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.

Necrotizing Gallbladder Torsion Masking as Acalculous Cholecystitis: A Review of Two Cases Treated with Successful Laparoscopic Cholecystectomy

Gallbladder torsion is a rare disease and it is very difficult to diagnose preoperatively because the signs, symptoms, and image findings are very similar to the other cases of acute cholecystitis. However, in cases of gallbladder torsion, conservative treatments such as intravenous antibiotics and percutaneous cholecystostomy could be ineffective and result in even fatal. Hence, for urgent surgical management, gallbladder torsion must be considered especially in the elderly female patients with radiologic findings such as acalculous cholecystitis and a free-floating gallbladder. The author presents two cases of necrotizing gallbladder torsion in an elderly female patient who was treated successfully with laparoscopic cholecystectomy.

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). miR221 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.

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 importance of 18F-fluorodeoxyglucose positron emission tomography and carbohydrate antigen 19-9 in patients with periampullary tumors

No abstract available.

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.

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.

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.

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.

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.

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.

Giant pedunculated hepatocellular carcinoma masquerading as a pelvic mass: a case report

Hepatocellular carcinoma (HCC) is one of the most common malignancies in the world, with high frequency rates in Asia. Many of the patients have unresectable disease at the time of diagnosis, and early detection and surgical resection is the best hope for survival. But, if HCC is presenting as an extrahepatic mass, the diagnosis is difficult. Herein, we report a case of primary HCC masquerading as a pelvic mass. A 74-year-old woman was admitted to our hospital due to a palpable mass in the lower abdomen. CT scan detected an approximately 15.0x13.4x11.4 cm-sized multilobulated homogeneous enhancing mass in the right adnexa. Operative findings showed that the pelvic mass originated from the liver. We performed hepatic wedge resection. Permanent histopathologic report revealed primary HCC. Exophytic-growing hepatocellular carcinoma should be carefully diagnosed.

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.

Expression of RhoA in Colorectal Cancers and Its Clinicopathological Significance

PURPOSE: The Rho family of GTPases are involved in actin cytoskeleton organization and are associated with carcinogenesis and progression of human cancers. The clinicopathological significance of RhoA is not yet well known in the case of colorectal cancer. To investigate the expression of RhoA protein in colorectal carcinoma and to evaluate the relationship between RhoA protein expression and invasion and metastasis of colorectal cancer, we examined the expression of RhoA protein by using Western blotting and immunohistochemistry. METHODS: The protein levels of RhoA in colorectal carcinomas of surgical specimens were analyzed in 71 consecutive patients with colorectal cancers by using immunohistochemistry and Western blotting. The relationships between the protein levels of RhoA in tumor tissues and the clinicopathological features of the patients were also assessed. RESULTS: RhoA was highly expressed in 48 colorectal carcinomas (67.6%). There was a significant association between RhoA expression and lymph nodal status. The expression of RhoA protein was related to lymph-node metastasis (P=0.032) and advanced TNM tumor staging (P=0.020). RhoA expression had a significant prognostic value for overall survival. Kaplan-Meier plots of survival in patients with high RhoA showed that high RhoA expression was associated with a shorter overall survival. However, no association was found between RhoA and other pathologic or clinical variables, including age, gender, degree of differentiation, and presence of perineural spread. CONCLUSIONS: The RhoA protein may be related to malignant transformation and development of colorectal caricinomas and may play an important role in the invasion and the metastasis of colorectal carcinomas.

Three Cases of Urine Abnormalities Associated with Ketogenic Diet

Ketogenic diet is a high-fat, low carbohydrate, low protein diet used in treatment of pediatric epilepsy since the 1920s. Currently it is used primarily to treat refractory childhood epilepsy. Few serious complications caused by ketogenic diet have been reported. Short-term complications include dehydration, hypoglycemia, vomiting, diarrhea, and refusal to eat. Long-term complications include kidney stones, recurrent infections, metabolic derangement, hypercholesterolemia, irritability, lethargy, and refusal to eat. We experienced 3 cases of infantile spasm patients, whose refractory seizures were controlled with ketogenic diet, but various urinary abnormalities developed.

Catecholaminergic Polymorphic Ventricular Tachycardia in Children

PURPOSE: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is the disease entity of adrenergic dependent, potentially lethal tachyarrhythmia in a child with no structural heart disease, which manifest itself as a syncope or sudden death. The objective of this study is to present our experiences on this important, although rare, disease. METHODS: Retrospective analysis of 5 patients with episodes of syncope related to exercise, who were referred to our hospital from January 1985 to December 1998. RESULTS: All patients were male and the mean age at the time of the first syncopal episode was 5.1+/-3.2 years (range 1.3 to 10 years). There were no structural cardiac abnormalities in clinical and laboratory evaluations. In all, polymorphic ventricular tachycardia showing the characteristic pattern of CPVT in which, as the heart became stimulated adrenergically, isolated ventricular premature beats appeared, increased with rate, became polymorphic, finally formed burst with bidirectional salvoes and disappeared in resting state was induced during exercise test and/or isoproterenol infusion test. During the mean follow up period of 3.75+/-3.1 years (range 1 month to 7.3 years), one died suddenly. In this case, low dose of beta-blocker was administered because of associated sinus bradycardia resulting in incomplete control of the syncopal episodes. The other 4 cases were alive and asymptomatic by means of adequate modification of beta-blocker dosage and method of administration. CONCLUSIONS: This study emphasizes that CPVT is an important, although rare, cause of exercise related syncope in children and can be diagnosed by means of exercise test and/or isoproterenol infusion. beta-blockers were very effective in all cases, even though increasing amount of beta-blocker was frequently necessary to control ventricular arrhythmia in some cases.