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.

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.

Intestinal transplantation in children: the first successful Italian series.

The preliminary experience of the first Italian program of pediatric intestinal transplantation is presented herein. A multidisciplinary group with broad experience in pediatric solid organ transplantation started the program. Nine children with complications of chronic intestinal failure were listed for transplantation. One child died on the waiting list; one received an isolated liver transplantation; three isolated intestinal; three multivisceral; and one, a combined liver/intestine transplantation. There was no in-hospital mortality, and all children were weaned from parenteral nutrition. The recipient of the multivisceral graft died after 14 months for unknown causes. All other recipients are alive after a median follow-up of 13 months. Patient and graft actuarial survivals for recipients of intestinal grafts were 100% at 1 year and 75% at 2 years.

Lung transplantation with grafts from elderly donors: a single-center experience.

INTRODUCTION: Use of extended criteria donors is one of the strategies to face the scarcity of donors for lung transplantation. METHODS: Between November 2002 and May 2009, we performed 52 LTs in 50 recipients, 10 of whom (group A) received lungs from donors aged 55 years or older (median, 58.5; range, 56-66 years) for comparison with 28 patients (group B) transplanted with lungs from donors younger than 55 years (median, 25.5; range, 15-54 years). We excluded 9 children and 3 recipients of combined liver plus lung transplantations from the study. RESULTS: Recipient age, gender, and indications for transplantation did not differ significantly between the 2 groups. Neither were there significant differences in PaO2/FiO2 ratios before lung retrieval, or length of the ischemic time The first PaO2/FiO2 on arrival to the intensive care unit (ICU) and the median length of ICU stay were similar. All patients, except 2 who died in the operating theatre, were extubated between 3 and 216 hours after the transplantation. Hospital mortality was similar in both groups: 3 patients in group A and 2 in group B (P = .1). The median portions of the predicted 1-second forced expiratory volume (FEV1) at 6 months after transplantation did not differ in the 2 groups: 62.4% in group A versus 70% in group B (P = .85). CONCLUSION: Lung grafts from donors older than 55 years can be effectively used for transplantation, thus increasing the total organ pool.

Combined double lung-liver transplantation for cystic fibrosis without cardio-pulmonary by-pass.

Sequential bilateral single lung-liver transplantation (SBSL-LTx) is a therapeutic option for patients with end stage lung and liver disease (ESLLD) due to cystic fibrosis (CF). A few cases have been reported, all of them were performed with the use of cardio-pulmonary by-pass (CPB). We performed SBSL-LTx in three young men affected by CF. All the recipients had respiratory failure and portal hypertension with hypersplenism. Along with lung transplants, two patients received a whole liver graft and one an extended right graft from an in situ split liver. During transplantation neither CPB nor veno-venous by-pass (VVB) were employed. Immunosuppression was based on basiliximab, tacrolimus, steroids and azathioprine. The three recipients are alive with a median follow-up of 670 days (range 244-1,533). Combined SBSL-LTx is a complex but effective procedure for the treatment of ESLLD due to CF, not necessarily requiring the use of CPB or VVB.

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.

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.

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.

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.

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.

[Thyroid nodule pathology: proposal of a diagnostic approach based on the experience of a thyroid disease unit]. / Patologia nodulare tiroidea: proposta di un approccio diagnostico sulla base dell'esperienza di una unità tiroidologica.

Thyroid nodules are commonly found in clinical practice, and their detection by either the physician or the patients always gives rise to concern as to the possible existence of a malignancy. Technological developments have had a major impact on the study and treatment of thyroid nodules. The application of fine-needle aspiration biopsies (FNAB) and the availability of high-resolution thyroid ultrasonography have modified thyroid nodule management even if important differences of opinion remain. This article describes the progress as well as contemporary controversies in thyroid nodule diagnosis and considers the effect these advances have had on the treatment of patients with nodular disease. It includes a brief description of the clinical importance of thyroid nodules, of the use and limitations of imaging studies in thyroid nodule diagnosis and of the usefulness, limitations, and impact of FNAB on nodule management.

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.

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.

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.

[The current indications for Madden's radical mastectomy in our experience. A critical review of 201 consecutive patients]. / Attuali indicazioni alla mastectomia radicale secondo Madden nella nostra esperienza. Revisione critica in 201 pazienti consecutive.

The clinical pathological data regarding the 201 patients (203 operations running) who underwent radical mastectomy according to Madden in the II Division of General Surgery at Brescia Civil Hospital in the period 1993-1994, have been reexamined in order to check the real need of radical surgery. This further analysis, apart from the patients with neoplasias of considerable dimensions (T2; > 2 cm), has been carried out on 100 tumors smaller dimensions (T1; < 2 cm) and has confirmed the necessity of radical surgery in 87 cases. Of the 13 operations (6.4%) that have been considered "improper" 2 were due to erroneous clinical staging (dubious cutaneous infiltration) and 5 (2.5%) presented a neoplastic diameter of exactly 2 cm which only partially justified radical surgery. In six patients (2.9%) we haven't found clinical pathological elements which contraindicated conservative surgery.

Maternal death from postpartum necrotizing fasciitis arising in an episiotomy: a case report.

BACKGROUND: Necrotizing fasciitis is a rare condition. We report a fatal case arising from an episiotomy in a previously healthy woman. CASE: A healthy 23-year-old prima gravida white female underwent vaginal delivery with repair of a proctoepisiotomy. Eighty-four hours postpartum, she developed increasing perineal swelling with severe pain. She presented on the 4th postpartum day with edema, erythema localized to the perineum, and vital signs significant only for tachycardia of 120/min. With a leukocytosis of 45,000/mul (87%) neutrophils, she was admitted to the hospital with an initial diagnosis of perineal cellulitis and empirically started on broad-spectrum intravenous antibiotic therapy. The patient's condition continued to deteriorate and she was then transferred to our facility on postpartum day 9 where a team performed two radical debridements of all necrotic tissue. Despite this and a broadened antibiotic coverage, the patient eventually experienced cardiopulmonary arrest and died on postpartum day 12. CONCLUSION: Necrotizing fasciitis must be considered in the differential diagnosis of the postpartum patient presenting with severe vulvar pain and erythema. Our patient exemplifies the obscure presentation with seemingly minimal skin changes. Any delay in diagnosis and treatment, which must include expeditious aggressive surgical debridement, will likely result in severe morbidity or mortality.