Mycotic aneurysm of the hepatic artery in pediatric liver transplantation: A case series and literature review.

Mycotic aneurysm of the hepatic artery (HA) is a rare, unpredictable, and potentially lethal complication of liver transplantation (LT). Pediatric LT is not exempt from it but the related literature is rather scanty. We present our experience with post-LT mycotic aneurysm of the HA in pediatric age, describing four cases occurred with a special focus on the possible risk factors for its development and a proposal for the management of high-risk recipients.

Rapamycin ameliorates the CTLA4-Ig-mediated defect in CD8(+) T cell immunity during gammaherpesvirus infection.

Latent viral infections are a major concern among immunosuppressed transplant patients. During clinical trials with belatacept, a CTLA4-Ig fusion protein, patients showed an increased risk of Epstein-Barr virus-associated posttransplant lymphoproliferative disorder, thought to be due to a deficient primary CD8(+) T cell response to the virus. Using a murine model of latent viral infection, we observed that rapamycin treatment alone led to a significant increase in virus-specific CD8(+) T cells, as well as increased functionality of these cells, including the ability to make multiple cytokines, while CTLA4-Ig treatment alone significantly dampened the response and inhibited the generation of polyfunctional antigen-specific CD8(+) T cells. However, the addition of rapamycin to the CTLA4-Ig regimen was able to quantitatively and qualitatively restore the antigen-specific CD8(+) T cell response to the virus. This improvement was physiologically relevant, in that CTLA4-Ig treated animals exhibited a greater viral burden following infection that was reduced to levels observed in untreated immunocompetent animals by the addition of rapamycin. These results reveal that modulation of T cell differentiation though inhibition of mTOR signaling can restore virus-specific immune competence even in the absence of CD28 costimulation, and have implications for improving protective immunity in transplant recipients.

Development and validation of an adsorption process for phosphate removal and recovery from municipal wastewater based on hydrotalcite-related materials.

In the current international context characterized by the tendency to stricter limits for P concentration in treated wastewater and a strong drive towards phosphate recovery, it is crucial to develop cost-effective technologies to remove and recover phosphate from municipal wastewater (MWW). In this study, an initial screening of the phosphate adsorption performances of 9 sorbents including several hydrotalcites led to the selection of calcined pyroaurite - an innovative material composed of mixed Mg/Fe oxides - as the best-performing one. The assessment of calcined pyroaurite by means of isotherms and continuous-flow adsorption/desorption tests conducted with actual MWW resulted in a high P sorption capacity (12 mgP g-1 at the typical phosphate concentration in MWW), the capacity to treat 730 BVs at the 1 mgP L-1 breakpoint imposed by the current EU legislation, and a 93 % phosphate recovery. Calcined pyroaurite resulted in satisfactory performances also in a test conducted with a saline MWW deriving from a hotspot of seawater intrusion, a rapidly increasing phenomenon as a result of climate change. Five consecutive adsorption/desorption cycles conducted in a 20-cm column at a 5-min empty bed contact time resulted stable in terms of P adsorption/recovery performances, specific surface area and chemical structure of calcined pyroaurite. In the perspective to apply phosphate recovery with calcined pyroaurite at full scale, the process scale-up to a 60-cm packed bed - close to the column heights of industrial applications - resulted in stable performances. Calcium phosphate, widely used to produce phosphate-based fertilizers, can be obtained from the desorbed product by precipitation with Ca(OH)2. These results point to calcined pyroaurite as a very promising material for phosphate removal and recovery from MWW and from other P-rich effluents in a circular economy perspective.

An anti-CD154 domain antibody prolongs graft survival and induces Foxp3(+) iTreg in the absence and presence of CTLA-4 Ig.

The use of monoclonal antibodies targeting the CD154 molecule remains one of the most effective means of promoting graft tolerance in animal models, but thromboembolic complications during early clinical trials have precluded their use in humans. Furthermore, the role of Fc-mediated deletion of CD154-expressing cells in the observed efficacy of these reagents remains controversial. Therefore, determining the requirements for anti-CD154-induced tolerance will instruct the development of safer but equally efficacious treatments. To investigate the mechanisms of action of anti-CD154 therapy, two alternative means of targeting the CD40-CD154 pathway were used: a nonagonistic anti-CD40 antibody and an Fc-silent anti-CD154 domain antibody. We compared these therapies to an Fc-intact anti-CD154 antibody in both a fully allogeneic model and a surrogate minor antigen model in which the fate of alloreactive cells could be tracked. Results indicated that anti-CD40 mAbs as well as Fc-silent anti-CD154 domain antibodies were equivalent to Fc-intact anti-CD154 mAbs in their ability to inhibit alloreactive T cell expansion, attenuate cytokine production of antigen-specific T cells and promote the conversion of Foxp3(+) iTreg. Importantly, iTreg conversion observed with Fc-silent anti-CD154 domain antibodies was preserved in the presence of CTLA4-Ig, suggesting that this therapy is a promising candidate for translation to clinical use.

Chloroform aerobic cometabolism by butane-growing Rhodococcus aetherovorans BCP1 in continuous-flow biofilm reactors.

This work focuses on chloroform (CF) cometabolism by a butane-grown aerobic pure culture (Rhodococcus aetherovorans BCP1) in continuous-flow biofilm reactors. The goals were to obtain preliminary information on the feasibility of CF biodegradation by BCP1 in biofilm reactors and to evaluate the applicability of the pulsed injection of growth substrate and oxygen to biofilm reactors. The attached-cell tests were initially conducted in a 0.165-L bioreactor and, then, scaled-up to a 1.772-L bioreactor. Glass cylinders were utilized as biofilm carriers. The continuous supply of growth substrate (butane), which led to the attainment of the highest CF degradation rate (8.4 mg(CF) day(-1) m (biofilm surface)(-2)), was compared with four schedules of butane and oxygen pulsed feeding. The pulsed injection technique allowed the attainment of a ratio of CF mass degraded per unit mass of butane supplied equal to 0.16 mg(CF) mg (butane)(-1), a value 4.4 times higher than that obtained with the continuous substrate supply. A procedure based on the utilization of integral mass balances and of average concentrations along the bioreactors resulted in a satisfactory match between the predicted and the experimental CF degradation performances, and can therefore be utilized to provide a guideline for optimizing the substrate pulsed injection schedule.

Liver transplantation in children weighting less than 6 kg: the Bergamo experience.

Liver transplantation (OLT) remains a major medical and surgical challenge in small patients. From October 1997 through July 2004, 17 babies less than 6 kg underwent 18 OLTs. Median age and weight were 3 months (range = 1 to 9) and 4.7 kg (range = 2.2 to 5.8). Two whole, one reduced, and 15 split-liver grafts (left lateral segments) were obtained from donors of median age and weight of 11.6 years (range = 0.5 to 62) and 50 kg (range = 7 to 63). Donor-to-recipient median weight ratio (D/R) was 9.1 kg (range = 1.3 to 17.6) and median graft-to-recipient weight ratio (GRWR) was 5% (range = 3.1 to 10). The incidence of biliary complications was 23%. The only vascular complication was a portal vein thrombosis (6%). Fourteen patients (79%) are alive with good graft function at a median follow-up of 39 months (range = 0.5 to 74). Three patients (all status 1) died on postoperative day 285 (brain death), 17 (multiorgan failure), and 229 (cardiovascular failure during retransplantation). Actuarial patient survivals at 6 months and 6 years are 94% and 78% while graft survivals are 89% and 74%, respectively. Currently all the patients listed as UNOS status 2 and 3 (73%) at the time of transplant are alive. During the same period one premature neonate (1.8 kg) who presented with fulminant hepatic failure died on the waiting list after 12 days. Our data confirm that the extensive use of a split-liver technique from small adult or pediatric cadaveric donors can offer the benefits of liver transplantation to small pediatric candidates with excellent results.

Use of extended right grafts from in situ split livers in adult liver transplantation: a comparison with whole-liver transplants.

INTRODUCTION: We report our experience of in situ split-liver transplantation (SLT) for adult patients and compare the results with those achieved with whole-liver transplantation (WLT). METHOD: From November 1997 to December 2003, 109 liver transplantation were performed in 104 adult patients including 90 WLT (83%) and 19 SLT (17%) grafts. Fifteen extended right grafts (ERG, segments I + IV to VIII) were obtained with in situ split-liver procedures, generating also left lateral segment grafts, which were transplanted at our institution or elsewhere. Four left lobe (LL, segments I to IV) and right lobe (segments V to VIII) grafts were obtained by a modified in situ procedure for adult recipients. UNOS status, percentage of primary or secondary transplantation, and underlying liver disease were similar among patients receiving whole versus split grafts. Donors were older in whole than ERG cohorts (53 vs 26 years, P < .001). Procurement parameters and intraoperative profiles of transplant procedure were comparable among the groups. RESULTS: Median follow-up was 18 months (range: 1 to 73). Four patients with whole (4%) and no patient with ERG underwent retransplantation (P = NS). One- and 3-year patient survivals were 86% and 79% with WLT versus 93% and 93% with ERG (P = NS). One- and 3-year graft survivals were 84% and 75% with WLT versus 93%, and 93% with ERG (P = NS). Incidence of vascular complications was 8% with WLT, 13% with ERG (P = NS). The incidence of biliary complications was 13% in WLT, 27% in ERG (P = NS). CONCLUSIONS: The use of ERG from in situ split livers for adult transplantation allowed us to obtain results comparable or even better than those obtained with WLT. Split-liver transplantation is an effective, safe mechanism to expand the cadaveric donor pool.

Early portal vein thrombosis after pediatric split liver transplantation with left lateral segment graft.

Early portal vein thrombosis (PVT) represents a serious complication after liver transplantation (OLTx). From October 1997 through July 2004, 260 OLTx were performed in 231 children, including 189 of left lateral segments (LLS). We retrospectively analyzed the incidence and the outcome of early PVT in this group. A daily doppler US scan was performed during the first week after transplantation. Early PVT occurred in 14 patients (8%), 10 males and four females of median age 0.77 years. The main indication for primary transplantation was biliary atresia (10), followed by Byler's disease (2), acute liver failure on cryptogenetic cirrhosis (1), and Alagille syndrome (1). Four children underwent retransplantation; three cases of thrombectomy and revision of the anastomosis, two children were treated with beta blockers, one of whom had a later failed attempt at percutaneous revascularization and eventually a meso-caval shunt. Five patients were followed with observation and no treatment. Among the four patients who died, three were in the retransplantation group and one in the thrombectomy and revision of the anastomosis group; the overall mortality was 28%. With a median follow up of 399 days, 10 patients are alive with an actuarial survival at 1 and 5 years of 72%, and graft survival rates at 1 and 5 years of 64%. PVT represents a serious complication after pediatric OLTx with LLS grafts. Prompt detection and aggressive surgical treatment in selected cases are required to reduce the mortality and graft loss.

Transplantation for acute liver failure in children.

We reviewed the clinical data of 30 children-hospitalized for acute liver failure in the last 6 years. Ten patients were not listed for liver transplantation OLTX. Their clinical conditions gradually improved and they are all alive without deficit. Among 20 patients listed, 15 underwent urgent OLTX. Two children died on the waiting list and three were suspended from waiting list after few days because of improvement. Survival according to age class was analyzed dividing the patients into two groups: A, age 1 year or less versus B, age between 1 and 16 years. The patient survival was 86% at 6 months and 61% both at 1 and 2 years. Survival at 6 months and 1 and 2 years was 88%, 67%, and 45% for the patients in group A and 83%, 83%, and 83% for the patients in group B (P = NS). Observing graft-to-recipient weight ratio and donor-to-recipient weight ratio most patients received an optimal sized graft. The split-liver technique is considered the preferred method of liver transplantation even in the pediatric patients with acute liver failure; especially in the setting of a cooperative system in which all livers that are suitable for split-liver transplantation are shared between centers. In order to have the best chance for survival, children with acute liver failure should be referred as soon as possible to an highly specialized pediatric liver transplantation center that can offer all the treatment modalities that are currently available.

Orthotopic liver transplantation for Byler's disease.

In this study we analyzed the features of 12 patients who underwent liver transplantation for progressive familial intrahepatic cholestasis (Byler's disease [BD]) in view of the technical features of the OLTx, incidence and type of complications, need for retransplantation, as well as patient and graft survivals. BD was the indication in 12 patients of median age 1.32 years and median weight 10 kg. Median follow-up was 670 days. Major surgical complications requiring reintervention occurred in three patients. No thrombosis of the hepatic artery was observed. Infections with positive blood cultures were diagnosed in four patients. One patient had a biliary anastomotic stenosis successfully treated by percutaneous techniques. Four patients had episodes of acute rejection treated with steroids. Two patients were retransplanted, both of whom died in the early postoperative period due to hepatic vein thrombosis and venoenteric fistula. The actuarial patient and graft survival was 83% at 1 year and 83% at 5 years. Split-liver grafts represent an excellent organ supply for these patients, achieving good results with no mortality on the waiting list.

Orthotopic liver transplantation for biliary atresia.

Biliary atresia (BA) represents the most frequent indication for liver transplantation (OLTX) in the pediatric population. The aim of this paper was to present a series collected over the last 7 years from October 1997 through July 2004, including 260 pediatric OLTX in 231 patients. BA was the indication in 137 patients. There were 69 boys and 68 girls of mean weight 10.68 kg and median age 0.9 years. As a primary transplant, 99 patients received a LLS graft; 27 a whole graft; four a I+IV-VIII segment, and two a I-IV segment. Mean follow up was 1047 days (range, 1-2496 day). Infections were diagnosed in 45 patients, vascular complications in 27 patients. Surgical complications that required reintervention occurred in 25 patients. In 41 cases biliary complications occurred, 11 requiring reintervention. 16 patients were retransplanted. In two cases another re-OLTx was performed. Currently 126 patients are alive, showing an actuarial 1 year survival of 92% and 5 year 91%, with actuarial graft survivals of 85% at 1 year and 82% at 3 and 5 years. Our results confirm the effectiveness of OLTx for the treatment of children with BA and a failed Kasai procedure. Split liver grafts represent an excellent organ supply for these patients, achieving optimal results with no mortality on the waiting list.

Orthotopic liver transplantation for alagille syndrome.

Alagille syndrome (AS) is a dominantly inherited, multisystem disorder involving the liver, heart, eyes, face, and skeleton. From October 1997 through July 2004, 260 pediatric orthotopic liver transplantations (OLTx) were performed in 231 patients. This report describes 21 patients of median age 1.95 years (range, 0.7-16.7) who had alagille syndrome. We present the technical features of the OLTx, incidence and type of complications, medical conditions related to the syndrome, need for retransplantation, as well as patient and graft survival rates. A split liver technique was used in 16 patients (76%) who received a left lateral segment (LLS) graft whereas 7 patients (33%) received a whole liver. Only cadaveric donors were used. The major surgical complications requiring reintervention in 11 patients (52%) included biliary problems (19%) and vascular complications (17%). One case of hepatic artery thrombosis required retransplantation. Three recipients (14%) died. All other patients are alive with an actuarial survival rate of 90% at 1 year and 80% at 5 years. The actuarial graft survival rate is 85% at 1 year and 75% at 5 years. Patients with AS, despite the associated cardiovascular anomalies, can be treated successfully by a combined approach between cardiologist, radiologist, cardiothoracic, and liver transplant surgeons. With careful planning and operative management, the results are comparable with those obtained with other more common cholestatic diseases.

Hormonal modulation of Ishikawa cells during three-dimensional growth in vitro.

OBJECTIVES: The Ishikawa endometrial cancer cell line is hormonally responsive, expressing estrogen and progesterone receptors (ER, PR) when grown in traditional monolayer culture. The purpose of this paper is to demonstrate a three-dimensional spheroid culture system for cancer cells. We used this system to determine the response of the Ishikawa cell line to estradiol-17 beta (E), tamoxifen (T), megestrol acetate (MA), and progesterone (P). METHODS: Ishikawa cells were incubated in polyurethane culture bags using phenol red-free media containing ethanol (0.1%, controls), E (1 mumol, or 1 nmol), T (1 mumol, or 10 nmol), MA (1 mumol, or 10 nmol), or P (1 mumol). Cellular morphology was assessed by hematoxylin and eosin staining, and expression of estrogen and progesterone receptors was determined immunohistochemically using an immunoperoxidase technique. RESULTS: Cells in control cultures demonstrated minimal organization and lacked hormone receptors. In contrast, cells exposed to either E or T displayed significant glandular formation, with multicellular, microvilli-rich, columnar epithelia exhibiting polarized nuclear arrangements. Within 4 weeks, E- and T-treated cultures showed upregulated nuclear staining for PR, with little ER present. Cells treated with MA or P showed less glandular organization but expressed ER with PR downregulation. CONCLUSIONS: These data support the use of this novel three-dimensional culture system to study the modulation of tumor cell biologic activity in response to hormonal agents. Future applications of this model include examining in vitro responsiveness of cancer cell lines to additional biologic agents and chemotherapeutic regimens.

Bioremediation of a soil contaminated by hydrocarbon mixtures: the residual concentration problem.

The phenomenon of residual concentration was investigated in the aerobic biodegradation of three different petroleum commercial products (i.e., kerosene, diesel fuel and a lubricating mineral oil) in static microcosms. Two different soils exhibiting different physical-chemical characteristics were used (i.e., a biologically treated hydrocarbon-contaminated soil and a pristine soil). Residual concentrations were observed and a simple way to take this phenomenon into account was proposed.

Superior mesenteric artery emboli during renal PTA: successful surgical treatment after fibrinolysis failure.

The paper presents a rare case of iatrogenic embolization of the superior mesenteric artery which required an emergency operation after an unsuccessful fibrinolytic treatment. An old woman, who had undergone renal percutaneous angioplasty (r-PTA), presented sudden but transient abdominal pain. Angiographic control of the angioplasty showed the goal of r-PTA but also an embolic occlusion of the main trunk of the superior mesenteric artery that did not respond to a selective fibrinolytic treatment. Within a few hours, the abdominal pain appeared again and induced an exploratory laparotomy which showed an extensive ischaemia of the whole jejunum. A successful embolectomy was performed associated with the resection of about 20 cm of necrotic jejunum. The postoperative period was uncomplicated. The case underlines several topics: close collaboration is necessary between interventional radiologists and surgeons in order to get a surgical "stand-by" during PTA procedures; the embolic occlusion of the superior mesenteric artery can produce irreversible, even if segmentary intestinal damage, also within a very short time after onset and, therefore, it seems to be at high risk for a fibrinolytic approach.

Hyperthyroidism and concurrent thyroid cancer.

AIMS AND BACKGROUND: The aim of this study was to analyze the frequency of coexisting hyperthyroidism and thyroid malignancy in endemic goiter areas and review the current literature on the subject. METHODS: During the period January 1984 to June 1998, 1853 patients were examined for hyperthyroidism at the Spedali Civili Hospital of Brescia, Italy; 512 (27.6%) subjects underwent surgery. Of these patients 108 (21%) had Graves' disease, 251 (49%) multinodular toxic goiter (MTG) and 153 (30%) uninodular toxic goiter (UTG). RESULTS: Malignancy was found in 24 (4.7%) patients: 19 females and 5 males with a mean age of 52.2 years (range, 21-76 years). The frequency of cancer in Graves' disease was 6.4%, 5 females and 2 males; in MTG 3.9%, 2 females and 8 males, and in UTG 4.4%, 7 females and 1 male. CONCLUSIONS: Our data confirm previous reports on the frequency of thyroid cancer in hyperthyroidism. This association is more relevant than previously suspected. The frequent coexistence of hyperthyroidism and neoplasia, demonstrated by our study and the most recent literature, underlines the importance of studying and excluding the possibility of neoplastic degeneration by means of a systematic approach.

Results of a mammographic and clinical screening in a health district (USSL) of Brescia, Italy.

AIMS AND BACKGROUND: Screening by mammography has been shown to be effective in reducing breast cancer mortality. We present the results of a mammographic and clinical screening program carried out in an Italian health district. METHODS: The first screening round started in June 1987 and ended in July 1990, and 25,100 women between the age of 50 and 60 years were invited. The second screening round invited 34,332 women between the age of 50 and 64 years and was carried out from September 1990 to September 1993. Women with positive or equivocal results at palpation or mammography were referred for immediate diagnostic assessment followed by surgery, when required. RESULTS: The attendance rate was 67.3% at the first and 62.1% at the repeat screening. At the first screening, 206 biopsies were advised and 197 were performed; 129 of the 197 were found to be malignant. At repeat screening, 248 biopsies were recommended, 208 were performed, and 125 were found to be malignant. The cancer detection rate was 7.7 per thousand at the first and 5.9 per thousand at repeat screening. Of 129 cancers, 107 (83.0%) were T1 at first screening; 6.2% were in situ carcinomas. Axillary lymph nodes were histologically positive in 24% of cases. At repeat screening, 77.6% (97/125) of cancers were T1; 11.2% were in situ carcinomas. Positive axillary lymph nodes were found in 16.8% of cases. CONCLUSIONS: The attendance to screening was satisfactory. A higher frequency of small tumors (83.0%) was found at first screening than before the introduction of screening (56.6%). A marked difference in lymph node positivity (24.0% vs 40.6% in the pre-screening era) was also observed. Such a difference was even more evident at repeat screening. Quality standards of the screening in our study proved to be higher than those currently recommended. The reported results are encouraging, also considering the greater chance for conservative treatment.

Laser vaporization for vulvar intraepithelial neoplasia III.

Eighteen women with vulvar intraepithelial neoplasia (VIN) III were treated with laser vaporization. The majority had multifocal disease. After a single laser vaporization, 15 of the 18 remained free of recurrent disease, with a mean follow-up of 129.5 weeks (range, 24-253). There were no intraoperative complications. Two patients had delayed healing and persistent vulvar soreness for 4 and 10 months. Laser vaporization appears to be reasonably well tolerated and effective for VIN III, especially multifocal.

[Diagnostic role of mammography and clinical examination in the framework of a screening program for breast carcinoma in Brescia]. / Ruolo diagnostico della mammografia e dell'esame clinico nell'ambito del programma di screening per il carcinoma mammario a Brescia.

Screening by mammography is at present the only way to obtain good results in terms of diagnosis of breast cancer at an early stage. In this paper we present the results of first and second rounds of a mammographic and clinical screening programme carried out in the health district of Brescia. At the first round out of 129 cancers detected, mammography was diagnostic in 124 cases; in 82 cases, the examination also allowed the identification of a suspicious nodule, while in 42 cases non palpable neoplasm was diagnosed with mammography alone. In the remaining 5 cases mammography was negative and only clinical examination led to the discovery of breast neoplasms. In the second round, in the 125 cancers detected, mammography was diagnostic in 124 cases; clinical examination allowed the identification of 59 of these tumours, while in 65 cases non palpable tumours were found with mammography alone. Only in one case mammography was negative and clinical examination led to the identification of the tumour.

[Solitary splenic metastasis of bladder carcinoma. Report of a clinical case]. / Metastasi splenica solitaria di carcinoma vescicale. Discussione di un caso clinico.

Several authors assumed that spleen was resistant to neoplastic dissemination because of spleen metastasis are rare in relation to the incidence of metastasis in other parenchymatous organs. We report a clinical case of a symptomatic solitary spleen metastasis in cystic-looking bladder cancer; afterwards we'll examine real incidence of secondary splenic injury. In autopsy studies, the incidence of splenic metastatic spread is in contrast with the rarity of clinical manifestations of solitary metastasis. The case reported is really uncommon: a voluminous single metastasis, cystic-looking, with splenomegaly, abdominal pain and rapid onset. In the presence of a high malignancy primitive tumor, the evaluation of the effective utility of the surgical treatment carried out is premature, because of the relatively short follow-up. On the other hand, the painful symptomatology, the risk of disruption in peritoneal cavity, the impossibility to make inquiries about the nature of the cystic mass, imposed, in our opinion, a surgical treatment.