The second Mexican consensus on hepatocellular carcinoma. Part II: Treatment.

Hepatocellular carcinoma (HCC) is more frequently manifesting as one of the main complications of cirrhosis of the liver, its principal risk factor. There have been modifications in its incidence over the past decade, related to an epidemiologic transition in the etiology of cirrhosis, with a decrease in the prevalence of hepatitis C and an increase in nonalcoholic fatty liver disease (NAFLD) as a cause, as well as the development of HCC in the non-cirrhotic liver due to NAFLD. Genetic markers associated with the disease have been identified, and surveillance and diagnosis have improved. Regarding treatment, surgical techniques, in both resection and transplantation, have advanced and radiologic techniques, at the curative stage of the disease, have enhanced survival in those patients. And finally, there have been radical changes in the systemic approach, with much more optimistic expectations, when compared with the options available a decade ago. Therefore, the Asociación Mexicana de Hepatología decided to carry out the Second Mexican Consensus on Hepatocellular Carcinoma, which is an updated review of the available national and international evidence on the epidemiology, risk factors, surveillance, diagnosis, and treatment of the disease, to offer the Mexican physician current information on the different topics regarding hepatocellular carcinoma. In this second part of the document, the topics related to the treatment of HCC are presented.

The second Mexican consensus on hepatocellular carcinoma. Part I: Epidemiology and diagnosis.

Hepatocellular carcinoma (HCC) is more frequently manifesting as one of the main complications of cirrhosis of the liver, its principal risk factor. There have been modifications in its incidence over the past decade, related to an epidemiologic transition in the etiology of cirrhosis, with a decrease in the prevalence of hepatitis C and an increase in nonalcoholic fatty liver disease (NAFLD) as a cause, as well as the development of HCC in the non-cirrhotic liver due to NAFLD. Genetic markers associated with the disease have been identified, and surveillance and diagnosis have improved. Regarding treatment, surgical techniques, in both resection and transplantation, have advanced and radiologic techniques, at the curative stage of the disease, have enhanced survival in those patients. And finally, there have been radical changes in the systemic approach, with much more optimistic expectations, when compared with the options available a decade ago. Therefore, the Asociación Mexicana de Hepatología decided to carry out the Second Mexican Consensus on Hepatocellular Carcinoma, which is an updated review of the available national and international evidence on the epidemiology, risk factors, surveillance, diagnosis, and treatment of the disease, to offer the Mexican physician current information on the different topics regarding hepatocellular carcinoma. In this first part of the document, the topics related to epidemiology and diagnosis are presented.

Fever, haematuria, and acute graft dysfunction in renal transplant recipients secondary to adenovirus infection: two case reports.

We report two cases of adenoviral infection in kidney transplant recipients that presented with different clinical characteristics under similar demographic and posttransplant conditions. The first case presented with fever, gross haematuria, and acute graft dysfunction 15 days following renal transplantation. A graft biopsy, analyzed with immunohistochemistry, yielded negative results. However, the diagnosis was confirmed with blood and urine real-time PCR for adenovirus 3 days after the initial clinical manifestations. The immunosuppression dose was reduced, and ribavirin treatment was started, for which the patient quickly developed toxicity. Antiviral treatment allowed for transient response; however, a relapse occurred. The viral real-time PCR became negative upon immunosuppression reduction and administration of IVIG; graft function normalized. In the second case, the patient presented with fever and dysuria 1 month after transplantation. The initial imaging studies revealed graft enlargement and areas of hypoperfusion. In this case, the diagnosis was also confirmed with blood and urine real-time PCR for adenovirus 3 days after the initial clinical manifestations. Adenoviral nephritis was confirmed through a graft biopsy analyzed with light microscopy, immunohistochemistry, and PCR in frozen tissue. The immunosuppression dose was reduced, and IVIG was administered obtaining excellent clinical results along with a negative real-time PCR.

Role of major histocompatibility complex and ethnicity in acute renal graft rejection.

BACKGROUND: The major histocompatibility complex (MHC) plays a main role in antigen presentation. Class I, II, and III genes form defined "blocks" of conserved DNA sequences (conserved extended haplotypes) that are useful to follow the ancestry of a population. Each variant encodes a specific peptide that determines a particular individual's immune response. In addition, differential expression of HLA antigens in certain physiological and pathological conditions may participate in the pathogenesis of allograft rejection versus tolerance. OBJECTIVES: The aim of this study was to determine whether the specific HLA ancestry was associated with acute renal graft rejection among the Mexican mestizo population. MATERIALS AND METHODS: We studied 544 Mexican mestizo renal donors and their respective recipients for their serologically determined HLA and based on antigens haplotype assignments. The acute rejection group was compared with the nonrejection group among donors and recipients, correspondingly. RESULTS: Frequent Mexican alleles were observed in this study. Moreover, HLA-B*61/-DR*04, HLA-A*35/-DR*06 (Amerindian ancestry), HLA-A*68/-DR*01, HLA-A*28/-B*65/-DR*01 (African ancestry), and HLA-A*33/-B*65 (Caucasian ancestry) in donors were associated with acute renal graft rejection episodes. CONCLUSION: Knowing the ancestry of a donor's HLA molecules may help to individualize immunosuppressive therapy for posttransplant surveillance, because they may be more membrane-exposed in parenchymal cells, making them more susceptible of being recognized by the recipient's immune system.

Parameters of Doppler ultrasound at five days posttransplantation as predictors of histology and renal function at one year.

INTRODUCTION: In our center, a Doppler ultrasound (DU) is performed at 5 days after transplantation. The normal upper limit of flow velocity (FV) in the renal artery is 200-250 cm/s. The resistance index (RI) is considered elevated when >0.8. Elevation of the RI can be shown in all the forms of graft dysfunction. OBJECTIVE: The objective of this study was to evaluate the capacity of the DU to predict the prognosis of graft function and histological damage at 1 year. METHODS: We examined a retrospective cohort of patients undergoing renal transplantation between January 2004 and May 2007. The renal function was evaluated with serum creatinine measurements and glomerular filtration rate (GFR) estimates by the quadratic Modification of Diet in Renal Disease study equation. The biopsy specimen was evaluated according to the Banff 1997 classification. RESULTS: The overall average age was 35 years, and 58% of the subjects were men. Eight cases (25.8%) showed abnormal DU. The Delta among those with normal DU was -0.94 versus 0.27 +/- 0.39 with abnormal DU (P < .005). There was no significance as far as the biopsy at 1 year. CONCLUSIONS: Renal DU allows physicians to suspect complications at the first posttransplantation year. It shows a tendency to elevated blood pressure, as well as increased deterioration of renal function over the first year.

17beta-estradiol differentially activates mitogen-activated protein-kinases and improves survival following reperfusion injury of reduced-size liver in mice.

Ischemia-reperfusion injury (I/R-I), which is unavoidable in liver transplantation, impairs liver regeneration and predisposes to liver failure. The three major mitogen-activated protein-kinases (MAPKs): ERK, p38, and JNK, are critical in the transmission of signals triggered by proinflammatory cytokines, by stress, and by growth factors. JNK and p38alpha activation have been associated with apoptosis; p38beta with cell survival; and ERK with proliferation. Previous studies have demonstrated gender dimorphism in hepatocellular dysfunction after experimental trauma and hemorrhage. Female mice are protected to a much greater extent from I/R-I than male mice. We assessed the effects of 17beta-estradiol (17beta-E) on liver function, host survival, and cellular activation of MAPK in a murine model of I/R-I in reduced-size livers. C57BL/6 mice were subjected to 45 minutes of warm ischemia (70% of the liver mass). After reperfusion, the nonischemic lobes were excised. Vehicle, 17beta-E or the estrogen receptor antagonist ICI-182780, was delivered 1 hour before the injury. We evaluated AST and apoptosis as well as activation of JNK, p38, and ERK. Female mice showed a lower level of hepatocellular injury (AST = 445 +/- 82 IU/L) after I/R-I compared with male mice (AST = 1400 +/- 210). 17beta-E decreased the liver injury in male mice (AST = 522 +/- 77), an effect that was partially reversed by ICI-182,780 (910 +/- 92). A higher rate of apoptosis was observed in male animals given saline (enrichment factor = 7.22 +/- 0.8) versus those treated with 17beta-E (5.85 +/- 0.3, P < .05). A significant increase in liver regeneration, as assessed by the percentage of liver weight/body weight was demonstrated in females (184% +/- 24%) and male mice given 17beta-E (168% +/- 22%) compared with male mice given vehicle (9% +/- 4%). 17beta-E significantly down-regulated JNK and p38alpha activities, whereas I/R-I promoted p38beta and ERK activation. These results suggest that the cytoprotective effects of 17beta-E on I/R-I to reduced-size livers are associated with selective modulation of MAPK kinases.

Improved reduction in pain in chronic pancreatitis with combined intraoperative celiac axis plexus block and lateral pancreaticojejunostomy.

PURPOSE:Severe abdominal pain secondary to chronic pancreatitis is often multifactorial in origin. Lateral pancreaticojejunostomy (LPJ) is currently the accepted surgical treatment of choice when the main pancreatic duct is dilated. Chemical ablation of the celiac plexus for the treatment of intractable pain in chronic pancreatitis has been used without clear benefit. The aim of this study is to compare treatment outcomes of 2 groups of patients with the diagnosis of chronic pancreatitis and intractable abdominal pain (LPJ alone versus LPJ with intraoperative alcohol celiac ablation).Between 1994 and 1997, 34 patients underwent LPJ to control intractable pain secondary to chronic pancreatitis. These patients were divided into 2 groups, group 1 was LPJ only (16 patients) and group 2 was LPJ and intraoperative celiac ablation with 50% absolute alcohol (18 patients). Preoperative diagnosis and treatment criteria were similar for both groups. The clinical characteristics and outcome of both groups were retrospectively analyzed. Fisher exact test was used for statistical analysis.Demographic characteristics were similar in both groups. Pain control at short- and long-term follow-up was significantly improved in group 2 compared with group 1 (p < 0.035).Intraoperative celiac ablation in addition to LPJ appears to have a better response than does LPJ alone. Even though the number of patients is small, these results provide a basis for pursuing a prospective, randomized study to definitively answer this question.