Suppressive effect of Lactobacillus fermentum Lim2 on Clostridioides difficile 027 toxin production.

Clostridioides difficile is a spore-forming, Gram-positive, anaerobic pathogen that caused gastrointestinal illness. During dysbiosis, overgrowth of C. difficile resulting in higher levels of toxin production. Since Lactobacillus has been commonly used to alleviate gastrointestinal discomfort, this study aimed to investigate the effects of Lactobacillus isolated from kimchi on the quorum-sensing and virulence factors of C. difficile 027. Among the isolated Lactobacillus strains, the acid and bile tolerant L. fermentum Lim2 was only able to reduce C. difficile 027 growth by one log10 CFU per ml. In keeping with this finding, C. difficile 027 growth was unaffected by either untreated or heat-inactivated cell extracts from L. fermentum Lim2. Both untreated and heat-inactivated cell extracts did, however, significantly reduce the autoinducer-2 (AI-2) activity of C. difficile 027, with the most prominent suppression effect (654-fold) being found from 100 mg ml-1 of heat-inactivated cell extract. A gene expression analysis indicated that in the presence of 100 mg ml-1 heat-inactivated cell extract, the quorum-sensing (luxS) and the virulence factors (tcdA, tcdB and tcdE) were significantly suppressed, whereas the negative regulator gene (tcdC) was significantly up-regulated. Taken together, the significant anti-pathogenic effect from L. fermentum Lim2 could potentially be used to treat C. difficile-infections. SIGNIFICANCE AND IMPACT OF THE STUDY: Clostridioides difficile is a Gram-positive pathogenic bacteria that caused gastrointestinal illness via toxic production. The emergence of highly virulence and foodborne C. difficile strains has further increased the incident and severity of C. difficile-infections (CDIs). Numerous studies have reported the immunomodulatory activity of Lactobacillus, a member of healthy gut microbiota, to maintain gastrointestinal health. Here, we successfully isolated L. fermentum Lim2 from kimchi, and identified a promising anti-pathogenic effect against C. difficile 027, from the heat-inactivated L. fermentum cell extract via suppression on the C. difficile 027 quorum-sensing system and toxin production, which could potentially be used to treat and prevent CDIs.

Donor-Transmitted Bacterial Infection in Deceased Donor Liver Transplantation: Experience of Southern Taiwan Medical Center.

BACKGROUND: Bacterial Infection is the most important source of mortality and morbidity in liver transplantation recipients. Donor transmitted bacterial infection is rare but one of the most important infection sources. This kind of infection is difficult to identify, causing treatment dilemma. PATIENTS AND METHODS: In this article, we retrospectively reviewed our deceased donor liver transplants performed from January 2014 to December 2016. Forty-two recipients in Kaohsiung Chang Gung Memorial Hospital receiving liver grafts from 35 deceased liver donors were evaluated. The demography, donor transmitted infection, and outcomes were evaluated. RESULT: Two patients had probable donor transmitted bacterial infection and 1 patient died of suspected transmitted infection. CONCLUSION: Early identification of donor infection and adequate antibiotic treatment for the donor and recipient are the keys to preventing donor transmitted bacterial infection. Donor infection is not an absolute contraindication for organ donation in the area of organ shortage. Organ procurement organizations or similar authorities may establish the platform for sharing the data about donor and recipient infections.

Subcranial craniofacial resection for advanced sinonasal malignant tumours involving the anterior skull base.

BACKGROUND: The subcranial approach is a modification of traditional craniofacial resection. It provides similar broad access to the anterior skull base, but with lower mortality and morbidity. It has been the surgical technique of choice at our institution since 2006 for treating advanced stage sinonasal tumours (American Joint Committee on Cancer stage III or above). This paper reports our experience and outcomes. METHOD AND RESULTS: Eighteen patients underwent subcranial craniofacial resection over a seven-year period, this being combined with a second adjunctive procedure in 89 per cent of cases. Forty per cent of patients required reconstruction of the primary defect. No peri-operative deaths occurred. One patient had a transient cerebrospinal fluid leak. The major complication rate was 33 per cent, of which 67 per cent were directly related to soft tissue reconstruction. Tumour recurrence rate was 17 per cent and the five-year disease-free survival estimate was 40 per cent. CONCLUSION: The subcranial approach is a safe and effective technique that may be used to successfully treat advanced sinonasal malignancies with anterior skull base extension.

Short-term Total Hepatic Vascular Exclusion in Difficult Caudate Lobe Dissection in Living-donor Liver Transplantation Recipients.

BACKGROUND: Recipient hepatectomy can be complicated by severe bleeding during caudate lobe dissection in living-donor liver transplantation (LDLT), especially when the inferior vena cava is encased or with dense adhesions from prior interventions. Total hepatic vascular exclusion (TVE) including total hepatic inflow (Pringle maneuver) and occlusion of supra- and infra-hepatic inferior vena cava during the partial hepatectomy has been studied well, but it has not been mentioned regarding recipient hepatectomy in LDLT. The aim of this study is to evaluate hemodynamic impact and surgical outcome by using the technique of TVE in LDLT. METHODS: From April 2010 to June 2010, 30 consecutive LDLT recipients at Kaohsiung Chang Gung Memorial Hospital with TVE (TVE group, n = 14) or without TVE (non-TVE group, n = 16) for the caudate lobe dissection were analyzed retrospectively. RESULTS: The TVE group had a mean decrease in systolic blood pressure and cardiac index of 21% and 41% during caudate dissection in recipient hepatectomy, respectively. The TVE group had shorter time for caudate mobilization and less blood loss compared with the non-TVE group (3904 mL vs. 5650 mL, P = .461). Two patients in the non-TVE group were shifted to TVE as a salvage procedure to control bleeding. Three patients in the non-TVE group underwent relaparotomy for homeostasis. CONCLUSIONS: Short-term TVE is a technically feasible procedure and should be considered during recipient hepatectomy with difficult caudate lobe dissection in LDLT to create a bloodless surgical field. Most patients tolerated the TVE without hemodynamic impact under anesthetic management.

Combined Hepatocellular Carcinoma and Cholangiocarcinoma: Diagnosis and Prognosis After Resection or Transplantation.

BACKGROUND: Primary liver malignancy is the leading cause of cancer death worldwide, with hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) representing the majority. Combined HCC-CC, in contrast, accounts for less than 5% of these liver cancers and has not been clearly characterized by imaging, making diagnosis and management difficult. MATERIALS AND METHODS: This retrospective study investigated 32 patients with early-stage combined HCC-CC tumor who underwent hepatectomy (n = 24) or liver transplantation (n = 8). Preoperative imaging and pathologic reports were retrospectively reviewed and correlated. Survival and recurrence rates were then analyzed. RESULTS: Twelve patients with more than 50% CC component showed typical CC enhancement, whereas 17 patients with less than 50% CC component exhibited typical HCC enhancement. Those with equivocal imaging findings resulted near equal tumor component. The majority demonstrated either heterogeneous or peripheral enhancement. Considering the major tumor component, 66% of the images were consistent with histopathology. The over-all 3-year recurrent rate was 59%, with a mean time to recurrence of about 7 months. The 3-year survival rate of combined tumor after hepatectomy was 76% and after transplant was 75%, regardless of major tumor component. However, patients with more than 50% CC component showed a decrease in 3-year survival rate to 50% when transplantation was performed. CONCLUSION: The overall survival rate for combined tumor after either hepatectomy or transplantation seems to be satisfactory but carries a high risk of recurrent when compared to pure HCC. On the other hand, a major CC component tumor after transplantation is associated with poor survival outcome; thus, liver transplantation has no role and is not a good management option.

The 4-week serum creatinine level predicts long-term renal dysfunction after adult living donor liver transplantation.

OBJECTIVES: Recipients after liver transplantation. (OLT) often experience renal dysfunction. Acute kidney injury (AKI) and chronic kidney disease (CKD) after OLT occur among 20% to 50% and 30% to 90% of recipients, respectively; 2% to 5% of them deteriorate into end-stage renal disease each year. Since the predictable factors for CKD have not been well identified. We sought to investigate the incidence and predictors of CKD at 5 years after OLT. PATIENTS AND METHODS: Between August 2002 and December 2005, we enrolled 77 patients who underwent adult living donor OLT with over 2 years of follow-up. The strategies to prevent renal dysfunction included induction with basiliximab to delay the use of tacrolimus: addition of mycophenolate mofetil to reduce the tacrolimus dosage; avoidance of the calcineurin inhibitor using sirolimus or administration of an angiotensin II receptor antagonist. The clinical variables were reviewed for analysis. RESULTS: The mean follow-up was 76 ± 14 months. The incidence of AKI (over 50% increase level of creatinine) was 29%. Ten (13.0%) patients developed CKD (creatinine > 2 mg/dL). One (1.3%) subject developed end-stage renal disease requiring hemodialysis. Upon multivariate analysis the development of CKD was significantly associated with the posttransplant 4-week creatinine level: 0.92 ± 0.23 versus 1.37 ± 0.93 mg/dL (P = .008). CONCLUSION: The 4-week creatinine value was predictive of the occurence of CKD over 5 years after OLT.

Hemodynamics of portal venous stenosis before and after treatment in pediatric liver transplantation: evaluation with Doppler ultrasound.

AIM: The aim of this study was to evaluate portal vein stenosis (PVS) in pediatric liver transplantation (PLT) using Doppler ultrasound (DUS) before and after interventional management for hemodynamic changes. MATERIALS AND METHODS: From 2000 to 2010, we encountered 11 PVS cases among 180 PLT that were evaluated using DUS and computed tomography (CT) angiography (CTA); all underwent portal stenting. DUS was used to monitor portal hemodynamics. For the diagnosis of PVS, we investigated multiple parameters including stenotic size (SS), stenotic ratio (SR) (SR [%]=PRE-SS/PRE [PRE=stenotic size]), portal flow velocity ratio (VR) (VR=VS/PRE [PRE=velocity at prestenotic site; VS=peak velocity at stenotic site]), spleen size, and platelet count. RESULTS: The incidence of PVS was 5.6% (11/180). The PV was 2.5 mm using DUS and 2.7 mm using CTA. The average SR was 65% fitting the criterion. Low prestenotic portal flow<12 cm/sec and high peak velocity in the stenotic segment (up to 147 cm/sec) were observed in 6 cases. The VR value was high at 7.5:1 and there was splenomegaly with thrombocytopenia. After portal vein stenting, hyperperfusion occurred might after reopening the stenosis: the flow increased to an average of 34 cm/sec and then flow decreased slowly to a stable level 2 weeks later. The size of the spleen decreased from 17 to 12 cm and the thrombocytopenia also improved with platelet counts increasing from 67×10(3) to 178×10(3)/µl at 2 months follow-up. The changes in portal flow, portal vein size, spleen size, and platelet count were significant (P<.05). CONCLUSION: PVS is diagnosed using DUS by increased intrahepatic PV dilatation, peak flow at the stenotic site, discrepant VR. Early portal stenting showed a better prognosis. DUS is essential and effective for hemodynamic monitoring and management of PVS.

Using ileocolic artery for successful graft salvage in a recipient with hepatic artery thrombosis after living donor liver transplantation: case report.

Hepatic artery (HA) occlusion is a sinister complication after liver transplantation. It frequently leads to graft loss if untreated. Urgent arterial reconstruction with thrombectomy may reduce the need for retransplantation. Living donor liver transplantation (LDLT) offers further challenges due to smaller-caliber vessels, shorter vascular stumps, and occasional multiple HA. Alternatives to the HA are needed when the native HA cannot be used or when HA complications develop. We describe the use of the recipient's ileocolic artery as an alternate HA in adult LDLT. Graft revascularization and timely salvage resulted in good patient recovery. A 6-month computed tomography angiography follow-up showed patency of the alternate vessels reconstructed.

Decreased fresh gas flow cannot compensate for an increased operating room temperature in maintaining body temperature during donor hepatectomy for living liver donor hepatectomy.

BACKGROUND: The purpose of this study was to compare the effect of various combinations of fresh gas flow (FGF) of anesthesia and different ambient operation room temperatures (ORT) on changes in nasopharyngeal temperature (NT) among living donors undergoing partial hepatectomy. METHODS: The anesthesia records of 167 patients were reviewed retrospectively. The patients were allocated into 4 groups: GI (n=37): isoflurane in 2 L FGF and at typical ambient ORT (19 degrees C-21 degrees C); GII (n=11) isoflurane in 1 L FGF and 1 L air at typical ORT; GIII (n=31) isoflurane in 0.5 L FGF at typical ORT; and GIV (n=88) isoflurane in 0.5 L FGF at ORT of 24 degrees C. The changes in NT were compared using a two-way repeated measure analysis of variance (ANOVA) followed by Bonferroni post hoc tests. RESULTS: Changes of NTs of GIV were significantly higher compared with the other 3 groups, whereas the changes of NTs were the same among GI, GII, and GIII. CONCLUSION: FGF of different volumes seemed to have no significant effect on intraoperative changes of NT in regular ORT. Low-flow anesthesia combined with ORT of 24 degrees C provided significantly higher NTs at all measured points compared with GI, GII, and GIII.

Vascular stents in the management of portal venous complications in living donor liver transplantation.

To evaluate the efficacy of stent placement in the treatment of portal vein (PV) stenosis or occlusion in living donor liver transplant (LDLT) recipients, 468 LDLT records were reviewed. Sixteen (10 PV occlusions and 6 stenoses) recipients (age range, 8 months-59 years) were referred for possible interventional angioplasty (dilatation and/or stent) procedures. Stent placement was attempted in all. The approaches used were percutaneous transhepatic (n = 10), percutaneous transsplenic (n = 4), and intraoperative (n = 2). Technical success was achieved in 11 of 16 patients (68.8%). The sizes of the stents used varied from 7 mm to 10 mm in diameter. In the five unsuccessful patients, long-term complete occlusion of the PV with cavernous transformation precluded catherterization. The mean follow-up was 12 months (range, 3-24). The PV stent patency rate was 90.9% (10/11). Rethrombosis and occlusion of the stent and PV occurred in a single recipient who had a cryoperserved vascular graft to reconstruct the PV during the LDLT operation. PV occlusion of >1 year with cavernous transformation seemed to be a factor causing technical failure. In conclusion, early treatment of PV stenosis and occlusion by stenting is an effective treatment in LDLT. Percutaneous transhepatic and transsplenic, and intraoperative techniques are effective approaches depending on the situation.

Liver graft regeneration in right lobe adult living donor liver transplantation.

Optimal portal flow is one of the essentials in adequate liver function, graft regeneration and outcome of the graft after right lobe adult living donor liver transplantation (ALDLT). The relations among factors that cause sufficient liver graft regeneration are still unclear. The aim of this study is to evaluate the potential predisposing factors that encourage liver graft regeneration after ALDLT. The study population consisted of right lobe ALDLT recipients from Chang Gung Memorial Hospital-Kaohsiung Medical Center, Taiwan. The records, preoperative images, postoperative Doppler ultrasound evaluation and computed tomography studies performed 6 months after transplant were reviewed. The volume of the graft 6 months after transplant divided by the standard liver volume was calculated as the regeneration ratio. The predisposing risk factors were compiled from statistical analyses and included age, recipient body weight, native liver disease, spleen size before transplant, patency of the hepatic venous graft, graft weight-to-recipient weight ratio (GRWR), posttransplant portal flow, vascular and biliary complications and rejection. One hundred forty-five recipients were enrolled in this study. The liver graft regeneration ratio was 91.2 +/- 12.6% (range, 58-151). The size of the spleen (p = 0.00015), total portal flow and GRWR (p = 0.005) were linearly correlated with the regeneration rate. Patency of the hepatic venous tributary reconstructed was positively correlated to graft regeneration and was statistically significant (p = 0.017). Splenic artery ligation was advantageous to promote liver regeneration in specific cases but splenectomy did not show any positive advantage. Spleen size is a major factor contributing to portal flow and may directly trigger regeneration after transplant. Control of sufficient portal flow and adequate hepatic outflow are important factors in graft regeneration.

Effects of different operating room temperatures on the body temperature undergoing live liver donor hepatectomy.

OBJECTIVE: We sought to compare the effects of operation room temperature (ORT) at typical ambient environment (19-21 degrees C) and ORT at 24 degrees C on the core temperature of patients undergoing living donor hepatectomy. METHODS AND PATIENTS: Sixty-two patients undergoing living donor hepatectomy were divided into 2 groups. In group I (n = 31), surgery was performed at typical ambient ORT, and in group II (n = 31) in ORT at 24 degrees C. Anesthesia and measures to prevent heat loss, except ORT, were all the same. Nasopharyngeal temperature (NT) was recorded after anesthesia induction, then hourly until completion of the operation. Changes in NTs were analyzed as well as patient age, weight, anesthetic duration, blood loss, intravenous fluids, total urine output, and pre- and postoperative hemoglobin and hematocrit values. The Mann-Whitney U test was used for comparisons between groups. RESULTS: The patient's characteristics between groups were not statistically different. However, a significantly higher core temperature was noted in group II compared with group I. Increased ORT from 19 to 21 degrees C to 24 degrees C resulted in an increased core temperature of at least 0.5 degrees C during living donor hepatectomy.

Retransplantation for end-stage liver disease: a single-center Asian experience.

Liver retransplantation carries a significantly higher morbidity and mortality compared with patients after single transplantations. The aim of this study was to review our outcomes in liver retransplantations. From February 1984 to February 2007, 409 liver transplantations were performed on 396 patients, including 13 retransplantations (3.2%) in 12 patients. The mean follow-up was 1.6 +/- 0.4 years (range, 0.1-5.2). The mean duration between the first and the second transplantation was 2.8 +/- 1.0 years (range, 15 days-11.6 years). The indications for the first liver transplantation included biliary atresia (n = 3), hepatitis B virus (HBV)-related cirrhosis with hepatoma (n = 3), fulminant hepatic failure (n = 2), HBV-related end-stage liver disease (n = 1), hepatitis C virus (HCV)-related end-stage liver disease (n = 1), neonatal hepatitis (n = 1), and glycogen storage disease (n = 1). The indications for retransplantations were secondary biliary cirrhosis (n = 3), veno-occlusive disease-related liver failure (n = 2), hepatic arterial occlusion and graft failure (n = 2), chronic rejection with hepatic graft failure (n = 2), recurrent HBV (n = 1) and de novo HBV-related decompensated cirrhosis (n = 1), and idiopathic graft failure (n = 1). There were 4 living donor and 9 deceased donor liver retransplantations. The cumulative survival rate was 71.4 +/- 14.4%, with an estimated mean survival time of 3.9 +/- 0.7 years. Our results showed that minimizing the rate of retransplantation was critical to enhance overall patient survival. Moreover, living donor liver retransplantation is another option within the short, yet critical, waiting period, after failure of the first graft. Provided that a suitable living donor is available, we recommend early retransplantation to minimize the risk of morbidity and mortality.

Active immunization to prevent de novo hepatitis B virus infection in pediatric live donor liver recipients.

This study aims to evaluate the efficacy of HBV vaccination as an alternative preventive measure against de novo HBV infection in pediatric living donor liver transplantation (LDLT). Sixty recipients were enrolled in this study. Thirty received grafts from anti-HBc(+) donors, and another 30 received grafts from anti-HBc(-) donors. HBV vaccine was given pretransplant to every candidate. Posttransplant, lamivudine was routinely given to recipients receiving anti-HBc(+) grafts for about 2 years. Forty-seven (78%) recipients achieved high levels of anti-HBs titer (>1000 IU/L). Two (3.3%) recipients developed de novo HBV infection where one received an anti-HBc(-) graft and another received an anti-HBc(+) graft. Both recipients were in the lower anti-HBs titer group (<1000 IU/L). The incidence of de novo HBV infection was significantly higher in the lower titer group (15.4% vs. 0%, p = 0.04). The median follow-up period was 51 months in recipients with anti-HBc(-) grafts and 57 months in those with anti-HBc(+) grafts. Active immunization is an effective method to prevent de novo HBV infection. It can result in high levels of anti-HBs titer (>1000 IU/L) which may prevent de novo HBV infection in pediatric patients with efficient primary vaccination undergoing LDLT.

Liver graft-to-recipient spleen size ratio as a novel predictor of portal hyperperfusion syndrome in living donor liver transplantation.

Portal hyperperfusion in a small-size liver graft is one cause of posttransplant graft dysfunction. We retrospectively analyzed the potential risk factors predicting the development of portal hyperperfusion in 43 adult living donor liver transplantation recipients. The following were evaluated: age, body weight, native liver disease, spleen size, graft size, graft-to-recipient weight ratio (GRWR), total portal flow, recipient portal venous flow per 100 g graft weight (RPVF), graft-to-recipient spleen size ratio (GRSSR) and portosystemic shunting. Spleen size was directly proportional to the total portal flow (p = 0.001) and RPVF (p = 0.014). Graft hyperperfusion (RPVF flow > 250 mL/min/100 g graft) was seen in eight recipients. If the GRSSR was < 0.6, 5 of 11 cases were found to have graft hyperperfusion (p = 0.017). The presence of portosystemic shunting was significant in decreasing excessive RPVF (p = 0.059). A decrease in portal flow in the hyperperfused grafts was achieved by intraoperative splenic artery ligation or splenectomy. Spleen size is a major factor contributing to portal flow after transplant. The GRSSR is associated with posttransplant graft hyperperfusion at a ratio of < 0.6.

Living donor liver transplantation for biliary atresia: a single-center experience with first 100 cases.

The aim of this study is to present our institutional experience in living donor liver transplantation (LDLT) as a treatment for end-stage liver disease in children with biliary atresia (BA). A retrospective review of transplant records was performed. One hundred BA patients (52 males and 48 females) underwent LDLT. The mean follow-up period was 85.5 months. The mean age was 2.4 years. The mean preoperative weight, height, and computed GFR were 12.2 kg, 82.5 cm, and 116.4 ml/min/1.73 m2, respectively. Twenty-seven patients were below 1 year of age, and 49 patients were below 10 kg at the time of transplantation. Ninety-six had had previous Kasai operation prior to transplant. The mean recipient operative time was 628 min. The mean recipient intraoperative blood loss was 176 ml. Thirty-five did not require blood or blood component transfusion. The left lateral segment (64) was the most common type of graft used. There were 27 operative complications which included 3 reoperations for postoperative bleeding, 9 portal vein, 4 hepatic vein, 4 hepatic artery, and 7 biliary complications. There was one in-hospital mortality and one retransplantation. The overall rejection rate was 20%. The overall mortality rate was 3%. The 6-month, 1-year and 5-year actual recipient survival rates were 99%, 98% and 98%, respectively.

Liver transplantation from an uncontrolled non-heart-beating donor maintained on extracorporeal membrane oxygenation.

Liver transplantation, a definitive treatment for end-stage liver disease, has achieved excellent results. However, potential recipients on the waiting list outnumber donors. To expand the donor pool, marginal grafts from older donors, steatotic livers, and non-heart-beating liver donors (NHBD) have been used for transplantation. Reducing the warm ischemia time of NHBD is the critical factor in organs preservation. Liver transplantation using grafts from NHBD have been reported to display a high incidence of primary graft nonfunction and biliary complications. The authors report a liver graft donor who was maintained on extracorporeal membrane oxygenation (ECMO) after successful cardiopulmonary resuscitation. Core body temperature was 5 degrees C. Procurement of the liver using a rapid flush technique was performed 4 hours after instituting ECMO. Graft function recovered fully after transplantation. In conclusion, ECMO may be used to reduce warm ischemia time in liver grafts obtained from uncontrolled NHBD, thereby increasing graft salvage rates.

Benzoyl peroxide gel therapy in acne in Singapore.

The results of an open clinical trial of 200 patients in Singapore show that benzoyl peroxide, in a stable gel formulation, both in 2.5% and 5% strengths, was highly efficacious in the topical treatment of acne vulgaris without concomitant systemic therapy. The series included a small number of Caucasians (13 patients) who were also treated effectively. Side effects noted were generally mild and transient.