Prognostic significance of programmed cell death-ligand 1 expression on immune cells and epithelialmesenchymal 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), tumorinfiltrating 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.

Enlarged lymph nodes diagnosed with Langerhans cell histiocytosis found in a direct inguinal hernia: a case report

It is unusual that an unexpected mass is encountered within a hernia sac. This report describes a patient diagnosed with Langerhans cell histiocytosis (LCH) after surgery for an inguinal hernia. A 64-year-old male patient presented with inguinal mass over a 1-year period. Direct inguinal hernias were found in both sides, and enlarged lymph nodes were found in both hernia sacs. Laparoscopic totally extraperitoneal repair was done, and one enlarged lymph node within inguinal hernia sac was excised for diagnostic purposes.Microscopic findings showed the distinctive cytologic features of Langerhans cells and immunohisto chemical staining are positive for CD1a and S-100. LCH is a rare disorder, and the involvement of the lymph nodes with no other sites of disease is uncommon. To the best of our knowledge, this is the first report of LCH within an inguinal hernia sac. Multidisciplinary approach should be considered to provide better detection and treatment.

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.

Overexpression of PD-L1 and PD-L2 Is Associated with Poor Prognosis in Patients with Hepatocellular Carcinoma / Journal of the Korean Cancer Association, 대한암학회지

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.

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.

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.

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.

Complete tubular duplication of colon in an adult: a rare cause of colovaginal fistula

Alimentary tract duplications are uncommon congenital anomalies that usually present during the first decade of life. Complete duplication of the colon in adults is very rare and difficult to diagnose preoperatively. We report a case of a 40-year-old female with complete tubular duplication which was initially misdiagnosed as a salpingeal abscess due to colovaginal fistula.

Life-threatening Hemobilia following Removal of a Biliary Stent in a Patient with a Bile Leak / 대한췌담도학회지

Biliary plastic stent induced life-threatening hemobilia is very rare. In this case, hemobilia seriously worsened following removal of a biliary stent, which had been placed for treatment of a postoperative bile leak in a patient who had undergone lateral liver segmentectomy for abdominal trauma. Following placement of the biliary stent, the bile leak improved, but hemobilia and cholangitis developed five days later. To manage the stent malfunction, we removed the biliary stent. However, life-threatening hemobilia developed immediately after removal. Endoscopic hemostasis was impossible; therefore, emergency angiographic embolization and stent graft were performed successfully. In such cases, angiographic embolization and stent-graft placement are effective diagnostic and therapeutic alternatives. When a patient develops hemobilia or cholangitis after biliary stent placement, endoscopists should pay special attention to remove the stent, which might exacerbate hemobilia.

Astrocyte elevated gene-1 overexpression in hepatocellular carcinoma: an independent prognostic factor

PURPOSE: Astrocyte elevated gene-1 (AEG-1) plays important roles in tumorigenesis such as proliferation, invasion, metastasis, angiogenesis, and chemoresistance. We examined the expression of AEG-1 in patients with hepatocellular carcinoma (HCC). METHODS: Eighty-five samples were collected from patients with HCC who underwent surgery and were histopathologically confirmed to have HCC. Two independent pathologists, experienced in evaluating immunohistochemistry and blinded to the clinical outcomes of the patients, reviewed all samples. They determined AEG-1 expression semiquantitatively by assessing the percentage of positively stained immunoreactive cells and staining intensity. Clinicopathological data were analyzed in association with prognosis. RESULTS: The association was estimated by univariate and multivariate analyses with Cox regression. Tumor size (hazard ratio [HR], 2.285; 95% confidence interval [CI], 1.175-4.447; P = 0.015), microvascular invasion (HR, 6.754; 95% CI, 1.631-27.965; P = 0.008), and AEG-1 expression (HR, 4.756; 95% CI, 1.697-13.329; P = 0.003) were independent prognostic factors for overall survival. Those for disease-free survival rate were tumor size (HR, 2.245; 95% CI, 1.282-3.933; P = 0.005) and AEG-1 expression (HR, 1.916; 95% CI, 1.035-3.545; P = 0.038). The cumulative 5-year survival and recurrence rates were 89.2% and 50.0% in the low-expressing group and 24.5% and 82.4% in the high-expressing group, respectively. CONCLUSION: The results suggest that AEG-1 overexpression could serve as a valuable prognostic marker in patients with HCC.