Fate of Patients With Intraductal Papillary Mucinous Neoplasms of Pancreas After Resection According to the Pathology and Margin Status: Continuously Increasing Risk of Recurrence Even After Curative Resection Suggesting Necessity of Lifetime Surveillance.

OBJECTIVE: This study evaluated the associated factors and prognosis according to pathology and margin after surgical resection of intraductal papillary mucinous neoplasms (IPMN). BACKGROUND: There is limited information on recurrence patterns according to pathology and margin in IPMN. METHODS: Total 577 patients who underwent operation for IPMN at a tertiary center were included. Factors associated with recurrence, survival, and recurrence outcomes according to pathology and margin were analyzed. RESULTS: Among 548 patients analyzed, 353 had low-grade dysplasia (LGD), 78 had high-grade dysplasia (HGD), and 117 had invasive IPMN. Total 50 patients developed recurrences, with 4 resection margins, 10 remnant pancreas, 11 locoregional, and 35 distant recurrences. Invasive IPMN showed worse 5-year cumulative recurrence risk (LGD vs HGD vs invasive: 0.7% vs 4.3% vs 37.6%, P < 0.001) and 5-year survival rate (89.0% vs 84.0% vs 48.4%, P < 0.001). Recurrence risk increased after 5 years, even in LGD and HGD. Malignant margin (HGD and invasive) had worse 5-year cumulative recurrence rate (R0 vs LGD vs malignant: 8.3% vs 5.9% vs 50.6%, P < 0.001) and 5-year survival rate (80.7% vs 83.0% vs 30.8%, P < 0.001). Carbohydrate antigen 19-9 >37 ( P = 0.003), invasive IPMN ( P < 0.001), and malignant margin ( P = 0.036) were associated with recurrence. CONCLUSIONS: Invasive IPMN developed more recurrences and had worse survival than LGD or HGD, indicating the need for more efficient postoperative treatment strategies. Patients with LGD and HGD also need regular follow-up for recurrence after 5 years. Malignant margins need additional resection to achieve negative or at least LGD margin.

The Roles of IL-22 and Its Receptor in the Regulation of Inflammatory Responses in the Brain.

Interleukin (IL)-22 is a potent mediator of inflammatory responses. The IL-22 receptor consists of the IL-22Rα and IL-10Rß subunits. Previous studies have shown that IL-22Rα expression is restricted to non-hematopoietic cells in the skin, pancreas, intestine, liver, lung, and kidney. Although IL-22 is involved in the development of inflammatory responses, there have been no reports of its role in brain inflammation. Here, we used RT-PCR, Western blotting, flow cytometry, immunohistochemical, and microarray analyses to examine the role of IL-22 and expression of IL-22Rα in the brain, using the microglial cell line, hippocampal neuronal cell line, and inflamed mouse brain tissue. Treatment of BV2 and HT22 cells with recombinant IL-22 increased the expression levels of the pro-inflammatory cytokines IL-6 and TNF-α, as well as cyclooxygenase (COX)-2 and prostaglandin E2. We also found that the JNK and STAT3 signaling pathways play an important role in IL-22-mediated increases in inflammatory mediators. Microarray analyses revealed upregulated expression of inflammation-related genes in IL-22-treated HT22 cells. Finally, we found that IL-22Rα is spontaneously expressed in the brain and is upregulated in inflamed mouse brain. Overall, our results demonstrate that interaction of IL-22 with IL-22Rα plays a role in the development of inflammatory responses in the brain.

Preventive Effect of Vitamin C on Dextran Sulfate Sodium (DSS)-Induced Colitis via the Regulation of IL-22 and IL-6 Production in Gulo(-/-) Mice.

Reactive oxygen species (ROS), which are exceptionally high in IBD lesions, are known to cause abnormal immune responses to inflammatory reactions in inflammatory bowel diseases (IBD) through damage to the intestinal mucosal linings. Moreover, they are theorized to be an agent of IBD development. Vitamin C is widely known to be an effective antioxidant for its ability to regulate inflammatory responses through its ROS scavenging effect. Therefore, we examined vitamin C's influence on the development and progression of IBD in Gulo(-/-) mice, which cannot synthesize vitamin C like humans due to a defect in the expression of L-gulono-γ-lactone oxidase, an essential enzyme for vitamin C production. First, we found extensive oxidative stress and an inflammation increase in the colon of vitamin C-insufficient Gulo(-/-) mice. We also found decreased IL-22 production and NKp46(+) cell recruitment and the impaired activation of the p38MAPK pathway. Additionally, comparing vitamin C-insufficient Gulo(-/-) mice to vitamin C-sufficient Gulo(-/-) mice and wild-type mice, the insufficient group faced a decrease in mucin-1 expression, accompanied by an increase in IL-6 production, followed by the activation of the STAT3 and Akt pathways. The results suggest that vitamin C insufficiency induces severe colitis, meaning vitamin C could also take on a preventative role by regulating the production of cytokines and the induction of inflammation.

Alloferon and Zanamivir Show Effective Antiviral Activity against Influenza A Virus (H1N1) Infection In Vitro and In Vivo.

The use of vaccines is the most effective and reliable method for the prevention of viral infections. However, research on evaluation of effective therapeutic agents for use in treatment after infection is necessary. Zanamivir was administered through inhalation for treatment of pandemic influenza A/H1N1 in 2009. However, the emergence of drug-resistant strains can occur rapidly. Alloferon, an immunomodulatory drug developed as an NK cell activator, exerts antiviral effects against various viruses, particularly influenza viruses. Therefore, alloferon and zanamivir were administered in combination in an effort to improve the antiviral effect of zanamivir by reducing H1N1 resistance. First, we confirmed that administration of combined treatment would result in effective inhibition of viral proliferation in MDCK and A549 cells infected with H1N1. Production of IL-6 and MIP-1α in these cells and the activity of p38 MAPK and c-Jun that are increased by H1N1 were inhibited by combined treatment. Mice were then infected intranasally with H1N1, and examination of the antiviral efficacy of the alloferon/zanamivir combination was performed. The results showed that combined treatment after infection with H1N1 prevented weight loss, increased the survival rate, and improved lung fibrosis. Combined treatment also resulted in reduced infiltration of neutrophils and macrophages into the lungs. Combined treatment effectively inhibited the activity of p38 MAPK and c-Jun in lung tissue, which was increased by infection with H1N1. Therefore, the combination of alloferon/zanamivir effectively prevents the development of H1N1-mediated inflammation in the lungs by inhibiting the production of inflammatory mediators and migration of inflammatory cells into lung tissue.

Radiological tumour invasion of splenic artery or vein in patients with pancreatic body or tail adenocarcinoma and effect on recurrence and survival.

BACKGROUND: Major vessel invasion is an important factor for determining the surgical approach and long-term prognosis for patients with pancreatic head cancer. However, clinical implications of vessel invasion have seldom been reported in pancreatic body or tail cancer. This study aimed to evaluate the clinical relevance of splenic vessel invasion with pancreatic body or tail cancer compared with no invasion and investigate prognostic factors. METHODS: This study enrolled patients who underwent upfront distal pancreatectomy from 2005 to 2018. The circular degree of splenic vessel invasion was investigated and categorized into three groups (group 1, no invasion; group 2, 0-180°; group 3, 180° or more). Clinicopathological variables and perioperative and survival outcomes were evaluated, and multivariable Cox proportional analysis was performed to evaluate prognostic factors. RESULTS: Among 249 enrolled patients, tumour size was larger in patients with splenic vessel invasion (3.9 versus 2.9 cm, P = 0.001), but the number of metastatic lymph nodes was comparable to that in patients with no vessel invasion (1.7 versus 1.4, P = 0.241). The 5-year overall survival rates differed significantly between the three groups (group 1, 38.4 per cent; group 2, 16.8 per cent; group 3, 9.7 per cent, P < 0.001). Patients with both splenic artery and vein invasion had lower 5-year overall survival rates than those with one vessel (7.5 versus 20.2 per cent, P = 0.021). Cox proportional analysis revealed adjuvant treatment, R0 resection and splenic artery invasion as independent prognostic factors for adverse outcomes in pancreatic body or tail cancer. CONCLUSION: Splenic vessel invasion was associated with higher recurrence and lower overall survival in pancreatic body or tail cancers suggesting a need for a neoadjuvant approach.

Perioperative and oncologic outcome of robot-assisted minimally invasive (hybrid laparoscopic and robotic) pancreatoduodenectomy: based on pancreatic fistula risk score and cancer/staging matched comparison with open pancreatoduodenectomy.

BACKGROUND: Robotic surgery is a novel approach that scores over conventional minimally invasive approaches, even in pancreatic surgery. We investigated clinical outcomes of robot-assisted minimally invasive (hybrid laparoscopic and robotic) pancreatoduodenectomy (RA-MIPD). METHODS: Total 150 patients who underwent RA-MIPD between 2015 and 2018 were compared with 710 patients who underwent open pancreatoduodenectomy (PD) during the same period. Demographics and surgical outcomes were analyzed, and propensity score-matched (PSM) analysis was performed to evaluate complications including clinically relevant postoperative pancreatic fistula (CR-POPF) and oncologic outcomes in patients with malignancy. RESULTS: PSM analysis was performed based on the pancreatic fistula risk. Patients undergoing RA-MIPD were younger (RA-MIPD vs. open PD: 61.2 vs. 65.5 years, P < 0.001); however, no significant intergroup difference was observed in sex (P = 0.091) and body mass index (P = 0.281). Operation time was longer in the RA-MIPD group (361.2 vs. 305.7 min, P < 0.001); however, estimated blood loss did not significantly differ (515.6 vs. 478.0 mL, P = 0.318). Overall complication (24.7% vs. 30.9%, P = 0.178) and CR-POPF rates (6.7% vs. 6.9%, P > 0.999) were similar. The RA-MIPD group showed lower pain scores and shorter length of postoperative hospitalization (11.5 vs. 17.2 days, P < 0.001). After PSM analysis for cancer and staging among patients with malignancies, no significant intergroup difference was observed in the R0 resection rate (96.7% vs. 93.3%, P = 0.527), tumor size (2.59 vs. 2.60 cm, P = 0.954), total number of retrieved lymph nodes (17.0 vs. 16.6, P = 0.793), and 2-year survival rates (84.4% vs. 77.8%, P = 0.898). CONCLUSIONS: Compared with open PD, RA-MIPD is associated with better or at least similar early perioperative and equivalent midterm survival outcomes. RA-MIPD is safe and feasible and enables early postoperative recovery. RA-MIPD is expected to play a key role in near future.

A comparison of outcomes in patients with intracholecystic papillary neoplasms or conventional adenocarcinomas of the gallbladder.

BACKGROUND: Intracholecystic papillary neoplasm (ICPN) of the gallbladder (GB) is an exophytic intraepithelial neoplasm. This study aimed to investigate clinicopathologic findings, prognosis and recurrence patterns of patients with ICPN as compared to those patients with conventional adenocarcinoma of the gallbladder (GBC). METHODS: Patients who underwent surgical resection for suspected GB cancer between 2000 and 2018 were included. ICPN was defined as an exophytic papillary mass within the GB lumen with a size ≥1.0 cm. RESULTS: Of 607 patients, 241 patients (40%) were pathologically diagnosed with ICPN. Of the 241 patients with ICPNs, 110 (46%) were T1 or less. Following T stage-matched analysis, the rate of lymph node metastases were comparable (50 [52%] vs. 37 [49%], P = 0.581). The five-year survival rate was higher in ICPN, but after T stage-matching, they were comparable (69.1 vs. 63.2%, P = 0.171). Overall recurrence rates were also comparable, with the exception of lower peritoneal seeding in patients with ICPN. CONCLUSION: Patients with ICPN who underwent resection were more likely to have an earlier T stage. There was no significant difference in prognosis and recurrence between ICPN and conventional GBC after stage matching. Therefore, the treatment strategy for ICPN should follow the same protocols used for conventional GBC.

Adverse oncologic effects of preoperative biliary drainage on early stage ampulla of Vater cancer.

BACKGROUND: The preoperative biliary drainage (PBD) in ampulla of Vater (AoV) cancer is indiscriminately performed without logical backgrounds. This study was performed to evaluate the effect of PBD on short and long-term outcomes in AoV cancer. METHODS: 313 patients who underwent pancreaticoduodenectomy and were pathologically diagnosed as AoV cancer between January 2000 and December 2014 were reviewed. RESULTS: 167 patients (53.4%) underwent PBD: Endoscopic drainage was performed in 106 patients (33.9%) and percutaneous drainage in 61 (19.5%). The postoperative complication rate of PBD group was significantly higher than that of upfront surgery group (48.5% vs. 38.4%, p = 0.045). The 5-year disease-free survival rate (5Y-DFSR) was significantly lower in PBD group compared to upfront surgery group (53.8% vs. 74.3%, p < 0.001). Worse 5Y-DFSR of PBD group was more evident in T1/T2 stage (59.2% vs. 84.1%, p < 0.001). In multivariate analysis with T1/T2 staged patients, PBD was independently associated with worse outcome (hazard ratio 2.145 [95% confidence interval, 1.202-3.826], p = 0.010). CONCLUSION: For T1/T2 AoV cancer, PBD adversely affected the short-term postoperative complication rate as well as the long-term oncologic outcomes. Therefore, especially in patients with T1/T2 AoV cancer, routine practice of PBD should be refrained and be reserved for selected cases such as cholangitis.

Optimal stapler cartridge selection to reduce post-operative pancreatic fistula according to the pancreatic characteristics in stapler closure distal pancreatectomy.

BACKGROUND: Postoperative pancreatic fistula (POPF) is associated with potentially fatal complications, but there is lack of data on relationship between pancreas thickness, and stapler size and the POPF rate. This study aimed to suggest optimal stapler that reduces POPF rate according to the pancreas thickness. METHODS: This retrospective cohort study was conducted in two tertiary high-volume pancreas centers. 599 patients who underwent distal pancreatectomy were assessed for stump reinforcement methods, pathology findings, pancreas thickness, and cartridge used. The cartridges were grouped as I, II, III according to the closed height ≤1.5 mm, 1.8 mm, and ≥2.0 mm, respectively. RESULTS: The POPF rate increased according to the thickness. The stapler Groups I, II, and III had an overall POPF rate of 66.4% vs. 61.7% vs. 57.8%, but Group II stapler cartridge showed a significant reduction in the POPF rate than other cartridges in pancreas with thickness <13 mm (53.5% vs. 21.7% vs. 36.0%, p = 0.031). There was no significant difference between the POPF rate according to stapler groups when the pancreas was thicker than 13 mm. CONCLUSION: Thickness is the strongest risk factor in predicting POPF. Use of Group II stapler cartridge for pancreas with a thickness of <13 mm can help reduce POPF.

Robotic extended cholecystectomy in gallbladder cancer.

BACKGROUND: The application of minimally invasive surgery (MIS) in advanced gallbladder cancer (GBC) requiring extended cholecystectomy is challenging, in terms of achieving clinically safe and complete oncologic resection. Recently developed robotic systems, however, may provide advantages in overcoming difficulties faced by laparoscopic MIS. The purpose of this study is to investigate the feasibility and advantages of a robotic system to assist with extended cholecystectomy. METHODS: Patients diagnosed with clinically suspected stage T2 or above, GBC (as determined by preoperative computed tomography or ultrasonography) underwent robotic extended cholecystectomy (REC) from February 2018 to January 2020. The attached video shows the detailed procedure in the following order: the positioning of the patient and the trocars, Kocher maneuver, lymph node dissection (#8, 9, 12, 13), skeletonization of hepatoduodenal ligament, ligation of the cystic duct and liver resection. RESULTS: Of 16 patients who underwent REC, mean operation time was 198.3 min and the median estimated blood loss was 295 ml. 11 patients (68.8%) were pathologically diagnosed as stage T2 or above, and the metastatic lymph node was identified in 3 patients (18.8%). All cases had secured tumor-free resection margins, and 3 patients (18.8%) showed invasion to the hepatic parenchyma. The mean number of retrieved lymph nodes was 7.2. The median duration of hospital stay was 7 days. There were no mortality or recurrence within 90 days after the operation. CONCLUSION: This study suggests that robotic systems can be safely utilized in advanced stage GBC, facilitating oncologically sufficient lymph node dissection and rapid recovery.

Progression of Pancreatic Branch Duct Intraductal Papillary Mucinous Neoplasm Associates With Cyst Size.

BACKGROUNDS & AIMS: Most guidelines for management of patients with intraductal papillary mucinous neoplasms (IPMN) vary in proposed surveillance intervals and durations-these are usually determined based on expert opinions rather than substantial evidence. The progression of and optimal surveillance intervals for branch-duct IPMNs (BD-IPMN) has not been widely studied. We evaluated the progression of BD-IPMN under surveillance at a single center, and determined optimal follow-up intervals and duration. METHODS: We performed a retrospective analysis of 1369 patients with BD-IPMN seen at Seoul National University Hospital in Korea from January 2001 through December 2016. We included only patients whose imaging studies showed classical features of BD-IPMN, and collected data from each patient over time periods of at least 3 years. We reviewed radiologic and pathologic findings, and performed linear and binary logistic regressions to estimate cyst growth. RESULTS: The median annual growth rate of the cyst was 0.8 mm over a median follow-up time of 61 months. During surveillance, 46 patients (3.4%) underwent surgery because of disease progression after a median follow-up time (in this group) of 62 months. Worrisome features were observed in 209 patients (15.3%) during surveillance, including cyst size of 3 cm or more (n = 109, 8.0%), cyst wall thickening (n = 51, 3.7%), main pancreatic duct dilatation (n = 77, 5.6%), and mural nodule (n = 43, 3.1%). Along with annual rate of cyst growth, incidences of main pancreatic duct dilatation and mural nodules associated with the sizes of cysts at detection (P < .001). CONCLUSIONS: In a retrospective analysis of patients with BD-IPMN followed for more than 5 years, we found most cysts to be indolent, but some rapidly grew and progressed. Surveillance protocols should therefore be individualized based on initial cyst size and rate of growth.

Enhancement of lipid content and inflammatory cytokine secretion in SZ95 sebocytes by palmitic acid suggests a potential link between free fatty acids and acne aggravation.

A relationship between acne and free fatty acids (FFAs) has been suggested recently. However, the effects of FFAs on sebaceous glands are still largely unknown. At the same time, the role of FFAs during chronic inflammation is well established. Considering that FFAs are also a major component of sebum, it is likely that changes in FFA affect both the synthesis of sebum and the inflammatory response in sebaceous glands. In this study, we examined a hypothesis that FFAs increase the production of sebum and induce inflammation in the sebaceous glands. We found that treatment of SZ95 sebocytes with exogenously applied palmitic acid (PA), a major saturated FFA, induced a significant increase in intracellular lipid levels. Moreover, PA treatment also increased the expression and secretion of the proinflammatory cytokines in SZ95 sebocytes. We also found that Toll-like receptors were required for the inflammatory response triggered by PA. The results of our study strengthen the notion about the link between acne and FFAs and suggest the mechanism underlying this relationship. Our results serve as a foundation for future work that will explore the association between FFA and acne and pave way to the development of novel treatment options for acne.

Hydrazine-Selective Fluorescent Turn-On Probe Based on Ortho-Methoxy-Methyl-Ether (o-MOM) Assisted Retro-aza-Henry Type Reaction.

Hydrazine (N2H4) is one of the most widely used industrial chemicals that can be utilized as a precursor of pesticides, pharmaceutics, and rocket propellant. Due to its biological and environmental toxicity with potential health risks, various sensing tools have been developed. Among them, fluorescence-based molecular sensing systems have been highlighted due to its simple-operation, high selectivity and sensitivity, and biocompatibility. In our recent report, we disclosed a ratiometric type fluorescent probe, called HyP-1, for the detection of hydrazine, which is based on ortho-methoxy-methyl-ether (o-MOM) moiety assisted hydrazone-formation of the donor (D)-acceptor (A) type naphthaldehyde backbone. As our follow-up research, we disclose a turn-on type fluorescent probe, named HyP-2, as the next-generation hydrazine probe. The sensing rational of HyP-2 is based on the o-MOM assisted retro-aza-Henry type reaction. The dicyanovinyl moiety, commonly known as a molecular rotor, causes significant emission quenching of a fluorescent platform in aqueous media, and its cleavage with hydrazone-formation, which induces a significant fluorescence enhancement. The high selectivity and sensitivity of HyP-2 shows practical explicabilities, including real-time paper strip assay, vapor test, soil analysis, and real water assay. We believe its successful demonstrations suggest further applications into a wide variety of fields.

Characterization of Clinical Isolates of Bartonella henselae Strains, South Korea.

Bartonella henselae, a gram-negative bacterium, is a common causative agent of zoonotic infections. We report 5 culture-proven cases of B. henselae infection in South Korea. By alignment of the 16S rRNA sequences and multilocus sequencing typing analysis, we identified all isolates as B. henselae Houston-1 strain, which belongs to sequence type 1.

Influence of preoperative nutritional status on clinical outcomes after pancreatoduodenectomy.

BACKGROUND: This study investigated the clinical outcomes according to the preoperative nutritional status and to identify factors influencing long-term unrecovered nutritional status. METHODS: Data were prospectively collected from 355 patients who underwent PD between 2008 and 2014. Nutritional status was evaluated by Mini Nutrition Assessment (MNA) and patients were classified into group A (malnourished), group B (risk-of-malnutrition), or group C (well-nourished). MNA score, complications, body mass index (BMI), stool elastase level, biochemical parameters, and quality-of-life (QOL) were collected serially for 1 year. RESULTS: Preoperatively, 60 patients were categorized into group A, 224 into group B, and 71 into group C. Overall complication and pancreatic fistula were higher in groups A and B compared with group C (P = 0.003 vs P = 0.004). QOL, biochemical parameters, BMI and stool elastase level were lowest in group A preoperatively. BMI and stool elastase level remained low after surgery in all groups. Advanced age, low BMI, pre-existing diabetes mellitus, jaundice, exocrine insufficiency and adjuvant therapy were factors influencing long-term unrecovered nutritional status. CONCLUSION: Preoperative malnourished patients suffer from poor clinical outcomes. Therefore, those with risk factors of malnutrition should be monitored and vigorous efforts are needed to improve their nutrition.

Clinicopathologic and survival differences in younger patients with pancreatic ductal adenocarcinoma-A propensity score-matched comparative analysis.

BACKGROUND/OBJECTIVES: Early-onset pancreatic cancer (EOPC) is not optimally characterized because of its extremely low incidence. We investigated clinicopathologic differences between younger or older patients with pancreatic cancer, and compared their outcomes. METHODS: We enrolled 699 consecutive patients who were diagnosed with pancreatic ductal adenocarcinoma and admitted to our surgical department between 2000 and 2014. We compared demographics and clinical outcomes in patients who were younger and older than 45 years at diagnosis. We estimated 1:2 case propensity score matching (PSM) by a logistic regression model based on patients' ASA scores, postoperative AJCC stages, adjuvant chemotherapy and radiotherapy. RESULTS: At diagnosis 34 patients (4.9%) were younger than 45 years. After PSM, tested variables and median survival periods were not significantly different between two groups. Some 441 patients (63.1%) suffered postoperative recurrence, but did not significantly differ by age for local (14.7 vs. 18.5%, P = 0.658) or systemic recurrence (70.6 vs. 54.4%, P = 0.077). There was a significant difference of disease-free survival (DFS) after PSM (8.9 vs. 29.3%, P = 0.011). CONCLUSIONS: Five-year OS and recurrence patterns did not significantly differ between two groups. But five-year DFS was significantly worse after PSM and systemic recurrence tended to be more frequent in the younger group.

Prediction of Pancreatic Fistula After Distal Pancreatectomy Based on Cross-Sectional Images.

BACKGROUND: Postoperative pancreatic fistula (POPF) is one of the most common and clinically relevant complications after distal pancreatectomy (DP), occurring in 5-40% of patients. Determining risk factors for this complication may aid in its prevention. This study sought to predict the development of POPF after DP preoperatively and objectively based on radiologic findings. METHODS: This study included 60 patients who underwent DP using a stapler for pancreatic division between June 2011 and January 2013. Fatty infiltration, apparent diffusion coefficients (ADC) on preoperative MRI, pathologic fat, and fibrosis were measured. Pancreatic thickness and cross-sectional area of the pancreas stump on CT scan were also measured. RESULTS: Mean patient age was 60.5 years, 26 patients (46.3%) had pancreatic cancer and 20 (33.3%) underwent laparoscopic surgery. Clinically relevant POPF was observed in 12 patients (20.0%). Linear regression analysis showed a significant correlation between fat quantification on MRI and pathologic fat (pathologic fat = 1.978 × MR fat -6.393, p < 0.001, R 2 = 0.777). Univariate analysis showed that ≤8% fat on MRI (p = 0.040), ≤5% pathologic fat (p = 0.002), ADC ≤ 1.3 × 10-3 mm2/s (p = 0.020), thicker pancreas (p = 0.007), and wider cross-sectional area of the pancreas (p = 0.013) were significantly associated with clinically relevant POPF after DP. Multivariate analysis revealed that pancreas thickness >17.6 mm [odds ratio (OR) 6.532, p = 0.064] and cross-sectional area >377 mm2 (OR 12.676, p = 0.052) were marginally related to clinically relevant POPF. CONCLUSIONS: Pancreatic thickness and cross-sectional area of the transected surface of the pancreas are marginally significant risk factors for POPF development after DP. Measuring pancreatic thickness and cross-sectional area can be a promising tool for the preoperative prediction of POPF.

The crucial role of IL-22 and its receptor in thymus and activation regulated chemokine production and T-cell migration by house dust mite extract.

House dust mite (HDM) is known as one of the factors that causes atopic dermatitis (AD). Interleukin (IL)-22 and thymus and activation regulated chemokine (TARC) are related to skin inflammatory disease and highly expressed in AD lesions. However, the effects of HDM on IL-22 production in T cells and on TARC production and IL-22Rα receptor expression in keratinocytes are unknown. To identify the role of HDM in keratinocytes and T cells, we investigated IL-22Rα expression and TARC production in the human keratinocyte cell line HaCaT and IL-22 production in T cells treated with HDM extract as well as their roles in HDM-induced skin inflammation. HDM extract not only increased IL-22Rα expression and TARC production in HaCaT but also enhanced IL-22, tumor necrosis factor (TNF)-α and interferon (IFN)-γ production in T cells. The HDM extract-induced IL-22 from T cells significantly increased the production of IL-1α, IL-6 and TARC in HaCaT cells. In addition, we found that TARC produced in HDM extract-treated HaCaT induced T-cell recruitment. These results suggest that there is a direct involvement of HDM extract-induced IL-22 in TARC production and T-cell migration. Taken together, TARC production in HaCaT through the interaction between IL-22 and IL-22Rα facilitates T-cell migration. These data show one of the reasons for inflammation in the skin lesions of AD patients.

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.

Generation of protective immunity against Orientia tsutsugamushi infection by immunization with a zinc oxide nanoparticle combined with ScaA antigen.

BACKGROUND: Zinc oxide nanoparticle (ZNP) has been applied in various biomedical fields. Here, we investigated the usage of ZNP as an antigen carrier for vaccine development by combining a high affinity peptide to ZNP. RESULTS: A novel zinc oxide-binding peptide (ZBP), FPYPGGDA, with high affinity to ZNP (K a  = 2.26 × 106 M-1) was isolated from a random peptide library and fused with a bacterial antigen, ScaA of Orientia tsutsugamushi, the causative agent of scrub typhus. The ZNP/ZBP-ScaA complex was efficiently phagocytosed by a dendritic cell line, DC2.4, in vitro and significantly enhanced anti-ScaA antibody responses in vivo compared to control groups. In addition, immunization with the ZNP/ZBP-ScaA complex promoted the generation of IFN-γ-secreting T cells in an antigen-dependent manner. Finally, we observed that ZNP/ZBP-ScaA immunization provided protective immunity against lethal challenge of O. tsutsugamushi, indicating that ZNP can be used as a potent adjuvant when complexed with ZBP-conjugated antigen. CONCLUSIONS: ZNPs possess good adjuvant potential as a vaccine carrier when combined with an antigen having a high affinity to ZNP. When complexed with ZBP-ScaA antigen, ZNPs could induce strong antibody responses as well as protective immunity against lethal challenges of O. tsutsugamushi. Therefore, application of ZNPs combined with a specific soluble antigen could be a promising strategy as a novel vaccine carrier system.