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.

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.

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.

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.

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.

MyD88 is essential to sustain mTOR activation necessary to promote T helper 17 cell proliferation by linking IL-1 and IL-23 signaling.

Myeloid differentiation primary response protein 88 (MyD88) is classically known as an adaptor, linking TLR and IL-1R to downstream signaling pathways in the innate immune system. In addition to its role in innate immune cells, MyD88 has been shown to play an important role in T cells. How MyD88 regulates helper T-cell differentiation remains largely unknown, however. Here we demonstrate that MyD88 is an important regulator of IL-17-producing CD4(+) T helper cells (Th17) cell proliferation. MyD88-deficient CD4(+) T cells showed a defect in Th17 cell differentiation, but not in Th1 cell or Th2 cell differentiation. The impaired IL-17 production from MyD88-deficient CD4(+) T cells is not a result of defective RAR-related orphan receptor γt (RORγt) expression. Instead, MyD88 is essential for sustaining the mammalian target of rapamycin (mTOR) activation necessary to promote Th17 cell proliferation by linking IL-1 and IL-23 signaling. MyD88-deficient CD4(+) T cells showed impaired mTOR activation and, consequently, reduced Th17 cell proliferation. Importantly, the absence of MyD88 in T cells ameliorated disease in the experimental autoimmune encephalomyelitis model. Taken together, our results demonstrate that MyD88 has a dual function in Th17 cells by delivering IL-1 signaling during the early differentiation stage and integrating IL-23 signaling to the mTOR complex to expand committed Th17 cells.

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.

Saikosaponin C inhibits lipopolysaccharide-induced apoptosis by suppressing caspase-3 activation and subsequent degradation of focal adhesion kinase in human umbilical vein endothelial cells.

Bacterial lipopolysaccharide (LPS) is an important mediator of inflammation and a potent inducer of endothelial cell damage and apoptosis. In this study, we investigated the protective effects of saikosaponin C (SSc), one of the active ingredients produced by the traditional Chinese herb, Radix Bupleuri, against LPS-induced apoptosis in human umbilical endothelial cells (HUVECs). LPS triggered caspase-3 activation, which was found to be important in LPS-induced HUVEC apoptosis. Inhibition of caspase-3 also inhibited LPS-induced degradation of focal adhesion kinase (FAK), indicating that caspase-3 is important in LPS-mediated FAK degradation as well as in apoptosis in HUVECs. SSc significantly inhibited LPS-induced apoptotic cell death in HUVECs through the selective suppression of caspase-3. SSc was also shown to rescue LPS-induced FAK degradation and other cell adhesion signals. Furthermore, the protective effects of SSc against LPS-induced apoptosis were abolished upon pretreatment with a FAK inhibitor, highlighting the importance of FAK in SSc activity. Taken together, these results show that SSc efficiently inhibited LPS-induced apoptotic cell death via inhibition of caspase-3 activation and caspase-3-mediated-FAK degradation. Therefore, SSc represents a promising therapeutic candidate for the treatment of vascular endothelial cell injury and cellular dysfunction.

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.

Interleukin-23 production in dendritic cells is negatively regulated by protein phosphatase 2A.

IL-12 and IL-23 are produced by activated antigen-presenting cells but the two induce distinct immune responses by promoting Th1 and Th17 cell differentiation, respectively. IL-23 is a heterodimeric cytokine consisting of two subunits: p40 that is shared with IL-12 and p19 unique to IL-23. In this study, we showed that the production of IL-23 but not IL-12 was negatively regulated by protein phosphatase 2A (PP2A) in dendritic cells (DC). PP2A inhibits IL-23 production by suppressing the expression of the IL-23p19 gene. Treating DC with okadaic acid that inhibits the PP2A activity or knocking down the catalytic subunit of PP2A with siRNA enhanced IL-23 but not IL-12 production. Unlike PP2A, MAP kinase phosphatase-1 or CYLD did not show an effect on IL-23 production supporting the specificity of PP2A. PP2A-mediated inhibition requires a newly made protein that is likely responsible for bringing PP2A and IKKbeta together upon LPS stimulation, which then results in the termination of IKK phosphorylation. Thus, our results uncovered an important role of the protein phosphatase in the regulation of IL-23 production and identified PP2A as a previously uncharacterized inhibitor of IL-23p19 expression in DC.

Negative regulation of MyD88-dependent signaling by IL-10 in dendritic cells.

IL-10 produced by dendritic cells (DC) can limit or terminate ongoing inflammatory responses by inhibiting the proinflammatory cytokine production. Currently, the molecular mechanism by which IL-10 suppresses cytokine production is still ill-defined. In this study, we showed that IL-10 produced by DC dampens myeloid differentiation factor (MyD)88-dependent, but not MyD88-independent signaling. At the molecular level, IL-10 induces ubiquitination and subsequent protein degradation of MyD88-dependent signaling molecules, including IL-1 receptor-associated kinase 4 and TNF-receptor associated factor 6. Protein degradation by IL-10 was associated with decreased phosphorylation of p38, JNK, and IKK. All of these events were prevented by either blocking IL-10 receptor signaling or inhibiting proteasome degradation. IL-10 induced LPS hyporesponsiveness using the same mechanisms, i.e., ubiquitination and protein degradation. Thus, a previously undescribed regulatory mechanism by which IL-10-mediated protein degradation contributes to the inhibition of inflammatory cytokine production and endotoxin tolerance in DC.

Dendritic cells produce inflammatory cytokines in response to bacterial products from Staphylococcus aureus-infected atopic dermatitis lesions.

Atopic Dermatitis (AD) patients often acquire secondary skin infections resulting in increased inflammation. The increased inflammation occurs through the activation of multiple cell types including dendritic cells (DC). In this study, we investigated the activity of soluble products present in infected AD lesions by measuring the ability of patients' wash fluids from a quantitative culture of lesions to activate DC. We found that wash fluid derived from AD lesions induced cytokine production by murine bone marrow-derived DC, including IL-1ß, IL-6, ΙL-10, and tumor necrosis factor-α. The lipoprotein lipoteichoic acid (LTA) from Staphylococcusaureus was implicated as a potent stimulus in the wash fluids as only wash fluid samples that contained LTA exerted this activity, and exogenous LTA triggered similar DC cytokine activation. Wash fluid- and LTA-stimulated DC cytokine production required MyD88, but not the platelet-activating factor receptor (PAF-R), despite the ability of LTA to function through this receptor in keratinocytes. Thus, our results support a role for DC in the worsening of AD inflammation due to secondary bacteria infections.

Correlation of electromyogram and muscle biopsy in myopathy of young age.

OBJECTIVE: To investigate the accuracy of electromyogram (EMG) compared to muscle biopsy in young myopathic patients. DESIGN: Observational study. SETTING: A university rehabilitation hospital. PARTICIPANTS: Cases (N=62) were included if the patient was 18 years or younger, and if data were available from muscle biopsy, EMG, and final clinical diagnosis. INTERVENTION: No intervention. MAIN OUTCOME MEASURE: Sensitivity of EMG. RESULTS: EMG showed myopathic findings in 55 patients, and microscopy revealed myopathy in 50 patients and nonspecific findings in 5 patients. Twenty-eight out of 33 patients showed myogenic EMG findings with a conventional EMG, and histology revealed myopathy in 24 patients. In comparison, turns/amplitude analysis (TAA) with a conventional EMG detected myogenic findings in 27 of 29 patients. Twenty-six of these 27 patients showed myogenic findings in the biopsy. CONCLUSIONS: We concluded that EMG is useful for the detection of myopathy in young patients. In addition, TAA may be helpful in cases of no definite conventional EMG findings and less cooperative patients.

Arthroscopic treatment for limitation of motion of the elbow: the learning curve.

PURPOSE: The aim of this study was to demonstrate our learning curve in arthroscopic treatment for limitation of motion of the elbow. METHODS: To verify the surrogates for learning curve, operative time in 120 consecutive elbows were plotted by case number and the learning curve was illustrated by the best-fit curve. The study population was divided into eight consecutive blocks (15 patients per block) by observing a notable change in the learning from the curve. Mean operative time and mean improvement in motion and clinical score in each block were compared. RESULTS: Mean operative time decreased significantly from the first block to the second block (133-98). No further significant change was noted thereafter. Contrarily, no significant increase in motion improvement or clinical score improvement was identified but a significant decrease was found between the fourth and fifth block (47-36 and 30-24, respectively). Operative time was negatively correlated with preoperative range of motion (P=0.003). Clinical score improvement was also negatively correlated with preoperative range of motion (P<0.001). Motion improvement was more strongly correlated with preoperative range of motion (P<0.001). CONCLUSIONS: This study demonstrated a learning curve in which a significant decrease in operative time was shown after an initial 15 patients. Motion and clinical score improvement were not satisfactory surrogate for learning curve and found to be closely related to preoperative range of motion. Qualification of the learning curve for arthroscopic treatment for limitation of motion of the elbow provides a guide for surgeons assuming the expected time line to become proficient in this technique.

Altered cytokine production by dendritic cells from infants with atopic dermatitis.

Dendritic cells (DC) are potent initiators of immune responses, compared to other professional antigen-presenting cells, based on their ability to capture antigen, express high amounts of MHC and co-stimulatory molecules, and to secrete immunostimulatory cytokines. Altered functions of DC in atopic individuals have been observed, though it is not clear if this is a cause or a result of the development of allergic disease. In this report we demonstrate altered cytokine production by DC isolated from infants with atopic dermatitis but without a diagnosis of asthma, compared to infants with non-atopic dermatitis. Increased production of IL-6, IL-10 and IFNα from DC isolated from atopic infants is less apparent when DC from infants were examined 1 year later. An increase in the same cytokines was observed in neonatal mice that are genetically predisposed towards allergic inflammation. These results suggest that an atopic environment promotes altered cytokine production by DC from infants.

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.

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.].

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.

Posterior cruciate ligament reconstruction in patients with generalized joint laxity.

UNLABELLED: Generalized joint laxity has been considered a risk factor causing late failure of reconstructed anterior cruciate ligaments, although it is unknown whether that is the case for reconstructed posterior cruciate ligaments. We hypothesized patients with generalized joint laxity, compared with those without laxity, would have similar postoperative knee stability, range of motion, and functional scores after posterior cruciate ligament reconstruction. The Beighton and Horan criteria were used to determine generalized joint laxity. We enrolled 24 patients with generalized joint laxity (Group L) and 29 patients without any positive findings of joint laxity (Group N) matched by gender and age. The average side-by-side differences of posterior tibial translation were 4.72 mm in Group L and 3.63 mm in Group N. We observed no differences in posterior tibial translation with differing graft materials or combined procedures. In Group L the International Knee Documentation Committee score was normal in 12.5% and nearly normal in 45.8% whereas in Group N, 24.1% were normal and 55.2% nearly normal. Patients with generalized joint laxity showed more posterior laxity than patients without joint laxity. Generalized joint laxity therefore appears to be a risk factor associated with posterior laxity after posterior cruciate ligament reconstruction. LEVEL OF EVIDENCE: Level III, prognostic study. See the Guidelines for Authors for a complete description of levels of evidence.