 (52%) had metastatic disease. Median follow up for the entire group was 42 months. All patients with nonmetastatic pNET underwent pancreatic resection with 95 per cent postoperative survival. Overall survival in this group at 3 years was 86 per cent and disease-free survival was 81 per cent. In patients presenting with metastatic pNET, multiple treatment modalities were used, including liver resection or ablation (n = 15), hepatic chemoembolization (n = 17), pancreatic resection (n = 12), and systemic treatments (n = 7). Three-year survival was 70 per cent. Pancreatic resection results in greater than 80 per cent 3-year survival in nonmetastatic pNET. In patients presenting with metastatic pNET, excellent survival rates are also achievable using a multidisciplinary multimodal approach.

A disease-based comparison of liver transplantation outcomes.

An increasing demand for transplant donor organs has made optimal allocation of resources a priority. Our objective was to evaluate outcomes for orthotopic liver transplantation (OLT) performed in the United States. A query of the United Network for Organ Sharing registry between 1988 and 2007 was performed for patients who underwent OLT for all etiologies. Patients were stratified by pathology necessitating OLT and clinical and pathologic factors were compared. Multivariate Cox-regression analysis was used to assess the association of pathology with survival. Of 61,823 patients, 33 per cent (n = 20,305) of OLTs were secondary to hepatitis C virus, 21 per cent autoimmune disease, 17 per cent alcohol-induced injury, 11 per cent cryptogenic cirrhosis, 8 per cent hepatocellular carcinoma (HCC), 6 per cent hepatitis B virus, and 4 per cent metabolic disease. Patients with autoimmune disease and HCC demonstrated the best and worst survival, respectively, after OLT (median survival 16.0 vs 6.4 yrs, respectively, P < 0.001). By multivariate analysis, OLT for HCC was significantly associated with poorer overall survival (hazard ratio [HR] 2.19, 95% confidence interval [CI]: 2.02-2.37, P < 0.001). Our results indicate that outcomes for liver transplantation vary by primary hepatic pathology with HCC patients having the poorest overall survival. To optimize organ allocation for all patients with end-stage liver disease, a better understanding of poor survival for HCC is necessary.

Adrenal metastasis with inferior vena cava tumor thrombus through adrenal vein.

A 69-year-old woman was evaluated for anemia. Abdominal ultrasonography showed a large right renal mass. Magnetic resonance imaging revealed a 12-cm renal mass and a separate 7.5-cm ipsilateral adrenal mass, with a tumor thrombus extending through the adrenal vein and into the inferior vena cava. Right radical nephrectomy/adrenalectomy with caval tumor thrombectomy was performed, and both lesions were diagnosed as renal cell carcinoma. We report on an unusual case of a large renal cell carcinoma with metastasis to the adrenal gland and vena caval extension by way of the adrenal venous system, without renal vein thrombus.

Morbidity in live liver donors: standards-based adverse event reporting further refined.

HYPOTHESIS: The true extent of morbidity among live liver donors remains poorly understood. In this unique and often high-profile area of surgery, the development of standards for defining and reporting complications would foster a better understanding of the incidence and magnitude of such adverse events (AEs). DESIGN: Retrospective review of AEs among live liver donors. SETTING: University-affiliated teaching hospital. PATIENTS AND METHODS: Of 202 individuals undergoing evaluation for live liver donation, 42 (20.8%) proceeded to surgery. Thirty-four underwent a right lobectomy without the middle hepatic vein; 3, a left lateral segmentectomy. Any event causing a deviation from a patient's ideal course was considered an AE and subsequently classified according to a derived framework. Morbidity was defined as 1 or more AEs. MAIN OUTCOME MEASURES: Incidence, timing, type, severity, and impact of AEs. RESULTS: No deaths or significant hepatic dysfunction occurred. In 5 (12%) of the 42 donors, the hepatectomy was aborted for anatomic reasons before parenchymal transection. Eight (22%) of the remaining 37 experienced 11 AEs, of which 10 completely resolved, whereas 1 AE (3%) resulted in a permanent disability (brachial plexopathy). The overall incidence of AEs was 0.30 per case. Ten (91%) of the 11 AEs presented within the first postoperative month. CONCLUSIONS: Most live liver donations are uncomplicated or do not lead to permanent consequence. The adoption of a standards-based classification framework for AEs in live liver donors would allow for an inclusive, consistent, and universally applicable method to collect, analyze, and report donor morbidity.

Endoscopically placed nasogastrojejunal feeding tubes: a safe route for enteral nutrition in patients with hepatic encephalopathy.

Patients with hepatic encephalopathy are at particular risk for aspiration when given oral or gastric feedings. An ideal strategy might combine distal enteral feeding with proximal gastric decompression, which is offered by a nasogastrojejunal (NGJ) feeding tube. One objective was to determine the efficacy and safety of endoscopically placed NGJ feeding tubes in patients with hepatic encephalopathy. Charts of patients who underwent NGJ tube placements between April 1997 and January 2000 were retrospectively reviewed. Two endoscopic techniques ("push" and "pull") were used. Eighteen patients (nine male and nine female) underwent 32 procedures. Twelve patients had undergone liver transplantation, four had decompensated cirrhosis, and two had fulminant hepatic failure. Twenty procedures used the push technique and 12 required the pull technique. The insertion time was shorter for the push technique compared with the pull technique (21.8 vs 39.6 min, P < 0.05). Enteral feedings were begun at an average of 5.2 hours after tube placement. The tubes remained in place for an average of 13.9 days. Complications related to the NGJ tubes included self-removal in eight, tube clogging in five, proximal migration in four, and intraduodenal migration of the gastric port in one. No aspiration episodes occurred. We conclude that NGJ feeding tubes may be placed endoscopically as a bedside procedure for patients with hepatic encephalopathy and provide a safe, efficacious, and rapid route for enteral nutrition in these patients.