Recipient hepatectomy technique may affect oncological outcomes of liver transplantation for hepatocellular carcinoma.

To date, caval sparing (CS) and total caval replacement (TCR) for recipient hepatectomy in liver transplantation (LT) have been compared only in terms of surgical morbidity. Nonetheless, the CS technique is inherently associated with an increased manipulation of the native liver and later exclusion of the venous outflow, which may increase the risk of intraoperative shedding of tumor cells when LT is performed for HCC. A multicenter, retrospective study was performed to assess the impact of recipient hepatectomy (CS vs. TCR) on the risk of posttransplant HCC recurrence among 16 European transplant centers that used either TCR or CS recipient hepatectomy as an elective protocol technique. Exclusion criteria comprised cases of non-center-protocol recipient hepatectomy technique, living-donor LT, HCC diagnosis suspected on preoperative imaging but not confirmed at the pathological examination of the explanted liver, HCC in close contact with the IVC, and previous liver resection for HCC. In 2420 patients, CS and TCR approaches were used in 1452 (60%) and 968 (40%) cases, respectively. Group adjustment with inverse probability weighting was performed for high-volume center, recipient age, alcohol abuse, viral hepatitis, Child-Pugh class C, Model for End-Stage Liver Disease score, cold ischemia time, clinical HCC stage within Milan criteria, pre-LT downstaging/bridging therapies, pre-LT alphafetoprotein serum levels, number and size of tumor nodules, microvascular invasion, and complete necrosis of all tumor nodules (matched cohort, TCR, n = 938; CS, n = 935). In a multivariate cause-specific hazard model, CS was associated with a higher risk of HCC recurrence (HR: 1.536, p = 0.007). In conclusion, TCR recipient hepatectomy, compared to the CS approach, may be associated with some protective effect against post-LT tumor recurrence.

Evolution of minimally invasive techniques and surgical outcomes of ALPPS in Italy: a comprehensive trend analysis over 10 years from a national prospective registry.

BACKGROUND: Since 2012, Associating Liver Partition and Portal vein ligation for Staged hepatectomy (ALPPS) has encountered several modifications of its original technique. The primary endpoint of this study was to analyze the trend of ALPPS in Italy over a 10-year period. The secondary endpoint was to evaluate factors affecting the risk of morbidity/mortality/post-hepatectomy liver failure (PHLF). METHODS: Data of patients submitted to ALPPS between 2012 and 2021 were identified from the ALPPS Italian Registry and evaluation of time trends was performed. RESULTS: From 2012 to 2021, a total of 268 ALPPS were performed within 17 centers. The number of ALPPS divided by the total number of liver resections performed by each center slightly declined (APC = - 2.0%, p = 0.111). Minimally invasive (MI) approach significantly increased over the years (APC = + 49.5%, p = 0.002). According to multivariable analysis, MI completion of stage 1 was protective against 90-day mortality (OR = 0.05, p = 0.040) as well as enrollment within high-volume centers for liver surgery (OR = 0.32, p = 0.009). Use of interstage hepatobiliary scintigraphy (HBS) and biliary tumors were independent predictors of PHLF. CONCLUSIONS: This national study showed that use of ALPPS only slightly declined over the years with an increased use of MI techniques, leading to lower 90-day mortality. PHLF still remains an open issue.

Indocyanine Green Fluorescence Navigation in Liver Surgery: A Systematic Review on Dose and Timing of Administration.

BACKGROUND: Indocyanine green (ICG) fluorescence has proven to be a high potential navigation tool during liver surgery; however, its optimal usage is still far from being standardized. METHODS: A systematic review was conducted on MEDLINE/PubMed for English articles that contained the information of dose and timing of ICG administration until February 2021. Successful rates of tumor detection and liver segmentation, as well as tumor/patient background and imaging settings were also reviewed. The quality assessment of the articles was performed in accordance with the Scottish Intercollegiate Guidelines Network (SIGN). RESULTS: Out of initial 311 articles, a total of 72 manuscripts were obtained. The quality assessment of the included studies revealed usually low; only 9 articles got qualified as high quality. Forty articles (55%) focused on open resections, whereas 32 articles (45%) on laparoscopic and robotic liver resections. Thirty-four articles (47%) described tumor detection ability, and 25 articles (35%) did liver segmentation ability, and the others (18%) did both abilities. Negative staining was reported (42%) more than positive staining (32%). For tumor detection, majority used the dose of 0.5 mg/kg within 14 days before the operation day, and an additional administration (0.02-0.5 mg/kg) in case of longer preoperative interval. Tumor detection rate was reported to be 87.4% (range, 43%-100%) with false positive rate reported to be 10.5% (range, 0%-31.3%). For negative staining method, the majority used 2.5 mg/body, ranging from 0.025 to 25 mg/body. For positive staining method, the majority used 0.25 mg/body, ranging from 0.025 to 12.5 mg/body. Successful segmentation rate was 88.0% (range, 53%-100%). CONCLUSION: The time point and dose of ICG administration strongly needs to be tailored case by case in daily practice, due to various tumor/patient backgrounds and imaging settings.

Controlling Nutritional Status score does not predict patients' overall survival or hepatocellular carcinoma recurrence after deceased donor liver transplantation.

BACKGROUND: The Controlling Nutritional Status (CONUT) score is a newly developed laboratory-derived immunonutritional score which has been validated as prognostic marker for survival and tumor recurrence in surgically treated patients with various tumor types, including hepatocellular carcinoma (HCC). The aim of the present study was to test the CONUT score performance in HCC patients treated with liver transplantation (LT). METHODS: A retrospective study on a bi-centers cohort of 280 HCC patients submitted to LT between 2006 and 2017 was performed. Indication to LT was limited to Milan criteria or UCSF criteria, defined by preoperative imaging. RESULTS: Median pre-LT CONUT score was 5 (interquartile range 3-7). Overall patients' survival at 1, 3, and 5 years was 84%, 76.6%, and 68.3%, respectively. Multivariate analysis showed that HCC recurrence (hazard ratio [HR] = 1.987, P = .012] and pre-LT neutrophil to lymphocyte ratio (NLR) (HR = 1.064, P = .003) were independent risk factors for reduced survival. Cumulative incidence of HCC recurrence at 1, 3, and 5 years was 5.1%, 11.5%, and 15.5%, respectively. Pre-LT platelet-to-lymphocyte ratio (PLR) (subdistribution hazard ratio [SHR] = 1.086, P = .044], tumor max diameter (SHR = 1.695, P < .001), and bilobar tumor distribution (SHR = 6.892, P = .006) were independent risk factors for tumor recurrence. The CONUT score did not show any prognostic value. CONCLUSIONS: The CONUT score did not predict poor survival or tumor recurrence in LT recipients.

Liver transplantation for metastatic wild-type gastrointestinal stromal tumor in the era of molecular targeted therapies: Report of a first case.

The gastrointestinal stromal tumor (GIST) is a digestive neoplasm of mesenchymal lineage. The treatment strategy for receptor tyrosine kinase-mutated GISTs is well defined. Wild-type GISTs (WT-GISTs) respond unsatisfactorily to specific kinase inhibitors. Moreover, evidence shows that repeat surgery has limited benefit. We report the case of a young female patient who was diagnosed with liver metastatic WT-GIST, after initial radical resection and adjuvant therapy with molecular targeted drugs. Due to the disease progression, a two-stage surgery was performed, with the removal of extrahepatic lesions followed by a total hepatectomy. The patient is disease-free after 4 years from liver transplantation (LT), performed under everolimus-based immunosuppression. The treatment of WT-GISTs remains a significant challenge due to the frequent resistance to tyrosine kinase inhibitors (TKIs). Liver transplantation might represent an effective treatment option for such disease.

Surgery for cholangiocarcinoma.

Surgical resection is the only potentially curative treatment for patients with cholangiocarcinoma. For both perihilar cholangiocarcinoma (pCCA) and intrahepatic cholangiocarcinoma (iCCA), 5-year overall survival of about 30% has been reported in large series. This review addresses several challenges in surgical management of cholangiocarcinoma. The first challenge is diagnosis: a biopsy is typically avoided because of the risk of seeding metastases and the low yield of a brush of the bile duct. However, about 15% of patients with suspected pCCA are found to have a benign diagnosis after resection. The second challenge is staging; even with the best preoperative imaging, a substantial percentage of patients has occult metastatic disease detected at staging laparoscopy or early recurrence after resection. The third challenge is an adequate volume and function of the future liver remnant, which may require preoperative biliary drainage and portal vein embolization. The fourth challenge is a complete resection: a positive bile duct margin is not uncommon because the microscopic biliary extent of disease may be more extensive than perceived on imaging. The fifth challenge is the high post-operative mortality that has decreased in very high volume Asian centres, but remains about 10% in many Western referral centres. The sixth challenge is that even after a complete resection most patients develop recurrent disease. Recent randomized controlled trials found conflicting results regarding the benefit of adjuvant chemotherapy. The final challenge is to determine which patients with cholangiocarcinoma should undergo liver transplantation rather than resection.

Early post-liver transplant surgical morbidity in HIV-infected recipients: risk factor for overall survival? A nationwide retrospective study.

The aim of the study was to analyse the risk factors for early surgical complications requiring relaparotomy and the related impact on overall survival (OS) in HIV-infected patients submitted to liver transplantation. Thus a retrospective investigation was conducted on a nationwide multicentre cohort of 157 HIV patients submitted to liver transplantation in six Italian Transplant Units between 2004 and 2014. An early relaparotomy was performed in 24.8% of cases and the underlying clinical causes were biliary leak (8.2%), bleeding (8.2%), intestinal perforation (4.5%) and suspect of vascular complications(3.8%). No differences in terms of prevalence for either overall or cause-specific early relaparotomies were noted when compared with a non-HIV control group, matched for MELD, recipient age, HCV-RNA positivity and HBV prevalence. While in the control group an early relaparotomy appeared a negative prognostic factor, such impact on OS was not noted in HIV recipients. Nonetheless increasing number of relaparotomies were associated with decreased survival. In multivariate analysis, preoperative refractory ascites and Roux-en-Y choledochojejunostomy reconstruction were significant risk factors for early relaparotomy. To conclude, in HIV liver transplanted patients, an increasing number of early relaparotomies because of surgical complications does negatively affect the OS. Preoperative refractory ascites reflecting a severe portal hypertension and a difficult biliary tract reconstruction requiring a Roux-en-Y choledochojejunostomy are associated with increased risk of early relaparotomy.

Impact of aberrant left hepatic artery ligation on the outcome of liver transplantation.

The preservation of a graft's aberrant left hepatic artery (LHA) during liver transplantation (LT) ensures optimal vascularization of the left liver but can also be considered a risk factor for hepatic artery thrombosis (HAT). In contrast, ligation of an aberrant LHA may lead to hepatic ischemia with the potential risk of graft dysfunction and biliary complications. The aim of this study was to prospectively analyze the impact on the surgical strategy for LT of 5 tests performed to establish whether an aberrant LHA was an accessory or a replaced artery, thus leading to the design of a decisional algorithm. From August 2005 to December 2016, 395 whole LTs were performed in 376 patients. Five parameters were evaluated to determine whether an aberrant LHA was an accessory or a replaced artery. On the basis of our decision algorithm, an aberrant LHA was ligated during surgery when assessed as accessory and preserved when assessed as replaced. A total of 138 anatomical variants of hepatic arterial vascularization occurred in 120/395 (30.4%) grafts. Overall, the incidence of an aberrant LHA was 63/395 (15.9%). The LHA was ligated in 33 (52.4%) patients and preserved in 30 (47.6%) patients. After a mean follow-up period of 50.9 ± 39.7 months, the incidence of HAT, primary nonfunction, early allograft dysfunction, biliary stricture or leaks, and overall survival was similar in the 2 groups. In conclusion, once shown to be an accessory, an LHA can be safely ligated without clinical consequences on the outcome of LT. Liver Transplantation 24 204-213 2018 AASLD.

Carbapenem-Resistant Klebsiella pneumoniae influences the outcome of early infections in liver transplant recipients.

BACKGROUND: Infections remain a leading cause of morbidity and mortality among liver transplant (LT) recipients. The aim of our study was to define the factors associated with outcome of early bacterial and fungal infections in a cohort of patients who underwent LT at the University Hospital of Ancona over a nine year period. METHODS: All consecutive patients who underwent LT in our center were considered. An early infection was defined as occurring in the first month post-transplantation. RESULTS: Among 330 patients who underwent LT from August 2005 to October 2014, 88 (27 %) had at least one infection documented within 30 days after transplantation. In 54 cases only one site was involved, in 34 cases ≥2 sites. There were 43 (30 %) pneumonia, 40 (27 %) surgical site infections, 31 (22 %) blood stream infections, and 30 (21 %) urinary tract infections. Gram-negative bacteria accounted for 64 % of the culture-positive cases, followed by Gram-positive bacteria (30 %) and fungi (6 %). A high proportion of drug-resistant strains was found within either Gram-negative (79 %) or Gram-positive (81 %) bacteria. There were 27 out 88 patients (31 %) who died within 180 days from the transplant. Factors independently associated with a higher risk of mortality were: renal replacement therapy (HR 11.797 [CI95 % 3.082-45.152], p < 0.0001), multisite infections (HR 4.865 [CI95 % 1.417-16.700], p = 0.012) and being infected with carbapenem-resistant Klebsiella pneumoniae (CRKP; HR 5.562 [CI95 % 1.186-26.088], p = 0.030). CONCLUSIONS: Overall, these data indicate that early infections in LT patients are characterized by significant mortality. In particular, an early infection caused by CRKP has an adverse impact on survival in these patients suggesting an urgent need for adopting preventive measures to avoiding this complication.

Semaphorin 7A contributes to TGF-ß-mediated liver fibrogenesis.

Semaphorin7A (SEMA7A) is a membrane-anchored protein involved in immune and inflammatory responses, exerting an effect on pulmonary fibrosis. Thus, we aimed to investigate the role of SEMA7A in hepatic fibrosis. Liver injury was induced in vivo by carbon tetrachloride i.p. injection or bile duct ligation in wild-type and SEMA7A knockout (KO) mice. Human and mouse liver samples and primary mouse hepatic cell populations were used for Western blot analysis, quantitative real-time RT-PCR, and immunohistochemistry. SEMA7A is highly expressed in hepatic stellate cells (HSCs). The expression of SEMA7A and its receptor ß1-integrin subunit increase during liver injury and in activated HSCs. Transforming growth factor ß-stimulated HSCs showed increased expression of SEMA7A in a SMAD2/3-independent manner, leading to increased expression of fibrogenic and inflammation markers. This pattern was significantly blunted in SEMA7A KO HSCs. Overexpression of SEMA7A in HSCs showed increased fibrogenic and inflammation markers expression. In vivo, SEMA7A KO mice treated with carbon tetrachloride and bile duct ligation developed reduced fibrosis versus wild-type mice. Moreover, SEMA7A expression increased in liver samples of patients with fibrosis versus healthy controls. SEMA7A was expressed in the liver and was increased in the course of liver fibrosis, both in mice and in humans. SEMA7A was mainly expressed in HSCs with respect to other cell types in the liver and plays a critical role in regulating fibrosis.

Metastatic breast cancer mimicking a hilar cholangiocarcinoma: case report and review of the literature.

BACKGROUND/AIMS: Breast cancer is the most common tumor in women and the first cause of death for malignancy in the female population. Bile ducts are not among the common sites of metastasis from breast cancer; few cases of obstructive jaundice due to metastatic breast cancer have been described in the literature and they mostly resulted from widespread liver metastases that eventually involved the bile ducts. We report an exceptional case of metastatic infiltration of the extrahepatic bile ducts in absence of liver metastases. CASE PRESENTATION: A 56-year-old woman who had undergone a right mastectomy 13 years earlier due to infiltrating ductal breast cancer and had remained tumor free, presented at a follow-up examination with obstructive jaundice.Imaging (computed tomography, magnetic resonance and endoscopic retrograde cholangiopancreatography) scans showed features that were suggestive of a primary tumor of the extrahepatic bile duct. At surgery, the intraoperative findings were also those of a tumor of the bile duct, however, an histological examination showed no evidence of malignancy in the mucosa, but did shown an infiltration of the external wall from adenocarcinoma. Immunohistochemistry analysis demonstrated that the tumor was metastatic breast cancer. CONCLUSIONS: Indeterminate stenosis of the extrahepatic bile ducts should be examined with suspicion in women with a history of breast cancer, and bile duct metastases are to be considered among the possible diagnoses. A differential diagnosis from cholangiocarcinoma is of paramount importance and mainly relies on pathology.

A Novel Use of Autologous Fibrin by Intracatheter Injection in Persistent Postoperative Biliary Defects: Technical Note on a Preliminary Experience.

PURPOSE: To introduce percutaneous selective injection of autologous platelet-rich fibrin as a novel technique for persistent bile leakage repair and sharing the results of our preliminary experience. MATERIALS AND METHODS: Seven patients (57.1% females; mean age 69.6 ± 8 years) with the evidence of persistent bile leak secondary to hepatobiliary surgery and ineffective treatment with percutaneous transhepatic biliary drainage were submitted to fibrin injection. Platelet-rich fibrin, a dense fibrin clot promoting tissue regeneration, was obtained from centrifuged patient's venous blood. Repeated percutaneous injections through a catheter tip placed in close proximity to the biliary defect were performed until complete obliteration at fistulography. Technical and clinical success were evaluated. RESULTS: Bile leaks followed pancreaticoduodenectomy in five and major hepatectomy in two patients. Technical success defined as fibrin injection at BD site was achieved in all seven patients, and clinical success defined as a complete healing of the BD at fistulography was achieved in six patients. The median time to BD closure was 76.7 ± 40.5 days and the average procedure number was 3 ± 1 per patient. In one patient, defect persistance after four treatments required gelatin sponge injection. No major complications occurred. One case of post-procedural transitory hyperpirexia was registered. CONCLUSION: In persistent biliary defects, despite prolonged biliary drainage stay, percutaneous injection of autologous platelet-rich fibrin appears as a readily available and feasible emergent technique in promoting fistulous tracts obliteration still mantaining main ducts patency.

Prevention of Post-Hepatectomy Liver Failure in Cirrhotic Patients Undergoing Minimally Invasive Liver Surgery for HCC: Has the Round Ligament to Be Preserved?

Post-hepatectomy liver failure (PHLF) represents a major cause of morbidity and mortality after liver resection. The factors related to PHLF are represented not only by the volume and function of the future liver remnant but also by the severity of portal hypertension. The aim of this study was to assess whether the preservation of the round ligament (RL) may mitigate portal hypertension, thus decreasing the risk of PHLF and ascites in cirrhotic patients while undergoing minimally invasive liver surgery (MILS). All the cirrhotic patients who underwent MILS for HCC from 2016 to 2021 in two international tertiary referral centers were retrospectively analyzed, comparing cases with the RL preserved vs. those with the RL divided. Only patients with cirrhosis ≥ Child A6, portal hypertension, and ICG-R15 > 10% were included. Main postoperative outcomes were compared, and the risk factors for postoperative ascites (severe PHLF, grade B/C) were investigated through a logistic regression. After the application of the selection criteria, a total of 130 MILS patients were identified, with 86 patients with the RL preserved and 44 with the RL divided. The RL-preserved group showed lower incidences of severe PHLF (7.0% vs. 20.5%, p = 0.023) and ascites (5.8% vs. 18.2%, p = 0.026) in comparison with the RL-divided group. After uni/multivariate analysis, the risk factors related to postoperative ascites were RL division and platelets < 92 × 103/µL, calculated with ROC analysis. The preservation of the round ligament during MILS may mitigate portal hypertension, preventing PHLF and ascites in cirrhotic patients with borderline liver function.

The efficacy of the quorum sensing inhibitor FS8 and tigecycline in preventing prosthesis biofilm in an animal model of staphylococcal infection.

We investigated the efficacy of tigecycline and FS8, alone or combined, in preventing prosthesis biofilm in a rat model of staphylococcal vascular graft infection. Graft infections were established in the back subcutaneous tissue of adult male Wistar rats by implantation of Dacron prostheses followed by topical inoculation with 2 x 107 colony-forming units of Staphylococcus aureus, strain Smith diffuse. The study included a control group, a contaminated group that did not receive any antibiotic prophylaxis, and three contaminated groups that received: (i) intraperitoneal tigecycline, (ii) FS8-soaked graft, and (iii) tigecycline plus FS8-soaked graft, respectively. Each group included 15 animals. The infection burden was evaluated by using sonication and quantitative agar culture. Moreover, an in vitro binding-study was performed to quantify the how much FS8 was coated to the surface of the prosthesis. Tigecycline, combined with FS8, against the adherent bacteria showed MICs (2.00 mg/L) and MBCs (4.00 mg/L) four-fold lower with respect to tigecycline alone in in vitro studies. The rat groups treated with tigecycline showed the lowest bacterial numbers (4.4 x 104 ± 1.2 x 104 CFU/mL). The FS8-treated group showed a good activity and significant differences compared to control group with bacterial numbers of 6.8 x 104 ± 2.0 x 104 CFU/mL. A stronger inhibition of bacterial growth was observed in rats treated with a combined FS8 and tigecycline therapy than in those that were singly treated with bacterial numbers of 101 CFU/mL graft. In conclusion, the ability to affect biofilm formation as well, its property to be an antibiotic enhancer suggests FS8 as alternative or additional agent to use in conjunction with conventional antimicrobial for prevention of staphylococcal biofilm related infection.

Intraductal papillary neoplasm of the bile duct: The new frontier of biliary pathology.

Intraductal papillary neoplasms of the bile duct (IPNBs) represent a rare variant of biliary tumors characterized by a papillary growth within the bile duct lumen. Since their first description in 2001, several classifications have been proposed, mainly based on histopathological, radiological and clinical features, although no specific guidelines addressing their management have been developed. Bile duct neoplasms generally develop through a multistep process, involving different precursor pathways, ranging from the initial lesion, detectable only microscopically, i.e. biliary intraepithelial neoplasia, to the distinctive grades of IPNB until the final stage represented by invasive cholangiocarcinoma. Complex and advanced investigations, mainly relying on magnetic resonance imaging (MRI) and cholangioscopy, are required to reach a correct diagnosis and to define an adequate bile duct mapping, which supports proper treatment. The recently introduced subclassifications of types 1 and 2 highlight the histopathological and clinical aspects of IPNB, as well as their natural evolution with a particular focus on prognosis and survival. Aggressive surgical resection, including hepatectomy, pancreaticoduodenectomy or both, represents the treatment of choice, yielding optimal results in terms of survival, although several endoscopic approaches have been described. IPNBs are newly recognized preinvasive neoplasms of the bile duct with high malignant potential. The novel subclassification of types 1 and 2 defines the histological and clinical aspects, prognosis and survival. Diagnosis is mainly based on MRI and cholangioscopy. Surgical resection represents the mainstay of treatment, although endoscopic resection is currently applied to nonsurgically fit patients. New frontiers in genetic research have identified the processes underlying the carcinogenesis of IPNB, to identify targeted therapies.

Alarming correlation between multidrug-resistant bacteriobilia and morbidity after pancreatic surgery.

BACKGROUND: Pancreatic surgery is characterized by high morbidity and mortality. Biliary colonization may affect clinical outcomes in these patients. AIMS: This study aimed to verify whether bacteriobilia and multidrug resistance (MDR) detected during and after pancreatic surgery may have an impact on post-operative outcomes. METHODS: Data from patients undergoing pancreatic surgery involving bile duct transection (2016-2022) in two high-volume centers were analyzed in relationship to overall morbidity, major morbidity and mortality after pancreato-duodenectomy (PD) or total pancreatectomy (TP). Simple and multivariable regressions were used. RESULTS: 227 patients submitted to PD (n=129) or TP (n=98) were included. Of them, 133 had preoperative biliary drainage (BD; 56.6%), mostly with the employment of endoscopic stents (91.7%). Bacteriobilia was detected in 111 patients (48.9%), and remarkably, observed in patients with BD (p=0.001). In addition, 25 MDR pathogens were identified (22.5%), with a significant prevalence in patients with BD. Multivariable regression analysis showed BD was strongly related to MDR isolation (odds ratio [OR]: 5.61; p=0.010). MDR isolation was the main factor linked to a higher number of major complications (OR: 2.75; p=0.041), including major infection complications (OR: 2.94; p=0.031). CONCLUSIONS: Isolation of MDR from biliary swab during PD or TP significantly increases the risk of a worse post-operative outcome. Pre-operative precautions could improve patient safety.

Efficacy of tigecycline and rifampin alone and in combination against Enterococcus faecalis biofilm infection in a rat model of ureteral stent.

BACKGROUND: We investigated the efficacy of tigecycline and rifampin alone or combined in preventing ureteral stent infection due to Enterococcus faecalis. MATERIALS AND METHODS: The activities of the two antibiotics were previously studied in vitro in absence or in presence of biofilm. For in vivo research, the study included a control group without bacterial challenge to evaluate the sterility of surgical procedure, a challenged control group that did not receive any antibiotic prophylaxis and, for each bacterial strain, three challenged groups that received: (1) 2 mg/kg intraperitoneal tigecycline, immediately after stent implantation; (2) rifampin-coated ureteral stents where 0.2 cm(2) sterile ureteral stents were incubated in 10 mg/L rifampin solution for 30 min immediately before implantation; and (3) intraperitoneal tigecycline plus rifampin-coated ureteral stent at the above concentrations. Ureteral stents were explanted at d 5 following implantation and biofilm bacteria enumerated. RESULTS: The in vitro studies showed that the biofilm was strongly affected by the presence of rifampin and, in its presence, tigecycline had MICs and MBCs lower than those obtained in the absence of rifampin. Intraperitoneal tigecycline exerted stronger effect than rifampin on bacterial numbers. The combination rifampin plus tigecycline showed efficacies higher than that of each single compound. CONCLUSION: These results highlight the potential usefulness of tigecycline in preventing enterococcal ureteral stent infections and the role of rifampin as an interesting antibiotic enhancer.

Re-thinking of T-tube use in whole liver transplantation: an analysis on the risk of delayed graft function.

The liver-gut axis has been identified as crucial mediator of liver regeneration. Thus, the use of a T-tube in liver transplantation (LT), which interrupts the enterohepatic bile circulation, may potentially have a detrimental effect on the early allograft functional recovery. We retrospectively analyzed a cohort of 261 patients transplanted with a whole liver graft, with a duct-to-duct biliary anastomosis, who did not develop any surgical complication within postoperative day 14. Early allograft dysfunction (EAD) was defined according to the criteria of Olthoff et al. (EAD-O), and graded according to the Model for Early Allograft Function (MEAF) score. EAD-O developed in 24.7% of recipients and the median MEAF score was 4.0 [interquartile range 2.9-5.5]. Both MEAF and EAD predicted 90-day post-LT mortality. A T-tube was used in 49.4% of cases (n = 129). After a propensity score matching for donor age, cold and warm ischemia time, donor risk index, balance of risk score, Child-Pugh class C, and MELD score, the T-tube group showed a significantly higher prevalence of EAD-O and value of MEAF than the no-T-tube group (EAD-O: 29 [34.1%] vs 16 [19.0%], p = 0.027; MEAF 4.5 [3.5-5.7] vs 3.7 [2.9-5.0], p = 0.014). In conclusion, T-tube use in LT may be a risk factor for EAD and higher MEAF, irrespective of graft quality and severity of pre-LT liver disease.

Neoadjuvant Treatment in Resectable Pancreatic Cancer. Is It Time for Pushing on It?

Pancreatic resection still represents the only curative option for patients affected by pancreatic ductal adenocarcinoma (PDAC). However, the association with modern chemotherapy regimens is a key factor in improving the inauspicious oncological outcome. The benefit of neoadjuvant treatment (NAT) for borderline resectable/locally advanced PDAC has been demonstrated; this evidence raises the question of whether even resectable PDAC should undergo NAT rather than upfront surgery. NAT may avoid futile surgery because of undetected distant metastases or aggressive tumor biology, providing more effective systemic control of the disease, which is hampered when adjuvant chemotherapy is delayed or precluded. However, recent data show controversial results regarding the efficacy and safety of NAT in resectable PDAC compared to upfront surgery. Although several prospective studies and meta-analyses indicate better oncologic outcomes after NAT, there are some biases, such as the methodological approaches used to capture the events of interest, which could make these results hardly reproducible. For instance, per-protocol studies, considering only the postoperative outcomes, tend to overestimate the performance of NAT by excluding patients who will never be suitable for surgery due to the development of chemotoxicity or tumor progression. To draw reliable conclusions, the studies should capture the events of interest of both strategies (NAT/upfront surgery) from the time of allocation to a specific treatment in an intention-to-treat fashion. This critical review highlights the current literature data concerning the use of NAT in resectable PDAC, summarizing the results of high-quality studies and focusing on the methodological issues of the most recent pieces of evidence.