PFDN4 as a Prognostic Marker Was Associated with Chemotherapy Resistance through CREBP1/AURKA Pathway in Triple-Negative Breast Cancer.

Breast cancer is the most common malignancy and its incidence is increasing. It is currently mainly treated by clinical chemotherapy, but chemoresistance remains poorly understood. Prefolded proteins 4 (PFDN4) are molecular chaperone complexes that bind to newly synthesized polypeptides and allow them to fold correctly to stabilize protein formation. This study aimed to investigate the role of PFDN4 in chemotherapy resistance in breast cancer. Our study found that PFDN4 was highly expressed in breast cancer compared to normal tissues and was statistically significantly associated with stage, nodal status, subclasses (luminal, HER2 positive and triple negative), triple-negative subtype and disease-specific survival by TCGA database analysis. CRISPR knockout of PFDN4 inhibited the growth of 89% of breast cancer cell lines, and the triple-negative cell line exhibited a stronger inhibitory effect than the non-triple-negative cell line. High PFDN4 expression was associated with poor overall survival in chemotherapy and resistance to doxorubicin and paclitaxel through the CREBP1/AURKA pathway in the triple-negative MDAMB231 cell line. This study provides insightful evidence for the value of PFDN4 in poor prognosis and chemotherapy resistance in breast cancer patients.

Effects of Luteolin on Human Breast Cancer Using Gene Expression Array: Inferring Novel Genes.

Taraxacum officinale (dandelion) is often used in traditional Chinese medicine for the treatment of cancer; however, the downstream regulatory genes and signaling pathways mediating its effects on breast cancer remain unclear. The present study aimed to explore the effects of luteolin, the main biologically active compound of T. officinale, on gene expression profiles in MDA-MB-231 and MCF-7 breast cancer cells. The results revealed that luteolin effectively inhibited the proliferation and motility of the MDA-MB-231 and MCF-7 cells. The mRNA expression profiles were determined using gene expression array analysis and analyzed using a bioinformatics approach. A total of 41 differentially expressed genes (DEGs) were found in the luteolin-treated MDA-MB-231 and MCF-7 cells. A Gene Ontology analysis revealed that the DEGs, including AP2B1, APP, GPNMB and DLST, mainly functioned as oncogenes. The human protein atlas database also found that AP2B1, APP, GPNMB and DLST were highly expressed in breast cancer and that AP2B1 (cut-off value, 75%) was significantly associated with survival rate (p = 0.044). In addition, a Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that the DEGs were involved in T-cell leukemia virus 1 infection and differentiation. On the whole, the findings of the present study provide a scientific basis that may be used to evaluate the potential benefits of luteolin in human breast cancer. Further studies are required, however, to fully elucidate the role of the related molecular pathways.

Excellent Outcome in Living Donor Liver Transplantation: Treating Patients With Acute-on-Chronic Liver Failure.

Acute-on-chronic liver failure (ACLF) is a fatal condition, and liver transplantation (LT) is a vital option for these patients. However, the result of living donor LT (LDLT) for ACLF is not well investigated. This study investigated the outcomes of LDLT in patients with ACLF compared with patients without ACLF. This was a single-center, retrospective, matched case-control study. From July 2002 to March 2017, a total of 112 patients with ACLF who underwent LDLT were enrolled according to the consensus of the Asian Pacific Association for the Study of the Liver. A total of 224 patients were selected for control comparison (non-ACLF) with demographic factors (sex, age, and body mass index) matched (1:2). Patients with ACLF were stratified into ACLF 1, 2, and 3 categories according to the number of organ failures based on the Chronic Liver Failure-Sequential Organ Failure Assessment score. Survival and surgical outcomes after LDLT were analyzed. The Model for End-Stage Liver Disease and Child-Turcotte-Pugh scores in the ACLF group were significantly higher than those in the non-ACLF group (P < 0.001). The 90-day, 3-year, and 5-year survival rates in the ACLF and non-ACLF groups were 97.3%, 95.5%, 92.9%, respectively, and 96.9%, 94.2%, and 91.1%, respectively (P = 0.58). There was more intraoperative blood loss in the ACLF group than in the non-ACLF group (P < 0.001). The other postoperative complications were not significantly different between the groups. A total of 20 patients (17.9%) in the ACLF group presented with 3 or more organ system dysfunctions (ACLF 3), and the 90-day, 3-year, and 5-year survival rates were comparable with those of ACLF 1 and ACLF 2 (P = 0.25). In carefully selected patients, LDLT gives excellent outcomes in patients with ACLF regardless of the number of organs involved. Comprehensive perioperative care and timely transplantation play crucial roles in saving the lives of patients with ACLF.

P4 Stump Approach for Intraoperative Portal Vein Stenting in Pediatric Living Donor Liver Transplantation: An Innovative Technique for a Challenging Problem.

OBJECTIVE: The aim of this study was to evaluate the utility of the P4 stump stenting approach for treating portal vein (PV) complications in pediatric living donor liver transplantation (LDLT). BACKGROUND: PV complications cause significant morbidity and mortality in pediatric LDLT. Biliary atresia in the backdrop of pathological PV hypoplasia and sclerosis heightens the complexity of PV reconstruction. The authors developed a novel approach for intraoperative PV stenting via the graft segment 4 PV stump (P4 stump) to address this challenge. METHODS: From April 2009 to December 2016, 15 pediatric LDLT recipients (mean age 10.3 ±â€Š5.0 months, mean graft-recipient weight ratio 3.70%) underwent intraoperative stenting for suboptimal PV flow (<10 cm/s) or PV occlusion after collateral ligation and graft repositioning. Under portography, metallic stents were deployed via the reopened P4 stump of the left lateral segment grafts. RESULTS: PV diameter and peak flow increased significantly after stent placement (2.93 ±â€Š1.74 to 7.01 ±â€Š0.91 mm and 2.0 ±â€Š9.2 to 17.3 ±â€Š3.5 cm/s, respectively, P = 0.001 for both), and there were no technical failures. Stents in all surviving patients remained patent up to 8 years (mean 27.7 months), with no vascular or biliary complications. After implementation of the P4 approach, the incidence of variceal bleeding as a late complication decreased from 7% to zero. CONCLUSION: The P4 stump stenting approach affords procedural convenience, ease of manipulation, and consistent results with the potential for excellent long-term patency in children despite continued growth. This technique obviates the need for more demanding post-transplant stenting, and may become a substitute for complicated revision surgery, portosystemic shunting, or retransplantation.

Active immunization for prevention of De novo hepatitis B virus infection after adult living donor liver transplantation with a hepatitis B core antigen-positive graft.

De novo hepatitis B virus (DNHB) infections may occur in recipients who do not receive prophylaxis after liver transplantation (LT) with antibody to hepatitis B core antigen (anti-HBc)-positive donor grafts. Active immunization has been shown to prevent DNHB in pediatric recipients. Our aim is to investigate the efficacy of HBV vaccination for preventing DNHB in adult living donor liver transplantation (LDLT). In total, 71 adult antibody to hepatitis B surface antigen (anti-HBs)-negative LDLT patients who received anti-HBc+ grafts from 2000 to 2010 were enrolled into this study. Patients were given hepatitis B virus vaccinations with the aim of achieving anti-HBs > 1000 IU/L before transplant and >100 IU/L after transplant. The cohort was stratified into 3 groups: patients with pretransplant anti-HBs titer of > 1000 IU/L without the need for posttransplant prophylaxis (group 1, n = 24), patients with pretransplant low titer of <1000 IU/L who were given posttransplant lamivudine prophylaxis and responded appropriately to posttransplant vaccination by maintaining anti-HBs titers of > 100 IU/L (group 2, n = 30), and low titer nonresponders (anti-HBs titer of < 100 IU/L despite vaccination), for whom lamivudine was continued indefinitely (group 3, n = 17). All DNHB occurred in group 3 patients with posttransplant anti-HBs levels of < 100 IU/L, with an incidence rate of 17.6% compared with 0% in patients with posttransplant anti-HBs levels of > 100 IU/L (P = 0.001). A pretransplant anti-HBs level of >1000 IU/L was significantly associated with early attainment and a sustained level of posttransplant anti-HBs of >100 IU/L (P < 0.001). Active immunization is effective in preventing DNHB in adult LDLT if the posttransplant anti-HBs level is maintained above 100 IU/L with vaccination. Antiviral prophylaxis can be safely discontinued in patients who obtain this immunity. Liver Transplantation 23 1266-1272 2017 AASLD.

Less cost by using hanging maneuver and Pringle maneuver in left lateral hepatectomy through small laparotomy wound--experience of Southern Taiwan.

BACKGROUND: Laparoscopic segmentectomy for liver tumor located in the left lateral segment (LLS) is thought to be a standard protocol nowadays with several advantages, such as small wound, few blood loss, and short hospital stay. However, there are still many disadvantages during executing laparoscopic LLS segmentectomy. This manuscript aims to present the technique to execute LLS segmentectomy with small incision, hanging maneuver without Pringle maneuver in patients with tumor at LLS of the liver. MATERIAL AND METHODS: Between November 2010 and July 2011, hepatectomies through small incision for nine patients with benign and malignant tumors were performed at Kaohsiung Chang Gung Memorial Hospital, Taiwan. Perioperative and postoperative results, such as operation time, blood loss, incisional width, and postoperative stay were used to determine consequents for this technique. RESULT: Results demonstrated that modified LLS segmentectomy by the author's team was performed successfully in patient with liver tumor with fewer blood loss, smaller incisional width, and lower hospital cost than traditional open surgery. In addition, the instrument cost and blood loss in our series were less than that in laparoscopic LLS segmentectomy in published literature. CONCLUSION: Authors concluded that minimally incisional segmentectomy, with less cost and technical demanding, could be an alternative choice in patient with liver tumor at LLS.

Outcomes of long storage times for cryopreserved vascular grafts in outflow reconstruction in living donor liver transplantation.

The outflow reconstruction of the right anterior sector in a right liver graft (RLG) with cryopreserved vascular grafts (CVGs) is crucial for preventing graft congestion in living donor liver transplantation (LDLT). The impact of the duration of cryopreservation has not been evaluated so far. From 2006 to 2009, 250 LDLT were performed: 47 of these patients (group 1) received CVGs stored for ≦1 year, and 33 patients (group 2) received CVGs stored for >1 year. Single or multiple segment 8 hepatic veins were reconstructed. The number of anastomoses did not affect vascular graft patency (P = 0.21). The length of the cryopreservation time did not affect the histological findings for CVGs. The preoperative and postoperative liver graft volumes were 783.8 ± 129.7 and 1102 ± 194.7 cc, respectively, for group 1 and 753.7 ± 158.5 and 1097.2 ± 178.7 cc, respectively, for group 2. The regeneration indices for liver grafts in the whole patient group, group 1, and group 2 were 48.9%, 47.4%, and 51.05%, respectively. In conclusion, the storage duration has no impact on the patency of CVGs in outflow reconstruction or on the regeneration of RLGs in LDLT. CVGs stored for >1 year can be safely used for the outflow reconstruction of RLGs in LDLT.

A single center analysis of long-term outcomes and survival related risk factors in liver retransplantation.

Background: Liver retransplant is the only option to save a patient with liver graft failure. However, it is controversial due to its poor survival outcome compared to primary transplantation. Insufficient deceased organ donation in Taiwan leads to high waitlist mortality. Hence, living-donor grafts offer a valuable alternative for retransplantation. This study aims to analyze the single center's outcome in living donor liver retransplantation (re-LDLT) and deceased donor liver retransplantation (re-DDLT) as well as the survival related confounding risk factors. Methods: This is a single center retrospective study including 32 adults who underwent liver retransplantation (re-LT) from June 2002 to April 2020. The cohort was divided into a re-LDLT and a re-DDLT group and survival outcomes were analyzed. Patient outcomes over different periods, the effect of timing on survival, and multivariate analysis for risk factors were also demonstrated. Results: Of the 32 retransplantations, the re-LDLT group (n=11) received grafts from younger donors (31.3 vs. 43.75 years, P=0.016), with lower graft weights (688 vs. 1,457.2 g, P<0.001) and shorter cold ischemia time (CIT) (45 vs. 313 min, P<0.001). The 5-year survival was significantly better in the re-LDLT group than in the re-DDLT group (100% vs. 70.8%, P=0.02). This difference was adjusted when only retransplantation after 2010 was analyzed. Further analysis showed that the timing of retransplantation (early vs. late) did not affect patient survival. Multivariate analysis revealed that prolonged warm ischemia time (WIT) and intraoperative blood transfusion were related to poor long-term survival. Conclusions: Retransplantation with living donor graft demonstrated good long-term outcomes with acceptable complications to both recipient and donor. It may serve as a choice in areas lacking deceased donors. The timing of retransplantation did not affect the long-term survival. Further effort should be made to reduce WIT and massive blood transfusion as they contributed to poor survival after retransplantation.

Long-term outcomes of active vaccination against de novo hepatitis B among pediatric recipients of living donor liver transplantations with anti-HBc (+) grafts: a retrospective case-control study.

BACKGROUND: Active vaccination has been utilized to prevent de novo hepatitis B virus infection (DNHB) in anti-HBc (+) grafts after liver transplantation (LT). However, the long-term efficacy of active vaccination and graft/patient outcomes of anti-HBc (+) grafts have yet to be comprehensively investigated. MATERIALS AND METHODS: Among 204 pediatric patients enrolled in the study, 82 recipients received anti-HBc (+) grafts. For DNHB prevention, active vaccination was repeatedly administered prior to transplant. Anti-viral therapy was given to patients with pre-transplant anti-HBs<1000 IU/ ml (non-robust response) for 2 years and discontinued when post-transplant patients achieved anti-HBs>1000 IU/mL, while anti-viral therapy was not given in patients with an anti-HBs titer over 1000 IU/mL. The primary outcome was to investigate the long-term efficacy of active vaccination, while the secondary outcomes included the graft and patient survival rates. RESULTS: Among the 82 anti-HBc (+) transplant patients, 68% of recipients achieved a robust immune response, thus not requiring antiviral therapy. Two patients (2.4%) developed DNHB infection, one of which was due to an escape mutant. With a median follow-up of 150 months, the overall 10-year patient and graft survival rates were significantly worse in recipients of anti-HBc (+) grafts than those of anti-HBc (-) grafts (85.2% vs 93.4%, P=0.026; 85.1% vs 93.4%, P=0.034, respectively). Additionally, the 10-year patient and graft outcomes of the anti-HBc (+) graft recipients were significantly worse than those of the anti-HBc (-) graft recipients after excluding early mortality and non-graft mortality values (90.8% vs 96.6%, P=0.036; 93.0% vs 98.3%, P=0.011, respectively). CONCLUSION: Our long-term follow-up study demonstrates that active vaccination is a simple, cost-effective strategy against DNHB infection in anti-HBc (+) graft patients, whereby the need for life-long antiviral therapy is removed. Notably, both the anti-HBc (+) grafts and patients exhibited inferior long-term survival rates, although the exact mechanisms remain unclear.

Early and long-term results of routine microsurgical biliary reconstruction in living donor liver transplantation.

We describe our early and long-term experience with routine biliary reconstruction via a microsurgical technique in living donor liver transplantation (LDLT). One hundred seventy-seven grafts (including 3 dual grafts) were primarily transplanted into 174 recipients. The minimum follow-up was 44 months. Biliary reconstructions were based on biliary anatomical variations in graft and recipient ducts. The recipient demographics, graft characteristics, types of biliary reconstruction, biliary complications (BCs), and outcomes were evaluated. There were 130 right lobe grafts and 47 left lobe grafts. There were single ducts in 71.8%, 2 ducts in 26.0%, and 3 ducts in 2.3% of the grafts. The complications were not significantly related to the size and number of ducts, the discrepancy between recipient and donor ducts, the recipient age, the ischemia time, or the type of graft. The overall BC rate was 9.6%. The majority of the complications occurred within the first year, and only 1 patient developed a stricture at 20 months. No new complications were noted after 2 years. When the learning-curve phase of the first 15 cases was excluded, the overall BC rate was 6.79%, and the rate of complications requiring interventions was 2.5%. In conclusion, the routine use of microsurgical biliary reconstruction decreases the number of early and long-term anastomotic BCs in LDLT.

Resection of an intra-operative ruptured hepatocellular carcinoma with continuous pringle maneuver and in situ hypothermic perfusion through the inferior mesenteric vein: a case report.

Intra-operative tumor rupture is a serious complication during resection of large hepatocellular carcinoma (HCC) leading to more blood loss. We report our experience in applying continuous Pringle maneuver with in situ hypothermic perfusion via inferior mesenteric vein catheterization to the portal vein of the remnant liver for resection during an extended left lobectomy of a large HCC which ruptured intraoperatively. Using this method, we successfully managed the patient without any further morbidity. This technique provides easier accessibility of in situ perfusion, decreases operative blood loss and prevents warm ischemic injury to the remnant liver during parenchymal transection. This method could be effective for the resection of large ruptured HCC.

Primary small bowel malignancy: a 10-year clinical experience from Southern Taiwan.

BACKGROUND/AIMS: The difficulty in establishing early definitive diagnosis and treatment of primary small bowel malignancy (PSBM) is a challenge for clinicians. This study aimed to analyze the symptomatology, diagnosis and outcomes of PSBM. METHODOLOGY: A retrospective chart review study was conducted on 49 patients who underwent surgical treatment for PSBM at a tertiary hospital between May 2000 and January 2010. RESULTS: The patients with PSBM had non-specific clinical symptoms. Major diagnostic tools in the current study were computed tomography (CT) (n=40), gastrointestinal series radiography (n=10), angiography (n=5), double-balloon enteroscopy (n=3), gastroduodenoscopy (n=2), magnetic resonance imaging (n=1) and exploratory laparotomy (n=8). Gastrointestinal stromal tumor (GIST) was the most common PSBM (n=21), followed by lymphoma (n=14), adenocarcinoma (n=8), leiomyosarcoma (n=3) and sarcoma (n=3). The overall 5-year cumulative survival rate of the patients with PSBM was 57.1% with a mean survival time of 31.8±7.8 months. The 5-year cumulative survival rates for the different PSBMs were 79.1%, 46.9% and 33.2% for GIST, adenocarcinomas and lymphomas, respectively (p=0.087). CONCLUSIONS: CT is very useful in detecting PSBM. Poor prognosis in PSBM patients detected by CT or angiography could be the result of delayed diagnosis prior to the procedure.

Vorinostat decrease M2 macrophage polarization through ARID1A6488delG/HDAC6/IL-10 signaling pathway in endometriosis-associated ovarian carcinoma.

Endometriosis is a common disease in women and may be one of the factors that induces malignant epithelial ovarian tumors. Previous studies suggested that endometriosis is related to ARID1A mutation mediating the expression of HDAC6, but the detailed pathogenic mechanism is still unclear. First, we collected endometriosis-associated ovarian carcinoma (EAOC) clinical samples and examined the expression of HDAC6. Our results found that the high HDAC6 expression group was positively correlated with EAOC histology (P = 0.015), stage (P < 0.000), and tumor size (P < 0.000) and inversely correlated with survival (P < 0.000). We also found that ARID1A6488delG/HDAC6 induced M2 polarization of macrophages through IL-10. In addition, the HDAC inhibitor (HDACi) vorinostat inhibited cell growth and blocked the effect of HDAC6. Tomographic microscopy was used to monitor the live cell morphology of these treated cells, and we found that vorinostat treatment resulted in substantial cell apoptosis by 3 h 42 min. Next, we established a transgenic mouse model of EAOC and found that vorinostat significantly reduced the size of ovarian tumors by inhibiting M2 macrophage polarization in mice. Together, these data demonstrate that the signaling pathway of E4F1/ARID1A6488delG/HDAC6/GATA3 mediates macrophage polarization and provides a novel immune cell-associated therapeutic strategy targeting IL-10 in EAOC.

Management of difficult hepatic artery reconstructions to reduce complications through continual technical refinements in living donor liver transplantations.

BACKGROUND: Hepatic artery reconstruction (HAR) for liver transplantation is crucial for successful outcomes. We evaluated transplantation outcome improvement through continual technical refinements. MATERIALS AND METHODS: HAR was performed in 1448 living donor liver transplants by a single plastic surgeon from 2008 to 2020. Difficult HARs were defined as graft or recipient hepatic artery ≤2 mm, size discrepancy (≥2 to 1), multiple hepatic arteries, suboptimal quality, intimal dissection of graft or recipient hepatic artery (HA), and immediate redo during transplantation. Technique refinements include early vessel injury recognition, precise HA dissection, the use of clips to ligate branches, an oblique cut for all HARs, a modified funneling method for size discrepancy, liberal use of an alternative artery to replace a pathologic HA, and reconstruction of a second HA for grafts with dual hepatic arteries in the graft. RESULTS: Difficult HARs were small HA (21.35%), size discrepancy (12.57%), multiple hepatic arteries (11.28%), suboptimal quality (31.1%), intimal dissection (20.5%), and immediate redo (5.18%). The overall hepatic artery thrombosis (HAT) rate was 3.04% in this series. The average HAT rate during the last 4 years (2017-2020) was 1.46% (6/408), which was significantly lower than the average HAT rate from 2008 to 2016 (39/1040, 3.8%) with a statistical significance (p = 0.025). Treatment for posttransplant HAT included anastomosis after trim back (9), reconstruction using alternatives (19), and nonsurgical treatment with urokinase (9). CONCLUSION: Careful examination of the HA under surgical microscope and selection of the appropriate recipient HA are key to successful reconstruction. Through continual technical refinements, we can reduce HA complications to the lowest degree.

Liver transplantation for primary biliary cirrhosis in a hepatitis endemic region: a single-center Asian experience.

From March 1984 to November 2008, we performed 539 primary liver transplantations (LTs). Nineteen (19, 3.5%) were transplanted for end-stage liver disease secondary to primary biliary cirrhosis (PBC). There were 17 (89%) female and 2 (11%) male recipients. The overall mean age was 50.3 ± 6.3 yr. The mean model for end-stage liver disease, and Child-Turcotte-Pugh scores were 20.7 ± 2.1, and 11.0 ± 0.5, respectively. There were 2 (11%) United Network for Organ Sharing status 3, 16 (84%) 2B, and 1 (5%) 2A patients. Fourteen patients (14, 73.7%) underwent living donor LT, and five patients (26.3%) received deceased donor LT. The primary immunosuppression consisted of cyclosporine (n = 5) and tacrolimus (n = 14). Liver function returned to normal one month after transplantation. The overall mean follow-up was 5.8 ± 0.8 yr (range, four months to 15.7 yr). The overall one-, three-, and five-yr survival rates were 94.7%, 89.2%, and 89.2%, respectively. Without hepatitis B virus (HBV) prophylaxis, one patient acquired de novo HBV infection after receiving a graft from an anti-HBc(+) donor. Another patient developed recurrent hepatitis C infection and expired 25 months after transplantation. Our results showed that HBV prophylaxis was effective not only against de novo infection, but it also worked on pre-transplant HBV carrier with PBC and helped in virus clearance.

Hepatic arterial embolization for massive bleeding from an intrahepatic artery pseudoaneurysm using N-butyl-2-cyanoacrylate after living donor liver transplantation.

Parenchymal pseudoaneurysm of the hepatic arteries with massive intraperitoneal bleeding is rare but a serious life-threatening complication when it occurs following liver transplantation. We report a case of an adult postliving donor liver transplant recipient who developed massive subcapsular bleeding combined with massive right pleural effusion from ruptured multiple small intrahepatic arteries, which developed from a pseudoaneurysm that was treated by hepatic arterial embolization. Successful embolization was performed via a percutaneous trans-catheter approach by depositing 20-25%N-butyl-2-cyanoacrylate (NBCA) through the multiple small intrahepatic arteries into the pseudoaneurysm. Complete occlusion of the feeding arteries and pseudoaneurysm cavity resulted to immediate cessation of bleeding. There was no re-bleeding; and normal liver graft function was noted postembolization. Hepatic arterial embolization with NBCA can be used as treatment for postliver transplant peripheral intrahepatic artery pseudoaneurysm bleeding.

The efficacy and toxicity of adjuvant S-1 schedule with 2-week administration followed by 1-week rest in gastric cancer patients.

BACKGROUND: This study aimed to investigate the clinical outcome of adjuvant S-1 with 2-week administration followed by a 1-week rest for locally advanced gastric cancer (GC) patients. METHODS: The current study was a single retrospective cohort study that focused on the efficacy and toxicity of adjuvant S-1 with a 3-week schedule. A total of 60 patients who underwent total or subtotal gastrectomy plus D2 lymph node dissection and adjuvant S-1 treatment were identified. S-1 treatment began within 4 weeks after the operation; it was administered orally for 2 weeks, followed by a 1-week rest. The dose of S-1 was adjusted depending on adverse events (AEs), with at least 80 mg administered daily. The completion of 1-year S-1 was defined as S-1 continuation for 1 year with over 70% of the planned dose. Patients were followed up with for 5 years postoperatively and underwent hematologic tests and assessments of clinical symptoms every 3-6 weeks for 1 year after surgery. Computed tomography of the abdomen and panendoscopy were performed every 6 months during the first 2 years and at 1-year intervals thereafter until year 5 after surgery. RESULTS: The completion rate of 1-year adjuvant S-1 was 71.7%, and the 3-year disease-free survival and overall survival rates were 70.2% and 79.5%, respectively. Seventeen patients did not complete S-1 for 1 year, including 11 patients with tumor recurrence and 6 patients who developed intolerance. Most AEs of S-1 were grade 1-2, and the most frequent AEs (>20%) included anemia, fatigue, pigmentation, nausea, and diarrhea. The most common grade 3-4 AE was fatigue, which was observed in 6.7% of patients. Most patients tolerated the side effects. CONCLUSIONS: The results of our study confirm that the efficacy and safety of schedule modification of adjuvant S-1 treatment in patients with GC who underwent gastrectomy with D2 lymph node dissection are equal to those in a previous phase 3 study.

Metronomic vinorelbine is an excellent and safe treatment for advanced breast cancer: a retrospective, observational study.

Advanced breast cancer (ABC) has become a chronic disease. In such a situation, an effective therapy with low toxicities and economically acceptable is needed. Metronomic vinorelbine (mVNR) has been proved to be effective on the control of MBC. The aim of this study is to evaluate the efficacy and safety of mVNR as the salvage therapy for patients with ABC. Oral vinorelbine (VNR) was administered at 70 mg/m2, fractionated on days 1, 3, and 5, for 3 weeks on and 1 week off. Once the mVNR was combined with trastuzumab, or was combined with bevacizumab, the schedule was changed to 2 weeks on and 1 week off. Clinical data of patients with ABC who had received treatment with mVNR and tumor characteristics were collected and analyzed. From Mar. 2013 to Dec, 2020, there were 90 patients with ABC received mVNR. The overall response rate was 53.3% and overall disease control rate (DCR) was 78.9% in this study, including 4 (4.4%) cases reached complete response, 44 (48.9%) cases reached partial response and 23 (25.6%) cases were table disease. The median time to treatment failure (TTF) of the Lumina A patients was 13.3 months, Lumina B patients was 9.1 months, Her-2 enrich patients was 8.9 months, and triple negative breast cancer (TNBC) patients was 5.6 months. Median overall survival time for Lumina A, Lumina B, Her-2 enrich and TNBC were 54.6 months, 53.3 months, 59.5 months and 24.5 months separately. Side effects were minimal and manageable. Metronomic VNR can be an effective treatment for ABC either works as a switch maintenance or salvage therapy. In combination with target therapy or hormonal therapy, mVNR can further improve TTF and DCR with minimal toxicities. Further study should focus on the optimal dosage, schedule and combination regimen.

Can Microscopic Biliary Reconstruction Reduce Biliary Complication Rate in ABO-Incompatible Adult Living Donor Liver Transplantation?

BACKGROUND With the introduction of rituximab, ABO-incompatible (ABOi) living donor liver transplantation (LDLT) has been considered a feasible and safe procedure to overcome the shortage of organ donors. However, higher biliary complication rates remain an unresolved problem in the ABOi group. In our center, biliary anastomosis has been done with microscopic biliary reconstruction (MBR), which effectively reduced the biliary complication rate. The aim of the current study was to investigate whether the microscopic approach reduced anastomotic biliary complications in ABOi LDLT. MATERIAL AND METHODS From March 2006 to December 2018, 30 adult ABOi and 60 ABO-compatible (ABOc) LDLT patients were selected from over 1300 recipients through 1: 2 propensity score-matched cohorts. All patients received MBR during the transplantation. Biliary complications included bile leakage and biliary stricture. Patients with diffuse intrahepatic biliary stricture were excluded from analysis. RESULTS Patient characteristics were similar in the 2 groups. There was no in-hospital mortality in the ABOi LDLT. The long-term survival rates of the ABOi patients were comparable to those of the patients that underwent ABOc LDLT (87.1% vs 87.4%, P=0.964). Those in the ABOi group with anastomotic biliary complications were about 40%, which was higher than in the ABOc patients (40% vs 15%, P=0.01). CONCLUSIONS Microscopic biliary reconstruction does not help to reduce the high biliary complication rate in ABOi LDLT. Further investigation and identification regarding other risk factors and precautionary measures involving immunologic and adaptation mechanisms are needed.

Solitary pulmonary nodule in the liver transplant candidate: importance of diagnosis and treatment.

Our objectives were to define the incidence and etiology of solitary pulmonary nodules (SPNs) in patients undergoing living donor liver transplantation (LDLT), describe a diagnostic approach to the management of SPNs in LDLT, and define the impact of SPNs on the overall survival of adult LDLT recipients. Nine patients (9/152, 5.9%) were diagnosed with an SPN on the basis of chest radiography findings during the pretransplant survey. All were male. The mean age was 52 years. All the patients had hepatitis B virus-related cirrhosis with hepatocellular carcinoma. All were asymptomatic for the lung lesion. All underwent contrast-enhanced chest computed tomography (CT) to verify the presence and possible etiology of the SPNs. In 3 cases, CT was used to definitely determine that there was no pulmonary nodule; in 2, CT led to a definite diagnosis of pulmonary tuberculosis. In 4, CT led to a definite identification of an SPN but not to an etiological diagnosis. Two patients underwent outright thoracoscopy and biopsy of their SPNs. Biopsy showed cryptococcosis in both patients. One received a therapeutic trial of an antituberculosis treatment, and repeat CT after 1 month showed a regression in the size of the SPN. A diagnosis of tuberculosis was made. One patient had an inconclusive whole body positron emission tomography scan and subsequently underwent thoracoscopy where biopsy showed tuberculosis. A concomitant malignancy, either primary lung cancer or metastasis from the liver tumor, was not identified. All patients were surviving with their original grafts and were lung infection-free. The overall mean posttransplant follow-up was 54 months (range = 33-96 months).