Jose L. Hernandez

Liver transplantation for hepatocellular carcinoma: The MELD impact

The new allocation policy of the United Network of Organ Sharing (UNOS) based on the model for end‐stage liver disease (MELD) gives candidates with stage T1 or stage T2 hepatocellular carcinoma (HCC) a priority MELD score beyond their degree of hepatic decompensation. The aim of this study was to determine the impact of the new allocation policy on HCC candidates before and after the institution of MELD. The UNOS database was reviewed for all HCC candidates listed between July 1999 and July 2002. The candidates were grouped by two time periods, based on the date of implementation of new allocation policy of February 27, 2002. Pre‐MELD candidates were listed for deceased donor liver transplantation (DDLT) before February 27,2002, and post‐MELD candidates were listed after February 27, 2002. Candidates were compared by incidence of DDLT, time to DDLT, and dropout rate from the waiting list because of clinical deterioration or death, and survival while waiting and after DDLT. Incidence rates calculated for pre‐MELD and post‐MELD periods were expressed in person years. During the study, 2,074 HCC candidates were listed for DDLT in the UNOS database. The DDLT incidence rate was 0.439 transplant/person years pre‐MELD and 1.454 transplant/person years post‐MELD (P < 0.001). The time to DDLT was 2.28 years pre‐MELD and 0.69 years post‐MELD (P < 0.001). The 5‐month dropout rate was 16.5% pre‐MELD and 8.5% post‐MELD (P < 0.001). The 5‐month waiting‐list survival was 90.3% pre‐MELD and 95.7% post‐MELD (P < 0.001). The 5‐month survival after DDLT was similar for both time periods. The new allocation policy has led to an increased incidence rate of DDLT in HCC candidates. Furthermore, the 5‐month dropout rate has decreased significantly. In addition, 5‐month survival while waiting has increased in the post‐MELD period. Thus, the new MELD‐based allocation policy has benefited HCC candidates. (Liver Transpl 2004;10:36–41.)

Longitudinal changes in cognition and behavior in asymptomatic carriers of the APOE e4 allele

Objective: To determine whether memory loss is detectable before the symptomatic presentation of mild cognitive impairment (MCI) in those at greater genetic risk for Alzheimer disease (AD) based upon presence or absence of the e4 allele of APOE. Methods: Participants were age 50 years or older who responded to newspaper advertisements. A total of 212 cognitively normal individuals of known APOE genotype were initially enrolled in a match paradigm that included e4 homozygotes, e3/4 heterozygotes, and e4 noncarriers in a 1:1:2 ratio (53 sets). Of the original 212 individually matched participants, 180 completed at least two epochs of testing including 45 APOE e4/4 homozygotes, 42 APOE e3/4 heterozygotes, and 93 APOE e4 noncarriers, mean age 60 (±6.2) years. Of these, four developed MCI or AD during the follow-up period and were excluded from analysis. Longitudinal neuropsychological study included two verbal (Auditory Verbal Learning Test [AVLT], Selective Reminding Test [SRT]) and two visual (Complex Figure Test [CFT], Visual Retention Test) memory tests. Results: Multiple measures on both verbal memory tests showed poorer performance over a mean interval of 33 months in e4 carriers than noncarriers: AVLT total learning, long term delayed recall; SRT free and cued recall. Among those age 50 to 59 years, AVLT long term delayed recall, SRT free and cued recall, and CFT recall declined more in APOE e4 carriers. No differences were found in the domains of language, spatial skills, or executive function. Conclusions: Memory declined in APOE e4 carriers before the symptomatic presentation of MCI in a cohort whose mean age was 60 years over a median period of 33 months. The decline began prior to age 60.

DIEP and pedicled TRAM flaps: A comparison of outcomes

Background: Studies comparing similar and sizable numbers of deep inferior epigastric perforator (DIEP) and pedicled transverse rectus abdominis musculocutaneous (TRAM) flap reconstructions are lacking. The authors hoped to determine whether the DIEP flap has advantages over the pedicled TRAM flap for breast reconstruction. Methods: The authors retrospectively reviewed the records of women undergoing breast reconstruction over a 9-year period at a single institution. Patients were grouped by type of reconstruction: DIEP or pedicled TRAM. Only patients with at least 3 months of postoperative follow-up were studied. Results: A total of 190 women underwent unilateral breast reconstructions (96 DIEP and 94 pedicled TRAM flaps). The patient groups were similar in terms of age, body mass index, preoperative chest wall irradiation and abdominal operations, and cancer stage. The median hospital stay for the DIEP group was shorter than that for the pedicled TRAM group (4 versus 5 days, p < .001). Operative time for the DIEP group (5:53 hours) was longer than that for the pedicled TRAM group (4:46 hours, p < .001). The fat necrosis rates for the pedicled TRAM group were higher (58.5 percent) than those for the DIEP group (17.7 percent, p < .001). Abdominal wall hernias occurred more frequently in pedicled TRAM (16.0 percent) than DIEP patients (1.0 percent, p < .001). Abdominal wall bulge rates were similar for both groups (DIEP 9.4 percent versus pedicled TRAM 14.9 percent). Conclusions: DIEP flap reconstruction can be performed with lower morbidity rates and shorter hospital stays than pedicled TRAM reconstruction. Specifically, fat necrosis and abdominal wall hernias are less common in DIEP patients than in pedicled TRAM patients, while flap failure and abdominal wall bulging rates are similar in the two patient groups. These data support the DIEP flap as the preferred option over the pedicled TRAM flap for autologous breast reconstruction in postmastectomy patients.

Breast Cancer: Presentation and Intervention in Women With Gastrointestinal Metastasis and Carcinomatosis

BackgroundBreast cancer metastatic to the gastrointestinal tract or peritoneum is rare. We reviewed the natural history of ductal and lobular carcinoma in women with breast cancer metastatic to the gastrointestinal tract, peritoneum, or both.MethodsWe performed a retrospective review of all patients (1985–2000) with a pathologic diagnosis of breast cancer metastatic to the gastrointestinal tract or peritoneum. Patients were categorized into three groups: those with gastrointestinal metastasis, carcinomatosis, or both.ResultsOf 73 patients, 23 (32%) had gastrointestinal metastasis only, 32 (44%) had carcinomatosis only, and 18 (25%) had both. The median age at initial breast cancer diagnosis was 55 years. The mean interval between the primary diagnosis and metastatic presentation was 7 years. Sites of gastrointestinal metastases included the esophagus (8%), stomach (28%), small intestine (19%), and colon and rectum (45%). Infiltrating lobular carcinoma represented 34 (64%) of the 53 gastrointestinal metastases. The median overall survival after diagnosis was 28 months. Palliative surgical intervention in 47 patients (64%) did not affect overall survival. Some survival benefit may have accrued to select patients with gastrointestinal metastasis who underwent surgical palliation (44 vs. 9 months). Advanced age at diagnosis and gastric metastases had a negative effect on survival, whereas treatment with systemic chemotherapy or tamoxifen had a positive effect on survival.ConclusionsGastrointestinal metastasis occurred more often in patients with invasive lobular carcinoma. Surgical intervention did not significantly extend overall survival but may be considered in a select group of patients.

Reduced T-Cell and Dendritic Cell Function Is Related to Cyclooxygenase-2 Overexpression and Prostaglandin E2 Secretion in Patients With Breast Cancer

Background: In several neoplastic diseases, including breast cancer, immunosuppression correlates with disease stage, progression, and outcome. Thus, thorough analysis of immune parameters in breast cancer patients may be beneficial in designing effective anticancer immune-based therapies.Methods: We investigated dendritic cell and T-cell function in breast cancer patients at various stages of the disease and in age-matched controls. We also evaluated cyclooxygenase-2 (COX-2) expression and prostaglandin E2 (PGE2) levels within the tumor milieu and in the circulation.Results: T cells from cancer patients showed decreased proliferation in response to CD3 antibody stimulation. Analysis of T-cell helper type 1 and 2 cytokines revealed reduced levels of interferon-γ, tumor necrosis factor-α, interleukin (IL)-12, and IL-2 and increased levels of IL-10 and IL-4. Dendritic cells from these patients showed significantly reduced expression of co-stimulatory molecules (B7 and CD40) and demonstrated reduced phagocytic ability, reduced antigen presentation to T cells, and reduced ability to mature in response to lipopolysaccharide. Data revealed increased synthesis of PGE2, an immune suppressor, along with increased expression of COX-2, a key regulator of PGE2 synthesis.Conclusions: COX-2–induced PGE2 may contribute to immunosuppression and may directly block antitumor immunity while promoting tumor growth, providing us with the rationale for using COX-2 inhibition combined with immunotherapy.

Postpolypectomy lower gastrointestinal bleeding: Potential role of aspirin

INTRODUCTION:Limited data exist on the role of aspirin in increasing the risk of clinically significant postpolypectomy bleeding (PPB), which is defined as lower gastrointestinal (GI) hemorrhage following colonoscopic polyp removal requiring transfusion, hospitalization, endoscopic intervention, angiography, or surgery.OBJECTIVES:To determine if aspirin use prior to colonoscopy increases the risk of clinically significant PPB.METHODS:A case-control study of patients with clinically significant PPB at Mayo Clinic Scottsdale and Rochester was performed. Information collected included age, gender, recent use of aspirin or NSAIDs (within three days of colonoscopy), polyp characteristics, and polypectomy technique. The control group consisted of patients matched for age (±3 yr), gender, and cardiovascular morbidity who had undergone polypectomy without any complications. The populations were compared to determine the odds ratio (OR) of PPB with aspirin use.RESULTS:During the study period, 20,636 patients underwent colonoscopy with polypectomy at the two institutions and 101 patients presented with clinically significant PPB. Twenty patients were excluded from analysis because of prior anticoagulant use. The remaining 81 patients were matched to 81 patients who had undergone colonoscopy without complications. The two groups were comparable in terms of polyp size (97%≤ 10 mm, bleeding group; 95%≤ 10 mm, control group). Aspirin use prior to polypectomy was 40% in the bleeding group and 33% in the control group (OR 1.41; 95% C.I. 0.68 to 3.04).CONCLUSION:Postpolypectomy bleeding is an uncommon but important complication of endoscopic polypectomy. There was no statistically relevant difference in prior aspirin use before polypectomy in the bleeding group and the matched controls.

Yield of repeat wireless video capsule endoscopy in patients with obscure gastrointestinal bleeding.

PURPOSE:Capsule endoscopy (CE) has been shown to have a high diagnostic yield in patients with obscure gastrointestinal bleeding (OGIB). It is not known if repeating CE improves diagnostic yield or changes patient management when the initial CE is negative or nondiagnostic. The aims of this study are (1) to understand the reasons for repeat CE, (2) to determine the diagnostic yield of repeat CE, and (3) to establish if findings on repeat CE resulted in a change in patient management.METHODS:Between August 2001 and October 2003, we performed 391 capsule studies. Of these, 24 were repeat studies in patients with OGIB. We retrospectively reviewed the charts of these 24 patients.RESULTS:The reasons for repeat CE were: recurrent gastrointestinal bleeding (13), limited visualization on first exam due to poor prep or blood (10), complication (1) (capsule impaction at cricopharyngeus). Eighteen of 24 (75%) repeat capsule studies revealed additional findings (7 arteriovenous malformations, 2 gastropathy, 2 erosions, 2 masses, 1 ulcer, 2 red spots, 1 linear streak, 1 erythema). These findings led to changes in patient management in 15 of the 24 (62.5%) cases.CONCLUSIONS:Indications for repeat CE most commonly include recurrent gastrointestinal bleeding and limited visualization on initial study. Repeat CE results in a high yield of new findings that lead to changes in patient management. Repeat CE should be considered in patients with persistent OGIB when the initial study is negative or inconclusive.

No evidence for cognitive dysfunction or depression in patients with mild restless legs syndrome.

Restless legs syndrome is a common disoder that may interrupt sleep and has been reported to produce daytime fatigue and/or mood changes. This study assessed whether patients with RLS have more cognitive dysfunction and depression than individuals of the same age and education who do not have RLS. The study showed that older individuals with mild RLS for at least 1 year do not have cognitive dysfunction and are not depressed compared with a control group of similar age and education.

Hepatic steatosis in hepatitis C virus genotype 3 infection: Does it correlate with body mass index, fibrosis, and HCV risk factors?

Hepatic steatosis is a recognized feature of hepatitis C viral infection, particularly in genotype 3. The demographics and the associations contributing to moderate to severe steatosis in genotype 3 are not very well studied. The aim of this study is to determine the demographics and association of steatosis with fibrosis, obesity, diabetes, lipid levels, and risk factors among patients with hepatitis C virus (HCV) genotype 3. Two hundred ninety-three consecutive HCV patients (genotype 1, n = 218; genotype 2, n = 43; genotype 3, n = 32) at our institution were studied retrospectively. Demographic information such as height, weight, genotype, risk factors, serum cholesterol and triglyceride, and liver biopsy was collected. Steatosis was graded using the Brunt classification. HCV genotype 3-infected patients were younger (P < 0.04) and had lower serum cholesterol levels (P < 0.02) compared to nongenotype 3 patients. Moderate to severe steatosis was more prevalent in HCV genotype 3 patients (P < 0.001) with intravenous drug abuse as a risk factor (P = 0.04). Genotype 3 was the independent predictor of steatosis in all patients. There was no statistical association between grade of steatosis and body mass index, fibrosis, necroinflammation, or hyperlipidemia when only HCV genotype 3 patients were included in the multivariate logistic model. Hepatic steatosis is a feature of genotype 3. Patients with HCV genotype 3 are younger and have lower serum cholesterol levels. Genotype 3 is the independent predictor for steatosis in HCV patients. HCV genotype 3 patients with moderate to severe steatosis are more likely to have intravenous drug use as a risk factor.

Restless legs syndrome in Parkinson's disease patients may improve with subthalamic stimulation

We report on 6 advanced Parkinsons disease (PD) patients who underwent bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) surgery whose restless legs syndrome (RLS) improved postoperatively. Despite a mean 56% decrease in their levodopa equivalents postoperatively, their RLS scores dropped by a mean of 84% (100% in three). Our findings suggest that bilateral STN DBS surgery can improve RLS in patients with advanced PD.