bluuebunny/crossref_metadata_2025 huggingface dataset:
Canine trachealis muscle shortening and cartilage mechanics
Authors: Robinson P. J. , Schellenberg R. R. , Wakai Y. , Road J. , Paré P. D.
Published: February 2004

Canine trachealis muscle will shorten by 70% of resting length when maximally stimulated in vitro. In contrast, trachealis muscle will shorten by only 30–40% when stimulated in vivo. To examine the possibility that an elastic load applied by the tracheal cartilage contributes to the in vivo limitation of shortening, single pairs of sonomicrometry crystals were inserted into the trachealis muscle at the level of the fifth cartilage ring in five dogs. The segment containing the crystals was then excised and mounted on a tension-testing apparatus. Points on the active length-tension curve and the passive length-tension relation of the cartilage only were determined. The preload applied to the muscle before contraction varied from 10 to 40 g (mean 21 ± 4 g). The afterload applied by the cartilage during trachealis contraction ranged from 13 to 56 g (30 ± 6 g). The calculated elastic afterloads were substantial and appeared to be sufficient to explain the degree of shortening observed in four of the seven rings; in the remaining three rings, the limitation of shortening was greater than would be expected from the elastic load provided by the cartilage. Additional sources of loading and/or additional mechanisms may contribute to limited in situ shortening. In summary, tracheal cartilage applies a preload and an elastic afterload to the trachealis that are substantial and contribute to the limitation of trachealis muscle shortening in vivo.
Covalent and Noncovalent Modification of Thin Filament Action
Authors: Metzger Joseph M. , Westfall Margaret V.
Published: February 2004

Troponin is essential for the regulation of cardiac contraction. Troponin is a sarcomeric molecular switch, directly regulating the contractile event in concert with intracellular calcium signals. Troponin isoform switching, missense mutations, proteolytic cleavage, and posttranslational modifications are known to directly affect sarcomeric regulation. This review focuses on physiologically relevant covalent and noncovalent modifications in troponin as part of a thematic series on cardiac thin filament function in health and disease.
Belief, Affect, and Attitude: Alternative Models of the Determinants of Attitude
Authors: Onur Bodur H. , Brinberg David , Coupey Eloïse
Published: February 2004

A recent debate in theJournal of Consumer Psychologyillustrates many of the unresolved issues concerning the development and application of models to predict attitude. A central issue in the debate is whether a noncognitive factor, such as affect, may exert a direct influence on attitude, or whether its influence is mediated by the cognitive structure. We describe the results of two studies designed to determine (a) whether affect and attitude are separate constructs and (b) whether affect influences attitude independently of cognitive structure. The studies address the methodological criticisms levied against previous research and provide results to indicate that affect does influence attitudes directly and independently of cognitive structure.
Perceived Retail Crowding and Shopping Satisfaction: What Modifies This Relationship?
Authors: Machleit Karen A. , Eroglu Sevgin A. , Mantel Susan Powell
Published: February 2004

Research has shown that an increase in perceived crowding in a retail store (created from either human or spatial density) can decrease the level of satisfaction that shoppers have with the store. The three studies reported here examine the retail crowding‐satisfaction relationship to determine the extent to which it is a simple, direct relationship. Specifically, we consider the possibility that the crowding–satisfaction relationship is mediated by emotional reactions that are experienced while shopping. In addition, moderating variables such as prior expectations of crowding, tolerance for crowding, and store type are examined for their influence on the crowding–satisfaction relationship. The results of two field studies indicate that whereas emotions only partially mediate the relationship, the decrease in shopping satisfaction due to crowding is moderated by expectations of crowding and personal tolerance for crowding. A laboratory experiment replicated the field studies and shows, in addition, that although ceiling and floor effects may be present, the relationship between perceived crowding and shopping satisfaction appears to vary by store type.
Dialectical Thinking in Consumer Decision Making
Authors: Kahle Lynn R. , Liu Raymond R. , Rose Gregory M. , Kim Woo‐Sung
Published: February 2004

In this article, we examine the four processes of dialectical thinking: interconnection, development and change, transformation of quantitative into qualitative, and unity and struggle of opposites. We argue that the decisions of some consumers reflect dialectical thinking, at least some of the time.
Chiral synthesis of (2S,3S)‐2‐(2‐morpholin‐2‐yl‐2‐phenylmethoxy)phenol
Authors: Prabhakaran Jaya , Majo Vattoly J. , Mann J. John , Dileep Kumar J. S.
Published: February 2004

Resolution of (2RS,3RS)‐2‐[α‐(2‐methoxymethoxyphenoxy)phenylmethyl]morpholine, 11, with (+) mandelic acid led to the formation of (+)‐(2S,3S)‐2‐[α‐(2‐methoxymethoxyphenoxy)phenyl methyl] morpholine (11a). Compound 11 was synthesized in seven steps from (2RS,3RS)‐cinnamyl alcohol‐2,3‐epoxide (4), with an overall yield of 17%. Cleavage of the methoxymethyl group of the Fmoc derivative 12 with catalytic amounts of p‐toluenesulfonic acid in methanol afforded (+)‐(2S,3S)‐2‐(2‐morpholin‐2‐yl‐2‐phenylmethoxy)phenol 2. The synthetic utility as well as the configuration of compound 2 has been demonstrated by converting (S,S)‐2‐(2‐morpholin‐2‐yl‐2‐phenylmethoxy)phenol 2 to (2S,3S)‐2‐[α‐(2‐ethoxyphenoxy)phenylmethyl]morpholine (1) and (2S,3S)‐2‐(2‐methoxyphenoxy) benzyl)morpholine (16), two potential norepinephrine reuptake inhibitors under clinical evaluation. Chirality 16:168–173, 2004. © 2004 Wiley‐Liss, Inc.
Evaluation of Breast Imaging Reporting and Data System Category 3 mammograms and the use of stereotactic vacuum‐assisted breast biopsy in a nonacademic community practice
Authors: Mendez Angela , Cabanillas Fernando , Echenique Miguel , Malekshamran Keyvan , Perez Iris , Ramos Edwin
Published: February 2004

BACKGROUND

Breast Imaging Reporting and Data System (BI‐RADS) Category 3 represents ‘probably benign’ mammographic abnormalities requiring close follow‐up, but biopsies sometimes are performed on Category 3 abnormalities. Controversy exists as to when these biopsies are justified. The goals of the current study were to evaluate the use of stereotactic vacuum‐assisted breast biopsy (SVABB) for BI‐RADS 3 lesions in a nonacademic community hospital–based practice, to evaluate the false‐ negative rate of Category 3 mammograms, and to determine whether any specific lesions misinterpreted as BI‐RADS 3 abnormalities might commonly be associated with malignant disease.

METHODS

From August 2000 to December 2002, the authors performed 947 SVABB procedures on 911 patients. They focused on 156 SVABBs of BI‐RADS 3 abnormalities.

RESULTS

Of 634 SVABB procedures requested by outside sources, 114 (18%) were performed for BI‐RADS 3 abnormalities, compared with 42 (13%) of 313 SVABB procedures that were performed based on mammographic findings at the authors' practice (P = 0.075). After SVABB, 7 of 156 patients with BI‐RADS 3 lesions were diagnosed with breast carcinoma and 1 was diagnosed with atypical ductal hyperplasia. Therefore, the false‐negative rate of BI‐RADS 3 mammograms was 4.5% (i.e., 7 of 156 patients). Patients with linear microcalcifications had the highest rate of cancer (4 of 14 [29%]) compared with patients without microcalcifications (1 of 64 [1.5%]) and patients with nonlinear microcalcifications (2 of 69 [2.9%]).

CONCLUSIONS

The use of SVABB for BI‐RADS 3 lesions reflected uncertainty regarding the potential for a diagnosis of malignant disease rather than the financial incentive of performing a biopsy. SVABB was not necessary for patients with BI‐RADS 3 lesions without microcalcifications or for patients with nonlinear microcalcifications. Lesions with linear (casting or branching) microcalcifications should not be considered BI‐RADS 3 abnormalities. Cancer 2004;100:710–4. © 2004 American Cancer Society.
Learning and knowledge processes in inter‐organizational communities of practice
Authors: Soekijad Maura , Huis in 't Veld Mirjam A. A. , Enserink Bert
Published: February 2004

Communities of practice (CoPs) have increasingly become popular in recent years, in particular within large multinational organizations. They are defined as learning groups in which new insights can be transformed into knowledge through mutual engagement around a joint enterprise (Wenger, 1998: 214). Close interaction of experience and competence is seen as the central prerequisite for leading‐edge learning and innovative practices in CoPs. In particular, learning in the context of a concrete practice that is shared by all members of the CoP, is central to the concept.

In this empirically based paper it is argued that, contrary to expectations, this model can be deployed successfully. Authors observed CoPs in which inter‐organizational multidisciplinary groups voluntarily engaged in analysing and solving real‐life problems. These problems all concerned design and management of innovative and sustainable industrial and commercial zones. The inter‐organizational CoP presented in this paper, proved to be a fruitful environment for generating innovative ideas and practices. The joint enterprise in this community was the generator of momentum and the catalyst of community development. Copyright © 2004 John Wiley & Sons, Ltd.
Technique for expanding the donor liver pool: Heat shock preconditioning in a rat fatty liver model
Authors: Mokuno Yasuji , Berthiaume François , Tompkins Ronald G. , Balis Ulysses J. , Yarmush Martin L.
Published: January 2004

Fatty liver is a common predisposing risk factor for postoperative liver failure and accounts for most discarded livers during triage of donors. We investigated the effect of heat shock preconditioning (HPc) on recipient survival in a rat fatty liver transplantation model. Fatty liver donor rats were exposed to brief whole-body hyperthermia (10 minutes at 42.5°C) and allowed to recover. HPc induced heat shock proteins (HSPs) (HSP72, HSP90, and heme oxygenase [HO]-1) in donor livers, with levels peaking 12 to 48 hours after HPc. Subsequently, donor livers were harvested 24 hours after HPc, placed in cold storage for 10 hours, and transplanted into normal rats. At 3 hours posttransplantation, HPc reduced serum liver enzymes in the recipients and almost completely suppressed the release of tumor necrosis factor (TNF)-α and interleukin (IL)-10. Histologic evaluation 3 and 24 hours after transplantation showed that HPc significantly reduced hepatic inflammation and hepatocellular necrosis without affecting the steatotic appearance of hepatocytes. One week after transplantation, control non-heat-shocked and heat-shocked fatty liver recipients exhibited survival rates of less than 10% and more than 80%, respectively. The evaluation of the survival of recipients receiving fatty livers at different times after HPc showed that the protective effect of HPc was significant when donor livers were transplanted 3 to 48 hours after HPc, with the maximum effect seen 6 to 48 hours after HPc. In conclusion, HPc is a promising avenue to salvage rejected donor fatty livers and enhance the survival rate of fatty liver recipients. We estimate that this technique could increase the annual donor pool by 600 livers. (Liver Transpl 2004;10:264-272.)
Hepatopulmonary syndrome and portopulmonary hypertension: A report of the multicenter liver transplant database
Authors: Krowka Michael J. , Mandell Susan M. , Ramsay Michael A.E. , Kawut Steve M. , Fallon Michael B. , Manzarbeitia Cosme , Pardo Manuel , Marotta Paul , Uemoto Shinji , Stoffel Markus P. , Benson Joanne T.
Published: January 2004

Hepatopulmonary syndrome (HPS) and portopulmonary hypertension (PortoPH) are pulmonary vascular consequences of advanced liver disease associated with significant mortality after orthotopic liver transplantation (OLT). Data from 10 liver transplant centers were collected from 1996 to 2001 that characterized the outcome of patients with either HPS (n = 40) or PortoPH (n = 66) referred for OLT. Key variables (PaO2 for HPS, mean pulmonary artery pressure [MPAP], pulmonary vascular resistance [PVR], and cardiac output [CO] for PortoPH) were analyzed with respect to 3 definitive outcomes (those denied OLT, transplant hospitalization survivors, and transplant hospitalization nonsurvivors). OLT was denied in 8 of 40 patients (20%) with HPS and 30 of 66 patients (45%) with PortoPH. Patients with HPS who were denied OLT had significantly worse PaO2 compared with patients who underwent transplantation (47 vs. 52 mm Hg, P < .005). Transplant hospitalization survival was associated with higher pre-OLT PaO2 (55 vs. 37 mm Hg; P < .005). MPAP was significantly higher (53 vs. 45 mm Hg; P < .015) and PVR was significantly worse (614 vs. 335 dynes · s · cm−5; P < .05) in patients with PortoPH who were denied OLT compared with patients who underwent transplantation. Transplant hospitalization mortality was 16% (5/32) in patients with HPS and 36% (13/36) in patients with PortoPH. All of the deaths in patients with PortoPH occurred within 18 days of OLT; 5 of the 13 deaths in patients with PortoPH occurred intraoperatively. We concluded that patients with HPS (based on a combination of low PaO2 and nonpulmonary factors) and patients with PortoPH (based on pulmonary hemodynamics) were frequently denied OLT because of pre-OLT test results and comorbidities. For patients who subsequently underwent OLT, transplant hospitalization mortality remained significant for both those with HPS (16%) and PortoPH (36%). (Liver Transpl 2004;182:10.)
Estimation of glomerular filtration rates before and after orthotopic liver transplantation: Evaluation of current equations
Authors: Gonwa Thomas A. , Jennings Linda , Mai Martin L. , Stark Paul C. , Levey Andrew S. , Klintmalm Goran B.
Published: January 2004

The ability to estimate rather than measure the glomerular filtration rate (GFR) in patients before and after liver transplantation would be helpful in estimating risk, dosing drugs, and assessing long-term toxicity of calcineurin inhibitors. Currently available equations for estimating the GFR have not been validated in either the pre- or post-liver transplant population. We have evaluated the performance of currently used formulas for the estimation of the GFR in this setting. Data were collected prospectively on patients who underwent liver transplantation between 1984 and 2001. GFR per 1.73 m2 was measured by I125 iothalamate in patients at the pretransplant evaluation and at 3 months, 1 year, and yearly posttransplant thereafter. GFR estimated by the Cockcroft-Gault equation, the Nankivell equation, and the equations from the Modification of Diet in Renal Disease (MDRD) Study (6, 5, and 4 variables) was compared with the measured GFR. Pretransplant GFR was available in 1,447 patients. The mean GFR was 90.7 ± 40.5 mL/min. Values for r and r2 were highest for the MDRD Study 6-variable equation (0.70 and 0.49, respectively). Only 66% of estimates were within 30% of the measured GFR. At 3 months, 1 year, and 5 years posttransplant, the mean GFR was 59.5 ± 27.1 mL/min, 62.7 ± 27.8 mL/min, and 55.3 ± 26.1 mL/min, respectively. Values for r and r2 for the MDRD Study 6-variable equations at 1 and 5 years posttransplant were 0.74 (0.55) and 0.76 (0.58), respectively. At these time points, however, only 67% and 64% of the estimated GFR were within 30% of the measured GFR. MDRD Study equations had greater precision than other equations, but the precision was lower than reported for MDRD estimation of GFR in other populations. Better methods for estimating the GFR are required for evaluation of renal function before and after liver transplantation. (Liver Transpl 2004;10:301-309.)
Post-liver-transplant anemia: Etiology and management
Authors: Maheshwari Anurag , Mishra Rajnish , Thuluvath Paul J.
Published: January 2004

Anemia is common after liver transplantation, with the incidence ranging from 4.3% to 28.2% depending on the criteria used to define anemia. The cause of anemia is unidentified in the majority of patients, and it is likely to be multifactorial. Immunosuppressive-medication-induced bone marrow suppression is perhaps the most common cause of unexplained anemia. Chronic blood loss, iron deficiency, hemolysis, and renal insufficiency are other potential causes of chronic anemia. Rare causes, somewhat unique to transplantation, include aplastic anemia, graft-versus-host disease (GVHD), and lymphoproliferative disease. Anemia due to immunosuppressive medication is challenging, since almost all drugs currently used for this purpose cause anemia, but the renal-sparing property of sirolimus may benefit the subgroup in which renal insufficiency is contributing to anemia. Aplastic anemia is seen in young patients transplanted for non-A, non-B, non-C, fulminant hepatic failure. It is thought to be immunologically mediated, secondary to an unknown viral infection, and is associated with a grave prognosis. GVHD is another infrequent (approximately 1% of transplant recipients) but serious cause of severe anemia that carries a dismal prognosis. Lymphoproliferative disorder, too may rarely rare cause anemia and it may respond to reduction of immunosuppression. Recipients of solid-organ transplants do not mount a significant increase in erythropoietin in response to anemia. In conclusion, though there are no data on the response of anemia to erythropoietin in liver transplant recipients, it appears to benefit other solid-organ-transplant recipients with anemia. (Liver Transpl 2004;10:165-173.)
Obesity and diabetes as a risk factor for hepatocellular carcinoma
Authors: Regimbeau Jean M. , Colombat Magali , Mognol Philippe , Durand François , Abdalla Eddie , Degott Claude , Degos Françoise , Farges Olivier , Belghiti Jacques
Published: January 2004

Ten percent of patients who undergo resection for hepatocellular carcinoma (HCC) associated with chronic liver disease have no detectable cause for this underlying liver disease. Recent studies have shown that patients with cryptogenic chronic liver disease frequently have risk factors for nonalcoholic fatty liver disease (NAFLD). This study examines the incidence of risk factors for NAFLD in patients with chronic liver disease who underwent resection for HCC. Among 210 patients with chronic liver disease who underwent resection for HCC, 18 (8.6%) had no identifiable cause for the underlying liver disease. These patients were assessed for obesity, diabetes mellitus, and histological features of the tumor and the adjacent liver parenchyma. Comparisons were made with matched patients with alcohol- and chronic-viral-hepatitis-related HCC. The prevalence of obesity (50% vs. 17% vs. 14%), diabetes (56% vs. 17% vs. 11%), aspartate aminotransferase / alanine aminotransferase ratio < 1 (50% vs. 19% vs. 17%), and steatosis > 20% (61% vs. 17% vs. 19%) was significantly higher in patients with cryptogenic liver disease than in patients with alcohol abuse and chronic viral hepatitis (P < 0.0001 for each). Well-differentiated tumors were significantly more common in patients with cryptogenic liver disease (89% vs. 64% in patients with alcohol-related HCC vs. 55% in patients with chronic viral hepatitis-related HCC, P < 0.0001).

In conclusion, the hypothesis that obesity and diabetes mellitus may be important risk factors for cryptogenic chronic liver disease in patients with HCC is supported by the analysis of surgically treated patients. Whether HCC is primarily related to obesity and diabetes mellitus or secondarily to a NAFLD-like parenchymal lesions remains to be clarified. (Liver Transpl 2004;10:S69-S73.)
The Barcelona approach: Diagnosis, staging, and treatment of hepatocellular carcinoma
Authors: Llovet Josep M. , Fuster Josep , Bruix Jordi
Published: January 2004

Hepatocellular carcinoma (HCC) is the fifth most common neoplasm in the world, and the third most common cause of cancer-related death. It affects mainly patients with cirrhosis of any etiology. Patients with cirrhosis are thus usually included in surveillance plans aiming to achieve early detection and effective treatment. Only patients who would be treated if diagnosed with HCC should undergo surveillance, which is based on ultrasonography and α-fetoprotein every 6 months. Upon diagnosis, the patients have to be staged to define tumor extent and liver function impairment. Thereafter, the best treatment option can be indicated and a prognosis estimate can be established. The present manuscript depicts the Barcelona-Clínic Liver Cancer Group diagnostic and treatment strategy. This is based on the analysis of several cohort and randomized controlled studies that have allowed the continuous refinement of treatment indication and application. Surgical resection is considered the first treatment option for early stage patients. It is reserved for patients with solitary tumors without portal hypertension and normal bilirubin. If these conditions are not met, patients are considered for liver transplantation (cadaveric or live donation) or percutaneous ablation if at an early stage (solitary ≤ 5 cm or up to 3 nodules ≤ 3 cm). These patients will reach a 5-year survival between 50 and 75%. If patients are diagnosed at an intermediate stage and are still asymptomatic and have preserved liver function, they may benefit from chemoembolization. Their 3-year survival will exceed 50%. There is no effective treatment for patients with advanced disease and thus, in such instances, the patients have to be considered for research trials with new therapeutic options. Finally, patients with end-stage disease should receive only palliative treatment to avoid unnecessary suffering. (Liver Transpl 2004;10:S115-S120.)
Major liver resections for hepatocellular carcinoma on cirrhosis: Early and long-term outcomes
Authors: Capussotti Lorenzo , Muratore Andrea , Massucco Paolo , Ferrero Alessandro , Polastri Roberto , Bouzari Hedayat
Published: January 2004

Since the lack of donors, liver resections continue to be the treatment of choice for cirrhotic patients with good liver function and resectable hepatocellular carcinoma (HCC). Moreover, over the past 2 decades, an increasing number of major hepatic resections have been performed. The aim of this study is to evaluate short- and long-term outcomes of 55 cirrhotic patients undergoing major hepatic resection with particular attention to the survival of the patients with gross portal vein invasion or large size tumors. Twenty-two patients (40%) required intra- or post-operative blood transfusion. Medium tumor size was 66.6±29.2 mm; 7 patients had large size (> 10 cm) HCCs. A single node was present in 38 cases (69.1%). There was a gross portal vein tumor thrombus (PVTT) in 13 patients (23.6%). Resection was non-curative in 4 cases. In-hospital mortality and morbidity rates were 5.5% and 30.9%, respectively. The overall and disease-free survival rates were 36.2% and 42.8%, respectively. Overall 5-year survival rates of patients with large size tumors was 17.1%. Ten patients with a gross PVTT had an R0 resection with a 26.6% 5-year survival rate. In conclusion, major hepatic resections for HCC can be performed with low mortality and morbidity rates. HCCs with PVTT or greater than 10 cm in size have very limited options of treatment; the favorable long-term results of our study suggest that they should undergo surgery if a radical resection can be achieved. (Liver Transpl 2004;10:S64-S68.)
Hepatic arterial 90Yttrium glass microspheres (Therasphere) for unresectable hepatocellular carcinoma: Interim safety and survival data on 65 patients
Authors: Carr Brian I.
Published: January 2004

Hepatocellular carcinoma (HCC) generally arises in a cirrhotic liver and, in most cases, is multifocal and bilobar. Although trans-hepatic artery chemoembolization (TACE) can be highly affective in shrinking tumors, it is limited by virtue of the damage that it can cause to the liver that is already damaged by chronic disease. A high priority in HCC research, after primary prevention and early detection, is to find new treatment modalities that are both effective and non-toxic to the underlying cirrhotic liver. A cohort of 65 patients with biopsy-proven unresectable HCC have been treated with hepatic arterial 90Yttrium microspheres (Therasphere), and the interim results are reported here. Only 1 cycle of Therasphere treatment ever was performed on 46 patients, 17 patients had 2 cycles, and 2 patients had 3 cycles of therapy. The median dose delivered was 134 Gy, typically as either 5 or 10 GBq (2-4 million microspheres). Clinical toxicities include 9 episodes of abdominal pain and 2 episodes of acute cholecystitis, requiring cholecystectomy. A main lab toxicity was elevated bilirubin which increased by more than 200 % in 25 patients (30.5 %) during 6 months of therapy, although 18 of these patients had only transient elevation. A prominent finding was prolonged and profound (> 70%) lymphopenia in more than 75% of the patients, but without clinical significance. Forty-two patients (64.6%) had a substantial decrease in tumor vascularity in response to therapy, and 25 patients (38.4%) had a partial response, by computed tomography scan. Median survival for Okuda stage I patients (n = 42) was 649 days (historical comparison 244) and for Okuda stage II patients (n = 23) was 302 days (historical comparison 64 days). All patients were followed after therapy for a minimum of 6 months. There were 42 deaths, 21 due to liver failure, 6 from HCC progression, and 3 from metastases. Therasphere appears to be a relatively safe and effective therapy for advanced-stage unresectable HCC. (Liver Transpl 2004;10:S107-S110.)
Fine needle biopsy of focal liver lesions: The hepatologist’s point of view
Authors: Caturelli Eugenio , Ghittoni Giorgia , Roselli Paola , De Palo Mariagrazia , Anti Marcello
Published: January 2004

Guided biopsy of hepatocellular carcinoma has been recently discussed again due to the progress of imaging techniques and the risk of malignant seeding after the procedure. Ultrasound is probably still the most accurate imaging modality for early detection of nodules arising on cirrhosis, even when compared with more advanced imaging techniques. It can be easily employed in the surveillance of high-risk cirrhotic patients. Ultrasound-guided biopsy has very high sensitivity and almost absolute specificity, which allows the appropriate treatment to start after a positive diagnosis. It also allows correct diagnosis of lymphomatous nodules, the incidence of which is increased in hepatitis C virus-related cirrhosis. The risk of seeding appears limited according to the currently available epidemiological data; this should be considered against the risk of false-positive diagnosis of malignancy based on imaging studies alone. Ultrasound-guided biopsy is a valuable tool also for the diagnosis of small nodules (less than 10 mm in diameter). The best accuracy in the sampling of hepatocellular carcinoma nodules is obtained by combining smear cytology and microhistology. This can be achieved by a single biopsy with a fine cutting needle that furnishes pathologic material suitable for both examinations, reducing risks and costs. (Liver Transpl 2004;10:S26-S29.)
The current status of imaging diagnosis of hepatocellular carcinoma
Authors: Choi Byung Ihn
Published: January 2004

Early detection of hepatocellular carcinoma (HCC) is important, since the most effective treatment for HCC is surgical resection or local ablation therapy when the tumor is small. Fortunately, recent advances in liver imaging techniques have facilitated the detection of small HCCs.

Recent progression of noninvasive imaging technology includes various techniques of harmonic ultrasound (US) imaging with several kinds of US contrast agents, multislice helical computed tomography (CT), and rapid high-quality magnetic resonance (MR) technique with new, tissue-specific contrast agents. These techniques seem to have a strong potential to improve detection and characterization of HCC.

In this review, the technique and efficacy of new imaging methods including contrast enhanced US, multislice CT, and recent MR techniques with new contrast agents for detecting and diagnosing HCC will be described.
Underestimation of the influence of satellite nodules as a risk factor for post-transplantation recurrence in patients with small hepatocellular carcinoma
Authors: Plessier Aurélie , Codes Liana , Consigny Yann , Sommacale Daniele , Dondero Federica , Cortes Alexandre , Degos Françoise , Brillet Pierre-Yves , Vilgrain Valérie , Paradis Valérie , Belghiti Jacques , Durand François
Published: January 2004

Liver transplantation offers good results in patients with small hepatocellular carcinoma. However, 3 to 15% of patients still have recurrence, suggesting that factors other than the size and number of nodules are implicated. The aim of our study was to identify predictive factors of recurrence in patients with small hepatocellular carcinoma. Seventy consecutive patients fulfilling Milano criteria and who were transplanted for hepatocellular carcinoma were studied. Forty-six patients had pretransplantation adjuvant local therapy. The size and number of tumors, the clinical and biological characteristics of the patients were recorded before liver transplantation, and histological analysis was performed on the explanted liver. Overall survival rates at 1 and 3 years were 81% and 66%, respectively. Recurrence-free survival rates at 1 and 3 years were 80% and 65%, respectively. Seven patients had tumor recurrence with 1- and 3-year recurrence rates of 5% and 10%, respectively. Satellite nodules on the explanted liver were the only statistically significant predictor of recurrence (P = .0003). None of the patients who did not have satellite nodules had recurrence. There was a significant correlation between satellite nodules and microvascular invasion. Patients with pretransplantation adjuvant therapy had significantly more tumor necrosis, but did not have less satellite nodules. In conclusion, microscopic satellite nodules are a significant predictive factor of tumor recurrence in patients transplanted for small hepatocellular carcinoma. (Liver Transpl 2004;10:S86-S90.)
Hepatectomy for hepatocellular carcinoma: Patient selection and postoperative outcome
Authors: Poon Ronnie Tung-Ping , Fan Sheung-Tat
Published: January 2004

Hepatic resection and liver transplantation are considered the only curative treatments for hepatocellular carcinoma (HCC). Liver transplantation for HCCs ≤ 5 cm in diameter has been shown to produce favorable survival results, but its application is limited by the lack of donors. Hepatic resection remains the treatment of choice for patients who are not transplantation candidates because of large tumor, macroscopic vascular invasion, or advanced age. For small HCCs associated with Child’s A cirrhosis, hepatic resection should still be considered the first-line treatment, but salvage transplantation for intrahepatic recurrence may be a feasible strategy. Recent improvement in surgical techniques and perioperative care has increased the safety and expanded the indication of hepatic resection for HCC to include large tumors that require extended hepatectomy in cirrhotic patients. Selection of appropriate candidates for hepatectomy depends on careful assessment of the tumor status and liver function reserve. Evaluation of the general fitness of patients is also critical because comorbid illness is an important cause of postoperative mortality, even if the patients have good liver function reserve. With careful patient selection and surgical expertise, the current operative mortality of hepatectomy for HCC is about 5% or less in major centers. Improved long-term survival results after resection of HCC have also been reported recently, with an overall 5-year survival rate of about 50%. The improved perioperative and long-term survival results have strengthened the role of hepatectomy as the mainstay of treatment for HCC despite the availability of a number of other treatment options for localized HCC. (Liver Transpl 2004;10:S39-S45.)
Surgical resection of hepatocellular carcinoma. Post-operative outcome and long-term results in Europe: An overview
Authors: Jaeck Daniel , Bachellier Philippe , Oussoultzoglou Elie , Weber Jean-Christophe , Wolf Philippe
Published: January 2004

A multicenter retrospective review of 1467 patients treated by liver resection (LR) for hepatocellular carcinoma (HCC) in Europe over a 13-year period showed a mean mortality rate of 10.6%, which was correlated with the extent of LR, the etiology of cirrhosis and the study period with an improvement during the last years. Improved 5-year overall survival (20-51%) and disease-free survival (20-33%) reached similar rates in cirrhotic than in non-cirrhotic patients. Overall results were similar to those reported in Asian series as far as patients and tumor characteristics were comparable. (Liver Transpl 2004;10:S58-S63.)
Focus on dysplastic nodules and early hepatocellular carcinoma: An Eastern point of view
Authors: Kojiro Masamichi
Published: January 2004

Although increasing numbers of equivocal nodular lesions have been detected in patients with liver cirrhosis with the development of various diagnostic imaging modalities, the pathological diagnosis of small, well-differentiated hepatocellular carcinoma (HCC) in the early stage and of high-grade dysplastic nodules (DNs) is a controversial issue among both Japanese and Western pathologists. In particular, many of the vaguely nodular HCCs of well-differentiated HCC diagnosed by Japanese pathologists tend to be interpreted as high-grade DNs rather than HCC by Western pathologists. In contrast, many of the high-grade DNs diagnosed by Western pathologists are interpreted as well-differentiated HCC by Japanese pathologists. The reasons for the discrepancy between Japanese and Western pathologists can be explained by the following: for Western pathologists, most information comes from the study of HCC and advanced cirrhosis explanted at liver transplantation without detailed clinical information about the nodules; for Japanese pathologists, most information comes from the examination of surgical and biopsy materials together with detailed clinical information that includes meticulous follow-up data on the clinical course of the nodular lesions. To resolve the diagnostic confusion concerning equivocal nodular lesions in the cirrhotic liver, it is necessary to promote the active exchange of clinicopathologic information between Japan and Western countries. (Liver Transpl 2004;10:S3-S8.)
Percutaneous ablation of hepatocellular carcinoma: State-of-the-art
Authors: Lencioni Riccardo , Cioni Dania , Crocetti Laura , Bartolozzi Carlo
Published: January 2004

Percutaneous ablation is considered the best treatment option for patients with early-stage hepatocellular carcinoma (HCC) who are not candidates for surgical resection or liver transplantation. Several methods have been developed, including intratumoral injection of ethanol or acetic acid, and thermal ablation with radiofrequency, laser, microwaves, or cryosurgery. Percutaneous ethanol injection (PEI) has been the most widely used technique. Several series have provided indirect evidence that PEI improves the natural history of HCC. Patients with Child-Pugh class A cirrhosis and either a single tumor smaller than 5 cm or as many as three lesions each smaller than 3 cm may achieve a 5-year survival of 50%. The major limitation of PEI is the high local recurrence rate, which may reach 33-43%. Radiofrequency (RF) ablation has emerged as the most powerful alternate method for percutaneous ablation. Recent studies have shown that RF ablation can achieve more effective local tumor control than PEI with fewer treatment sessions. In a randomized trial, local recurrence-free survival rates were significantly higher in patients who received RF ablation than in those treated by PEI, and treatment allocation was confirmed as an independent prognostic factor by multivariate analysis. RF ablation could therefore be considered as the percutaneous treatment of choice for patients with early-stage tumors. Further investigation is warranted to clarify whether current RF technology could offer improved results in patients with intermediate-stage HCC. (Liver Transpl 2004;10:S91-S97.)
The surgical approach to HCC: Our progress and results in Japan
Authors: Makuuchi Masatoshi , Sano Keiji
Published: January 2004

Due to the prevalence of hepatitis virus infection, the incidence of hepatocellular carcinoma (HCC) is very high in Japan. Many techniques have been devised by Japanese surgeons to reduce the mortality rate after hepatectomy for HCC: preoperative precise evaluation of hepatic functional reserve, portal venous embolization as preoperative preparation, anatomical and nonanatomical limited resections using intraoperative ultrasonography, and intermittent inflow occlusion during liver transection. Several challenging surgical procedures are also being tried for advanced HCC: HCC with portal and hepatic venous tumor thrombus, multiple and/or recurrent HCC, and HCC in the caudate lobe. As a result, the latest national survey of HCC revealed that operative mortality was 0.9% and the 5-year survival rate after surgery was 52%. Living-donor liver transplantation for adult patients with HCC is another surgical treatment developed in Japan. After the success of adult-to-adult living donor liver transplant using a left liver graft in 1993, a right liver graft, a left liver graft with caudate lobe, and a right lateral sector graft were developed. Indications for reconstructing the middle hepatic vein tributaries in right liver grafts were also proposed. Consequently, in our series of 36 patients with HCC who underwent living-donor liver transplantation, operative mortality was 3%, and the 2-year survival rate was 84%. (Liver Transpl 2004;10:S46-S52.)
Pedicle clamping with ischemic preconditioning in liver resection
Authors: Nuzzo Gennaro , Giuliante Felice , Vellone Maria , De Cosmo Germano , Ardito Francesco , Murazio Marino , D’Acapito Fabrizio , Giovannini Ivo
Published: January 2004

Hepatic pedicle clamping (HPC) is widely used to control intraoperative bleeding during hepatectomy; intermittent HPC is better tolerated but is associated with blood loss during each period of reperfusion. Recently, it has been shown that ischemic preconditioning (IP) reduces the ischemia-reperfusion damage for up to 30 minutes of continuous clamping in healthy liver. We evaluated the safety of IP for more prolonged periods of continuous clamping in 42 consecutive patients with healthy liver submitted to hepatectomy. IP was used in 21 patients (group A); mean ± SD of liver ischemia was 54 ± 19 minutes (range, 27-110; in 7 cases >60 minutes). In the other 21 patients, continuous clamping alone was used (Group B); liver ischemia lasted 36 ± 14minutes (range, 13-70; in 2 cases >60 minutes). Two patients in Group A (9.5%) and 3 in Group B (14.2%) received blood transfusions. In spite of the longer duration of ischemia (P = .001), patients with IP had lower aspartate aminotransferase (AST; P = .03) and alanine aminotransferase (ALT; P = not significant) at postoperative day 1, with a similar trend at postoperative day 3. This was reconfirmed by multiple regression analysis, which showed that although postoperative transaminases increased with increasing duration of ischemia and of the operation in both groups, the increases were significantly smaller (P < .001) with the use of preconditioning. In conclusion, the present study confirms that IP is safe and effective for liver resection in healthy liver and is also better tolerated than continuous clamping alone for prolonged periods of ischemia. This technique should be preferred to continuous clamping alone in healthy liver. Additional studies are needed to assess the role of IP in cirrhotic liver and to compare IP with intermittent clamping. (Liver Transpl 2004;10:S53-S57.)
Prevention and treatment of hepatocellular carcinoma
Authors: Omata Masao , Yoshida Haruhiko
Published: January 2004

Viral hepatitis, by either hepatitis C virus (HCV) or hepatitis B virus (HBV), is the dominant cause of hepatocellular carcinoma (HCC). This is to say that HCC may be prevented by controlling viral infection. Horizontal transmission of HCV has become obsolete owing to the discovery of the virus. Vertical transmission of HBV during delivery has been effectively prevented by vaccination and immunization of neonates. The efficacy of interferon therapy against HCV was recently much improved. We now possess several powerful antiviral drugs against HBV. There has been progress also in the treatment of HCC, and together with advances in diagnostics facilitating HCC detection at an early stage, tumor nodules can often be completely removed either by medical ablation or surgical resection. Nevertheless, recurrence of HCC after apparently curative treatment is extraordinarily frequent, since the remaining liver is still at a particularly high risk of HCC. An effective treatment of HCC should include measures to control de novo carcinogenesis. (Liver Transpl 2004;10:S111-S114.)
Hepatocellular nodules in cirrhosis: Focus on diagnostic criteria on liver biopsy. A Western experience
Authors: Roncalli Massimo
Published: January 2004

The spectrum of so-called space-occupying small (0.5-2.5 cm) sizable nodules arising in the cirrhotic liver includes a series of hyperplastic (large regenerative), dysplastic (low- and high-grade dysplastic), and malignant hepatocellular (well-differentiated hepatocellular carcinoma, HCC) nodules. Major progress in their classification and understanding was achieved through image analysis techniques and careful histological dissection of explanted native livers. Needless to say, the actual understanding of their natural history is crucial to a proper histological classification. The differential diagnosis of these hepatocellular nodules is difficult, particularly on biopsy specimens of focal liver lesions revealed by ultrasound (US), taken during the follow-up of cirrhotic patients. In this study we attempted to summarize, on the basis of our experience, essential clinicopathological features useful to distinguish the different nodules on needle biopsy. Synoptic tables of differential diagnosis and figures of elementar lesions, which have to be looked for, are provided. Only the continuous integration of clinical features, image analysis information of pathological findings, and follow-up data allows establishing the autonomy of these polymorphic and controversial entities and the boundaries between them. (Liver Transpl 2004;10:S9-S15.)
Liver transplantation in patients with hepatocellular carcinoma
Authors: Schwartz Myron
Published: January 2004

The preferred therapy for hepatocellular carcinoma (HCC) apparently confined to the liver is surgical removal of the tumor. If the location of the tumor and the functional status of the liver are such that resection with an adequate margin can be achieved with low likelihood of subsequent hepatic failure, liver resection is the preferred approach. When HCC apparently localized to the liver is diagnosed in a patient who, by virtue of tumor characteristics or diminished hepatic reserve, is not a candidate for liver resection, liver transplantation becomes a consideration. This work outlines the approach at The Mount Sinai Hospital to the diagnosis, evaluation, preoperative management, transplantation, and posttransplant follow-up in patients with unresectable HCC. The allocation of livers to patients with HCC is reviewed, and predictors of tumor recurrence and results of liver transplantation for HCC are discussed. Finally, the impact of viral hepatitis and of immunosuppression on transplant outcome are discussed. (Liver Transpl 2004;10:S81-S85.)
Clinical significance of early hepatocellular carcinoma
Authors: Inoue Kazuto , Takayama Tadatoshi , Higaki Tokio , Watanabe Yoshihiro , Makuuchi Masatoshi
Published: January 2004

Early hepatocellular carcinoma (HCC) is defined as a well-differentiated cancer containing Glisson’s triad, but it remains unknown whether this lesion is curable by surgery. We studied 70 patients who had a single HCC smaller than 2 cm in diameter (Stage T1) and who underwent curative hepatectomy and long-term follow-up. Based on our typing system, the tumors were assigned as early HCC (n = 15), overt HCC (n = 52), and non-HCC tumor (n = 3). The rate of microscopic regional spread was lower in early HCCs than in overt HCCs (7% vs. 42%; P = .01). After a median follow-up of 6.3 years, both overall survival and recurrence-free survival in the early HCC group were significantly better than those in the overt HCC group (P = .01; P = .001, respectively): the 5-year rates of overall survival were 93% and 54% and those of recurrence-free survival were 47% and 16%, respectively. The early HCC group was at a lower risk of recurrence (relative risk, 0.31; 95% confidence interval, 0.15-0.65; P = .002) and death (0.26; 0.09-0.73; P = .01) than was the overt HCC group. Early HCC is a distinct clinical entity with a high rate of surgical cure. (Liver Transpl 2004;10:S16-S19.)
Contrast-enhanced intraoperative ultrasonography in surgery for hepatocellular carcinoma in cirrhosis
Authors: Torzilli Guido , Olivari Natale , Moroni Eliana , Del Fabbro Daniele , Gambetti Andrea , Leoni Piera , Montorsi Marco , Makuuchi Masatoshi
Published: January 2004

Intraoperative ultrasonography (IOUS) is the most accurate diagnostic technique for staging hepatocellular carcinoma (HCC), but has low accuracy in differentiating the new nodules detected in the cirrhotic liver. The aim of this preliminary report is to evaluate whether contrast-enhanced intraoperative ultrasonography (CE-IOUS) could provide additional information to IOUS in patients with HCC. From August 2002 to July 2003, a prospective validation cohort study was conducted. For this purpose, 16 consecutive patients underwent liver resection for HCC using IOUS and CE-IOUS. Intraoperatively, in all patients 4.8 mL of SonoVue was injected intravenously through a peripheral vein. IOUS depicted 16 new focal liver lesions: 10 with no enhancement peculiar to HCC at CE-IOUS pattern and at histology (4) or imaging follow-up (6) proved to be benign; the remaining 6 had enhancement peculiar to HCC and histology confirmed this diagnosis. Two different patterns of enhancement were also recognized at CE-IOUS in those HCC nodules depicted preoperatively: one had no similarity to that observed at CT. CE-IOUS added findings to those of unenhanced IOUS in 50% of patients. These results show that IOUS accuracy and specificity is improved by CE-IOUS, with a great impact on surgical strategy and oncological radicality. Furthermore, a wider experience with vascular enhancement patterns with CE-IOUS could provide a new classification for HCC nodules. (Liver Transpl 2004;10:S34-S38.)