A Case of Nonalcoholic Steatohepatitis and Small Intestinal Bacterial Overgrowth with Peripheral Edema Caused by Intestinal Bypass Surgery and Relieved by Repair

Intestinal bypass surgery, particularly jejuno-ileal bypass surgery, performed for the purpose of weight reduction may cause an unexpected exacerbation of nonalcoholic steatohepatitis (NASH). Here, we report a case of NASH caused by small intestinal bacterial overgrowth, which developed after jejuno-colic bypass surgery and resolved dramatically after surgical correction.     

Promotion of hepatocellular carcinoma by the intestinal microbiota and TLR4

Increased translocation of intestinal bacteria is a hallmark of chronic liver disease and contributes to hepatic inflammation and fibrosis. Here we tested the hypothesis that the intestinal microbiota and Toll-like receptors (TLRs) promote hepatocellular carcinoma (HCC), a long-term consequence of chronic liver injury, inflammation, and fibrosis. Hepatocarcinogenesis in chronically injured livers depended on the intestinal microbiota and TLR4 activation in non-bone-marrow-derived resident liver cells. TLR4 and the intestinal microbiota were not required for HCC initiation but for HCC promotion, mediating increased proliferation, expression of the hepatomitogen epiregulin, and prevention of apoptosis. Gut sterilization restricted to late stages of hepatocarcinogenesis reduced HCC, suggesting that the intestinal microbiota and TLR4 represent therapeutic targets for HCC prevention in advanced liver disease.     

Prophylactic use of lamivudine for hepatitis B exacerbation in post-operative breast cancer patients receiving anthracycline-based adjuvant chemotherapy

Background:

With the increasing incidence of breast cancer worldwide, in particular in southeast Asia (including Korea), and the common use of anthracyclines in the adjuvant and metastatic settings, the occurrence of Hepatitis B virus (HBV) reactivation may develop in this patient population. The use of prophylactic antiviral agents in cancer patients may result in a reduced HBV exacerbation. The purpose of the current study was to assess the efficacy of prophylactic lamivudine in reducing the incidence and severity of HBV reactivation in post-operative breast cancer patients undergoing adjuvant doxorubicin-containing chemotherapy.

Methods:

The medical records of patients undergoing anthracycline-based adjuvant chemotherapy at Samsung Medical Center between January 2001 and September 2008 were reviewed.

Results:

From the database, 1912 breast cancer patients who had received anthracycline-based adjuvant chemotherapy were identified. Of 131 patients who were HBV surface antigen positive, 55 and 76 did and did not receive prophylactic lamivudine, respectively. In all, 30 patients (23%) developed hepatitis during doxorubicin-containing adjuvant chemotherapy. Of the 30 patients, 5 (9%) were in the prophylactic lamivudine group and 25 (33%) in the control group (P=0.001). In the prophylactic lamivudine group, there was significantly less HBV reactivation (1 patient (2%) vs 20 patients (16%); P=0.002), less disruption of chemotherapy (7 vs 14% P=0.04), and less severe hepatitis (0 vs 17% P=0.002).

Conclusion:

Prophylactic lamivudine significantly reduced the incidence and severity of HBV reactivation in breast cancer patients undergoing anthracycline-based adjuvant chemotherapy.     

Clinical Outcomes Following Letrozole Treatment according to Estrogen Receptor Expression in Postmenopausal Women: LETTER Study (KBCSG-006)

PurposeIn this trial, we investigated the efficacy and safety of adjuvant letrozole for hormone receptor (HR)-positive breast cancer. Here, we report the clinical outcome in postmenopausal women with HR-positive breast cancer treated with adjuvant letrozole according to estrogen receptor (ER) expression levels.MethodsIn this multi-institutional, open-label, observational study, postmenopausal patients with HR-positive breast cancer received adjuvant letrozole (2.5 mg/daily) for 5 years unless they experienced disease progression or unacceptable toxicity or withdrew their consent. The patients were stratified into the following 3 groups according to ER expression levels using a modified Allred score (AS): low, intermediate, and high (AS 3–4, 5–6, and 7–8, respectively). ER expression was centrally reviewed. The primary objective was the 5-year disease-free survival (DFS) rate.ResultsBetween April 25, 2010, and February 5, 2014, 440 patients were enrolled. With a median follow-up of 62.0 months, the 5-year DFS rate in all patients was 94.2% (95% confidence interval [CI], 91.8–96.6). The 5-year DFS and recurrence-free survival (RFS) rates did not differ according to ER expression; the 5-year DFS rates were 94.3% and 94.1%in the low-to-intermediate and high expression groups, respectively (p = 0.6), and the corresponding 5-year RFS rates were 95.7% and 95.4%, respectively (p = 0.7). Furthermore, 25 patients discontinued letrozole because of drug toxicity.ConclusionTreatment with adjuvant letrozole showed very favorable treatment outcomes and good tolerability among Korean postmenopausal women with ER-positive breast cancer, independent of ER expression.Trial RegistrationClinicalTrials.gov Identifier: {"type":"clinical-trial","attrs":{"text":"NCT01069211","term_id":"NCT01069211"}}NCT01069211     

Differences of perioperative liver function, transfusion, and complications according to the type of hepatectomy in living donors

Numerous living donor hepatectomy are being performed safely. However, donors are still exposed to various complications including hepatic failure. We examined the donor's potential risk and morbidity depending on the type of hepatectomy: left lateral segmentectomy (group LLS, n = 30), left lobectomy (group LL, n = 15), and right lobectomy (group RL, n = 128). The charts and computerized hospital data of 173 donors from March 2000 to September 2003 were retrospectively reviewed. We analyzed liver function tests (LFT), RBC transfusion, and complications. Although the graft weight was greatest, and surgical and anesthetic times were longest in the group RL, there were no significant differences in postoperative hospital stay, RBC transfusion, and major complications among the groups. However, minor complications were significantly higher in group RL than group LLS. Postoperative prothrombin time and total bilirubin were significantly higher in the group RL than the other groups (P < 0.05). Living donor hepatectomy is relatively safe, and it is evidenced by rapid recovery of LFT and low occurrence of major complications. However, noticeable depression of LFT and frequent minor complications occur after hepatectomy, especially RL.     

Development of a biodegradable bone cement for craniofacial applications

This study investigated the formulation of a two-component biodegradable bone cement comprising the unsaturated linear polyester macromer poly(propylene fumarate) (PPF) and crosslinked PPF microparticles for use in craniofacial bone repair applications. A full factorial design was employed to evaluate the effects of formulation parameters such as particle weight percentage, particle size, and accelerator concentration on the setting and mechanical properties of crosslinked composites. It was found that the addition of crosslinked microparticles to PPF macromer significantly reduced the temperature rise upon crosslinking from 100.3°C ± 21.6°C to 102.7°C ± 49.3°C for formulations without microparticles to 28.0°C ± 2.0°C to 65.3°C ± 17.5°C for formulations with microparticles. The main effects of increasing the particle weight percentage from 25 to 50% were to significantly increase the compressive modulus by 37.7 ± 16.3 MPa, increase the compressive strength by 2.2 ± 0.5 MPa, decrease the maximum temperature by 9.5°C ± 3.7°C, and increase the setting time by 0.7 ± 0.3 min. Additionally, the main effects of increasing the particle size range from 0-150 μm to 150-300 μm were to significantly increase the compressive modulus by 31.2 ± 16.3 MPa and the compressive strength by 1.3 ± 0.5 MPa. However, the particle size range did not have a significant effect on the maximum temperature and setting time. Overall, the composites tested in this study were found to have properties suitable for further consideration in craniofacial bone repair applications.     

Orthotopic bone formation by implantation of apatite-coated poly(lactide-co-glycolide)/hydroxyapatite composite particulates and bone morphogenetic protein-2

Bone morphogenetic proteins (BMPs) are the most potent osteoinductive growth factors. However, a delivery system is essential to take advantage of the osteoinductive effect of BMPs. In the present study, we tested the suitability of apatite-coated poly(D,L-lactide-co-glycolide)/nanohydroxyapatite (PLGA/HA) particulates as carriers for the controlled release of BMP-2. The release of BMP-2 from apatite-coated PLGA/HA particulates was sustained for at least 4 weeks in vitro. A delivery system of apatite-coated PLGA/HA particulates suspended in fibrin gel further slowed the BMP-2 release rate. In vivo implantation of either Fibrin gel + BMP-2 or Fibrin gel + apatite-coated PLGA/HA particulates showed enhanced new bone formation in critical-sized calvarial defects of rats 8 weeks after implantation, compared to implantation of fibrin gel only. Importantly, new bone formation was much higher in the defects treated with BMP-2 delivery using apatite-coated PLGA/HA particulates in fibrin gel (Fibrin gel + PLGA/HA + BMP-2 group) than in the defects treated either with apatite-coated PLGA/HA particulates in fibrin gel (Fibrin gel + BMP-2 group) or with BMP-2 delivery using fibrin gel alone (Fibrin gel + BMP-2 group). BMP-2 and osteoinductive HA had an additive effect on orthotopic bone formation. In conclusion, the apatite-coated PLGA/HA particulates showed good results as carriers for BMP-2. The BMP-2 delivery system showed high osteogenic capability in a rat calvarial bone defect model. The local and sustained delivery system for BMP-2 developed in this study may be useful as a carrier for BMP-2 and would enhance bone regeneration efficacy for the treatment of large bone defects.     

The comparison of esophageal variceal ligation plus propranolol versus propranolol alone for the primary prophylaxis of esophageal variceal bleeding

Background/Aims

To investigate the efficacy and longterm outcome of esophageal variceal ligation (EVL) plus propranolol in comparison with propranolol alone for the primary prophylaxis of esophageal variceal bleeding.

Methods

A total of 504 patients were retrospectively enrolled in this study. 330 patients were in propranolol group (Gr1) and 174 patients were in EVL plus propranolol group (Gr2). The endpoints of this study were esophageal variceal bleeding and mortality. Association analyses were performed to evaluate bleeding and mortality between Gr1 and Gr2.

Results

EVL was more applied in patients with high risk, such as large-sized varices (F2 or F3) or positive red color signs. Total 38 patients had bleeds, 32 in Gr1 and 6 in Gr2. The cumulative probability of bleeding at 120 months was 13% in Gr1 versus 4% in Gr2 (P=0.04). The predictive factors of variceal bleeding were red color signs (OR 2.962, P=0.007) and the method of propranolol plus EVL (OR 0.160, P=0.000). 20 patients died in Gr1 and 12 in Gr2. Mortality rates are similar in the two groups compared, 6.7% in Gr1 and 6.9% in Gr2. The cumulative probability of mortality at 120 months was not significantly different in the two groups (7% in Gr1, 12% in Gr2, P=0.798). The prognostic factors for mortality were age over 50 (OR 5.496, P=0.002), Child-Pugh class B (OR 3.979, P=0.001), and Child-Pugh class C (OR 10.861, P=0.000).

Conclusions

EVL plus propranolol is more effective than propranolol alone in the prevention of the first variceal bleeding in patients with liver cirrhosis.     

The experience of ligation of transverse or sigmoid sinus in surgery of large petroclival meningiomas

The authors present the experience of ligation of transverse or sigmoid sinus in the surgical removal of petroclival meningiomas. We reviewed the medical records and venograms of 14 patients with petroclival meningiomas, in whom the intraoperative ligation of transverse or sigmoid sinus had been done at our hospital between 1986 and 1999. All patients passed the intraoperative test clamping of the sinus. The drainage pattern of confluence of Herophili was classified into four types: type A, confluence and equal drainage on both transverse sinuses; type B, confluence and non-dominant transverse sinus on the tumor side; type C, confluence and dominant transverse sinus on the tumor side; and type D, unilateral transverse sinus only. Among the 14 cases, four cases were in type A, five cases in type B, and two were type C. There was no evidence of brain swelling after intraoperative test clamping of the sinus for more than 30 min. None of the patients experienced postoperative complications related with sinus ligation. Our observation suggests that the transverse or sigmoid sinus ligation is tolerable to patients who show the drainage patterns of type A, type B, and type C, if the test clamping proves to be safe.