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.

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 / 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.

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.

Modified Single Port Laparoscopic Cholecystectomy

PURPOSE: Currently, single port laparoscopic cholecystectomy (SLC) is gradually being expanded. However, its operative time and complications are reportedly variable according to the surgeon's expertise and experience. In order to overcome these problems, we introduced surgical methods using a 2 mm sized auxiliary device (NELIS, Korea) in cholecystectomy. METHODS: Between March 2010 and October 2010, laparoscopic cholecystectomy was performed in 53 patients for non-inflammatory gallbladder stones or gallbladder polyps based on the computed tomography findings. Fourteen of 53 consecutive patients underwent SLC and others underwent CLC. The patient's clinical characteristics and operative results were evaluated retrospectively. RESULTS: Comparison of clinical characteristics between SLC and CLC groups indicated that the SLC group included younger patients (p=0.008), however other characteristics (sex, mean body index, and previous abdominal operation history) were not significantly different. Operative outcomesparameters including the intensity of postoperative pain, rate of wound complication, and postoperative hospital stay did not differ significantly between the 2 groups. Operative time of the SLC group was longer than that of the CLC group (p=0.002). However, the operative time was decreased according to the increasing SLC cases. By 3 months, patients in the SLC group reported significantly better cosmesis (p=0.036). CONCLUSION: SLC with an auxiliary device (2 mm, Hold port, NELIS) is technically feasible and might be an alternative method for obtaining a critical view of safety and cosmetic results.

Incidental cholecystojejunal fistula treated with successful laparoscopic management

Internal biliary fistula (IBF) is occurred spontaneously due to the biliary disease in most cases. Bilioenteric, biliobiliary, bronchobiliary, and vasculobiliary type of IBF have been reported in the literature. We herein describe our experience with an incidental cholecystojejunal fistula, a very rare type of bilioenteric fistula in laparoscopic cholecystectomy. A 61-year-old woman with several years' history of intermittent right upper abdominal pain was admitted to Soonchunhyang University Cheonan Hospital. Abdominal CT scan showed the pneumobilia in gallbladder with common bile duct dilatation. Endoscopic retrograde cholangiopancreatography and endoscopic sphincterotomy were done. On operative findings, there was a cholecystojejunal fistula. We performed laparoscopic cholecystectomy and fistulectomy with jejunal partial resection. To our knowledge, this is the first report on incidental cholecystojejunal fistula uncombined with any other disease and was treated with laparoscopic procedure.

Laparoscopic Treatment for Psoas Abscess / 대한정형외과학회잡지

Psoas abscess is a rare and high mortality disease if there is no appropriate treatment. The surgical approach of psoas abscess is very difficult because psoas muscle is anatomically located within retroperitoneum. Recently, computed tomography guided percutaneous catheter drainage with proper antibiotic therapy has shown good results. If this therapy fails to resolve the psoas abscess, surgical treatment may be necessary. We experienced two cases of psoas abscess resolved by surgical drainage using laparoscopy. We report two successful results with relevant literatures.

Transformation of Castleman's Disease into Follicular Dendritic Cell Sarcoma, Presenting as an Asymptomatic Intra-abdominal Mass / 대한소화기학회지

Follicular dendritic cell (FDC) sarcoma is an extremely rare malignant neoplasm arising from FDCs. The exact origin of FDCs remains unclear; both a hematopoietic lineage origin and a stromal cell derivation have been proposed. Proliferation of FDCs can lead to benign reactive lesions or generate neoplastic conditions. The lesions are most commonly found in lymph nodes and usually involve the head and neck area. Castleman's disease is a rare non-neoplasitic lymphoproliferative disorder. Rare cases of hyaline-vascular Castleman's disease have been associated with FDC sarcoma, but a clonal relationship has not been convincingly demonstrated. A pathway toward tumor evolution, beginning with hyperplasia and dysplasia of FDCs, has been proposed. Despite this known association between Castleman's disease and FDC sarcoma, there have only been few reported cases of sarcoma arising as a complication of pre-existing Castleman's disease, especially in abdominal lesions. We describe here a 51-year-old female with an FDC sarcoma arising from unicentric, hyaline-vascular type Castleman's disease in an intra-abdominal mass. Pathologically, the lesion showed a series of changes during the process of transformation from Castleman's disease to FDC sarcoma.

Clinical Factors Related to Frailty Estimated by the Korean Frailty Index

BACKGROUND: On the point of entering into the aged society, frailty will be recognized as a new geriatric problem in Korea. This study was conducted to identify clinical factors related to frailty in the community dwelling elderly. METHODS: This was a cross-sectional study comprised of 515 participants among 834 potential subjects who were residents of three towns in Gyeong-ju and had health check-ups at a university hospital in the same region. Using the Korean Frailty Index, those with a total score of 5 or more were considered frail and those with scores 3 to 4 as prefrail. Socio-demographics, anthropometry and laboratory data were the selected clinical factors. Those younger than 65 years or with incomplete data were excluded. Finally, 447 participants were analyzed. RESULTS: Among the participants, those identified as frail were 20 (4.5%), prefrail 72 (16.1%) and robust 355 (79.4%). By gender, the percentage of frail, prefrail and robust individuals were 3.2%, 17.4% and 79.5%, respectively, in men and 5.4, 15.2% and 79.4% in women (p=0.447). On ordinal logistic regression analysis, factors related to frailty were increased age (odds ratio [OR], 1.08; 95% confidence interval [CI], 1.01 to 1.17), functional disability (OR, 8.88; 95% CI, 4.46 to 17.68), chronic disease such as pulmonary disease (OR, 4.69; 95% CI, 1.47 to 14.99) or hypertension (OR, 2.23; 95% CI, 1.15 to 4.32), increased waist circumference (OR, 1.06; 95% CI, 1.01 to 1.11), decreased serum cholesterol (OR, 0.98; 95% CI, 0.97 to 0.99) and elevated blood urea nitrogen (OR, 1.07; 95% CI, 1.01 to 1.14). CONCLUSION: Clinical factors related to frailty were age, functional disability, chronic disease, waist circumference, serum cholesterol and blood urea nitrogen. Primary physicians should assess frailty when seeing elderly patients who have these factors.

Comparison of the outcomes between laparoscopic totally extraperitoneal repair and prolene hernia system for inguinal hernia; review of one surgeon's experience / 대한외과학회지

PURPOSE: To compare the outcomes between laparoscopic total extraperitoneal (TEP) repair and prolene hernia system (PHS) repair for inguinal hernia. METHODS: A retrospective analysis of 237 patients scheduled for laparoscopic TEP or PHS repair of groin hernia from 2005 to 2009 was performed. RESULTS: The mean age was 52.3 years in TEP group and 55.7 years in PHS group. Of 119 TEP cases, 98 were indirect inguinal hernia, 15 direct type, 5 femoral hernia and 1 complex hernia; Of 118 PHS cases, 100 indirect, 18 direct type. All in TEP group were performed under general anesthesia and 64% of PHS group were performed under spinal or epidural anesthesia. Preoperatively, 10 cases of recurrent inguinal hernia were involved in our study (4 in TEP, 6 in PHS group). The mean operative time was similar in both groups (74.8 in TEP, 71.2 in PHS group), however mean hospital stay (1.6 days in TEP, 3.2 days in PHS group, P = 0.018) and mean usage of analgesics (0.54 times in TEP, 2.03 times in PHS group, P < 0.01), complications (36 cases in TEP, 6 cases in PHS group, P < 0.01) showed statistical differences. There is only 1 case of postoperative recurrence inguinal hernia in PHS group but it has no statistical significance (P = 0.314). CONCLUSION: Compared to PHS repair, laparoscopic TEP repair has some advantages; shorter hospital stay, less frequent need of analgesics; as well as more postoperative complications such as hematoma, seroma, scrotal swelling.

Clinicopathologic change of gastrointestinal stromal tumor after neoadjuvant imatinib followed by surgical resection / 대한외과학회지

A 53-year-old woman was diagnosed with gastrointestinal stromal tumor (GIST) of the stomach. Computed tomography (CT) revealed a huge mass (12 cm in diameter), likely to invade pancreas and spleen. In the operation field, the tumor was in an unresectable state. The patient was then started on imatinib therapy for 4 months. On follow-up imaging studies, the tumor almost disappeared. We performed total gastrectomy and splenectomy upon which two small-sized residual tumors were found on microscopy. In this paper, we describe a case of clinicopathologic change in unresectable GIST after neoadjuvant imatinib mesylate.

Stromal-cell-derived Factor 1-alpha Promotes Tumor Progression in Colorectal Cancer

PURPOSE: Although stromal-cell-derived factor (SDF)-1alpha is suggested to be involved in tumorigenicity and tumor angiogenesis, the clinicopathological significance of its expression in colorectal cancers is not fully understood. We examined SDF-1alpha expression in colorectal cancers and investigated its relationship to clinicopathological features such as tumor staging, lymph-node metastasis, vascular invasion (VI), lymphatic invasion (LI) and neural invasion (NI). METHODS: Specimens of 83 primary colorectal cancers were examined immunohistochemically, and the relationships between clinicopathological features and SDF-1alpha expression were analyzed. To compare the expressions between the normal colon tissue and colorectal cancer tissues, we performed Western blot analyses. RESULTS: According to the Western blot analyses, SDF-1alpha was more highly expressed in colorectal carcinoma tissues than in normal colonic mucosa (20/21). According to the immunohistochemical stain, SDF-1alpha was associated with nodal status, distant metastasis, tumor staging, VI and LI. SDF-1alpha expression had a significant prognostic value for overall survival. Kaplan-Meier plots of survival in patients with high SDF-1alpha showed that high SDF-1alpha expression was associated with a shorter overall survival. However, no association was found between SDF-1alpha expression and other pathologic or clinical variables, including age, gender, degree of differentiation, and presence of perineural invasion. CONCLUSION: The expression of SDF-1alpha might be associated with tumor progression in colorectal cancer. Inhibition of SDF-1alpha could be a therapeutic option in colorectal cancer patients.

Correlation between Liver Metastases and the Level of PRL-3 mRNA Expression in Patients with Primary Colorectal Cancer

PURPOSE: Phosphatase of regenerating liver-3 (PRL-3) has been associated with metastasis promotion. However, clinical applications of this association have not yet been clearly demonstrated. In this study, we evaluated the relation of PRL-3 mRNA level in primary colorectal cancer to the corresponding stage and to other clinicopathologic factors. METHODS: Two hundred forty-five patients with histologically-proven colorectal cancer underwent surgery between January 2004 and December 2006. RNA was extracted and cDNA was prepared by using reverse transcription. Quantification of PRL-3 was done using a real-time polymerase chain reaction. RESULTS: Eighty-six cases with well-preserved specimens were enrolled: 53 males and 33 females. The mean age was 63.4 years. According to tumour node metastasis (TNM) stage of the American Joint Committee on Cancer (AJCC), stage I was 11 cases, stage II was 38 cases, stage III was 23 cases, and stage IV was 14 cases. Among stage IV cases, one case was combined with liver and lung metastases, and one case was combined with liver metastases and peritoneal dissemination. The remaining stage IV patients were combined with only liver metastases. There was a significant correlation in PRL-3 mRNA expression between primary colorectal cancer and corresponding tumor stage. PRL-3 mRNA expression was increased in the liver metastases cases. Lymphatic and vascular invasion were significantly related with PRL-3 mRNA levels. CONCLUSION: Advanced stage prediction may be obtained by measuring the level of PRL-3 mRNA expression in primary colorectal cancer. Especially, the risk of liver metastases may be predicted by measuring the level of PRL-3 mRNA expression in primary colorectal cancer. Further study is required to confirm these preliminary results.

Perineal Reconstructive Surgery of a Cloaca-Like Perineal Defect: A Case Report

The perineal defect in female genitalia results from multiple etiologies, including obstetric injury, sexual assaults, and perineal trauma. Untreated defects may lead to significant physical, functional, and esthetic complaints. Numerous reconstruction methods are used for a perineal defect, but various complications, such as fecal impaction, fecal incontinence, and wound disruption, are introduced. We report a case of a 40-yr-old woman with a cloaca-like perineal defect, who was treated with reconstructive surgery of the perineal defect and recovered with a good anatomical and functional outcome.