Long-Wave Infrared Imaging for Intraoperative Cancer Detection-What is the True Temperature of a Cancer?

BACKGROUND: During cancer operations, the cancer itself is often hard to delineate-buried beneath healthy tissue and lacking discernable differences from the surrounding healthy organ. Long-wave infrared, or thermal, imaging poses a unique solution to this problem, allowing for the real-time label-free visualization of temperature deviations within the depth of tissues. The current study evaluated this technology for intraoperative cancer detection. METHODS: In this diagnostic study, patients with gastrointestinal, hepatobiliary, and renal cancers underwent long-wave infrared imaging of the malignancy during routine operations. RESULTS: It was found that 74% were clearly identifiable as hypothermic anomalies. The average temperature difference was 2.4°C (range 0.7 to 5.0) relative to the surrounding tissue. Cancers as deep as 3.3 cm from the surgical surface were visualized. Yet, 79% of the images had clinically relevant false positive signals [median 3 per image (range 0 to 10)] establishing an accuracy of 47%. Analysis suggests that the degree of temperature difference was primarily determined by features within the cancer and not peritumoral changes in the surrounding tissue. CONCLUSION: These findings provide important information on the unexpected hypothermal properties of intra-abdominal cancers, directions for future use of intraoperative long-wave infrared imaging, and new knowledge about the in vivo thermal energy expenditure of cancers and peritumoral tissue.

Laparoscopic narrow band imaging for detection of occult cancer metastases: a randomized feasibility trial.

BACKGROUND: Selection of cancer treatment fundamentally relies on staging of the underlying malignancy. The aim of this study was to evaluate the feasibility and effectiveness of laparoscopic narrow band imaging (NBI) for operative staging and detection of occult peritoneal cancer metastases. METHODS: A randomized, controlled feasibility trial with crossover design evaluating adult patients with gastrointestinal or gynecologic malignancies who have a clinical indication for diagnostic laparoscopy was conducted. Twenty-three patients were randomized to white-light followed by NBI laparoscopy (n = 11) or NBI followed by white-light laparoscopy (n = 12) using the Olympus Evis Exera II system. Three patients were excluded from analysis. RESULTS: In all 20 study patients, the abdominal cavity was sufficiently illuminated. An enhanced contrast of microvasculature and organ surface pattern was appreciated. Eight of the 20 patients (40%) were found to have metastases of the peritoneal surface. While NBI did not show any additional peritoneal lesions, 2 of the 63 suspicious-appearing nodules seen on white-light imaging were not visible on NBI (p = 0.50). The median diameter of all the nodules identified was 2 mm (range 1-50 mm) and was identical with each method. CONCLUSIONS: The information from this feasibility study demonstrated that NBI provides adequate illumination of the abdominal cavity and a unique contrast that enhances microvasculature and architectural surface pattern. The results suggest that NBI laparoscopy is not superior in detecting peritoneal metastases compared to standard white-light laparoscopy, but might provide a technology that could be applied for other abdominal pathologies.

Epoxyeicosanoids promote organ and tissue regeneration.

Epoxyeicosatrienoic acids (EETs), lipid mediators produced by cytochrome P450 epoxygenases, regulate inflammation, angiogenesis, and vascular tone. Despite pleiotropic effects on cells, the role of these epoxyeicosanoids in normal organ and tissue regeneration remains unknown. EETs are produced predominantly in the endothelium. Normal organ and tissue regeneration require an active paracrine role of the microvascular endothelium, which in turn depends on angiogenic growth factors. Thus, we hypothesize that endothelial cells stimulate organ and tissue regeneration via production of bioactive EETs. To determine whether endothelial-derived EETs affect physiologic tissue growth in vivo, we used genetic and pharmacological tools to manipulate endogenous EET levels. We show that endothelial-derived EETs play a critical role in accelerating tissue growth in vivo, including liver regeneration, kidney compensatory growth, lung compensatory growth, wound healing, corneal neovascularization, and retinal vascularization. Administration of synthetic EETs recapitulated these results, whereas lowering EET levels, either genetically or pharmacologically, delayed tissue regeneration, demonstrating that pharmacological modulation of EETs can affect normal organ and tissue growth. We also show that soluble epoxide hydrolase inhibitors, which elevate endogenous EET levels, promote liver and lung regeneration. Thus, our observations indicate a central role for EETs in organ and tissue regeneration and their contribution to tissue homeostasis.

From shadow to light: visualization of extrahepatic bile ducts using image-enhanced laparoscopy.

BACKGROUND: Correct recognition of the extrahepatic bile ducts is thought to be crucial to reduce the risk of bile duct injuries during various laparoscopic procedures. Image-enhanced laparoscopy techniques, utilizing various optical modalities other than white light, may help in detecting structures "hidden" underneath connective tissue. METHODS: A systematic literature search was conducted of studies describing image-enhanced laparoscopy techniques for visualization of the extrahepatic bile ducts. RESULTS: In all, 29 articles met inclusion criteria. They describe various techniques in the animal or human setting, including autofluorescence imaging, drug-enhanced fluorescence imaging, infrared thermography, and spectral imaging. This review describes these various techniques and their results. CONCLUSION: Image-enhanced laparoscopy techniques for real-time visualization of extrahepatic bile ducts are still in its infancy. Out of the techniques currently described, indocyanine green-enhanced near-infrared fluorescence laparoscopy has the most mature results, but other techniques also appear promising. It can be expected that in the future, image-enhanced laparoscopy might become a routine adjunct to any white-light laparoscopic operation near the hepatic hilum.

Evolution of anterior segment reconstruction after live donor adult liver transplantation: a single-center experience.

Controversy exists regarding the best method for venous outflow reconstruction after live donor liver transplantation using right lobe grafts. Some authors advocate routine inclusion of the middle hepatic vein with the graft, whereas others favor a more selective approach. In this report, we examine the evolution of our decision making and technique of selective anterior venous segment reconstruction during live donor adult liver transplantation performed in 226 recipients. We have developed a simplified back-bench procedure using sequential-composite anastomosis using various vascular conduits with syndactylization to the right hepatic vein creating a single large-outflow anastomosis in the recipient. Conduits used include iliac artery or vein allograft, recanalized umbilical vein, cryopreserved iliac artery allograft, and 6-mm synthetic expanded polytetrafluoroethylene vascular graft. This technique can be performed quickly, safely, and under cold storage conditions and results in excellent outcome while minimizing donor risk.

Combined en bloc liver-double kidney transplantation in an infant with IVC thrombosis.

We report a case of a pediatric en bloc liver-double kidney transplant in a patient with IVC thrombosis below the renal veins. The patient is an 11-month-old girl diagnosed with congenital nephrotic syndrome at two months of age. Multifocal liver masses were identified on routine ultrasound at eight months of age. Alpha fetoprotein level was 55 319. Biopsy confirmed hepatoblastoma. CT scan confirmed multiple lesions in both lobes, which would require liver transplantation for resection. She was also found to have thrombosis of her infrarenal IVC secondary to multiple central lines. She was listed for combined liver-kidney transplant and began chemotherapy. After four cycles of chemotherapy, she underwent bilateral nephrectomies followed by a combined en bloc liver-double kidney transplant from a size matched donor. In order to provide adequate venous outflow from the kidneys in the absence of a recipient infrarenal IVC, the donor liver and kidneys were procured en bloc with a common arterial inflow via the infrarenal aorta and common outflow via the suprahepatic IVC. Kidney transplantation in the absence of adequate recipient venous drainage may require unusual vascular reconstruction techniques. This case demonstrates a novel approach in patients who may require combined liver-kidney transplantation.

Patterns of recurrent hepatitis C after liver transplantation in a recent cohort of patients.

Clinicopathologic trends of recurrent hepatitis C after liver transplantation (LT) in hepatitis C (HCV) patients seem to have changed in recent years. Our aims were to define the current post-LT patterns of HCV recurrence and identify features of diagnostic and/or prognostic significance. Detailed analysis was performed on 92 HCV patients who underwent LT from June 1999 to December 2003 and survived early post-LT period. The study patients were grouped, as follows: no histologic recurrence (n = 31), "typical" recurrent HCV (n = 52), and post-LT autoimmune-like hepatitis ("AIH-like") (n = 9). The typical and AIH-like groups had mostly common features with post-LT progressive fibrosis (stage > or =2) more frequent in the latter. Based on post-LT progressive fibrosis (stage > or =2), the 2 post-LT hepatitis categories were regrouped as progressive (n = 24) and nonprogressive (n = 37). High viral counts, HCV genotype 1, and native liver inflammation grade 2 or higher with plasmacytic periseptitis were more frequent in progressive cases than nonprogressive or nonrecurrent cases. Sex mismatch of male recipient and female donor was more common in nonrecurrent group. Overall, death rate was comparable in all groups; however, post-LT HCV-related deaths were more common in progressive cases. In conclusion (1) two thirds (66.2%) of HCV patients developed histologic hepatitis after LT with either typical or AIH-like features; (2) progressive fibrosis was seen in 39.3% of patients with post-LT hepatitis and 26% of the entire study group and was more frequent in AIH-like cases; (3) inflammation grade 2 or higher with plasmacytic periseptitis in native livers may be a predictor of post-LT progressive fibrosis; and (4) male recipient/female donor combination was more common in nonrecurrent cases.

Distal splenorenal shunt: preferred treatment for recurrent variceal hemorrhage in the patient with well-compensated cirrhosis.

HYPOTHESIS: Distal splenorenal shunt (DSRS) is a safe and effective treatment for patients with Child-Pugh class A and B cirrhosis with recurrent variceal hemorrhage after failed transjugular intrahepatic portosystemic shunt. DESIGN: Retrospective case review. SETTING: Hepatobiliary surgery and liver transplantation department in a tertiary referral medical center. PATIENTS: Between August 1, 1985, and May 1, 2005, 119 patients with Child-Pugh class A and B cirrhosis underwent DSRS for recurrent variceal hemorrhage. Of these, 17 (14.3%) had thrombosed or failing transjugular intrahepatic portosystemic shunt prior to DSRS. INTERVENTION: Distal splenorenal shunt for recurrent variceal hemorrhage after failure of conservative management. MAIN OUTCOME MEASURES: Morbidity, mortality, and subsequent liver transplantation rate. RESULTS: The overall perioperative morbidity rate was 31.5%. Thirteen patients (11.7%) developed encephalopathy and 6 (5.4%) had recurrent variceal hemorrhage. Other complications included portal vein thrombosis, pancreatitis, pancreatic pseudocyst, pneumonia, and wound infection. The 30-day operative mortality rate was 6.4% (n = 7). The 1-year survival rate was 85.9%. The incidence of DSRS for failed transjugular intrahepatic portosystemic shunt during the first 12 years of the study (1985-1997) was 11.1% (9/81). This proportion increased to 26.7% (8/30) during the second half of the study (1997-2005). During the 20-year period, 15 patients (13.5%) underwent liver transplantation a mean of 5.1 years after DSRS without an increase in morbidity or mortality after transplantation. CONCLUSIONS: Distal splenorenal shunt may be the preferred treatment for recurrent variceal hemorrhage in the patient with well-compensated cirrhosis. In addition, DSRS does not cause increased morbidity or mortality in subsequent liver transplantation.

Isocitrate Dehydrogenase Mutations Confer Dasatinib Hypersensitivity and SRC Dependence in Intrahepatic Cholangiocarcinoma.

UNLABELLED: Intrahepatic cholangiocarcinoma (ICC) is an aggressive liver bile duct malignancy exhibiting frequent isocitrate dehydrogenase (IDH1/IDH2) mutations. Through a high-throughput drug screen of a large panel of cancer cell lines, including 17 biliary tract cancers, we found that IDH mutant (IDHm) ICC cells demonstrate a striking response to the multikinase inhibitor dasatinib, with the highest sensitivity among 682 solid tumor cell lines. Using unbiased proteomics to capture the activated kinome and CRISPR/Cas9-based genome editing to introduce dasatinib-resistant "gatekeeper" mutant kinases, we identified SRC as a critical dasatinib target in IDHm ICC. Importantly, dasatinib-treated IDHm xenografts exhibited pronounced apoptosis and tumor regression. Our results show that IDHm ICC cells have a unique dependency on SRC and suggest that dasatinib may have therapeutic benefit against IDHm ICC. Moreover, these proteomic and genome-editing strategies provide a systematic and broadly applicable approach to define targets of kinase inhibitors underlying drug responsiveness. SIGNIFICANCE: IDH mutations define a distinct subtype of ICC, a malignancy that is largely refractory to current therapies. Our work demonstrates that IDHm ICC cells are hypersensitive to dasatinib and critically dependent on SRC activity for survival and proliferation, pointing to new therapeutic strategies against these cancers. Cancer Discov; 6(7); 727-39. ©2016 AACR.This article is highlighted in the In This Issue feature, p. 681.

Twenty-year experience with liver transplantation for hepatocellular carcinoma.

HYPOTHESIS: Liver transplantation (LT) has become the optimal treatment for stages I and II hepatocellular carcinoma (HCC). Based on our 20-year experience, changes in staging, techniques, and patient selection have improved survival over the past 20 years. Herein, we determine if pre-LT treatment for HCC alters the long-term outcomes in patients with HCC. DESIGN: Outcomes study. SETTING: Tertiary referral center. PATIENTS: We retrospectively reviewed prospectively collected data in a cohort of 92 patients who underwent LT for HCC between 1983 and 2003. MAIN OUTCOME MEASURES: Patient demographics, tumor stage in the explant liver, patient survival, and tumor recurrence data were analyzed. RESULTS: The average follow-up was 1052 (range, 0-6491) days. The average tumor size was 3.6 cm; 40% of tumors were multifocal and 60% unifocal. Of the 92 patients, 26% were classified as stage I; 42%, stage II; 24%, stage III; and 8%, stage IV. The overall 5-year survival rate was 50%, the 10-year survival rate was 32%, and the 15-year survival rate was 27%. Improvements in staging in the last 5 years reduced the number of patients with stages III and IV HCC from 39% to 19% and increased the 5-year survival rate to 69%. Tumor recurrence was relatively rare (13%); however, recurrence resulted in a poor prognosis (75% mortality rate; P = .02). The average time to recurrence was 458 (range, 179-1195) days. CONCLUSIONS: Liver transplantation for HCC results in excellent long-term survival for patients with stages I and II HCC, with relatively few patients dying from tumor recurrence. Improvements in preoperative staging have resulted in increased 5-year survival rates. Further refinements in pre-LT staging may increase the effectiveness of LT for HCC.

Liver regeneration and surgical outcome in donors of right-lobe liver grafts.

INTRODUCTION: Previous studies of healthy live-liver donors have suggested that complete liver regeneration occurs within a matter of weeks; however, there have been no long-term studies evaluating liver regeneration and few studies documenting long-term donor outcome. MATERIALS AND METHODS: Fifty-one donors who provided right-lobe grafts underwent volumetric spiral computed tomography scans preoperatively and postoperatively at time intervals of 1 week and 1, 3, 6, and 12 months. Patient demographics, surgical data, and postoperative outcome were correlated with liver regeneration data. Donor surgical outcome was followed prospectively and recorded in a comprehensive database. RESULTS: Thirty-three males and 18 females (mean age 36.0+/-9.6 years) provided 51 right-lobe grafts. Mean follow-up was 9.8+/-3.4 months. No donor operation was aborted, and surgical morbidity and mortality rates were 39% and 0%, respectively. Donor remnant liver volume was 49.4+/-5.7% of the original total liver volume (TLV). Overall liver regeneration was 83.3+/-9.0% of the TLV by 1 year. Female donors had significantly slower liver regrowth when compared with males at 12 months (79.8+/-9.3% vs. 85.6+/-8.2%, P<0.01). There was no effect of age, body mass index, operative time, estimated blood loss, postoperative complications, or perioperative liver function tests on liver regeneration. DISCUSSION: Liver regeneration continues throughout the first postoperative year. Only one donor achieved complete liver regeneration during this time period; however, all donors have maintained normal liver function without long-term complications. Longer follow-up is needed to determine whether donors ever achieve original TLV.

Centrilobular histopathologic changes in liver transplant biopsies.

We evaluated centrilobular histologic changes seen on post-orthotopic liver transplantation (OLT) biopsies to refine the pathologic diagnosis by systematic study of morphologic and clinical data with possible identification of prognostic criteria. A total of 110 biopsies with zone 3 pathology from 59 patients were reviewed and correlated with clinical findings. Within the first 6 months post-OLT (group I), 39 of 47 patients had combinations of centrilobular hepatocytic dropout, ballooning, and cholestasis on single or multiple biopsies attributed to perioperative ischemic/perfusion injury; 12 of 39 patients with all 3 features present had increased incidence of biliary complications and sepsis and decreased 1-year patient and graft survival; 17 of 39 patients with 2 of the 3 features had increased biliary complications but not decreased 1-year survival; and the remaining 8 of 47 patients had central venulitis associated with acute cellular rejection. After 6 months post-OLT (group II), 14 patients, including 2 from group I, had biopsies with centrilobular pathology; 8 of 14 had central venulitis related to rejection (acute, 4; chronic, 4), and fibrosis was seen in 8 (rejection, 6; cardiac problems, 2). In conclusion, combinations of centrilobular hepatocytic ballooning, dropout, and cholestasis are seen in association with reversible or irreversible ischemic/perfusion damage in the early post-OLT period. The presence of all 3 features is associated with a poor outcome. Central venulitis as a feature of acute/chronic rejection is seen at any time post-OLT and is not a predictor of poor graft/patient survival.

Liver transplantation for primary sclerosing cholangitis: a long-term clinicopathologic study.

The course and outcome of patients after liver transplantation (LT) for primary sclerosing cholangitis (PSC) are still debated. Our purpose is to define retrospectively, the post-LT clinicopathologic findings seen in 51 PSC patients with a follow-up of 2 to 14 years. Of the total 51 patients, 16 with native liver hilar xanthogranulomatous cholangiopathy (XGC) had median graft and patient survival of 573 and 835 days, respectively compared with 2489 and 2794 days, respectively, in 35 patients without XGC. Perioperative complications resulted in 9 early deaths (day 0 to 52). Of the remaining 42 patients, 6 had recurrent PSC (R-PSC) with typical histologic and cholangiographic findings, 12 had autoimmune liver disease-not otherwise specified with histology of autoimmune hepatitis/overlap syndrome, 3 had chronic rejection, 4 had ischemic cholangiopathy, and 17 had no recurrence. The presence of inflammatory bowel disease, total ischemia time of > or =11 hours, recipient-donor ABO and HLA Class I and II matches, and the type of immunosuppression did not affect the post-LT outcome. Recipient-donor gender mismatch was more common in R-PSC than in the nonrecurrent group (P=0.045). Post-LT malignancies were significantly more common in the nonrecurrent cases compared with all others combined (P=0.031) and caused deaths in 4. The majority of deaths (11/13) in other groups were due to sepsis complicating graft dysfunction. In conclusion, allograft autoimmune liver disease was seen in 18 (43%) of 42 long-term post-LT PSC patients, with progression in 5 of 18 patients. Features of PSC were seen in 6 (33%) of 18. Native liver XGC negatively impacted post-LT graft and patient survival. Increased incidence of malignancies in the nonrecurrent group may reflect overimmunosuppression in those patients.

Severe steatosis as the initial histologic manifestation of recurrent hepatitis C genotype 3.

Steatosis is a common finding that is seen in patients with both chronic hepatitis C and alcoholic liver disease; however, the extent of involvement in the former is generally minimal to mild. We present 2 patients who underwent live donor liver transplantation for end-stage liver disease that was caused by chronic hepatitis C (genotype 3) and alcohol abuse. Both patients presented with liver allograft dysfunction, with liver biopsy findings of moderate to marked steatosis. Exclusion of a relapse of alcohol use required intense questioning of both the patients and their families. A definitive diagnosis of recurrent hepatitis C was established by viral markers with institution of the proper therapy and resolution of graft dysfunction. We conclude that recurrent hepatitis C, particularly genotype 3, may present with severe steatosis. Recognition of this phenomenon is important, and confirmation with viral markers is necessary to provide optimal patient care.

Cryptogenic cirrhosis: clinicopathologic findings at and after liver transplantation.

The incidence of cryptogenic cirrhosis (CC) has decreased since the discovery of hepatitis C virus (HCV), still the etiology in 5% of cases with cirrhosis remains unresolved. Our aims were to define the clinicopathologic features of CC at liver transplantation (LT), evaluate the post-LT course with outcome and define the possible pathogenetic mechanisms. 27/534 LT recipients (5%) over a period of 16.5 years were entered in the LT database as cases of CC. A detailed analysis of pre- and post-LT clinical and all liver pathology specimens was performed. Based on clinicopathologic findings, a more definite diagnosis was possible in 23 of 27 (85%): Nonalcoholic steatohepatitis (NASH) in 9 (33%), autoimmune liver disease (AILD) in 6 (22%), alcoholic liver disease in 4, secondary biliary cirrhosis in 2 and 1 each of hepatitis C and portal venopathy. 4/27 cases remained unresolved. In the NASH group, native livers had focal steatosis, Mallory's hyalin, glycogenated hepatocytic nuclei, high-grade inflammation, and 3+ bile duct proliferation. Large cell dysplasia was more common in this group compared to other patients. Two patients had recurrence of NASH after LT. In AILD group native livers had little or no bile duct proliferation. Two patients had recurrence in AILD group. Of 27 patients 19 are alive (70%) with a follow-up of 407-3647 days. Based on the study results, the following conclusions were reached: (1) CC results from varying etiologies, which can be defined by a careful clinicopathologic analysis in a majority (85%) of cases; (2) Nonalcoholic steatohepatitis (33%) and AILD (22%) are the common underlying causes of CC; and (3) Post-LT outcome for CC is disease dependent with, recurrent disease seen in both nonalcoholic steatohepatitis (22%) and autoimmune liver disease (33%).

Excellent outcome following transplantation of a domino donor liver with high-grade macrosteatosis.

Severe macrosteatosis in the donor liver is considered a major predictive factor of primary graft non-function. Such livers are usually discarded despite an ever-growing need for donor livers. We report our recent experience in a patient (#1) who had an excellent outcome following liver transplantation (LT) of a 65-70% macrosteatotic graft and compare his findings with those of two other (#2 and #3) recipients of moderate to severe macrosteatotic grafts. Both patients (#2 and #3) had initial diminished function, with recovery in patient #2 but delayed graft non-function requiring re-LT (day 24) in patient #3. Patient #1 had no intra-operative complications, while patient #2 had mild complications due to prior adhesions and graft capsular laceration. In patient #3, extensive intra-abdominal adhesions resulting in excessive bleeding occurred during recipient hepatectomy. Total ischemic times: 2.48, 6.10, and 8.18 h; total blood product usage: 43, 81, and 223 units; post-LT hospital stay: 9, 21, and 69 days were seen in patients #1, #2 and #3, respectively. In conclusion, post-LT excellent graft function was seen in one recipient of 65-70% macrosteatotic graft. Transplantation of grafts with moderate/severe macrosteatosis may be inadvisable in patients with extensive intra-abdominal adhesions with expectant excessive bleeding and long ischemia times.

Pathologic analysis of right-lobe graft failure in adult-to-adult live donor liver transplantation.

Live donor adult liver transplantation (LDALT) utilizing right-lobe grafts is now acceptable as an alternative to cadaveric orthotopic liver transplantation (OLT). However, some LDALTs fail and require urgent OLT or result in recipient death. Our aim was to determine the basis of LDALT failure. Liver specimens from 49 LDALT recipients were evaluated and the findings correlated with clinical outcome. Ten patients (20.4%) had either early (< or = 1 month) or late (> 1 month) graft failure. Eight early failures, 7 of which occurred among our first 25 cases, were due to extensive liver parenchymal necrosis as a result of hepatic artery thrombosis (n=3), portal vein thrombosis (n=1), hyperperfusion syndrome (n=1), complete graft thrombosis (n=1) with Factor V Leiden on a regimen of therapeutic heparin (n=1), sepsis and concomitant graft dysfunction with venous outflow tract injury (n=1), and venous outflow tract thrombosis and parenchymal thermal injury with sepsis (n=1). Preoperative, intraoperative, or postoperative severe vessel wall injury was evident in 6/8 early failures. Two patients had late graft failure, 1 from recurrent hepatitis C and 1 with sepsis/multisystem organ failure. There were no significant differences in graft size, rejection episodes, or operative or ischemic times between patients with and without graft failure. In conclusion, LDALT failed in 10/49 (20%) of our patients, with 8/10 occurring within 1 month post-LDALT owing to vascular/thrombotic complications experienced during the early phase of our institutional experience. Perioperative vessel wall injury appeared to be a major factor in predicting early graft loss.

Liver transplantation for alcoholic liver disease with or without hepatitis C.

Alcoholic cirrhosis with or without hepatitis C is a common indication for liver transplantation (LT). Comparative post-LT data for the 2 groups are not available. Our aim is to compare the clinicopathologic features of patients with alcoholic liver disease (ETOH) and ETOH/HCV at the time of and after LT and to determine the impact of concomitant hepatitis C virus (HCV) on ETOH patients undergoing LT. A comparative clinical and pathologic analysis at LT and after LT was performed for 56 patients with ETOH and 32 patients with ETOH/HCV. All 88 had cirrhosis at LT. Other native liver features for ETOH and ETOH/HCV, respectively, were: >2+ inflammation 50/56 and 26/32, Mallory's hyalin 12/56 and 6/32, steatosis 9/56 and 7/32, large cell dysplasia 12/56 and 6/32, hepatoma 4/56 and 4/32, iron deposition 24/56 and 12/32; none was statistically significant. The post-LT findings for ETOH and ETOH/HCV were as follows: 1-year survival 93% and 97%; alive 36/56 (419-4,348 days) and 27/32 (488-5,516 days); deaths 20/56 and 5/32; ETOH recurrence 5/56 (all alive) and 3/32 (1 dead); post-LT HCV 4/56 (acquired) and 22/32 (recurrent). Native liver histology in ETOH and ETOH/HCV patients was similar. Post-LT HCV recurrence was common (69%) in ETOH/HCV patients but resulted in death in only 6%. Post-LT ETOH recurrence was uncommon (9%) and progression to liver failure was rare (1.1%). Post-LT outcome for ETOH was excellent, and concomitant HCV did not affect survival.

Staging laparoscopy in pancreatic cancer: a potential role for advanced laparoscopic techniques.

BACKGROUND: The role of staging laparoscopy in pancreatic cancer in the age of high-resolution CT scans is under debate. This study's aim is to evaluate the efficacy of staging laparoscopy in this disease. STUDY DESIGN: A retrospective cohort study was conducted evaluating patients who underwent operative treatment for radiographic stage I to III pancreatic cancer between July 2003 and October 2012. Radiographic follow-up was 94% at 6 months. RESULTS: Of 274 patients who met inclusion criteria, 136 underwent staging laparoscopy, which identified radiographic occult distant metastases in 2% (3 of 136). However, subsequent laparotomy identified an additional 9% (12 of 136) harboring distant metastases in regions not visualized on standard staging laparoscopy; specifically, the posterior liver surface, paraduodenal retroperitoneum, proximal jejunal mesentery, and lesser sac. The remaining 138 patients underwent initial staging laparotomy, which showed similar results identifying radiographic occult distant disease in 11% (15 of 138). Within 6 months after the operation, peritoneal or subcapsular liver metastases developed in an additional 6% (15 of 257)-disease that potentially could have been diagnosed at the time of operation-providing a false-negative rate of 88% for staging laparoscopy compared with 36% for staging laparotomy. CONCLUSIONS: Despite the availability of high-resolution CT scans, occult distant metastases can still be found in 11% of patients during the operation. In the absence of reliable risk factors to predict distant metastases, staging laparoscopy should be offered to all patients with radiographic localized disease. However, the results favor extended laparoscopic staging with evaluation of the posterior liver surface, mobilization of the duodenum, evaluation of the proximal jejunal mesentery, and visualization of the lesser sac.

Safety of minimal immunosuppression in liver transplantation for hepatoblastoma.

BACKGROUND: Despite aggressive chemotherapy, recurrence of disease remains the leading cause of death after liver transplantation (LTx) for hepatoblastoma (HB). Unfortunately, little is known about the effects of immunosuppression on recurrence and posttransplant outcomes. We hypothesized that minimal immunosuppression can be safely used in these recipients. METHODS: In 2004, we adopted a minimal immunosuppression regimen using daclizumab induction and tacrolimus monotherapy. Kaplan-Meier survival curves were generated. RESULTS: From 2004 to 2006, 6 children underwent primary LTx for HB with neoadjuvant and adjuvant chemotherapy. Patient survival was 100% at 12 months and at 24 months, without graft loss. One patient died 28 months after transplantation. Recurrence-free survival was 83% at 12 months and at 24 months. Despite minimal immunosuppression (IS), 4 of 6 HB recipients remained rejection-free. When compared to other LTx recipients receiving minimal IS, HB recipients trended to have better rejection-free survival (HB, 83% at 12 months and 62.5% at 24 months vs all others, 36% and 36%, respectively; P = .19). CONCLUSION: Our short-term patient and graft survival rates are comparable to those reported for all HB recipients in the United Network for Organ Sharing database. Although not statistically significant, our rejection-free survival data suggest that HB recipients may be less likely to reject than other recipients.