Multi-functional dual-layer nanofibrous membrane for prevention of postoperative pancreatic leakage.

Postoperative pancreatic leakage due to pancreatitis in patients is a life-threatening surgical complication. The majority of commercial barriers are unable to meet the demands for pancreatic leakage due to poor adhesiveness, toxicity, and inability to degrade. In this study, we fabricated mitomycin-c and thrombin-loaded multifunctional dual-layer nanofibrous membrane with a combination of alginate, PCL, and gelatin to resolve the leakage due to suture line disruption, promote hemostasis, wound healing, and prevent postoperative tissue adhesion. Electrospinning was used to fabricate the dual-layer system. The study results demonstrated that high gelatin and alginate content in the inner layer decreased the fiber diameter and water contact angle, and crosslinking allowed the membrane to be more hydrophilic, making it highly biodegradable, and adhering firmly to the tissue surfaces. The results of in vitro biocompatibility and hemostatic assay revealed that the dual-layer had a higher cell proliferation and showed effective hemostatic properties. Moreover, the in vivo studies and in silico molecular simulation indicated that the dual layer was covered at the wound site, prevented suture disruption and leakage, inhibited hemorrhage, and reduced postoperative tissue adhesion. Finally, the study results proved that dual-layer multifunctional nanofibrous membrane has a promising therapeutic potential in preventing postoperative pancreatic leakage.

Prognostic significance of programmed cell death-ligand 1 expression on immune cells and epithelial-mesenchymal transition expression in patients with hepatocellular carcinoma.

Purpose: Immune checkpoint inhibitors (ICIs) have been shown significant oncological improvements in several cancers. However, ICIs are still in their infancy in hepatocellular carcinoma (HCC). Programmed cell death-ligand 1 (PD-L1), tumor-infiltrating lymphocytes (TILs), and epithelial-mesenchymal transition (EMT) have been known as prognostic factors in HCC. Therefore, we have focused on identifying the molecular mechanisms between each marker to evaluate a predictive role. Methods: Formalin-fixed paraffin-embedded samples were obtained from 166 patients with HCC who underwent surgery. The expression of PD-L1 and TILs and EMT marker were evaluated by immunohistochemical analysis. Results: The multivariate analysis showed that TIL expression (hazard ratio [HR], 0.483; 95% confidence interval [CI], 0.269-0.866; P = 0.015) were independent prognostic factors for overall survival. The prognostic factors for disease-free survival were EMT marker expression (HR, 1.565; 95% CI, 1.019-2.403; P = 0.005). Patients with high expression of TILs had significantly better survival compared to patients with low expression (P = 0.023). Patients who were TIL+/EMT- showed a significantly better prognosis than those who were TIL-/EMT+ (P = 0.049). Conclusion: This study demonstrates that PD-L1 expression of TILs is closely associated with EMT marker expression in HCC. Clinical investigations using anti-PD-1/PD-L1 inhibitors in patients with EMT-associated PD-L1 upregulation are warranted.

Curative resection of leiomyosarcoma of the descending colon with metachronous liver metastasis: A case report.

BACKGROUND: Leiomyosarcoma (LMS) has a poor prognosis and rarely originates from the colon. If resection is possible, surgery is the first treatment most commonly considered. Unfortunately, no standard treatment exists for hepatic metastasis of LMS; although, several treatments, such as chemotherapy, radiotherapy, and surgery, have been used. Subsequently, the management of liver metastases remains controversial. CASE SUMMARY: We present a rare case of metachronous liver metastasis in a patient with LMS originating from the descending colon. A 38-year-old man initially reported abdominal pain and diarrhea over the previous two months. Colonoscopy revealed a 4-cm diameter mass in the descending colon, 40 cm from the anal verge. Computed tomography revealed intussusception of the descending colon due to the 4-cm mass. The patient underwent a left hemicolectomy. Immunohistochemical analysis of the tumor revealed that it was positive for smooth muscle actin and desmin, and negative for cluster of differentiation 34 (CD34), CD117, and discovered on gastrointestinal stromal tumor (GIST)-1, which are characteristic of gastrointestinal LMS. A single liver metastasis developed 11 mo post-operatively; the patient subsequently underwent curative resection thereof. The patient remained disease-free after six cycles of adjuvant chemotherapy (doxorubicin and ifosfamide), and 40 and 52 mo after liver resection and primary surgery, respectively. Similar cases were obtained from a search of Embase, PubMed, MEDLINE, and Google Scholar. CONCLUSION: Early diagnosis and surgical resection may be the only potential curative options for liver metastasis of gastrointestinal LMS.

Physico-mechanical and in-vivo evaluations of tri-layered alginate-gelatin/polycaprolactone-gelatin-ß-TCP membranes for guided bone regeneration.

Guided bone regeneration (GBR) membranes favor periodontal regrowth, but they still have certain limitations, such as improper biodegradation and poor mechanical property. To overcome these shortcomings, we have generated a unique multifunctional membrane. A polycaprolactone/gelatin/ß-TCP and alginate/gelatin trilayered construction was fabricated through electrospinning and casting technology. The prepared membranes have suitable physicomechanical and in-vitro properties to confirm the compatibility of the product in the body. Phase analysis, functional groups, surface microstructure, and contact angle were measured as basic characteristics. For a mechanical performance evaluation, the tensile strength at suturing point was measured through pullout tensile strength test, and it showed the suture capability of bi-layered membranes. Highest tensile strength for A75G25 was recorded with 2.9 ± 0.15 MPa with 105% strain. Further, the osteoblast and fibroblast-type cell toxicity results showed that the electrospun membrane offered compatible environment to cells while the alginate sheet was found to be sufficiently capable to suppress the cellular attachment while also being a nontoxic material. Post-implantation, according to the in-vivo conclusions of the tri-layered membrane, there was appreciable bone formation. Compared to an implant without membrane covering, enhanced new bone formation can be identified after 8 weeks of implantation with P1G4ß10 membranes-covered site.

Expression of miR-221 and miR-18a in patients with hepatocellular carcinoma and its clinical significance.

Purpose: Recently, microRNA (miRNA) has been evaluated to provide a new diagnostic and therapeutic modality hepatocellular carcinoma (HCC) and other tumors. They are small non-coding RNA molecules that function as transcriptional and post-transcriptional regulators of gene expression by silencing target genes. The aim of this study was to evaluate the clinical significance of microRNA-18a, 221 (miR-18a, miR-221) expression in HCC formalin-fixed paraffin-embedded (FFPE) tissue. Methods: miR-18a and miR-221 expressions were assessed by reverse transcription and real-time quantitative reverse transcription polymerase chain reaction in 50 pairs of FFPE HCC and the adjacent noncancerous liver tissues. And we evaluated the expression level in HCC tissues as compared with their adjacent noncancerous counterparts. And the relationship between miR-18a, miR-221 level and clinicopathological data and survival rates were analyzed. Results: miR-221 and miR-18a were overexpressed in HCC tissue as compared with their adjacent noncancerous liver tissue (P<0.001). miR-221 expression was found to be correlated with larger tumor size (P=0.048). miR-18a expression was correlated with modified Union for International Cancer Control stage (P=0.05). The overall survival (P=0.02) of HCC patients with high miR-221 expression was significantly poorer compared to those patients with low expression. Multivariate analyses demonstrated that miR-221 may be a poor prognostic factor of HCC patients. Conclusion: High expression of miR-221 in FFPE tissues could provide significance for prognosis of HCC patients. Although, miR-18a expression was significantly upregulated in HCC tissues, they are not correlated with prognosis. Further large prospective studies are needed to determine their clinical significance.

Jejunogastric intussusception after totally laparoscopic distal gastrectomy for gastric cancer: a rare case report and review of the literature.

Jejunogastric intussusception (JGI) is a rare complication of gastric surgery, with most cases occurring in the form of long-term complications following gastric surgeries. We present a case of JGI in a 74-year-old man who presented with progressive abdominal pain and distention, and was admitted to our hospital. The patient had undergone a totally laparoscopic distal gastrectomy with a Billroth II gastrojejunostomy 9 days previously. Computed tomography and endoscopic findings revealed the presence of a small bowel loop within the gastric lumen, which we failed to reduce in size. We performed an emergency laparoscopic exploration and immediate reduction of the JGI. The efferent and afferent loops were then fixed to the mesentery and the stomach. The postoperative course was uneventful and the patient remained asymptomatic during the 1-year follow-up period.

Polycaprolactone-gelatin membrane as a sealant biomaterial efficiently prevents postoperative anastomotic leakage with promoting tissue repair.

Anastomotic leakage due to post-surgical suture line disruption is one of the crucial factors affecting patient's survival and quality of life. To resolve the poor healing of surgical anastomosis and protect suture sites leakage, fibrous membrane sealing patch was developed using a synthetic polymer (polycaprolactone (PCL)) and biopolymer (gelatin). Electrospinning was used to develop fibrous architecture of membranes fabricated in different ratios (15% (w/v) PCL: 15% (w/v) gelatin mixing ratio of 1:1, 1:2, 1:3 and 1:4). Experimental findings suggested that, higher gelatin content in the membranes reduced the fiber diameter and contact angle, leading to a more hydrophilic scaffold facilitating attachment to the defect site. The degradation rate of various PCL-gelatin membranes (P1G1, P1G2, P1G3 and P1G4) was proportional to the gelatin content. Cytocompatibility was assessed using L929 cells while the P1G4 (PCL: gelatin 1:4 ratio) scaffold exhibited optimum outcome. From in vivo study, the wound site healed significantly without any leakage when the sutured area of rat caecum was covered with P1G4 membrane whereas rats in the control group (suture only) showed leakage after two weeks of surgery. In summary, the P1G4 membrane has potential to be applied as a post-surgical leakage-preventing tissue repair biomaterial.

Spontaneous rupture of pyogenic liver abscess with subcapsular hemorrhage mimicking ruptured hepatocellular carcinoma: A case report.

RATIONALE: Spontaneous rupture of PLA (pyogenic liver abscess) is an extremely rare and life-threatening event. Ruptured PLA is very difficult to distinguish from malignant HCC (hepatocellular cancer) rupture or cholangiocarcinoma rupture on CT (computed tomography) scan. PATIENT CONCERNS: We describe the case of a 71-year-old man with fever, right upper abdominal pain, nausea with intermittent vomiting, and general fatigue. He had no medical or surgical history. DIAGNOSIS: CT scan showed a hypodense mass in right hepatic lobe and MRI (magnetic resonance imaging) revealed a heterogenous mass of ∼6 cm in segment VI of the liver and heterogenous fluid in the subcapsular region. We made a tentative diagnosis of HCC rupture with subcapsular hemorrhage based on these findings. INTERVENTION: After improving the patient's condition by administering empirical therapy consisting of intravenous antibiotics and fluids, we performed surgical exploration. Gross examination of the abdomen showed that almost the entire right hepatic lobe was hemorrhagic and affected by peritonitis. Therefore, we performed right hepatectomy. The intraoperative frozen biopsy revealed suspicious PLA with marked necrosis, neutrophil infiltration, and hemorrhagic rupture, although no malignant tissue or fungus was observed. The postoperative secondary pathology report confirmed the diagnosis of PLA with hemorrhagic rupture. OUTCOMES: The patient was discharged 13 days after the operation. Follow-up CT was performed 5 months after discharge and revealed no abnormal findings. LESSONS: A high index of suspicion is key to preventing misdiagnosis of ruptured PLA and improving prognosis. Furthermore, even if rupture of the PLA is initially localized, delayed peritonitis may occur during medical treatment. Therefore, vigilant monitoring is essential.

Relations between hepatobiliary scintigraphy findings and histopathological factors in patients with recurrent biliary colic.

BACKGROUND/PURPOSE: The aim of the present study was to investigate the relationship between hepatobiliary scintigraphy findings and histopathological results in patients with recurrent biliary colic. METHODS: We retrospectively enrolled 107 patients who underwent hepatobiliary scintigraphy for recurrent biliary colic and subsequent cholecystectomy. According to the hepatobiliary scintigraphy findings, patients were categorized into a nonvisualization of gallbladder activity (nonvisualized GB) group, low gallbladder ejection fraction (GBEF) group, and normal GBEF group. Differences in histopathologic factors between the three groups were evaluated and multivariate logistic regression analyses were performed to identify histopathological predictors for hepatobiliary scintigraphy findings. RESULTS: The nonvisualized group had a higher frequency of patients with empyema and severe infiltration by neutrophils, lymphoplasma cells, and eosinophils. The low GBEF group had a higher muscle-to-total wall thickness ratio and muscle-to-fibrosis thickness ratio of the gallbladder wall than those in the normal GBEF group. On multivariate logistic regression analyses, severe degrees of lymphoplasma cell infiltration and eosinophil infiltration were independent predictors for nonvisualization of gallbladder activity, and a higher muscle-to-fibrosis thickness ratio was an independent predictor for low GBEF. CONCLUSIONS: In patients with recurrent biliary colic, nonvisualization of gallbladder activity on hepatobiliary scintigraphy was related to the degree of inflammation in the gallbladder, while low GBEF was related to muscular hypertrophy of the gallbladder.

Small-cell neuroendocrine carcinoma of the ileum: case report and literature review.

BACKGROUND: Poorly differentiated neuroendocrine carcinomas (NECs) originating from the gastrointestinal (GI) tract are rare and very highly malignant disease with a poor prognosis. Poorly differentiated NECs most commonly arise in the esophagus and the large bowel; however, they may occur within virtually any portion of the GI tract. It is known, however, that they do not typically occur in the small intestine. CASE REPORT: A 21-year-old woman visited an emergency room with acute abdominal pain that commenced 2 days prior to her presentation. Thereafter, a computed tomography (CT) scan was notable for a small-intestine perforation, and huge masses were observed in the small intestine and the mesentery. The mass that was located at the ileum site is approximately 100 cm above the ileocecal (IC) valve, and while it is located on the anti-mesenteric border and it seems that luminal narrowing had occurred, an obstruction is absent. Also, a same-nature mass is on the mesentery. The pathologic reports confirmed a small-cell-type NEC with a mass size of 7.5 × 6.5 cm. The mitotic count is up to 24/10 high-power fields (HPFs), the results of the immunohistochemical stain are positive for CD56 and synaptophysin, and the Ki-67 level is 50%. %. After the operation, she was treated with Etoposide-Cisplatin (EP) chemotheraphy. Stable disease was seen during Etoposide-Cisplatin chemotheraphy. Liver metastasis was also confirmed after chemotheraphy. Additionally, Irinotecan and cisplatin were used for 3 cycles, but progression of disease, neutropenic fever, thrombocytopenia, general weakness persisted. Eventually, she died 1 year and 6 months after surgery. CONCLUSION: Ileum-located NECs are diagnosed very rarely. The most common locations for these tumors along the GI tract are the esophagus and the large intestine, but they can arise anywhere. The prognosis for NECs is poor due to the metastatic disease of most patients at the time of diagnosis. The role of adjuvant treatment requires further evaluation for the attainment of a better understanding of the overall treatment effect.

Preoperative neutrophil-lymphocyte ratio and CEA is associated with poor prognosis in patients with synchronous colorectal cancer liver metastasis.

PURPOSE: Recently, the neutrophil-to-lymphocyte ratio (NLR), an inflammatory response marker, has been reported to be associated with the prognosis in patients with various type of cancer. However, there have been no studies until now that have explored the prognostic role of combined detection of NLR and CEA in patients with synchronous liver-limited colorectal metastases (sCRLM). METHODS: Eighty-three patients who histologically diagnosed as sCRLM were selected. Their laboratory and clinical data were collected retrospectively. Using receiver operating characteristic curve analysis, the cutoff value of NLR was calculated based on which patients were assigned to a high NLR (more than 1.94) group and low NLR (less than 1.94) group. A cutoff value of 100 ng/mL for serum CEA level was used in light of the previous literature. RESULTS: CEA level and Poorly differentiated histology of colon cancer was significantly correlated with high NLR (P = 0.005 and P = 0.048, respectively). The multivariate analysis identified the high NLR as independent prognostic factors for OS and DFS in all patients (P = 0.010 and P = 0.006, respectively). Patients with both low levels of NLR and CEA had a significantly longer OS and DFS (P = 0.026 and P = 0.009, respectively). CONCLUSION: In conclusion, elevated preoperative NLR is strongly correlated with both survival and recurrence in patients who have been diagnosed with resectable sCRLM. The combination of NLR and CEA level could be a more powerful prognostic marker than NLR alone.

Bone regeneration strategy by different sized multichanneled biphasic calcium phosphate granules: In vivo evaluation in rabbit model.

A variety of synthetic materials are currently in use as bone substitutes, among them a new calcium phosphate-based multichannel, cylindrical, granular bone substitute that is showing satisfactory biocompatibility and osteoconductivity in clinical applications. These cylindrical granules differ in their mechanical and morphological characteristics such as size, diameter, surface area, pore size, and porosity. The aim of this study is to investigate whether the sizes of these synthetic granules and the resultant inter-granular spaces formed by their filling critical-sized bone defects affect new bone formation characteristics and to determine the best formulations from these individual types by combining the granules in different proportions to optimize the bone tissue regeneration. We evaluated two types of multichanneled cylindrical granules, 1 mm and 3 mm in diameter, combined the granules in two different proportions (wt%), and compared their different mechanical, morphological, and in vitro and in vivo biocompatibility characteristics. We assessed in vitro biocompatibility and cytotoxicity using MC3T3-E1 osteoblast-like cells using MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and confocal imaging. In vivo investigation in a rabbit model indicated that all four samples formed significantly better bone than the control after four weeks and eight weeks of implantation. Micro-computed tomography analysis showed more bone formation by the 1 mm cylindrical granules with 160 ± 10 µm channeled pore and 50% porosity than the other three samples ( p<.05), which we confirmed by histological analysis.

Effect of intraperitoneal CO2 concentration on postoperative pain after laparoscopic cholecystectomy.

PURPOSE: This study set out to identify the association between the intraperitoneal CO2 concentrations and postoperative pain by dividing the participants into a control group and 2 experimental groups receiving irrigation (1 L and 2 L), and directly measuring their intraperitoneal CO2 concentrations with a CO2 gas detector. METHODS: A total of 101 patients, American Society of Anesthesiologists physical status classification I and II patients aged 18-65 years were enrolled in the study. Group 1 did not receive irrigation with normal saline, while groups 2 and 3 were administered irrigation with 1 L and 2 L of normal saline, respectively, after laparoscopic cholecystectomy. Intraperitoneal CO2 concentrations were measured with a CO2 gas detector through the port, and postoperative pain was assessed on a visual analogue scale at 6, 12, and 24 hours after surgery. RESULTS: The intraperitoneal CO2 concentrations were 1,016.0 ± 960.3 ppm in group 1, 524.5 ± 383.2 ppm in group 2, and 362.2 ± 293.6 ppm in group 3, showing significantly lower concentrations in groups 2 and 3. Postoperative pain was significantly lower in group 3 at 6 hours after surgery, and in groups 2 and 3 at 12 hours after the surgery. However, there was no significant difference between the 3 groups in postoperative pain 24 hours after the surgery. CONCLUSION: This study found a causal relationship between the amount of normal saline used for irrigation and the intraperitoneal CO2 concentrations in that irrigation with normal saline reduces pain on the day of the surgery.

In vitro and in vivo evaluation of effectiveness of a novel TEMPO-oxidized cellulose nanofiber-silk fibroin scaffold in wound healing.

In this study, a novel TEMPO-oxidized cellulose nanofiber (TOCN)-silk fibroin scaffold was prepared using a cost effective freeze drying method. Fundamental physical characterizations were carried out by scanning electron microscopy (SEM), pore diameter determination, FT-IR. PBS uptake behavior of the scaffold showed that, silk fibroin can enhance the swelling capacity of TOCN. L929 primary fibroblast cell was selected for in vitro studies, which showed that the scaffolds facilitated growth of cells. In vivo evaluation of TOCN, TOCN-silk fibroin composites was examined using critical sized rat skin excisional model for one and two weeks. The results of rat wound model revealed that, compared to only TOCN scaffold, TOCN-silk fibroin scaffold successfully promoted wound healing by the expression of wound healing markers. TOCN-silk fibroin 2% has the fastest wound healing capacity. Thus, it appears that TOCN-silk fibroin composite scaffolds can be useful as wound healing material in clinical applications.

Examination of In vitro and In vivo biocompatibility of alginate-hyaluronic acid microbeads As a promising method in cell delivery for kidney regeneration.

In this study, alginate (ALG) and alginate-hyaluronic acid (ALG-HA) injectable microbeads, with the purpose of delivering stem cells for tissue engineering, were prepared by a spraying method into a CaCl2 solution that shows high porosity for the exchange of nutrition and waste. In addition, the size distribution and surface morphology was investigated using optical and scanning electron microscopy, respectively. The chemical structural properties of the ALG-HA microbeads were examined by Fourier transform infrared spectroscopy. The biocompatibility of ALG and ALG-HA microbeads was examined in vitro. Rat bone marrow stem cells were encapsulated in microbeads to investigate cell release, cell viability, proliferation, and secretion of growth factors such as VEGF and PDGF. Growth factors were released for the 21day experimental period. Cells were found to be released from the microbeads after 7days. Furthermore, the in vivo biocompatibility of ALG-HA microbeads was examined using microbeads without cell encapsulation in the kidney capsule, in order to assess the foreign body reaction and inflammatory response, for 14days. The desired in vivo response to ALG-HA microbeads hydrogel makes it an exquisite candidate for subcapsular cell and drug delivery to kidney tissue.

Expressions and Clinical Significances of Angiopoietin-1, Angiopoietin-2, and Tie-2 Receptor in Patients With Colorectal Cancer.

PURPOSE: Angiopoietin-1 (Ang-1) plays a crucial role in vascular and hematopoietic development, mainly through its cognate receptor, Tie-2. Increased levels of Ang-2 have been shown to be correlated with abnormal tumor angiogenesis in several malignancies. Hence, we estimated the increased expression of Ang-2 relative to Ang-1 in patients with colorectal cancer and correlated our finding with prognosis in order to investigate the relationships between the expressions of Ang-1/Ang-2/Tie-2 receptor and the clinical parameters or overall survival of such patients. METHODS: We retrospectively analyzed 114 tissue samples from patients with colorectal cancer by using immunohistochemistry (IHC) to examine Ang-1, Ang-2, and Tie-2 expressions and to investigate the relationship between those expressions and clinical parameters or overall survival of such patients. A Western blot analysis was used for Ang-2 expression. RESULTS: IHC staining showed a link between Ang-1 and Tie-2 (P = 0.018), as well as meaningful correlations between Ang-2 and Tie-2 receptor (P = 0.022) and between lymph-node metastasis and Ang-2 (P = 0.025). The stronger the IHC staining for Ang-2 expression was, the shorter the cumulative survival was (P = 0.016). CONCLUSION: A relationship was found to exist between Ang-2 and Tie-2 expressions. The Ang-2 was correlated with lymph-node metastasis, and high expression of Ang-2 was indicative of poor overall survival. These findings suggest that Ang-2 is a useful prognostic marker in the management of patients with colorectal cancer. In addition, we suggest that Ang/Tie-2 signaling plays an important role in the progression of colorectal cancer.

The efficacy of laparoscopic cholecystectomy without discontinuation in patients on antithrombotic therapy.

PURPOSE: Laparoscopic cholecystectomy (LC) is one of the most commonly performed surgeries in the world today. However, there is no consensus regarding whether LC can be performed in patients with acute cholecystitis while on antithrombotic therapy. The objective of our study was to describe postoperative outcomes of patients who underwent emergent LC without interruption to antithrombotic therapy. METHODS: We performed a retrospective review of patients who underwent LC for acute cholecystitis while on antithrombotic therapy from 2010 to 2015 at Soonchunhyang Universtiy Cheonan Hospital. Patients were divided into 2 groups as underwent emergent LC and elective LC. RESULTS: A total of 67 patients (emergent group, 22; elective group, 45) were included in the analysis. Elective group had significantly longer duration between the admission and operation (8 [7-10] days vs. 2 [1-3] days, P < 0.001) and longer duration of antithrombotic drugs discontinuation (7 days vs. 1 [0-3] days, P < 0.001). Emergent group had significantly more postoperative anemia (6 patients vs. 0 patient, P = 0.001) and 3 of 6 patients received packed RBC transfusion in postoperative period. However, there was no significant difference in length of postoperative stays, length of intensive care unit stays and mortality rates. CONCLUSION: Emergent LC without interruption to antithrombotic therapy was relatively safe and useful. A well-designed multicenter study is needed to confirm the safety and efficacy of LC without suspension of antithrombotic therapy and to provide a simple guideline.

Overexpression of PD-L1 and PD-L2 Is Associated with Poor Prognosis in Patients with Hepatocellular Carcinoma.

PURPOSE: Hepatocellular carcinoma (HCC) is one of the most aggressive malignancies. Recently, the overexpression of programmed cell death 1 (PD-1) and PD-1 ligand 1 (PD-L1) has been shown to correlate with poor prognosis in many cancers. However, the expression of PD-L1 or PD-1 ligand 2 (PD-L2) and clinical outcomes have not been fully investigated in HCC. MATERIALS AND METHODS: Formalin-fixed paraffin-embedded samples were obtained from 85 patients with HCC who underwent surgery. The expression of PD-Ls (PD-L1, PD-L2) was evaluated by immunohistochemical analysis. RESULTS: The proportion of high expression groups of PD-L1 and PD-L2 was 27.1% and 23.5%, respectively. Univariate analysis revealed that tumor size (p < 0.001), histological differentiation (p=0.010), PD-L1 expression (p < 0.001), and PD-L2 expression (p=0.039) were significant prognostic factors of overall survival in patients with HCC. Multivariate analysis revealed that overall tumor size (hazard ratio [HR], 4.131; 95% confidence interval [CI], 2.233 to 7.643; p < 0.001 and HR, 3.455; 95% CI, 1.967 to 6.067; p < 0.001) and PD-L1 expression (HR, 5.172; 95% CI, 2.661 to 10.054; p < 0.001 and HR, 3.730; 95% CI, 1.453 to 9.574; p=0.006) were independent prognostic values for overall and disease-free survival. Patients with high expression of PD-Ls had a significantly poorer survival than those with low expression (p < 0.001, p=0.034). CONCLUSION: The overexpression of PD-Ls in HCC patients is correlated with survival and tumor recurrence. Further evaluation of PD-1 and PD-Ls as therapeutic targets and predictive biomarkers for HCC is warranted.

Primary hepatic malignant peripheral nerve sheath tumor successfully treated with combination therapy: a case report and literature review.

Primary malignant peripheral nerve sheath tumor (MPNST) in a young female patient, not associated with neurofibromatosis type-I is extremely rare in the liver. A 33-year-old female was admitted with a right flank pain for a weak. The CT scan showed 12.5-cm-sized mass located at the right hepatic lobe. At laparotomy, about 20.0-cm-sized mass was on the right hepatic lobe with attachment to right diaphragmatic pleura. Right hepatic lobe and adherent part of diaphragmatic pleura were resected. On histology and immunohistochemistry, it was diagnosed MPNST. Adjuvant radiotherapy for the right diaphragmatic pleura and adjuvant chemotherapy with adriamycin, ifosfamide and cisplatin were sequentially performed. The prognosis of MPNST is generally poor and it is associated with a highly aggressive course of recurrence, metastases, and death. Our case is probably a first report about combination therapy.