"Very early" intrahepatic cholangiocarcinoma in cirrhotic patients: should liver transplantation be reconsidered in these patients?

A retrospective cohort multicenter study was conducted to analyze the risk factors for tumor recurrence after liver transplantation (LT) in cirrhotic patients found to have an intrahepatic cholangiocarcinoma (iCCA) on pathology examination. We also aimed to ascertain whether there existed a subgroup of patients with single tumors ≤2 cm ("very early") in which results after LT can be acceptable. Twenty-nine patients comprised the study group, eight of whom had a "very early" iCCA (four of them incidentals). The risk of tumor recurrence was significantly associated with larger tumor size as well as larger tumor volume, microscopic vascular invasion and poor degree of differentiation. None of the patients in the "very early" iCCA subgroup presented tumor recurrence compared to 36.4% of those with single tumors >2 cm or multinodular tumors, p = 0.02. The 1-, 3- and 5-year actuarial survival of those in the "very early" iCCA subgroup was 100%, 73% and 73%, respectively. The present is the first multicenter attempt to ascertain the risk factors for tumor recurrence in cirrhotic patients found to have an iCCA on pathology examination. Cirrhotic patients with iCCA ≤2 cm achieved excellent 5-year survival, and validation of these findings by other groups may change the current exclusion of such patients from transplant programs.

Intrahepatic cholangiocarcinoma or mixed hepatocellular-cholangiocarcinoma in patients undergoing liver transplantation: a Spanish matched cohort multicenter study.

OBJECTIVE: To evaluate the outcome of patients with hepatocellular-cholangiocarcinoma (HCC-CC) or intrahepatic cholangiocarcinoma (I-CC) on pathological examination after liver transplantation for HCC. BACKGROUND: Information on the outcome of cirrhotic patients undergoing a transplant for HCC and with a diagnosis of HCC-CC or I-CC by pathological study is limited. METHODS: Multicenter, retrospective, matched cohort 1:2 study. STUDY GROUP: 42 patients undergoing a transplant for HCC and with a diagnosis of HCC-CC or I-CC by pathological study; and control group: 84 patients with a diagnosis of HCC. I-CC subgroup: 27 patients compared with 54 controls; HCC-CC subgroup: 15 patients compared with 30 controls. Patients were also divided according to the preoperative tumor size and number: uninodular tumors 2 cm or smaller and multinodular or uninodular tumors 2 cm or larger. Median follow-up: 51 (range, 3-142) months. RESULTS: The 1-, 3-, and 5-year actuarial survival rate differed between the study and control groups (83%, 70%, and 60% vs 99%, 94%, and 89%, respectively; P < 0.001). Differences were found in 1-, 3-, and 5-year actuarial survival rates between the I-CC subgroup and their controls (78%, 66%, and 51% vs 100%, 98%, and 93%; P < 0.001), but no differences were observed between the HCC-CC subgroup and their controls (93%, 78%, and 78% vs 97%, 86%, and 86%; P = 0.9). Patients with uninodular tumors 2 cm or smaller in the study and control groups had similar 1-, 3-, and 5-year survival rate (92%, 83%, 62% vs 100%, 80%, 80%; P = 0.4). In contrast, patients in the study group with multinodular or uninodular tumors larger than 2 cm had worse 1-, 3-, and 5-year survival rates than their controls (80%, 66%, and 61% vs 99%, 96%, and 90%; P < 0.001). CONCLUSIONS: Patients with HCC-CC have similar survival to patients undergoing a transplant for HCC. Preoperative diagnosis of HCC-CC should not prompt the exclusion of these patients from transplant option.

Effect of excess levels of lysine and leucine in wheat-based, amino acid-fortified diets on the mRNA expression of two selected cationic amino acid transporters in pigs.

An experiment was conducted to evaluate the effect of excess levels of Leu and Lys on the expression of b(0,+) and CAT-1 mRNA in jejunum, liver and the muscles Longissimus dorsi (LDM) and Semitendinosus (STM). Twenty pigs with an average initial BW of 16.4 ± 1.7 kg were used in a Randomized Complete Block. Dietary treatments (T) were as follows: T1, basal diet; T2, basal plus 3.5 g l-Lys/kg diet; T3, basal plus 1.5 g l-Leu/kg diet; T4, basal plus 3.5 g l-Lys plus 1.5 g l-Leu/kg diet. Diets in T1 and T3 met 100% the requirement of Lys for pigs within the 10 to 20 kg body weight range; diets in T2 and T4 contained 35% excess of Lys. Also, diets in T1 and T2 supplied 104%, whereas diets in T3 and T4 supplied 116% the requirement of Leu. The expression of b(0,+) in jejunum was reduced (p = 0.002) because of the supplementation of l-Leu, but l-Lys supplementation had no effect (p = 0.738). In contrast, the expression of b(0,+) in STM (p = 0.012) and liver (p = 0.095) was reduced by the high level of Lys, but Leu had no effect (p > 0.100). CAT-1 expression in STM increased by high Lys (p = 0.023) and Leu (p = 0.007) levels. In liver, the expression of CAT-1 substantially increased (p = 0.001) because of Lys. In conclusion, excess levels of dietary Lys and Leu affect the expression of cationic amino acid transporters, and this effect varies depending on the studied tissue.

Ileal digestibility of amino acids, phosphorus, phytate and energy in pigs fed sorghum-based diets supplemented with phytase and Pancreatin®.

The effects of phytase supplementation on the apparent ileal digestibility (AID) of amino acids (AA) have been inconsistent. Two experiments evaluated the effect of providing a mixture of pancreatic enzymes (Pancreatin(®) ) to growing pigs fed sorghum-soybean meal diets supplemented with phytase on the AID of AA, energy, and phosphorus (P), as well as the ileal digestibility (ID) of phytate; there were four periods per experiment. In Experiment 1, eight pigs (BW 22.1±1.3 kg) were fitted with a T-cannula at the distal ileum. Each period consisted of 9 days; 7 days for diet adaptation, and 2 days for digesta collection. Treatments (T) were: (i) basal sorghum-soybean meal diet, (ii) basal diet plus Pancreatin®, (iii) basal diet plus phytase and (iv) basal diet plus phytase and Pancreatin®. Phytase increased the digestibilities of phytate and P (p<0.001), but did not affect the AID of AA and energy (p>0.10). Except for methionine (p=0.07), Pancreatin® did not affect the AID of AA. Phytase and Pancreatin® did not interact (p>0.10). Experiment 2 was similar to Experiment 1, but Pancreatin® was infused into duodenum. Pancreatin® infusion did not affect the AID of AA (p>0.10); and tended to reduce (p=0.09) the AID of lysine. Phytase × Pancreatin® interactions were not observed (p>0.10). In conclusion, phytase and Pancreatin® did not improve the AID of AA in growing pigs fed sorghum-soybean meal diets indicating that phytates did not affect AA digestibility.

Imported cases of malaria admitted to two hospitals of Margarita Island, Venezuela, 1998-2005.

BACKGROUND: Imported cases of malaria constitute an important public health problem in many countries, even in those with autochthonous cases, where disease could be acquired in these areas and then seen in non-endemic regions. Non-immune populations are susceptible to complications due to malaria infection, particularly in malaria caused by Plasmodium falciparum. However, Plasmodium vivax the predominant Plasmodium spp. in Venezuela can also lead to severe malaria. METHODS: We reviewed retrospectively cases of malaria to identify the clinical features of those imported cases diagnosed at two institutions in Margarita Island (a non-endemic area), Venezuela, in an 8-year period. We conducted a retrospective observational study to identify the clinical and epidemiological features among hospitalized patients at Hospital Central and Hospital Agustin Hernández with malaria acquired at malaria-endemic locations. RESULTS: We identified eighteen imported cases of malaria confirmed by thin and thick peripheral blood smears at these two institutions over an 8-year period. The mean age of diagnosis was 27 years. P. vivax was responsible for the majority of cases. All patients presented with fever, 89% with malaise, 78% with chills, and 67% with myalgia, among others symptoms. Mean haemoglobin levels on admission were 8.1g/dL (100% <12g/dL); platelets: 79,283cells/mm(3) (89% had platelets below 150,000); and a mean total leukocyte count: 3.4x10(3)cells/mm(3) (78% had leukopenia). Thirty nine percent of patients required blood transfusions. Two fatalities were identified (CFR=11%), one associated to severe malaria due to P. falciparum and the other due to a complicated case of P. vivax malaria. DISCUSSION: Imported cases of malaria due to P. vivax and P. falciparum in the studied population are associated with significant hematological complications. These findings illustrate the importance of educating non-immune populations about the malaria risk and prevention strategies; and from a pubic health perspective, the need to develop further malaria prevention strategies at a national level.

Beetle (Ulomoides dermestoides) fat improves diabetes: effect on liver and pancreatic architecture and on PPARγ expression.

Ulomoides dermestoides is a beetle traditionally consumed to treat diabetes. In this study, we performed a composition analysis of U. dermestoides to obtain the principal fractions, which were used to assess the effect on glycemia, liver and pancreatic architecture, and PPARγ and GLUT4 expression. Normal mice and alloxan-induced diabetic mice were administered fractions of chitin, protein or fat, and the acute hypoglycemic effect was evaluated. A subacute study involving daily administration of these fractions to diabetic mice was also performed over 30 days, after which the liver and pancreas were processed by conventional histological techniques and stained with hematoxylin and eosin to evaluate morphological changes. The most active fraction, the fat fraction, was analyzed by gas chromatography-mass spectrometry (GC-MS), and PPARγ and GLUT4 mRNA expressions were determined in 3T3-L1 adipocytes. The protein and fat fractions exhibited hypoglycemic effects in the acute as well as in the 30-day study. Only the fat fraction led to elevated insulin levels and reduced glycemia, as well as lower intake of water and food. In the liver, we observed recovery of close hepatic cords in the central lobule vein following treatment with the fat fraction, while in the pancreas there was an increased density and percentage of islets and number of cells per islet, suggesting cellular regeneration. The GC-MS analysis of fat revealed three fatty acids as the major components. Finally, increased expression of PPARγ and GLUT4 was observed in 3T3-L1 adipocytes, indicating an antidiabetic effect.

Risk factors of hepatocellular carcinoma recurrence after liver transplantation: accuracy of the alpha-fetoprotein model in a single-center experience.

BACKGROUND: Recurrence of hepatocellular carcinoma (HCC) and cirrhosis after a liver transplantation (LT) is a major concern, and a strict Milan criteria selection of candidates does not accurately discriminate the relapse rate after LT. PURPOSE: This study sought to analyze the risk factors affecting tumor recurrence after LT for related cirrhosis HCC and the application of the French prognostic model (preLT alpha-fetoprotein [AFP], size, number) in a single center. METHODS: In a retrospective observational study of LT for HCC and cirrhosis, clinicopathological features were analyzed. Also, the preoperative and postoperative AFP model score was calculated with a cutoff of 2. RESULTS: Of 480, 109 patients underwent cadaveric LT for HCC. Eight of them had a relapse (7%). High AFP level, AFP model score >2, high pathological tumor-node-metastasis (pTNM) stage, poor differentiation, macrovascular-microvascular invasion, infiltration, and R1 margin were statistically significant (P < .05) for recurrence. Also, in the preoperative model, AFP score >2 was a predictor of worse survival (1-, 3-, 5-, 10-year survival of 81%, 51%, 30%, 30% vs 90%, 76%, 73%, 69% in ≤2, with P = .005). Regarding the postoperative model, similar results were found (1-, 3-, 5-, 10-year survival of 84%, 47%, 37%, 37% vs 90%, 78%, 73%, 52%, P = .028) between AFP model score >2 and ≤2, respectively. However, Milan and up-to-7 criteria were not accurate in recurrence nor in survival. CONCLUSIONS: The French AFP model has proven to be a more discerning prognostic tool than other established criteria in the prediction of recurrence and survival. Also, in postoperative prognosis, pathological risk factors for relapse such as pTNM, differentiation grade, macrovascular-microvascular invasion, infiltration, and R1 margin have been predictors of recurrence.

Statistical quality control charts for liver transplant process indicators: evaluation of a single-center experience.

Liver transplantation, the best option for many end-stage liver diseases, is indicated in more candidates than the donor availability. In this situation, this demanding treatment must achieve excellence, accessibility and patient satisfaction to be ethical, scientific, and efficient. The current consensus of quality measurements promoted by the Sociedad Española de Trasplante Hepático (SETH) seeks to depict criteria, indicators, and standards for liver transplantation in Spain. According to this recommendation, the Canary Islands liver program has studied its experience. We separated the 411 cadaveric transplants performed in the last 15 years into 2 groups: The first 100 and the other 311. The 8 criteria of SETH 2010 were correctly fulfilled. In most indicators, the outcomes were favorable, with an actuarial survivals at 1, 3, 5, and 10 years of 84%, 79%, 76%, and 65%, respectively; excellent results in retransplant rates (early 0.56% and long-term 5.9%), primary nonfunction rate (0.43%), waiting list mortality (13.34%), and patient satisfaction (91.5%). On the other hand, some indicators of mortality were worse as perioperative, postoperative, and early mortality with normal graft function and reoperation rate. After the analyses of the series with statistical quality control charts, we observed an improvement in all indicators, even in the apparently worst, early mortality with normal graft functions in a stable program. Such results helped us to discover specific areas to improve the program. The application of the quality measurement, as SETH consensus recommends, has shown in our study that despite being a consuming time process, it is a useful tool.

Health and safety hazards associated with subways: a review.

Subway systems are key components in mass transportation networks worldwide, providing rapid and affordable transportation to urban communities in 58 different countries. The benefits afforded by subway transit are numerous and mainly derived from the reduction in automobile use, thereby limiting environmental and health hazards associated with exhaust-air emissions. Additionally, by limiting congestion and providing vital transportation links within a city, subways also improve the overall quality of life of urban communities. However, to best maximize the positive impact on the urban environment, subway systems need to provide a safe and healthy environment for both passengers and subway transit workers. Periodically, safety concerns are raised, most recently in relation to the vulnerability of subways to terrorist attacks. To examine this issue more carefully, we conducted a structured review of the literature to identify and characterize potential health and safety hazards associated with subways. A secondary goal was to identify various risk management strategies designed to minimize the risk of these hazards. This information may be helpful to urban communities, urban planners, public health specialists, and others interested in subway safety.