Severe Hepatitis C Recurrence as a Risk Factor for Opportunistic Infections in Liver Transplant Recipients.

OBJECTIVE: The aim of the study was to determine the clinical characteristics, frequency of opportunistic infections (OI), and the outcomes for liver transplant recipients with severe hepatitis C virus (HCV) recurrence. In addition, the objective was to evaluate HCV recurrence as a risk factor for developing an OI. METHODS: We conducted a retrospective observational study recording all liver transplant recipients from July 1, 2003, to December 31, 2012. Patients with liver disease due to HCV were selected. Active surveillance of infections was conducted periodically, and patients were classified according to presence of severe HCV recurrence. RESULTS: Three hundred seventy patients underwent liver transplantation because of chronic HCV. One hundred forty-seven patients presented severe recurrence (SR) (49%) and 50 (17%) of them had post-liver transplant cholestatic hepatitis C. Patients with SR presented OI, especially cytomegalovirus (CMV) infections and invasive fungal infections, more frequently than patients without SR (33% vs 13%; P < .001). From the diagnosis of SR to the presentation of OI, the median number of days was 169 (6-2083). Acute allograft rejection (OR 1.8 95% confidence interval [CI] 1.1-3.3) donor age ≥60 years (OR 2.9 95% CI 1.3-6.8), and SR (OR 2.8, 95% CI 1.6-5.1) were independently associated with the development of OI in liver transplant recipients. CONCLUSION: A high index of suspicion of opportunistic infections must be maintained when faced with severe HCV recurrence in liver transplant recipients. Moreover, active surveillance against CMV infection and other prophylactic strategies against opportunistic infections should be considered.

Molecular Characterization of Acute Cellular Rejection Occurring During Intentional Immunosuppression Withdrawal in Liver Transplantation.

Acute cellular rejection occurs frequently during the first few weeks following liver transplantation. During this period, its molecular phenotype is confounded by peri- and postoperative proinflammatory events. To unambiguously define the molecular profile associated with rejection, we collected sequential biological specimens from 55 patients at least 3 years after liver transplantation who developed rejection during trials of intentional immunosuppression withdrawal. We analyzed liver tissue and blood samples obtained before initiation of drug withdrawal and at rejection, alongside blood samples collected during the weaning process. Gene expression profiling was conducted using whole-genome microarrays and real-time polymerase chain reaction. Rejection resulted in distinct blood and liver tissue transcriptional changes in patients who were either positive or negative for hepatitis C virus (HCV). Gene expression changes were mostly independent from pharmacological immunosuppression, and their magnitude correlated with severity of histological damage. Differential expression of a subset of genes overlapped across all conditions. These were used to define a blood predictive model that accurately identified rejection in HCV-negative, but not HCV-positive, patients. Changes were detectable 1-2 mo before rejection was diagnosed. Our results provide insight into the molecular processes underlying acute cellular rejection in liver transplantation and help clarify the potential utility and limitations of transcriptional biomarkers in this setting.

Recommendations of a gropu of experts for the pathological assessment of tumor regression of liver metastases of colorectal cancer and damage of non-tumour liver tissue after neoadjuvant theray

Colorectal cancer (CRC) incidence has increased during the past decades in Spain, being the first malignant tumour in incidence. Observed mortality for CRC is mainly due to liver and lung metastases. The only curative treatment is surgery; new surgical techniques and neoadjuvant treatments have increased the number of surgery candidate patients. Patients should be managed with a multidisciplinary approach that includes imaging techniques, chemotherapy, surgery and pathological assessment. As an answer to this approach, a group of pathology experts interested on CRC liver metastases aimed to review the diagnosis and prognosis of liver mestastases and developed practical recommendations for its assessment. The expert group revised the current literature and prepared questions to be discussed based on available evidence and on their clinical practise. As a result, recommendations for the assessment of tumour regression of liver metastases are proposed, which could be implemented in oncology centres allowing assessment standardisation for these patients. Prospective multi-center studies to evaluate these recommendations validity will further contribute to improve the standard care of CRC liver metastases patients (AU)

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Liver stiffness 1 year after transplantation predicts clinical outcomes in patients with recurrent hepatitis C.

The value of transient elastography (TE) to assess clinical outcomes in hepatitis C recurrence after liver transplantation (LT) has not been explored so far. We studied 144 hepatitis C-infected and 48 non-hepatitis C virus (HCV)-infected LT recipients and evaluated the prognostic value of TE 1 year after transplantation to predict clinical decompensations and graft and patient survival. In HCV patients, cumulative probabilities of liver decompensation 5 years after LT were 8% for patients with liver stiffness measurement (LSM) <8.7 kilopascals (kPa) versus 47% for patients with LSM ≥ 8.7 kPa (p<0.001). Five-year graft and patient cumulative survival were 90% and 92% in patients with LSM<8.7 kPa (p<0.001) and 63% and 64% in patients with LSM ≥ 8.7 kPa, respectively (p<0.001). Patients with low LSM 1 year after LT had excellent outcomes independently from receiving antiviral treatment or achieving sustained virological response (SVR). In contrast, graft survival significantly improved in patients with LSM ≥ 8.7 kPa who achieved SVR. No association between outcomes and LSM at 12 months was observed in non-HCV patients. In conclusion, LSM 1 year after LT is a valuable tool to predict hepatitis C-related outcomes in recurrent hepatitis C and can be used in clinical practice to identify the best candidates for antiviral therapy.

Recommendations of a group of experts for the pathological assessment of tumour regression of liver metastases of colorectal cancer and damage of non-tumour liver tissue after neoadjuvant therapy.

Colorectal cancer (CRC) incidence has increased during the past decades in Spain, being the first malignant tumour in incidence. Observed mortality for CRC is mainly due to liver and lung metastases. The only curative treatment is surgery; new surgical techniques and neoadjuvant treatments have increased the number of surgery candidate patients. Patients should be managed with a multidisciplinary approach that includes imaging techniques, chemotherapy, surgery and pathological assessment. As an answer to this approach, a group of pathology experts interested on CRC liver metastases aimed to review the diagnosis and prognosis of liver mestastases and developed practical recommendations for its assessment. The expert group revised the current literature and prepared questions to be discussed based on available evidence and on their clinical practise. As a result, recommendations for the assessment of tumour regression of liver metastases are proposed, which could be implemented in oncology centres allowing assessment standardisation for these patients. Prospective multi-center studies to evaluate these recommendations validity will further contribute to improve the standard care of CRC liver metastases patients.

Ischemic pre-conditioning in deceased donor liver transplantation: a prospective randomized clinical trial.

To assess the immediate and long-term effects of ischemic preconditioning (IPC) in deceased donor. liver transplantation (LT), we designed a prospective, randomized controlled trial involving 60 donors: control group (CTL, n = 30) or study group (IPC, n = 30). IPC was induced by 10-min hiliar clamping immediately before recovery of organs. Clinical data and blood and liver samples were obtained in the donor and in the recipient for measurements. IPC significantly improved biochemical markers of liver cell function such as uric acid, hyaluronic acid and Hypoxia-Induced Factor-1 alpha (HIF-1 alpha) levels. Moreover, the degree of apoptosis was significantly lower in the IPC group. On clinical basis, IPC significantly improved the serum aspartate aminotransferase (AST) levels and reduced the need for reoperation in the postoperative period. Moreover, the incidence of primary nonfunction (PNF) was lower in the IPC group, but did not achieve statistical significance. We conclude that 10-min IPC protects against I/R injury in deceased donor LT.

EUS FNA in intraductal papillary mucinous tumors of the pancreas.

BACKGROUND/AIMS: There is little information concerning the potential role of fine-needle aspiration guided by endoscopic ultrasonography in the pathologic diagnosis of intraductal papillary mucinous tumors of the pancreas. METHODOLOGY: Patients with an intraductal papillary mucinous tumor of the pancreas suggested by endoscopic ultrasonography underwent fine-needle aspiration guided by endoscopic ultrasonography in order to investigate the presence of mucin and/or cytologic changes consistent with this diagnosis. A group of 111 patients with other pancreatic lesions explored during the same period of time was used as a control group. RESULTS: Fine-needle aspiration guided by endoscopic ultrasonography was safely performed in 19 patients and supported the diagnosis in 17 of them. Nine out of the 17 patients with suspicion of intraductal papillary mucinous tumors of the pancreas went to surgery and this diagnosis was confirmed in the resected specimen in all of them. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of EUS FNA in the diagnosis of IPMT were 82%, 100%, 100%, 92% and 94% respectively. CONCLUSIONS: Fine-needle aspiration guided by endoscopic ultrasonography is a good technique to support the diagnosis of intraductal papillary mucinous tumors of the pancreas and should be considered in this group of patients if pathologic confirmation is judged to be necessary.

Does Helicobacter pylori have a pathogenic role in bronchiectasis?

AIM: To investigate the presence of Helicobacter pylori (H. pylori) in bronchial biopsies of patients with bronchiectasis, by histochemical and immunochemical staining. SETTING: 800-bed tertiary university hospital. METHODS: Observational study. PATIENTS: forty-six patients with bronchiectasis in a stable clinical condition and 8 control patients. INTERVENTIONS: Serum samples determination of IgG levels for H. pylori by ELISA. Immunostaining with an anti-H. pylori antibody (NCL-HPp, Novocastra) of bronchial mucosa obtained by fiberoptic bronchoscopy from both patients with bronchiectasis and controls. RESULTS: Twenty-one out of 46 patients with bronchiectasis (46%) had positive serology for H. pylori. We obtained 40 bronchial biopsies in patients with bronchiectasis and 8 bronchial biopsies in control patients. No evidence of H. pylori was obtained in the bronchial samples of both patients and controls. CONCLUSIONS: The results of our study could not demonstrate the presence of H. pylori in bronchial specimens from patients with bronchiectasis.

[Intestinal occlusion due to pancreatitis mimicking stenosing neoplasm of the splenic angle of the colon]. / Oclusión intestinal secundaria a pancreatitis que mimetiza una neoplasia estenosante del ángulo esplénico del colon.

Colonic involvement in patients with severe acute pancreatitis or chronic pancreatitis is common and complications such as paralytic ileus, segmental necrosis and pancreatic-colonic fistulae have been described. However, mechanical occlusion of the colon due to pancreatitis is infrequent. We present the case of a 45-year-old man with occlusion of the colon secondary to asymptomatic pancreatitis mimicking a locally advanced stenosing neoplasm of the splenic angle. Ten years prior to the present episode the patient had presented acute alcoholic pancreatitis complicated by a pseudocyst requiring surgery. The current reason for admission was abdominal colic pain and constipation with onset 5 days previously. Contrast enema was administered showing colonic occlusion caused by stenosis at the splenic flexure, suggesting the presence of a neoplasm. Urgent laparotomy showed the presence of a tumor originating in the colon that infiltrated the splenic hilum. Subtotal colectomy and en-bloc splenectomy were performed. Histopathological analysis showed pericolonic inflammation and fibrosis secondary to pancreatitis; the colonic mucosa showed no tumoral infiltration. To date, fewer than 30 cases of this infrequent complication have been published.

Oclusión intestinal secundaria a pancreatitis que mimetiza una neoplasia estenosante del ángulo esplénico del colon / Intestinal occlusion due to pancreatitis mimicking stenosing neoplasm of the splenic angle of the colon

La afectación del colon en pacientes con pancreatitis aguda grave o pancreatitis crónica es frecuente y se han descrito complicaciones como el íleo paralítico, la necrosis segmentaria y la fístulas pancreatocolónicas. Sin embargo, la oclusión mecánica del colon debida a la pancreatitis es infrecuente. Presentamos el caso de un paciente de 45 años con una oclusión de colon secundaria a una pancreatitis asintomática que mimetizaba una neoplasia estenosante y localmente avanzada del ángulo esplénico. El paciente había presentado una pancreatitis aguda alcohólica complicada con un seudoquiste que requirió cirugía 10 años antes del presente episodio. El motivo del ingreso actual fue dolor abdominal cólico y estreñimiento de 5 días de evolución. Se realizó un enema con contraste que mostraba una oclusión de colon causada por una estenosis en la flexura esplénica muy indicativa de neoplasia. La laparotomía de urgencia mostró la presencia de una tumoración originada en el colon que infiltraba el hilio esplénico. Se realizaron una colectomía subtotal y una esplenectomía en bloque. El examen histopatológico mostró una inflamación pericólica y fibrosis secundaria a una pancreatitis; la mucosa del colon no mostraba infiltración tumoral. Hasta ahora se han publicado menos de 30 casos de esta infrecuente complicación

Colonic involvement in patients with severe acute pancreatitis or chronic pancreatitis is common and complications such as paralytic ileus, segmental necrosis and pancreatic-colonic fistulae have been described. However, mechanical occlusion of the colon due to pancreatitis is infrequent. We present the case of a 45-year-old man with occlusion of the colon secondary to asymptomatic pancreatitis mimicking a locally advanced stenosing neoplasm of the splenic angle. Ten years prior to the present episode the patient had presented acute alcoholic pancreatitis complicated by a pseudocyst requiring surgery. The current reason for admission was abdominal colic pain and constipation with onset 5 days previously. Contrast enema was administered showing colonic occlusion caused by stenosis at the splenic flexure, suggesting the presence of a neoplasm. Urgent laparotomy showed the presence of a tumor originating in the colon that infiltrated the splenic hilum. Subtotal colectomy and en-bloc splenectomy were performed. Histopathological analysis showed pericolonic inflammation and fibrosis secondary to pancreatitis; the colonic mucosa showed no tumoral infiltration. To date, fewer than 30 cases of this infrequent complication have been published

Anti-inflammatory effects of pancreatitis associated protein in inflammatory bowel disease.

BACKGROUND AND AIMS: Increased pancreatitis associated protein (PAP) mRNA has been reported in active inflammatory bowel disease (IBD). The aims of the current study were to characterise PAP production in IBD and the effects of PAP on inflammation. PATIENTS AND METHODS: Serum PAP levels were determined in healthy controls (n = 29), inflammatory controls (n = 14), and IBD patients (n = 171). Ex vivo PAP secretion in intestinal tissue was measured in 56 IBD patients and 13 healthy controls. Cellular origin of PAP was determined by immunohistochemistry. The effects of exogenous PAP on nuclear factor kappaB (NFkappaB) activation, proinflammatory cytokine production, and endothelial adhesion molecule expression were also analysed ex vivo. RESULTS: Patients with active IBD had increased serum PAP levels compared with controls, and these levels correlated with clinical and endoscopic disease severity. Ex vivo intestinal PAP synthesis was increased in active IBD and correlated with endoscopic and histological severity of inflammatory lesions. PAP localised to colonic Paneth cells. Incubation of mucosa from active Crohn's disease with PAP dose dependently reduced proinflammatory cytokines secretion. PAP prevented TNF-alpha induced NFkappaB activation in monocytic, epithelial, and endothelial cells and reduced proinflammatory cytokine mRNA levels and adhesion molecule expression. CONCLUSIONS: PAP is synthesised by Paneth cells and is overexpressed in colonic tissue of active IBD. PAP inhibits NFkappaB activation and downregulates cytokine production and adhesion molecule expression in inflamed tissue. It may represent an anti-inflammatory mechanism and new therapeutic strategy in IBD.

Mitochondrial DNA depletion in liver tissue of patients infected with hepatitis C virus: contributing effect of HIV infection?

OBJECTIVES: It has been suggested that chronic hepatitis C virus (HCV) infection depletes mitochondrial DNA (mtDNA) in the liver. Because decreased mtDNA levels were also found in humans infected with HIV, we investigated whether HIV may have aggravated hepatic mtDNA depletion in individuals with HCV infection. METHODS: In this cross-sectional study, liver biopsies were performed in a total of 40 individuals prior to any antiviral therapy. The individuals were recruited from the Hospital Clinic, Barcelona and the HIV Centre, Dusseldorf. Seventeen patients were negative for HIV and HCV and were biopsied for liver enzyme elevation of unknown cause (controls), 14 individuals had chronic HCV but no HIV infection, and nine subjects were coinfected with both viruses. mtDNA and liver histology were centrally assessed. RESULTS: The groups did not differ with respect to age, gender, liver function tests and HCV viral load, where applicable. mtDNA levels were decreased by 19% in the HCV-monoinfected group (P=0.03) and by 27% in the HIV/HCV-coinfected subjects (P=0.02) compared to controls. The mtDNA content, however, did not differ between individuals with HCV monoinfection and HCV/HIV coinfection (P=0.75). The degrees of liver fibrosis, inflammatory activity or steatosis did not correlate with mtDNA content. CONCLUSIONS: Liver mtDNA content is reduced in both HCV-monoinfected and HIV/HCV-coinfected patients. Under the limitations of our study, we could demonstrate only a slight trend towards more pronounced mtDNA depletion in HIV/HCV-coinfected subjects.

Acute and chronic captopril, but not prazosin or nifedipine, normalize alterations in adrenergic intracellular Ca2+ handling observed in the mesenteric arterial tree of spontaneously hypertensive rats.

The effect of hypertension and acute (36-h) or chronic (from age 6 to 16 weeks) antihypertensive treatment with prazosin (2 mg kg(-1) per day), nifedipine (50 mg kg(-1) per day), or captopril (50 mg kg(-1) per day) on Ca2+ mobilization due to alpha1-adrenoceptor activation was analyzed in functional studies using arterial rings [four conductance/distributing vessels: aorta, main mesenteric, iliac, and tail arteries and two resistance vessels; first and second small mesenteric artery branches obtained from spontaneously hypertensive rats (SHR, 6 and 16 weeks old) and age-matched Wistar Kyoto rats (WKY)]. Maximal response to noradrenaline in the presence of extracellular Ca2+ is not affected by hypertension or by the antihypertensive treatment. The extracellular Ca2+-independent contractile responses increased with age in iliac, tail, and small mesenteric arteries (SMA) and were further increased in SHR in SMA from both young and adult animals and in the main mesenteric artery of adult SHR. In main mesenteric artery, this increased contraction in SHR was associated with a higher increase in cytosolic [Ca2+] mobilized by noradrenaline without changes in the total stored Ca2+. Acute or chronic treatment with captopril abolished the differences observed between WKY and SHR in the noradrenaline-induced contraction in mesenteric arteries loaded in Ca2+-free medium. In contrast, animals acutely treated with prazosin or chronically treated with either prazosin or nifedipine exhibit the same differences in Ca2+ handling than untreated rats. In conclusion, these differences are not a consequence of increased blood pressure but precede it and can only be normalized by inhibition of the rennin-angiotensin system.

[Hospital registry of pancreatic tumors. Experience of the Hospital Clínic in Barcelona (Spain)]. / Registro hospitalario de tumoraciones pancreáticas. Experiencia del Hospital Clínic de Barcelona.

OBJECTIVE: To describe the characteristics of patients included in the pancreatic tumor registry of the Hospital Clínic of Barcelona. PATIENTS AND METHOD: All patients with pancreatic tumors attended between July 1990 and March 2003 were registered. Data collection included: age, gender, date of diagnosis, diagnosis, histology, size, location and tumor stage, and treatment. The correlation between tumor stage and age, date of diagnosis, and tumor location was also evaluated. RESULTS: Six hundred thirty patients with pancreatic tumors were included, representing an incidence of 60 patients/year. The mean age was 66 years and the male-to-female ratio was 1,18:1. The most frequent lesion was malignant tumor of the pancreas (92%), and the most frequent histological type was pancreatic ductal adenocarcinoma (73%). The most frequent location was the head of the pancreas (64%). In 28% of the patients, pancreatic cancer was diagnosed in stage I and II. Resection was performed in 31% of patients, whereas 48% of the patients received no treatment. The ratio between local (stage I)/disseminated (stage IV) disease was 0,34. The ratio between stage I/IV increased with age, diagnosis prior to 1994, and tumor location in the head of the pancreas. CONCLUSION: Hospital tumor registries can be used to define the profile of the attended population, which can help to delineate the best diagnostic-therapeutic strategy and can be useful in clinical research.

Follow-up of a large-B-cell pancreatic lymphoma by endoscopic ultrasonography.

Although computed tomography and endoscopic ultrasound (EUS) are well-established procedures used to evaluate pancreatic masses, it is well known that imaging techniques alone cannot be used to distinguish between adenocarcinoma and tumors of less common cellular origin, such as primary pancreatic lymphoma. Clinicians must always consider this kind of malignancy in their differential diagnosis since, although rare, its treatment is nonsurgical and it has a better prognosis than adenocarcinoma. Histological examination of focal masses in the pancreas is therefore mandatory in order to establish the best therapeutic approach for every patient. Endoscopic ultrasound has developed as a very useful tool for the diagnosis of pancreatic tumors but could also be considered as a very useful method in the follow-up of these patients after treatment.

[Evaluation of the efficacy and efficiency of a multidisciplinary unit for the treatment of patients with colorectal cancer]. / Evaluación de la eficacia y eficiencia de una unidad multidisciplinaria para la atención de pacientes con cáncer colorrectal.

INTRODUCTION: Because of the increased complexity of the diagnostic-therapeutic approach to colorectal cancer (CRC), these patients should be managed in specialized multidisciplinary units. The aim of this study was to evaluate the efficacy and efficiency of a CRC unit (CRCU) in the diagnostic-therapeutic management of these patients. PATIENTS AND METHODS: Two groups of 50 patients with colon cancer treated in our center before and after the implementation of the CRCU were selected. Fulfillment with the protocol in terms of tumoral staging, surgical and adjuvant treatment, follow-up, interval until treatment, hospital stay, morbidity and early mortality, and the overall duration of the diagnostic-therapeutic process was analyzed. In addition, clinical workload was evaluated and a cost-minimization analysis was performed. RESULTS: The CRCU reduced the interval until surgery (20.3 12.0 vs 28.0 20.4 days; p = 0.05), hospital stay (9.8 7.7 vs 14.5 9.3 days: p = 0.01), the time to the start of adjuvant treatment (29.4 10.2 vs 39.7 19.8 days; p = 0.03) and the overall duration of the process (60.4 23,8 vs 82.1 46.1 days; p = 0.05), representing a saving of 978.85 E per patient. This improvement took place despite an increase in clinical workload (24% in 5 years in relation to the number of admissions) and had no effect on morbidity (26 vs 24%; NS) or immediate mortality (6 vs 4%; NS). CONCLUSION: Specialized multidisciplinary units increase the efficacy and efficiency of the management of patients with CRC.

Primary systemic amyloidosis presenting as a colonic stricture: successful treatment with left hemicolectomy followed by autologous hematopoietic stem-cell transplantation: report of a case.

Intestinal tract involvement by primary systemic amyloidosis is frequent but usually asymptomatic. Ischemic colitis caused by amyloid infiltration of wall blood vessels can occasionally be observed. We report a 62-year-old female with primary systemic amyloidosis who presented with intestinal obstruction caused by ischemic stricture of the sigmoid colon, secondary to submucosal amyloid deposition. The patient was successfully treated with surgical resection followed by high-dose chemotherapy and hematopoietic stem-cell transplantation. The clinical manifestations and differential diagnosis of gastrointestinal involvement of primary systemic amyloidosis, as well as its current treatment, are discussed.