Pre-Clinical Studies of a Novel Bispecific Fusion Protein Targeting C3b and VEGF in Neovascular and Nonexudative AMD Models.

INTRODUCTION: KNP-301 is a bi-specific fragment crystallizable region (Fc) fusion protein, which inhibits both C3b and vascular endothelial growth factor (VEGF) simultaneously for patients with late-stage age-related macular degeneration (AMD). The present study evaluated in vitro potency, in vivo efficacy, intravitreal pharmacokinetics (IVT PK), and injectability of KNP-301. METHODS: C3b and VEGF binding of KNP-301 were assessed by surface plasmon resonance (SPR) and enzyme-linked immunosorbent assay (ELISA), and cellular bioassays. A laser-induced choroidal neovascularization (CNV) model and a sodium iodate-induced nonexudative AMD model were used to test the in vivo efficacy of mouse surrogate of KNP-301. Utilizing fluorescein angiography (FA) and spectral-domain optical coherence tomography (SD-OCT) scans, the reduction in disease lesions were analyzed in a CNV mouse model. In the nonexudative AMD mouse model, outer nuclear layer (ONL) was assessed by immunofluorescence staining. Lastly, intravitreal pharmacokinetic study was conducted with New Zealand white rabbits via IVT administration of KNP-301 and injectability of KNP-301 was examined by a viscosity test at high concentrations. RESULTS: KNP-301 bound C3b selectively, which resulted in a blockade of the alternative pathway, not the classical pathway. KNP-301 also acted as a VEGF trap, impeding VEGF-mediate signaling. Our dual-blockade strategy was effective in both neovascular and nonexudative AMD models. Moreover, KNP-301 had an advantage of potentially less frequent dosing due to the long half-life in the intravitreal chamber. Our viscosity assessment confirmed that KNP-301 meets the criteria of the IVT injection. CONCLUSIONS: Unlike current therapies, KNP-301 is expected to cover patients with late-stage AMD of both neovascular and nonexudative AMD, and its long-term PK profile at the intravitreal chamber would allow convenience in the dosing interval of patients.

Clinical meaning of the World Health Organization morphologic classification (flat vs. tumoral) of gallbladder intraepithelial neoplasm as a prognostic factor in gallbladder cancer.

BACKGROUND: In the World Health Organization (WHO) classification, gallbladder (GB) intraepithelial lesions are grouped as flat or tumoral, according to their morphological features. The purpose of this study was to investigate the relationship between the morphologies and clinical features of GB cancer (GBC) and to examine the feasibility of using morphologic classification as a prognostic factor. METHODS: From January 2000 to December 2012, the available pathologic slide reviews of 381 patients were analyzed at the Seoul National University Hospital. All pathologic slides were evaluated by two pancreato-biliary tract pathology experts. GBCs were categorized into eight groups (Flat: F1-2, Borderline, Tumoral: Tu1-5), according to the thickness of the mucosal lesion, histologic patterns of the mucosa under microscopy, invasion extent, and patient history of premalignant lesions. According to the morphologic classification, clinical features were compared and survival analysis was performed. RESULTS: In three groups, flat lesions comprised 179 (46.9%) cases and borderline and tumoral comprised 97 (25.4%) and 105 (27.5%) cases, respectively. More favorable pathologic and clinical results were found within the tumoral group. The borderline group had an intermediate tendency between flat and intraluminal in clinicopathologic parameters. In the curative resected T2 stage group, the borderline group demonstrated an intermediate trend compared to that of the flat and tumoral groups, but this was statistically insignificant (P=0.08). CONCLUSIONS: Flat type GBCs show worse prognosis than tumoral GBCs. The morphological classifications between flat and tumoral on the basis of 1 cm and by papillary feature is feasible. Tumor morphology can be used as a reference while deciding the treatment plan, especially in T2 GBC.

CORRIGENDUM: Correction of IRB number: Comparison of clinical outcomes according to the history of previous gastrectomy in patients undergoing pancreatoduodenectomy: a propensity score matching analysis.

[This corrects the article on p. 177 in vol. 98, PMID: 32274365.].

Comparison of clinical outcomes according to the history of previous gastrectomy in patients undergoing pancreatoduodenectomy: a propensity score matching analysis.

PURPOSE: Although pancreatoduodenectomy (PD) in patients who have previously undergone gastrectomy is challenging, little is known about the clinical outcomes and the differences compared to those with conventional PD. We collected cases and conducted studies in retrospective review. METHODS: Of the 1,722 patients who underwent PD at Seoul National University Hospital between 2000 and 2014, 49 (2.8%) underwent previous gastrectomy. Clinical outcomes including operation-related factors and postoperative morbidities were analyzed. RESULTS: Among the 49 patients with curative surgery, 25 patients were male (51.0%) and the mean age was 64.7 years. Gastric cancer was the most frequent cause of previous gastrectomy (93.8%). With one-to-one propensity score matching analysis, lower preoperative body mass index (22.6 kg/m2 vs. 20.8 kg/m2, P = 0.002), higher EBL (390.0 mL vs. 729.5 mL, P = 0.027), and higher transfusion rates (10.2% vs. 36.7%, P = 0.002) were shown in the gastrectomy group. Operation time, postoperative hospital stay, and rate of clinically relevant pancreatic fistula were comparable. CONCLUSION: Secondary PD after prior gastrectomy remains challenging, with higher EBL and rate of transfusion. However, when performed by experienced surgeons, the patients with or without previous gastrectomy show comparable postoperative clinical outcomes, such as similar duration of postoperative hospital stay and rate of postoperative pancreatic fistula.

Interlayer exchange coupling in ferromagnetic semiconductor trilayers with out-of-plane magnetic anisotropy.

We report the observation of ferromagnetic (FM) and antiferromagnetic (AFM) interlayer exchange coupling (IEC) in GaMnAsP-based trilayer structures with out-of-plane magnetic anisotropy. Magnetization and anomalous Hall effect (AHE) measurements show well-resolved magnetization transitions corresponding to the two GaMnAsP layers. Minor loop measurements reveal a characteristic shift caused by IEC in all trilayer samples investigated. Interestingly, the FM IEC changes to AFM IEC for a trilayer with the thinnest (7 nm) top GaMnAsP layer as the temperature increases. The observation of temperature-induced transition of FM and AFM IEC in the same sample suggests the possibility of device applications by controlling the type of IEC in such GaMnAsP-based multilayers.

Magnetization reversal in trilayer structures consisting of GaMnAs layers with opposite signs of anisotropic magnetoresistance.

Magnetization reversal in a GaMnAs trilayer system consisting of two GaMnAs layers separated by a Be-doped GaAs spacer was investigated by magnetotransport measurements. The rotation of magnetization in the two GaMnAs layers is observed as two abrupt independent transitions in planar Hall resistance (PHR). Interestingly, one GaMnAs layer manifests a positive change in PHR, while the other layer shows a negative change for the same rotation of magnetization. Such opposite behavior of the two layers indicates that anisotropic magnetoresistance (AMR) has opposite signs in the two GaMnAs layers. Owing to this opposite behavior of AMR, we are able to identify the sequence of magnetic alignments in the two GaMnAs layers during magnetization reversal. The PHR signal can then be decomposed into two independent contributions, which reveal that the magnetic anisotropy of the GaMnAs layer with negative AMR is predominantly cubic, while it is predominantly uniaxial in the layer with positive AMR. This investigation suggests the ability of engineering the sign of AMR in GaMnAs multilayers, thus making it possible to obtain structures with multi-valued PHR, that can be used as multinary magnetic memory devices.

Effect of Polyglycolic Acid Mesh for Prevention of Pancreatic Fistula Following Distal Pancreatectomy: A Randomized Clinical Trial.

Importance: The rate of postoperative pancreatic fistula (POPF) after distal pancreatectomy ranges from 13% to 64%. To prevent POPF, polyglycolic acid (PGA) mesh was introduced, but its effect has been evaluated only in small numbers of patients and retrospective studies. Objective: To evaluate the efficacy of PGA mesh in preventing POPF after distal pancreatectomy. Design, Setting, and Participants: Prospective randomized clinical, single-blind (participant), parallel-group trial at 5 centers between November 2011 and April 2014. The pancreatic parenchyma was divided using a stapling device; no patient was given prophylactic octreotide. Perioperative and clinical outcomes were compared including POPF, which was graded according to the criteria of the International Study Group For Pancreatic Fistulas. A total of 97 patients aged 20 to 85 years with curable benign, premalignant, or malignant disease of the pancreatic body or tail were enrolled (44 in the PGA group and 53 in the control group). Interventions: Patients in the PGA group underwent transection of the pancreas and application of fibrin glue followed by wrapping the PGA mesh around the remnant pancreatic stump. Main Outcomes and Measures: The primary end point of this study was the development of a clinically relevant POPF (grade B or C by the International Study Group grading system). The secondary end point was the evaluation of risk factors for POPF. Results: The study therefore evaluated a total of 97 patients, 44 in the PGA group and 53 in the control group. Thirty-nine patients were women and 58 patients were men. There were no differences in mean (SD) age (59.9 [12.0] years vs 54.5 [14.1] years, P = .05), male to female ratio (1.0:1.3 vs 1.0:1.7, P = .59), malignancy (40.9% vs 32.1%, P = .37), mean (SD) pancreatic duct diameter (1.92 [0.75] mm vs 1.94 [0.95] mm, P = .47), soft pancreatic texture (90.9% vs 83.0%, P = .17), and mean (SD) thickness of the transection margin (16.9 [5.4] mm vs 16.4 [4.9] mm, P = .63) between the PGA and control groups. The rate of clinically relevant POPF (grade B or C) was significantly lower in the PGA group than in the control group (11.4% vs 28.3%, P = .04). Conclusions and Relevance: Wrapping of the cut surface of the pancreas with PGA mesh is associated with a significantly reduced rate of clinically relevant POPF. Trial Registration: clinicaltrials.gov Identifier: NCT01550406.

Impact of Type of Surgery on Survival Outcome in Patients With Early Gallbladder Cancer in the Era of Minimally Invasive Surgery: Oncologic Safety of Laparoscopic Surgery.

Laparoscopic surgery has been widely accepted as a feasible and safe treatment modality in many cancers of the gastrointestinal tract. However, most guidelines on gallbladder cancer (GBC) regard laparoscopic surgery as a contraindication, even for early GBC. This study aims to evaluate and compare recent surgical outcomes of laparoscopic and open surgery for T1(a,b) GBC and to determine the optimal surgical strategy for T1 GBC.The study enrolled 197 patients with histopathologically proven T1 GBC and no history of other cancers who underwent surgery from 2000 to 2014 at 3 major tertiary referral hospitals with specialized biliary-pancreas pathologists and optimal pathologic handling protocols. Median follow-up was 56 months. The effects of depth of invasion and type of surgery on disease-specific survival and recurrence patterns were investigated.Of the 197 patients, 116 (58.9%) underwent simple cholecystectomy, including 31 (15.7%) who underwent open cholecystectomy and 85 (43.1%) laparoscopic cholecystectomy. The remaining 81 (41.1%) patients underwent extended cholecystectomy. Five-year disease-specific survival rates were similar in patients who underwent simple and extended cholecystectomy (96.7% vs 100%, P = 0.483), as well as being similar in patients in the simple cholecystectomy group who underwent open and laparoscopic cholecystectomy (100% vs 97.6%, P = 0.543). Type of surgery had no effect on recurrence patterns.Laparoscopic cholecystectomy for T1 gallbladder cancer can provide similar survival outcomes compared to open surgery. Considering less blood loss and shorter hospital stay with better cosmetic outcome, laparoscopic cholecystectomy can be justified as a standard treatment for T1b as well as T1a gallbladder cancer when done by well-experienced surgeons based on exact pathologic diagnosis.

Actual Long-Term Survival Outcome of 403 Consecutive Patients with Hilar Cholangiocarcinoma.

BACKGROUND: Despite aggressive surgical resection, prognosis of patients with hilar cholangiocarcinoma is still unsatisfactory. There were limited data about actual long-term survival outcome. This study was designed to explore actual long-term survival outcome of hilar cholangiocarcinoma after surgical treatment, and to investigate the characteristics of patients with actual long-term survival. METHODS: The study cohort consisted of 403 consecutive patients with at least 5-year follow-up after surgical treatment for hilar cholangiocarcinoma at Seoul National University Hospital between 1991 and 2010. Prognostic factors were analyzed with Cox proportional hazard models, and the effect of adjuvant treatment was evaluated by propensity score analysis. RESULTS: Of all patients, R0 resection rate was 41.2 and 63.8 % among intended curative resection. Adjuvant therapy was performed in 48.8 % after curative surgery. Actual 5-year overall survival (OS) rate was 18.9, and 30.1 % after R0 resection. Actual 5-year disease-free survival rate was 25.8 % after resection. Adjuvant treatment improved prognosis in patients with positive metastatic lymph nodes (median OS 21.9 vs. 11.5 months, p = 0.003). Overall recurrence rate was 55.0 %, and distant metastasis (39.7 %) was more frequent than loco-regional recurrence (20.8 %). Lymph node metastasis (p = 0.021) and poor histologic grade (p < 0.001) were independent prognostic factors after curative resection. Patients who survived more than 5 years had less lymph node metastasis (p = 0.025), poor histologic differentiation (p = 0.010), R2 resection (p = 0.040), and recurrence (p < 0.001). CONCLUSION: Actual 5-year OS rate after R0 resection of hilar cholangiocarcinoma is 30.1 %. Adjuvant treatment could be beneficial in patients with lymph node metastasis.

Improvement of clinical outcomes in the patients with gallbladder cancer: lessons from periodic comparison in a tertiary referral center.

BACKGROUND: Current guidelines for gallbladder cancer (GBC) contain controversies and some reported no survival improvement in GBC during 20 years. This study was designed to explore the chronologic change of survival outcomes in GBC and prognostic factors. METHODS: Clinicopathologic features and survival outcomes were analyzed in 692 consecutive GBC patients who underwent surgery between 1987 and 2014, including 255 treated in Period (P) 1 (1987-2000) and 437 in P2 (2001-2014). RESULTS: The mean age was 63.3 years. Curative resection rate was 59.2% and 5-year survival rate (5-YSR) after curative resection was 67.1%. Comparisons between P1 and P2 showed that mean age, asymptomatic presentation, extended cholecystectomy, curative resection, adjuvant chemotherapy, and tumor ≤ T2 were significantly higher during P2. The overall 5-YSR after curative surgery was significantly lower in P1. In patients who underwent curative resection, poor prognostic factors included symptomatic presentation, CA 19-9 >37 IU/ml, poor differentiation, tumor ≥ T3, and lymph nodal involvement. In patients who received non-curative surgery, well- or moderately differentiated tumor and adjuvant chemotherapy provide survival benefit. CONCLUSIONS: Detection of GBC at an early stage and optimal curative surgery may improve survival outcomes in GBC. Chemotherapy provides survival benefit in palliative setting.

Metabolic effect of pancreatoduodenectomy: Resolution of diabetes mellitus after surgery.

BACKGROUND: It is considered natural that glucose tolerance worsens after pancreatectomy. However, diabetes mellitus (DM) resolves after metabolic bypass surgery and anatomic changes after PD resemble those after metabolic surgery. This study assessed the incidence of DM resolution after pancreatectomy and differences in metabolic parameters following pancreatoduodenectomy (PD) and distal pancreatectomy (DP). METHODS: Between 2007 and 2013, 218 consecutive patients with pancreatic diseases underwent PD (n = 112) or DP (n = 106) at Seoul National University Hospital. Factors associated with changes in glucose homeostasis were evaluated by assaying serum glucose concentrations in prospectively collected samples. RESULTS: Of the 218 patients, 88 (40.4%) had preoperative DM, with 27 (30.7%) of the latter showing postoperative resolution of DM, a rate significantly higher in patients who had undergone PD than DP (40.4% vs. 12.9%, p = 0.008). Fasting blood glucose (p = 0.001), PP2 (p < 0.001), and HOMA-IR (p = 0.005) significantly decreased after PD but not after DP. Multivariate analysis revealed that PD was independently associated with DM resolution (odds ratio 7.790, p = 0.003). PD was associated with a significantly higher DM resolution rate than DP among the 37 pancreatic cancer patients with preoperative DM (34.6% vs. 0%, p = 0.036). DM resolution rates were similar in pancreatic cancer and other pancreatic diseases (p = 0.419). CONCLUSION: More than 40% of patients with preoperative DM show resolution after PD. Decreased insulin resistance and suspected enhanced glucose stimulated insulin secretion decreasing PP2 seem to contribute improved glucose homeostasis after PD. BMI was unrelated to DM resolution, indicating that PD-associated physio-anatomical changes may help resolve DM independent of weight.

The clinical usefulness of 18F-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) in follow-up of curatively resected pancreatic cancer patients.

BACKGROUND: Computed tomography and serum tumor markers have limited value in detecting recurrence after curative surgery of pancreatic cancer. This study evaluated the clinical utility of 18F-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) in diagnosing recurrence. METHODS: One hundred ten patients underwent curative resection of pancreatic cancer were enrolled. The diagnostic value of abdominal computed tomography (CT), PET-CT and serum carbohydrate antigen (CA) 19-9 concentration were compared. The prognostic value of SUVmax on PET-CT was evaluated. RESULTS: PET-CT showed relatively higher sensitivity (84.5% vs. 75.0%) and accuracy (84.5% vs. 74.5%) than CT, whereas PET-CT plus CT showed greater sensitivity (97.6%) and accuracy (90.0%) than either alone. In detecting distant recurrences, PET-CT showed higher sensitivity (83.1% vs. 67.7%) than CT. Nineteen patients showed recurrences only on PET-CT, with eleven having invisible or suspected benign lesions on CT, and eight had recurrences in areas not covered by CT. SUVmax over 3.3 was predictive of poor survival after recurrence. CONCLUSIONS: PET-CT in combination with CT improves the detection of recurrence. PET-CT was especially advantageous in detecting recurrences in areas not covered by CT. If active post-operative surveillance after curative resection of pancreatic cancer is deemed beneficial, then it should include PET-CT combined with CT.

Endocrine Function Impairment After Distal Pancreatectomy: Incidence and Related Factors.

BACKGROUND AND AIM: Little is known about the incidence of and risk factors for glucose intolerance after distal pancreatectomy. This study investigated the clinicopathologic factors associated with the development of glucose intolerance or overt diabetes mellitus (DM) after distal pancreatectomy, and the correlation between resected pancreas volume and endocrine function impairment. METHODS: After excluding patients with preoperative DM, 101 patients who underwent distal pancreatectomy with a minimum of 1-year postoperative follow-up were enrolled in this prospective cohort. Patients were assessed preoperatively and 1 week and 12 months postoperatively by oral glucose tolerance tests and by measures of HbA1c and pancreatic volume. RESULTS: Mean patient age was 54.1 years, mean body mass index (BMI) was 23.3 kg/m(2), and the male-to-female ratio was 1:1.8. Of the 101 patients, 21 (20.8 %) had pancreatic ductal adenocarcinoma. The median percent resected pancreas volume was 28.0 % (range 5.0-71.3 %). One year after distal pancreatectomy, 51 patients (50.5 %) had glucose intolerance, including 26 with impaired fasting glucose and 25 with DM. ROC curve analysis showed that a resected pancreas volume of 25 % showed maximum diagnostic value for development of glucose intolerance. Univariate analysis showed that female sex (58.5 vs. 36.1 %, P = 0.031), BMI (24.1 vs. 22.5 kg/m(2), P = 0.010), larger resected volume (36.5 vs. 28.0 %, P = 0.026), and lower remnant volume relative to BMI (1.7 × 10(-3) vs. 2.1 × 10(-3) m(5)/kg, P = 0.021) were risk factors for postoperative endocrine function impairment. Multivariate analysis revealed that female sex (odds ratio [OR] 5.818, P = 0.003), higher BMI (OR 10.556, P = 0.006), and resected pancreatic volume (OR 3.192, P = 0.035) were independent risk factors for endocrine impairment. CONCLUSIONS: About 50 % of patients without preoperative DM developed impaired glucose tolerance or overt DM following distal pancreatectomy. Female sex, higher BMI, and resection of pancreatic volume >25 % were risk factors for endocrine function impairment, indicating the need for preoperative evaluation and careful perioperative glucose monitoring in these patients.

Clinicopathologic Differences in Patients with Gallbladder Cancer According to the Presence of Anomalous Biliopancreatic Junction.

BACKGROUND: Anomalous biliopancreatic junction (ABPJ) is a risk factor for gallbladder cancer (GBC). This study investigated the significance of ABPJ in patients with GBC. METHODS: Of the 453 patients with GBC underwent surgery at Seoul National University Hospital between 2000 and 2014, the 401 patients who can be assessed for the presence of ABPJ with radiologic image were analyzed. RESULTS: The 401 patients with GBC included 183 (45.6 %) males and 218 (54.4 %) females. ABPJ was identified in 69 (17.2 %) patients, 22 (31.9 %) males and 47 (68.1 %) females. Choledochal cyst (CC) was identified in 18 (4.5 %) patients, all of whom had ABPJ. Curative surgery was accomplished in 68.1 %. A comparison of patients with and without ABPJ showed that mean age (59.9 vs. 65.1 years, p < 0.001) and association with gallbladder stone (8.7 vs. 24.7 %, p = 0.002) were significantly lower in the ABPJ group, while the proportion of female (68.1 vs. 51.5 %, p = 0.012), bile duct resection rate (47.8 vs. 18.4 %, p < 0.001), and curative resection rate (81.1 vs. 65.7 %, p = 0.003) were significantly higher in the ABPJ group. Overall 5-year survival rates were similar in the ABPJ and non-ABPJ groups (74.4 vs. 69.0 %, p = 0.533). In patients with ABPJ, the presence of CC did not have a significant effect on survival (p = 0.099). CONCLUSIONS: ABPJ was found in 17.2 % of patients with GBC. ABPJ is associated with younger age, female gender, absence of gallbladder stones, higher BDR rate, and higher curative resection rate. However, neither ABPJ nor CC was prognostic of survival in curatively treated patients with GBC.

Effects of Surgical Methods and Tumor Location on Survival and Recurrence Patterns after Curative Resection in Patients with T2 Gallbladder Cancer.

BACKGROUND/AIMS: Extended cholecystectomy is generally recommended for patients with T2 gallbladder cancer. However, few studies have assessed the extent of resection relative to T2 gallbladder tumor location. This study analyzed the effects of surgical methods and tumor location on survival outcomes and tumor recurrence in patients with T2 gallbladder cancer. METHODS: Clinicopathological characteristics, extent of resection, survival rates, and recurrence patterns were retrospectively analyzed in 88 patients with pathologically confirmed T2 gallbladder cancer. RESULTS: The 5-year disease-free survival rate was 65.0%. Multivariate analysis showed that lymph node metastasis was the only independent risk factor for poor 5-year disease-free survival rate. Survival outcomes were not associated with tumor location. Survival tended to be better in patients who underwent extended cholecystectomy than in those who underwent simple cholecystectomy. Recurrence rate was not affected by surgical method or tumor location. Systemic recurrence was more frequent than local recurrence without distant recurrence. Gallbladder bed recurrence and liver recurrence were relatively rare, occurring only in patients with liver side tumors. CONCLUSIONS: Extended cholecystectomy is the most appropriate treatment for T2 gallbladder cancer. However, simple cholecystectomy with regional lymph node dissection may be appropriate for patients with serosal side tumors.

Use of TachoSil(®) patches to prevent pancreatic leaks after distal pancreatectomy: a prospective, multicenter, randomized controlled study.

BACKGROUND: We performed a prospective, multicenter, randomized controlled study to investigate the clinical outcomes, including postoperative pancreatic fistulas (POPF), after using the TachoSil® patch in distal pancreatectomy (NCT01550406). METHODS: Between June 2012 and September 2014, 101 patients at five centers were randomized into Control (n = 53) and TachoSil (n = 48) groups. In all patients, the pancreas was resected using a stapler with Endo-GIA™ staples. The TachoSil patch was wrapped around the pancreatic stump only in the TachoSil group, not in Control group. RESULTS: The patient characteristics, including age and diagnosis, were comparable in both groups. The mean operation time (159.4 vs. 172.3 min, P = 0.081) and postoperative hospital stay (10.0 vs. 9.7 days, P = 0.279) were similar in the Control and TachoSil groups, respectively. The overall incidence of POPF was 62.4% (n = 63). The distribution of grades A, B, and C POPF was similar in the Control (n = 14/14/1) and TachoSil (n = 23/11/0) groups, as were the overall incidence (54.7% vs. 70.8%, P = 0.095) and the incidence of grade B and C POPF (28.3% vs. 22.9%, P = 0.536). CONCLUSION: This study showed that the TachoSil® patch did not reduce the incidence of POPF after distal pancreatectomy.

Comparison of laparoscopic versus open left-sided hepatectomy for intrahepatic duct stones.

BACKGROUND: Laparoscopic hepatectomy for intrahepatic duct (IHD) stones is limited by technical difficulties caused by adhesion to adjacent tissue or distorted anatomy resulting from recurrent inflammation. This study compared perioperative and clinical outcomes in patients undergoing laparoscopic and open hepatectomy for left IHD stones. METHODS: From January 2002 to December 2013, 40 patients underwent laparoscopic left-sided hepatectomy [left hemihepatectomy (n = 7) or left lateral sectionectomy (n = 33)] and 54 patients without combined operations and previous operation histories underwent open left-sided hepatectomy [left hemihepatectomy (n = 24) or left lateral sectionectomy (n = 30)]. Their perioperative and clinical outcomes were compared, including stone clearance rates, stone recurrence rates, and median follow-up duration. RESULTS: There was no difference in age (56.8 ± 8.2 vs. 55.6 ± 9.6 years, p = 0.531), sex (1.0:4.0 vs. 1.0:1.8 male:female, p = 0.108), or BMI (22.8 ± 2.8 vs. 22.9 ± 3.0 kg/m(2), p = 0.802) between the laparoscopic and open hepatectomy groups. Lateral sectionectomy was more frequent in the laparoscopic group (33/40 vs. 30/54, p = 0.010). Operation time (174.2 ± 56.6 vs. 210.4 ± 51.6 min, p = 0.002) and postoperative hospital stay (7.9 ± 2.6 vs. 14.3 ± 5.5 days, p < 0.001) were shorter in the laparoscopic group, and complication rate (17.5 vs. 40.7%, p = 0.016), in particular surgical site infection rate (5.0 vs. 18.5%, p = 0.052), was lower in the laparoscopic group than in the open hepatectomy group. Similar results were observed in the hemihepatectomy and lateral sectionectomy subgroups. There was no operation-related mortality. There were no significant differences in follow-up periods (48 ± 33.6 vs. 59.2 ± 41.7 months, p = 0.235) and rates of initial stone clearance (87.5 vs. 75.9%, p = 0.159), final clearance (100 vs. 94.4%, p = 0.130), and stone recurrence (2.5 vs. 5.6%, p = 0.468). CONCLUSION: Laparoscopic hepatectomy is safe and effective for well-selected patients with left IHD stones, when performed by experienced surgeons. Laparoscopic hepatectomy resulted in shorter operation time and postoperative hospital stay, and a lower postoperative morbidity rate, than open hepatectomy.

Clinical implication of serum carcinoembryonic antigen and carbohydrate antigen 19-9 for the prediction of malignancy in intraductal papillary mucinous neoplasm of pancreas.

BACKGROUND: Little is known about the prognostic significance of serum carbohydrate antigen (CA) 19-9 and carcinoembryonic antigen (CEA) concentrations for predicting malignancy in patients with intraductal papillary mucinous neoplasm (IPMN) of pancreas. METHOD: The study cohort consisted of 367 patients with surgical biopsy proven IPMN at Seoul National University Hospital. Preoperative serum tumor markers were evaluated and compared with other clinical variables. RESULTS: Malignant pathology (high grade dysplasia [HGD] and invasive IPMN) was identified in 117 (31.9%) patients. Elevated serum CA19-9 was more frequent in patients with malignant (34.2%, P < 0.001; invasive IPMN vs. HGD 47.9% vs. 11.4%, P < 0.001) and main duct type (40.0%, P = 0.003) IPMN. Multivariate analysis showed main pancreatic duct (MPD) >5 mm (P < 0.001), mural nodules (P < 0.001), and elevated serum CA19-9 (P < 0.001) were independent predictors of malignancy. The sensitivity, specificity and accuracy were 34.2%, 92.4%, and 73.8%, respectively, for elevated serum CA19-9; 63.3%, 78.0%, and 73.3%, for MPD >5 mm; and 59.0%, 86.4%, and 77.7%, for mural nodules. CONCLUSION: Serum CA19-9 is significantly higher in patients with malignant IPMN, especially in patients with invasive and main duct type IPMN. The diagnostic power of serum CA19-9 in predicting malignancy is comparable to that of MPD >5 mm and mural nodules.

Co-stimulation of TLR4 and Dectin-1 Induces the Production of Inflammatory Cytokines but not TGF-ß for Th17 Cell Differentiation.

Collaboration of TLR and non-TLR pathways in innate immune cells, which acts in concert for the induction of inflammatory cytokines, can mount a specific adaptive immune response tailored to a pathogen. Here, we show that murine DC produced increased IL-23 and IL-6 when they were treated with LPS together with curdlan that activates TLR4 and dectin-1, respectively. We also found that the induction of the inflammatory cytokine production by LPS and curdlan requires activation of IKK. However, the same treatment did not induce DC to produce a sufficient amount of TGF-ß. As a result, the conditioned media from DC treated with LPS and curdlan was not able to direct CD4(+) T cells to Th17 cells. Addition of TGF-ß but not IL-6 or IL-1ß was able to promote IL-17 production from CD4(+) T cells. Our results showed that although signaling mediated by LPS together with curdlan is a potent stimulator of DC to secrete many pro-inflammatory cytokines, TGF-ß production is a limiting factor for promoting Th17 immunity.