Maria Carmen Lirosi

Bacterial Bloodstream Infections in Liver Transplantation: Etiologic Agents and Antimicrobial Susceptibility Profiles

Liver transplantation (OLT) is a lifesaving procedure for the treatment of many end-stage liver diseases, but infection and acute rejection episodes still remain the main causes of morbidity and mortality. Bloodstream infections (BSIs), particularly, are the major cause of mortality among these patients. BSIs in OLT, are from intra-abdominal, biliary, respiratory, urinary, wound and/or central venous catheter sources. A certain percentage are of unknown origin. Using the computerized database of our microbiology laboratory, we analyzed all BSIs in 75 consecutive adult liver transplant patients in a single center between January 2008 and July 2011. BSIs occurred in 21/75 (28%) patients. Thirteen subjects had a single; two, two episodes, and the other six patients each >4 episodes. All episodes occurred in the first 60 days following OLT; the majority (74%), in the first month. Among 44 microorganisms recovered, 52.3% were gram-negative, the most frequent being Pseudomonas aeruginosa and Klebsiella pneumoniae; 47.7% were gram-positive, the most frequent being coagulase-negative staphylococci, particularly Staphylococcus epidermidis. Overall 65.9% of the isolates were resistant to several antibiotics: 40.9% displayed the multiding-resistant and 25% the panding-resistant phenotype. There was a high incidence of gram-negative and most importantly, resistant bacteria, which required appropriate therapy. These data showed that it is imperative to promote strategies to prevention and contain antimicrobial resistance.

http://www.D‐MELD.com, the Italian survival calculator to optimize donor to recipient matching and to identify the unsustainable matches in liver transplantation

Optimization of donor‐recipient match is one of the exciting challenges in liver transplantation. Using algorithms obtained by the Italian D‐MELD study (5256 liver transplants, 21 Centers, 2002–2009 period), a web‐based survival calculator was developed. The calculator is available online at the URL http://www.D‐MELD.com. The access is free. Registration and authentication are required. The website was developed using PHP scripting language on HTML platform and it is hosted by the web provider Aruba.it. For a given donor (expressed by donor age) and for three potential recipients (expressed by values of bilirubin, creatinine, INR, and by recipient age, HCV, HBV, portal thrombosis, re‐transplant status), the website calculates the patient survival at 90 days, 1 year, 3 years, and allows the identification of possible unsustainable matches (i.e. donor‐recipient matches with predicted patient survival less than 50% at 5 years). This innovative approach allows the selection of the best recipient for each referred donor, avoiding the allocation of a high‐risk graft to a high‐risk recipient. The use of the D‐MELD.com website can help transplant surgeons, hepatologists, and transplant coordinators in everyday practice of matching donors and recipients, by selecting the more appropriate recipient among various candidates with different prognostic factors.

Fungal Infections After Liver Transplantation: Incidence and Outcome

BACKGROUND Fungal infections, although less frequent than bacterial infections, represent a severe comorbidity with an exponential increase in mortality rate in liver transplantation patients. The incidence of invasive fungal infections (IFIs) after solid organ transplantation ranges from 7% to 42%, with Candida spp. and Aspergillus spp. as the most common pathogens. Fungal infections in liver transplant recipients have been associated with poor outcome and mortality rates ranging from 65% to 90% for invasive aspergillosis and 30% to 50% for invasive candidiasis. The results largely depend on early diagnosis and early initiation of specific treatment for IFIs. Therefore, the diagnosis must be prompt, preferably based on microbiological data, both cultures and biomarkers, and/or based on clinical features and known risk factors. MATERIALS AND METHODS This study evaluated the incidence of fungal infections in patients after liver transplantation in our center between January 2003 and December 2012. The retrospective analysis of 215 consecutive liver transplantation patients was undertaken to estimate incidence, risk factors, and clinical courses of IFIs in the first 3 months after liver transplantation. RESULTS Candidemia and invasive candidiasis microbiologically proven were found in 26 patients (12%), whereas in 6 patients (2.8%) invasive fungal infections from other non-Candida fungi developed: Aspergillus (4 cases: 2 A fumigatus, 2 A terreus), Fusarium oxysporum (1 case), and Rhodotorula rubra (1 case). Two patients with Aspergillus and the patient with Fusarium died. The patient with Rhodotorula as well as 22 of the patients with candidemia (85%) survived. All of the episodes developed during the first 3 months posttransplantation. All cases have followed a previous polymicrobial bacterial infection (especially in the biliary tract) with large use of combined antibiotic therapies. CONCLUSIONS The rate of fungal infection was found to increase in parallel with the number of risk factors. Prophylactic strategies can decrease the risk of fungal infections. Early detection and treatment with adequate early empiric therapy is the key to obtaining a better outcome in liver transplantation patients.

Surveillance of bacterial and fungal infections in the postoperative period following liver transplantation: a series from 2005-2011.

Orthotopic liver transplantation (OLT) is a life-saving procedure for the treatment of many end-stage diseases, but infectious and acute rejection episodes remain major causes of morbidity and mortality. Bacterial and fungal infections can be due to intra-abdominal, biliary, respiratory, urinary, wound, central venous catheters (CVC) or unknown sources. Using the computerized database of our microbiology laboratory, we analyzed all the bacterial and fungal infections in the first three months following OLT among 151 consecutive adult recipients at single center between January 2005 and December 2011. Samples included blood, bile CVC, urine, and bronchoalveolar lavage (BAL) specimen. Culture and identification of the isolated microorganisms was done in accordance with standard microbiological procedures. Three hundred thirteen samples from the above sites showed positive results for gram-positive cocci (n = 137; 43.8%), gram-negative rods (n = 156; 49.8%), and Candida species (n = 19; 6.1%). One patient (0.3%) experienced a CVC-related infection caused by Fusarium oxysporum. Bacterial and particularly biliary tract infections seem to play major roles in morbidity and mortality in the first three months following OLT. The major contributors to patient morbidity and mortality were candidemia and/or invasive candidiasis mainly from the biliary tract and/or CVC-related infections.

Neo-adjuvant chemo(radio)therapy in gastric cancer: Current status and future perspectives

In the last 20 years, several clinical trials on neoadjuvant chemotherapy and chemo-radiotherapy as a therapeutic approach for locally advanced gastric cancer have been performed. Even if more data are necessary to define the roles of these approaches, the results of preoperative treatments in the combined treatment of gastric adenocarcinoma are encouraging because this approach has led to a higher rate of curative surgical resection. Owing to the results of most recent randomized phase III studies, neoadjuvant chemotherapy for locally advanced resectable gastric cancer has satisfied the determination of level I evidence. Remaining concerns pertain to the choice of the optimal therapy regimen, strict patient selection by accurate pre-operative staging, standardization of surgical procedures, and valid criteria for response evaluation. New well-designed trials will be necessary to find the best therapeutic approach in pre-operative settings and the best way to combine old-generation chemotherapeutic drugs with new-generation molecules.

Factors predicting ischemic-type biliary lesions (ITBLs) after liver transplantation

Among biliary complications, ischemic-type biliary lesions (ITBLs) remain a major cause of morbidity in liver transplant recipients, significantly affecting the chance of survival of both patients and grafts. We retrospectively reviewed 10 years of prospectively collected donor and recipient data from April 2001 to April 2011. We evaluated the incidence of ITBL occurrence, exploring the possible predisposing factors, including donor and recipient data. Two hundred fifty-one grafts were harvested: 222 of them were transplanted at our institution, the remaining 29 (11.6%) discarded by our donor team as showing >40% macrovesicular steatosis. Mild-moderate (20%-40%) macrovesicular steatosis (P < .001) and cold ischemia time (P = .048) significantly increased the risk of ITBL, also as an independent risk factor after multivariate analysis.

Model for end-stage liver disease dynamic stratification of survival benefit

Only patients with Model for End-stage Liver Disease (MELD) scores ≥18 or ≥17 experience a survival benefit (SB) at 12 and 36 months after liver transplantation (OLT). The SB calculation estimates the difference after stratification for risk categories between the survival rate of transplanted versus waiting list patients. The aim of this study was to perform a short- and long-term (60 months) SB analyses of a Italian OLT program. One-hundred seventy-one patients were stratified into four MELD classes (6-14, 15-18, 19-25, 26-40), and two groups: namely, waiting list (WL) and transplanted groups (TX). The median waiting time for transplanted patients was 4.4 months (range, 0-35). SB was expressed as mortality hazard ratio (MHR) as obtained through a Cox regression analysis using as a covariate the status of each patient in the waiting list (WL = 0, reference group) or the TX group (TX = 1). Values over 1 indicated the MHR in favor of the WL with the values below 1 indicating MHR in favor of Tx. In the MELD class 6 to 14, the MHR was above 1 at 3 and 6 months, indicating an SB in favor of WL; subsequently, the MHR dropped below 1, indicating an SB in favor of TX (P < .05). In the MELD class 15 to 18 the MHR was above 1 at 3 months, but below 1 subsequently (P < .05). For MELD classes 19 to 25 and 26 to 40, the MHR was always below 1 (P < .01). According to the SB approach, patients in the MELD class 6 to 14 could safely wait for at least 36 months; patients in the MELD class 15 to 18 should likely remain no longer than 12 months on the waiting list, and all the remaining patients with MELD > 18 should be transplanted as soon as possible. OLT should not be precluded but only postponed for MELD < 19 patients.

Incidence of Upper Aerodigestive Tract Cancer After Liver Transplantation for Alcoholic Cirrhosis: A 10-Year Experience in an Italian Center

INTRODUCTION The aim of this study was to evaluate the incidence, clinical characteristics, treatment, and outcome of de novo tumors (DNT) of the upper aerodigestive tract in patients with alcoholic cirrhosis after orthotopic liver transplantation (OLT). METHODS Among 225 consecutive OLT performed between January 2002 and January 2012, a total of 205 patients received a first liver allograft. Eleven (4.9%) patients developed DNT (lung, pancreas, bowel, esophagus, larynx, tongue, tonsil, and lymphoma). Among these, we observed 5 patients with DNT of the upper aerodigestive tract. RESULTS The 5 patients with DNT of the upper aerodigestive tract underwent OLT for alcoholic cirrhosis. There were 4 men and 1 woman with a mean age at transplantation of 47 years. The mean period of alcohol abuse was 90 months. The tumors occurred after a mean post-transplantation time of 39 months. The immunosuppressive regimen included Tacrolimus, mTOR, mycophenolate mofetil (MMF), and low-dose steroids. We observed 2 cases of squamous cell carcinoma of the esophagus, 1 case of tonsillar cancer, 1 case of larynx carcinoma, and 1 case of tongue carcinoma. All patients underwent surgical excision. After surgery, 4 patients received chemotherapy and 2 patients radiotherapy. At present, among the 5 patients with DNT of the upper aerodigestive tract, only 2 are alive without disease and 1 is alive with a local recurrence. CONCLUSION The incidence of DNT of the upper aerodigestive tract after OLT is higher among patients receiving a transplant for alcoholic cirrhosis. This could be due to an additional effect of post-transplantation immunosuppression in patients exposed to alcohol before transplantation. We suggest a careful post-transplantation follow-up and more attention to improve early diagnosis.

Anidulafungin--a new therapeutic option for Candida infections in liver transplantation.

INTRODUCTION In the last years, the incidence of Candida infections in liver transplant recipients has increased with still higher morbidity and mortality. Anidulafungin, a new echinocandin that does not interfere with cytochrome p450, shows no need for dosage adjustment based upon renal or hepatic function or weight. AIM To analyze tolerance to and microbiologic and clinical efficacy of Anidulafungin to treat Candida infections in liver transplant patients. MATERIALS AND METHODS This phase 3b, prospective, open-label, single-center study focused on liver transplant patients with a suspected and/or diagnosed Candida infection. The patients received Anidulafungin intravenously, optionally followed by oral therapy with azoles. The primary endpoint was the global response at the end of therapy; secondary endpoints were the efficacy of intravenous therapy, 90-day survival, as well as tolerance for and interaction with immunosuppresants. RESULTS We considered 42 consecutive liver recipients transplanted between 2009 and 2010 among whom 13 (31%) were recruited for the study and four patients were treated with Anidulafungin as empirical therapy, six as preemptive therapy, and three as targeted treatment for documented candidemia (7.1%). The immunosuppressive regimen consisted of tacrolimus and low dose of steroids. The Candida species were: C albicans (50%), C glabrata (12.5%), C parapsilosis (12.5%), C krusei (12.5%), C lusitaniae (6.2%), C tropicalis (6.2%), and multiple others (25%). The principle site of isolation was the bile (53.8%), followed by the bloodstream (23.1%), central venous catheters (15.4%), bronchoalveolar lavage (15.4%), peritoneum (7.7%), and other locations (7.7%). Two patients (15.4%) died of severe sepsis with multiple organ failure. There was no alteration of hepatic enzymes, indices of cholestasis or changes in immunosuppressant drug levels. CONCLUSION Anidulafungin was an effective, safe, and well-tolerated drug. There were neither toxic effects to the grafts or adverse interactions with immunosuppresants.

Surgical anatomy of gastric lymphatic drainage

The lymphatic system of the stomach is a multidirectional and complex network composed of lymphatic nodes and vessels. Lymph node metastasis is the most important prognostic factor in curable gastric cancer and lymph node dissection is one of the main areas of surgical research in gastric cancer. Therefore the anatomical classification and embryological development of the gastric lymphatic system have been well described in the literature. The current description of the gastric lymphatic system of the stomach has a surgical orientation and follows the recommendations of the Japanese Gastric Cancer Association. A thorough knowledge of the lymphatic system surrounding the stomach proves to be invaluable to surgeons treating patients with gastric cancer. The aim of this paper is to provide a concise review about surgical anatomy of the gastric lymphatic drainage.