Intrareservoir Administration of Alteplase to Treat a Distal Ventriculoatrial Shunt Obstruction.

BACKGROUND: Ventriculoatrial shunts can be afflicted with distal malfunctions due to thrombus formation at the distal tip. Distal tip thrombus formation may occur more commonly in oncologic patients who are predisposed to hypercoagulability. CASE DESCRIPTION: A patient who had a ventriculoatrial shunt placed for leptomeningeal carcinomatosis presented with headaches and confusion and was found to have a partial distal shunt obstruction. Intrareservoir administration of alteplase resulted in resolution of her symptoms. Nuclear medicine shunt patency test demonstrated restoration of distal flow. CONCLUSIONS: Intrareservoir administration of alteplase can be a useful nonoperative treatment strategy for ventriculoatrial shunt malfunction. This strategy may be particularly useful in cases with higher perioperative risk, such as patients with advanced metastatic cancer.

Delayed referral to specialist centre increases morbidity in patients with bile duct injury (BDI) after laparoscopic cholecystectomy (LC).

BACKGROUND: There is still a debate regarding the optimal management of bile duct injury following cholecystectomy. Our aim was to ascertain if delayed referral influenced clinical outcomes for patients with BDI treated in our institution. MATERIALS AND METHODS: We interrogated a prospectively maintained database, including all patients with BDI (Bismuth and Strasberg classifications) post LC managed in our unit from 2000-2014. Referrals were arbitrarily defined as early (<96 h from the injury) and delayed (>96 h). RESULTS: 68 patients with BDI were managed. Patient demographics, referral time, level of injury and morbidity data was collected. 50 patients (77%) required a surgical bile duct reconstruction. The Early referral Group included 33 patients (52.4%) and Delayed referral group 30 (47.6%). The patients referred late had a significantly high incidence of right hepatic artery injury (23% vs. 3%) and the overall number of complications (0.0001). The average number of surgical interventions (2.5 vs 1.8, p < 0.05) and invasive procedures (4 vs. 2.5, p < 0.05) per patient was high in the late referral group. There was significant difference in the interval between BDI-to-reconstruction (median 3 vs. median 88 days, p < 0.05) and referral-to-hospital discharge (median 9 vs. median days 59, p < 0.05). On multivariate analysis only delayed referral (OR 7.58, 95% CI 2.1-26.6) and Strasberg-E injuries (OR 4.86, 95% CI 1.1-20.9) were significant. CONCLUSION: A late referral was associated with a higher incidence of post-treatment complications, greater need for invasive procedures and a longer recovery period. These observations support the need for early patient transfer to a tertiary institution following BDI.

Gel-free proteomic methodologies to study reversible cysteine oxidation and irreversible protein carbonyl formation.

Oxidative modifications in proteins have been traditionally considered as hallmarks of damage by oxidative stress and aging. However, oxidants can generate a huge variety of reversible and irreversible modifications in amino acid side chains as well as in the protein backbones, and these post-translational modifications can contribute to the activation of signal transduction pathways, and also mediate the toxicity of oxidants. Among the reversible modifications, the most relevant ones are those arising from cysteine oxidation. Thus, formation of sulfenic acid or disulfide bonds is known to occur in many enzymes as part of their catalytic cycles, and it also participates in the activation of signaling cascades. Furthermore, these reversible modifications have been usually attributed with a protective role, since they may prevent the formation of irreversible damage by scavenging reactive oxygen species. Among irreversible modifications, protein carbonyl formation has been linked to damage and death, since it cannot be repaired and can lead to protein loss-of-function and to the formation of protein aggregates. This review is aimed at researchers interested on the biological consequences of oxidative stress, both at the level of signaling and toxicity. Here we are providing a concise overview on current mass-spectrometry-based methodologies to detect reversible cysteine oxidation and irreversible protein carbonyl formation in proteomes. We do not pretend to impose any of the different methodologies, but rather to provide an objective catwalk on published gel-free approaches to detect those two types of modifications, from a biologist's point of view.

Outcome after liver resection in patients presenting with simultaneous hepatopulmonary colorectal metastases.

BACKGROUND: The most common sites of metastasis from colorectal cancer (CRC) are hepatic and pulmonary; they can present simultaneously (hepatic and pulmonary metastases) or sequentially (hepatic then pulmonary metastases, or vice versa). Simultaneous disease may be aggressive, and thus may be approached with caution by the clinician. The aim of this study was to determine the outcomes following hepatic and pulmonary resection for simultaneously presenting metastatic CRC. METHODS: A retrospective review was undertaken of a prospectively maintained database to identify patients presenting with simultaneous hepatopulmonary disease who underwent hepatic resection. Patients' electronic records were used to identify clinicopathological variables. The log rank test was used to determine survival, and χ(2) analysis to determine predictors of failure of intended treatment. RESULTS: Fifty-nine patients were identified and underwent hepatic resection; median survival was 45·4 months and the 5-year survival rate 38 per cent. Twenty-two patients (37 per cent) did not have the intended pulmonary intervention owing to progression or recurrence of disease. Thirty-seven patients who progressed to hepatopulmonary resection had a median survival of 54·2 months (5-year survival rate 43 per cent). Those who had hepatic resection alone had a median survival of 24·0 months (5-year survival rate 30 per cent). Failure to progress to pulmonary resection was predicted by heavy nodal burden of primary colorectal disease and bilobar hepatic metastases. Redo pulmonary surgery following pulmonary recurrence did not confer a survival benefit. CONCLUSION: Selected patients with simultaneous hepatopulmonary CRC metastases should be considered for attempted curative resection, but some patients may not receive the intended treatment owing to progression of pulmonary disease after hepatic resection.

Performance of prognostic scores in predicting long-term outcome following resection of colorectal liver metastases.

BACKGROUND: Ten-year survival appears to define cure following resection of colorectal liver metastases (CRLMs). Various scores exist to predict outcome at 5 years. This study applied several scores to a patient cohort with 10 years of actual follow-up to assess their performance beyond 5 years. METHODS: The study included consecutive patients who underwent liver resection at a single institution between 1992 and 2001. The ability of eight prognostic scoring systems to predict disease-free (DFS) and disease-specific (DSS) survival was analysed using the C-statistic. RESULTS: Among 286 patients, the 1-, 3-, 5- and 10-year actual DSS rates were 86.6, 58.3, 39.5 and 24.5 per cent respectively. Seventy patients underwent 105 further resections for recurrent disease, of which 84.8 per cent were within 5 years of follow-up. Analysis of C-statistics showed only one score--the Rees postoperative index--to be a significant predictor of DFS and DSS at all time points. The remaining scores performed less well, and regularly showed no significant improvement in predictive accuracy over what would be expected by chance alone. No score yielded a C-statistic in excess of 0.8 at any time point. CONCLUSION: Although available risk scores can predict DFS and DSS, none does so with sufficient discriminatory accuracy to identify all episodes of recurrent disease. A non-negligible proportion of patients develop recurrent disease beyond 5 years of follow-up and so surveillance beyond this point may be advantageous.

[Evaluation of the risk of the clinical-surgical and pathology study findings in newborns with necrotizing enterocolitis who have received surgical treatment]. / Valoración de riesgo de los hallazgos clínico-quirúrgicos y de anatomía patológica en neonatos con enterocolitis necrotizante que han recibido tratamiento quirúrgico.

INTRODUCTION: Despite advances in neonatal care between 20% and 63% of children with necrotizing enterocolitis (NEC) require surgery. The aim was correlation the risk factors of infants with NEC "IIB / IIIA / IIIB" Bell and the clinical, surgical and pathological findings. METHOD: In the children with diagnosis of NEC surgically treated, were analyzed of variables: clinical, surgical and pathological findings. We studied two groups: control (n=5) and NEC group (n=12). Comparisons were made between groups using the Mann-Whitney U- and the Spearman coefficient (r). To assess the risk of morbidity / mortality associated with the extent of intestinal resection we applied the Cox regression. RESULT: We found differences (p < 0.05) between control group and the NEC group regarding Bell, the mean height of villi, Chiu and the number of goblet cells. In the NEC group we find correlations (p < 0.05) from Bell, regarding Chiu (r = 0.761), resection of the colon (r = 0.687), pneumatosis / perforation (r = 1) and the mean height of villi (r = -0.878). The gut reseccion was at 26 cm (3-107). We observed a risk of 1.04 in the neonatal period (p > 0.05) of mortality or consequence post-enterocolitis associated with the extent of bowel resection. CONCLUSION: The decrease in the average height of villi, the highest level of microscopic intestinal injury and reduced goblet cell population contributes to a greater extent of intestinal resection, which favors the risk of death or developing consequence post-enterocolitis.

[Inverted urothelial papilloma: our clinical experience]. / Papiloma invertido urotelial: nuestra experiencia clínica.

UNLABELLED: A study of inverted urothelial papilloma in our area. METHODS: A study was conducted of inverted urothelial papillomas diagnosed at our center from January 1994 to December 2007. This was a retrospective and prospective study with a descriptive statistical analysis: urological history, reason for consultation, diagnostic methods, tumor focality, follow-up method, prognosis, and recurrence. SPSS software version 13 was used for statistical analysis. RESULTS: Fourteen inverted papillomas were diagnosed in the study period in patients with a median age of 59 years. The presenting complaint was hematuria in 7 patients (50%), followed by low back pain in 2 patients (14.28%), and irritative syndrome in 1 patient (7.14%). The tumor was incidentally diagnosed in 4 patients (28.5%). A single relapse/recurrence occurred in a low-grade tumor during the follow-up period. CONCLUSIONS: Prognosis, recurrence, and malignant potential of this tumor are unclear, and controversy exists in the literature on this subject. Thus, although we think this is a benign tumor, we advise follow-up as if it were a low-grade urothelial tumor.

Renal graft outcome in simultaneous kidney transplantation combined with other organs: experience of a single center.

AIM: We report the renal graft outcomes among a series of patients who underwent simultaneous combined liver-kidney transplantations (CLKT) or heart-kidney transplantations (CHKT) at a single center. METHODS: From 1975 to December 31, 2007, we performed 1524 kidney transplantations, 427 liver transplantations, and 483 heart transplantations, including 7 simultaneous CLKT and 2 CHKT. We analysed the main patient characteristics, renal graft outcomes, and patient survivals. RESULTS: CLKT indications were as follows: alcoholic cirrhosis (n = 5) and hepatitis C virus (n = 2) with chronic glomerulonephritis (n = 5), hypertensive nephropathy (n = 1), and polycystic disease (n = 1). Cold renal ischemia time was 6.9 hours (range, 6-9). In 5 patients there were no kidney rejection episodes; 3 of these patients are alive with creatinine levels between 1.4 and 1.7 mg/dL with an average follow-up of 6.9 years (range, 10 months-8 years). One patient died of esophageal cancer at 13 years after transplantation with a serum creatinine level of 1.16 mg/dL and another died of breast cancer at 7 years after transplantation with a creatinine level of 1.1 mg/dL. One patient lost his renal graft just after the kidney transplantation due to renal vein thrombosis. The last patient suffered 1 episode of acute rejection and lost his kidney 5 years later due to chronic rejection. CHKT indications were as follow: dilated myocardiopathy (n = 2) and chronic glomerulonephritis (n = 1) or interstitial nephropathy (n = 1). The cold renal ischemia time was 4 hours. There were no acute rejection episodes. One patient is alive with a creatinine level of 2.05 mg/dL at 6 years after the transplantation; the other patient lost his kidney due to chronic rejection at 270 days after simultaneous CHKT, and 2 years later received a second kidney that is functioning normally. CONCLUSIONS: Simultaneous CLKT and CHKT in selected cases provided satisfactory long-term outcomes in both graft function and patient survival with lesser number of acute rejection episodes than nonsimultaneous transplantations. They are worthy options for patients with liver or heart failure associated with renal failure.

Surgery for hilar cholangiocarcinoma: the Leeds experience.

AIM: To review the experience with hilar cholangiocarcinoma and to determine the results of a radical surgical approach in a UK centre. METHODS: A 10-year review of all patients treated surgically for proximal bile duct carcinoma at a single surgical unit was conducted. Patient demographics, disease details and histopathology reports were reviewed. From January 1993 through December 2003, 106 patients were admitted with the diagnosis of hilar cholangiocarcinoma and 61 patients received surgical exploration. RESULTS: Tumours were staged as follows (UICC 6th edition): stage IB, n=10 IIA, n=9; IIB, n=20; III, n=8; IV, n=14. Out of 61 patients, 44 had a resection (3 bile duct resection alone, 41 liver resection with bile duct resection), 5 were considered unresectable and 12 underwent liver transplantation (LT). The caudate lobe was excised in 34 of the patients and regional lymphadenectomy was systematically carried out. Para-aortic lymphadenectomy was performed in 17 cases. Portal vein resection was needed in 17 and hepatic artery resection was performed in 4 cases. Negative histologic margins (R0) were achieved in 20 patients and microscopic margin involvement (R1) was seen in 16. In the remaining 8 resected patients, localised metastasis were found (peritoneal deposits in 2, liver metastasis in 4 and positive para-aortic lymph nodes in 2); nevertheless the resection was performed and it was considered R2. Overall survival at 3 and 5 years for patients who underwent a resection was 43% and 28% including postoperative deaths. The 1-, 3- and 5-year actuarial survival rates for patients who underwent R0 resection were 78%, 64% and 45% respectively, including the postoperative deaths (n=3). The median survival time was 41.1 months. The 1-, 3- and 5-year actuarial survival rates for R1 resection and R2 were 60%, 26%, 26% and 25% and 0% respectively, while the median survival time for these groups was 15.4 and 6.8 months respectively. The actuarial survival rate at 1, 3 and 5 years for well-differentiated tumours (G1) was 73%, 54% and 40% (median 39.7 months). The figures for G2 were 60%, 48% and 0%. The figures for G3 (poorly differentiated) were 16% and 0% at three years (p=0.03).The overall survival at 3 and 5 years for those patients who had a liver transplant was 41% and 20% including early postoperative mortality. The tumour grading (presence of poorly differentiated tumour) was found to be the only independent factor affecting the survival time producing a hazard ratio of 4.3 (p=0.0034, 95% confidence interval 0.1007-6.342). CONCLUSIONS: Radical surgical resection is the best treatment for hilar cholangiocarcinoma. R0 resection provides acceptable 5-year survival, but R1 resection may also provide acceptable palliation. In our experience TNM stage and tumour grade were the main determinants of long-term survival.

[Improvement in the results of surgical resection of hepatocellular carcinoma]. / Mejoría de los resultados de la resección quirúrgica del hepatocarcinoma.

AIM: To present the results of hepatectomies performed for hepatocellular carcinoma in a specialist unit and to compare the results of an initial period (1987-1993) with those obtained in a second period (1995-2000) in which the indications were limited to Child class A patients without portal hypertension. During the second period technical improvements such as intermittent selective hilar clamping and greater hiliar restrictions on transfusions were introduced. PATIENTS AND METHODS: One hundred and ten hepatectomies were performed in 105 patients with hepatocellular carcinoma in our unit over a 12-year period. Eighty percent of the tumors occurred in cirrhotic livers, mainly caused by hepatitis C virus. In the second period, upper gastrointestinal endoscopy was systematically performed to study the presence of varices. Hemodynamics studies were optionally performed to rule out portal hypertension. RESULTS: In the second period larger tumors were resected, a greater number of major hepatectomies were performed due to the increased frequency of hepatocellular carcinoma in non-cirrhotic liver, and fewer patients underwent transfusion. Early mortality was reduced from 21% to 1.8% and mean survival significantly increased from 37 to 52 months. Actuarial survival increased from 64% to 91% at 1 year and from 23% to 52% at 5 years in the first and second periods, respectively. Disease-free survival also increased significantly from 53% and 84% at 1 year and 27% and 40% at 5 years in the first and second periods, respectively. Analysis of the results in cirrhotic patients also showed a statistically significant improvement in early mortality and survival. Multivariate analysis of prognostic factors for survival demonstrated that the absence of blood transfusion, patients who underwent resection in the second period and the presence of pseudocapsules were independent factors for increased survival. CONCLUSIONS: The results of liver resection for hepatocellular carcinoma improved significantly due to the reduction in early mortality produced by more rigorous patient selection and the introduction of technical improvements.

Villoglandular adenocarcinoma of the vulva.

BACKGROUND: Only two previous cases of villoglandular adenocarcinoma of the vulva, an entity morphologically similar to tumors found in the uterine cervix and colorectum, have been reported. This paper communicates the first complete immunohistochemical study in villoglandular adenocarcinoma in order to determine its phenotype and histogenesis. CASE: A 69-year-old woman had a 1.5-cm nodule in the right labium majus. Histologically, it corresponded to a minimally atypical, villoglandular adenocarcinoma with a small microinvasion. Immunohistochemically, it was positive to OC125, CEA, and OC19.9 and coexpressed cytokeratins 7 and 20. Chromogranin, nuclear estrogen, and progesterone receptors were negative. CONCLUSION: Phenotypic expression was more consistent with a papillary mucinous ovarian or cervical neoplasm than of a colonic one. Its behavior was similar to that of its morphologic counterpart in the cervix, since the patient had no recurrence 3 years after a wide local excision.

Mechanisms underlying chlorhexidine-induced cytotoxicity.

Chlorhexidine (CLX) is the most widely used antiseptic for wound and skin disinfection. Despite its potent bactericidal action, skin irritation is observed when it is used topically. This study aimed to evaluate the mechanisms underlying CLX-induced toxicity on human dermal fibroblasts with special emphasis on factors that may mediate or counteract its undesirable effects. Cells were exposed to CLX concentrations of 0.00005-0.025% for 3, 6, 8 or 24 h in the absence or presence of different concentrations of foetal calf serum (FCS) (2, 5 and 10%). Depletion of cell ATP occurred, in a time- and concentration-dependent manner, in all experimental conditions at [CLX] >0.001%. At 24 h of CLX exposure time, the decrease in intracellular ATP was produced from a 10-times lower CLX concentration (0.0001%). Concentrations > or =0.02% produced total loss of ATP. However, cell survival was maintained after CLX treatment for 3 and 8 h and CLX concentrations > or =0.005% were required to produce total cell death. CLX exerted an inhibitory concentration-dependent effect on DNA synthesis from concentrations as low as 0.0001%. Only FCS at 10% appeared to have a cytoprotective action against CLX-induced cytotoxicity.

Outcome and hepatic hemodynamics in liver transplant patients with portal vein arterialization.

UNLABELLED: Few cases of successful portal vein arterialization in orthotopic and auxiliary liver transplantation have been reported. AIM: To evaluate the effect of portal vein arterialization on hepatic hemodynamics and long-term clinical outcome in three patients undergoing liver transplantation. METHODS: Two patients with extensive splanchnic venous thrombosis received an orthotopic liver transplant and one with fulminant hepatic failure received an auxiliary heterotopic graft. Portal vein arterialization was performed in all cases. RESULTS: One patient died 4 months after transplant and two are still alive. Auxiliary liver graft was removed 3 months post-transplant when complete native liver regeneration was achieved. Immediate post-transplant liver function was excellent in all cases. Only one patient developed encephalopathy and variceal bleeding owing to prehepatic portal hypertension secondary to arterioportal fistula 14 months after transplant. He was successfully treated by embolization of the hepatic artery. Hepatic hemodynamic measurements demonstrated a normal pressure gradient between wedged and free hepatic venous pressures in all cases. Liver biopsy showed acceptable graft architecture in two cases and microsteatosis in one. CONCLUSIONS: Liver transplantation with portal vein arterialization is an acceptable salvage alternative when insufficient portal venous flow to the graft is present. The double arterial supply does not imply changes in hepatic hemodynamics, at least in the early months post-transplant.

Auxiliary heterotopic liver transplantation with portal vein arterialization for fulminant hepatic failure.

Auxiliary liver transplantation for patients with fulminant hepatic failure supports the patient's failing liver for a period of time until the native liver (NL) has recovered and immunosuppression can be withdrawn. Auxiliary heterotopic liver transplantation (AHLT) with portal vein arterialization (PVA) has several advantages over auxiliary orthotopic liver transplantation: NL resection is not required, and the hepatic hilum is left untouched; thus, the chances of liver regeneration are optimal. The successful application of emergency AHLT with PVA in a young patient who developed toxic fulminant hepatic failure caused by tuberculostatic drugs is described. Two and one-half months after the procedure, the NL had completely regenerated; the graft was removed, and immunosuppression was suspended.

Adaptation of Spodoptera exigua (Lepidoptera: Noctuidae) to barley trypsin inhibitor BTI-CMe expressed in transgenic tobacco.

Nicotiana tabacum plants were transformed with the cDNA of barley trypsin inhibitor BTI-CMe under the control of the 35S CaMV promoter. Although the transgene was expressed and the protein was active in the homozygous lines selected, growth of Spodoptera exigua (Lepidoptera: Noctuidae) larvae reared on transgenic plants was not affected. The protease activity in larval midgut extracts after 2 days feeding on transformed tobacco leaves from the highest expressing plant showed a reduction of 25% in the trypsin-like activity compared to that from insects fed on non-transformed controls. The susceptibility of digestive serine-proteases to inhibition by BTI-CMe was confirmed by activity staining gels. This decrease was compensated with a significant induction of leucine aminopeptidase-like and carboxipeptidase A-like activities, while chymotrypsin-, elastase-, and carboxipeptidase B-like proteases were not affected.