Small bowel carcinoid: Location isn’t everything!

AIM: To investigate the prognostic significance of the primary site of disease for small bowel carcinoid(SBC) using a population-based analysis.METHODS: The Surveillance,Epidemiology and End Results(SEER) database was queried for histologically confirmed SBC between the years 1988 and 2009.Overall survival(OS) and disease-specific survival(DSS) were analyzed using the Kaplan-Meier method and compared using Log rank testing.Log rank and multivariate Cox regression analyses were used to identify predictors of survival using age,year of diagnosis,race,gender,tumor histology/size/location,tumor-node-metastasis stage,number of lymph nodes(LNs) examined and percent of LNs with metastases.RESULTS: Of the 3763 patients,51.2% were male with a mean age of 62.13 years.Median follow-up was 50 mo.The 10-year OS and DSS for duodenal primaries were significantly better when compared to jejunal and ileal primaries(P = 0.02 and < 0.0001,respectively).On multivariate Cox regression analysis,after adjusting for multiple factors,primary site location was not a significant predictor of survival(P = 0.752 for OS and P = 0.966 DSS) while age,number of primaries,number of LNs examined,T-stage and M-stage were independent predictors of survival.CONCLUSION: This 21-year,population-based study of SBC challenges the concept that location of the primary lesion alone is a significant predictor of survival.     

Analysis of long-term outcomes of 3200 liver transplantations over two decades: a single-center experience

OBJECTIVE: Few studies have evaluated long-term outcomes after orthotopic liver transplantation (OLT). This work analyzes the experience of nearly 2 decades by the same team in a single center. Outcomes of OLT and factors affecting survival were analyzed. METHODS: Retrospective analysis of 3200 consecutive OLTs that were performed at our institution, between February 1984 and December 31, 2001. RESULTS: Of 2662 recipients, 578 (21.7%) and 659 (24.7%) were pediatric and urgent patients, respectively. Overall 1-, 5-, 10-, and 15-year patient and graft survival estimates were 81%, 72%, 68%, 64% and 73%, 64%, 59%, 55%, respectively. Patient survival significantly improved in the second (1992-2001) versus the era I (1984-1991) of transplantation (P < 0.001). Similarly, graft survival was better in the era II of transplantation (P < 0.02). However, biliary and infectious complications increased in era II. When OLT indications were considered, best recipient survival was obtained in children with biliary atresia (82%, 79%, and 78% at 1, 5, and 10 years, respectively), while malignant disease in adult patients resulted in the worst outcomes of 68% and 43% at 1 and 5 years, post-OLT. Further, patients <18 years and nonurgent recipients exhibited superior survival when compared with recipients >18 years (P < 0.001) or urgent patients (P < 0.001). Of 13 donor and recipient variables, era of OLT, recipient age, urgent status, donor age, donor length of hospital stay, etiology of liver disease, retransplantation, warm and cold ischemia, but not graft type (whole, split, living-donor), significantly impacted patient survival. CONCLUSIONS: Long-term benefits of OLT are greatest in pediatric and nonurgent patients. Multiple factors involving the recipient, etiology of liver disease, donor characteristics, operative variables, and surgical experience influence long-term survival outcomes. By balancing and matching these factors with a given recipient, optimum results can be achieved.     

A novel iron chelator in combination with a P-selectin antagonist prevents ischemia/reperfusion injury in a rat liver model

BACKGROUND: Hepatic ischemia/reperfusion (I/R) injury is associated with early and late graft failure after liver transplantation. A major mechanism is leukocyte adhesion to endothelium followed by release of reactive oxygen intermediates. We examined whether desferriexochelin 772SM (D-Exo), a lipid soluble iron chelator that prevents hydroxyl radical formation, can enhance the capacity of recombinant P-selectin glycoprotein ligand immunoglobulin (rPSGL-Ig), a glycoprotein that binds to P-selectin and inhibits neutrophil adhesion, to protect against I/R injury in an ex vivo rat liver model. METHODS: Rat livers were harvested and stored for 6 hr at 4 degrees C in University of Wisconsin solution and then perfused with oxygenated whole blood for 2 hr. Three groups were studied (n=6 rats/group): an untreated control group; a group that received 0.4 mg/kg rPSGL-Ig intraportally at the time of harvest; and a group that received 0.4 mg/kg rPSGL-Ig plus 1 micromol D-Exo intraportally both at the time of harvest and at the onset of reperfusion. Liver portal venous blood flow was assessed during perfusion, and at the end of each experiment, liver samples were collected for blinded histological evaluation and biochemical analyses. RESULTS: Livers treated with D-Exo + rPSGL-Ig had significantly higher blood flow than livers treated with rPSGL-1Ig alone (P<0.05), and both treatment groups had higher blood flow than controls (P<0.001). Production of carbonyl proteins, a protein oxidation product, was significantly reduced in the D-Exo + rPSGL-1Ig group (P<0.02 vs. controls), but not in the rPSGL-Ig alone group. Total reduced glutathione was significantly higher than controls in the D-Exo + rPSGL-Ig group (P<0.001 vs. controls), but not in the rPSGL-Ig alone group, indicating less oxidative stress in the D-Exo-treated group. Production of malondialdehyde, an index of lipid peroxidation, was significantly less than controls in both treatment groups (P<0.03). Histopathological findings paralleled these results with Banffs scores of 3.3+/-0.5, 1.8+/-0.4, and 1.3+/-0.5 in the control, rPSGL-Ig alone, and D-Exo plus rPSGL-Ig groups, resp. CONCLUSION: rPSGL-Ig provides partial protection against I/R injury to ex vivo rat livers; however, the addition of D-Exo substantially increases protection by reducing oxidative injury. These findings may have clinical relevance in preventing the consequences of I/R injury after liver transplantation.     

Heme Oxygenase-1 Overexpression Protects Rat Livers from Ischemia/Reperfusion Injury with Extended Cold Preservation

This study analyzes the effects and mechanisms of heme oxygenase-1 (HO-1)-mediated cytoprotection in rat livers exposed to cold preservation. In the first series, rats were pretreated with cobalt protoporphyrin (CoPP) or zinc protoporphyrin (ZnPP), HO-1 inducer and antagonist, respectively. Livers were stored at 4 degrees C for 24 h, and then perfused ex vivo for 2 h. Livers pretreated with CoPP had significantly higher portal venous blood flow and increased total bile production, as compared with the ZnPP group. This correlated with histologic (Banff) criteria of hepatocyte injury/liver function. In the second series, rat livers were stored at 4 degrees C for 24 h or 40 h, and then transplanted into syngeneic recipients. After 24 h of preservation, 80% of rats bearing CoPP-pretreated liver grafts survived 21 days (vs. 50% in controls). After 40h of cold preservation, liver transplant survival at day 1, 7 and 21 for the CoPP group was: 100%, 71% and 57%, respectively (vs. 50%, 50% and 33% in controls). This correlated with improved hepatic function/histologic (Suzuki) criteria of hepatocyte injury after HO-1 overexpression (immunohistology/Western blots) by infiltrating macrophages. This study documents the potential utility of HO-1-inducing agents in preventing ischemia/reperfusion injury resulting from prolonged storage of liver transplants.     

Overuse of Preoperative Staging of Patients Undergoing Neoadjuvant Chemotherapy for Breast Cancer

Annals of Surgical Oncology - Guidelines of the American Society of Clinical Oncology (ASCO), the National Comprehensive Cancer Network (NCCN), and the European Society for Medical Oncology (ESMO)...     

Surgical advances in liver transplantation. Living related and split donors

Surgical innovations to expand an exceedingly small cadaveric liver pool have paved the way for the more complex procedure of adult-to-adult living donation. Although reduced-size liver transplant (RSLT) has provided children and small adults with much needed small size grafts, discarding a part of the liver can no longer be justified in the current era of severe organ shortage. Split liver transplantation may eliminate the need for RSLT and may replace adult-to-adult pediatric donation except in urgent situations. Adult-to-adult living donation is a formidable undertaking that tremendously impacts adult recipients. Adult-to-adult living donation should be approached cautiously to ensure the safety of living donors. Expansion of adult living donation can only be achieved when ethical issues of donation are resolved and long-term donor safety is established.