Immune modulation of i.v. immunoglobulin in women with reproductive failure.

BACKGROUND: The mechanism of maternal immune tolerance of the semi-allogenic fetus has been explored extensively. The immune reaction to defend from invasion by pathogenic microorganisms should be maintained during pregnancy. An imbalance between the immune tolerance to the fetus and immune activation to the pathogenic organisms is associated with poor pregnancy outcomes. This emphasizes that the immune mechanism of successful reproduction is not just immune suppression, but adequate immune modulation. METHODS: In this review, the action of i.v. immunoglobulin G (IVIg) on the immune system and its efficacy in reproductive failure (RF) was summarized. Also suggested is the indication of IVIg therapy for women with RF. MAIN FINDINGS RESULTS: Based on the mechanism of the immune regulation of IVIg and following confirmation of the immune modulation effects of it in various aberrant immune parameters in patients with RF, it is obvious that IVIg is effective in recurrent pregnancy losses and repeated implantation failures with immunologic disturbances. CONCLUSION: The authors recommend IVIg therapy in patients with RF with aberrant cellular immunologic parameters, including a high natural killer cell proportion and its cytotoxicity or elevated T helper 1 to T helper 2 ratio, based on each clinic's cut-off values. Further clinical studies about the safety of IVIg in the fetus and its efficacy in other immunologic abnormalities of RF are needed.

Short-term clinical outcomes for 100 consecutive cases of laparoscopic pylorus-preserving pancreatoduodenectomy: improvement with surgical experience.

BACKGROUND: Few reports describe the use of laparoscopic pylorus-preserving pancreaticoduodenectomy (LPPPD) in centers with experience using this technique. In addition, the clinical outcomes of this procedure remain undetermined. METHODS: In the current study, 100 patients with benign or malignant lesions in the pancreatic head underwent LPPPD between May 2007 and December 2011. The overall clinical outcomes and changes in these outcomes during the surgeon learning period were analyzed to assess the feasibility and safety of this procedure. RESULTS: Pathologic examination of the pancreas confirmed intraductal papillary mucinous neoplasms in 37 patients, solid pseudopapillary tumors in 17 patients, neuroendocrine tumors in 15 patients, serous cystic neoplasms in seven patients, pancreatic ductal adenocarcinomas in seven patients, ampulla of Vater tumors and duodenal gastrointestinal stromal tumors in five patients, and other disease in seven patients. The median operative time was 7.9 h, which decreased with accumulating experience of the surgeon using this procedure, from 9.8 h for the first 33 cases to 6.6 h for the last 34 cases. Complications developed in 25% of the patients, including six cases (6%) with significant pancreatic fistula [International Study Group on Pancreatic Fistula (ISGPF) grade B]. The complication rate decreased from 33.3% for the first 33 cases to 17.6% for the last 34 cases. The mean hospital stay was 14 days, which also decreased from 20.4 days for the first 33 cases to 11.5 days for the last 34 cases. For the 12 patients in the study cohort with invasive malignant disease, the median tumor size was 2.8 cm, and the median number of lymph nodes harvested was 13. All the patients had margin-negative R0 resections. CONCLUSION: The LPPPD procedure is technically safe and feasible, with an acceptable rate of morbidity and other clinical outcomes for benign and malignant diseases. Clinical outcomes can be improved once a learning curve has been overcome.

Clinical role of 18F-FDG PET-CT in suspected and potentially operable cholangiocarcinoma: a prospective study compared with conventional imaging.

OBJECTIVES: This study was conducted to evaluate the clinical role of integrated positron emission and computed tomography (PET-CT) in patients with suspected and potentially operable cholangiocarcinoma. METHODS: Between October 2005 and May 2007, 123 patients with suspected cholangiocarcinoma were enrolled in this study after diagnostic workup, including biliary dynamic computed tomography (CT) and magnetic resonance imaging/magnetic resonance cholangiopancreatography (MRI/MRCP) with magnetic resonance (MR) angiography. Patients with overt unresectable cholangiocarcinoma or gallbladder cancer diagnosed via conventional imaging were excluded. Consecutively, each enrolled patient underwent PET-CT. Data were prospectively collected and analyzed in comparison with CT and MRI/MRCP. RESULTS: The overall values for sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of PET-CT in primary tumor detection were 84.0%, 79.3%, 92.9%, 60.5%, and 82.9%, respectively. PET-CT demonstrated no statistically significant advantage over CT and MRI/MRCP in the diagnosis of primary tumor. According to different morphologic characteristics of cholangiocarcinoma, PET-CT showed no significant difference in detecting those of mass-forming, periductal-infiltrating, and intraductal-growing types. PET-CT revealed significantly higher accuracy over CT in the diagnosis of regional lymph nodes metastases (75.9%vs 60.9%, P= 0.004) and distant metastases (88.3%vs 78.7%, P= 0.004). Additional use of PET-CT for assessing resectability correctly showed different results from those determined by conventional imaging in 15 (15.9%) of 94 patients with cholangiocarcinoma. CONCLUSIONS: PET-CT improved the accuracy of preoperative staging in patients with cholangiocarcinoma planning to undergo curative resection. Thus, PET-CT had an important clinical impact on the selection of proper treatment.

Hepatitis B virus infection and intrahepatic cholangiocarcinoma in Korea: a case-control study.

OBJECTIVES: There is a wide variation in risk factors for intrahepatic cholangiocarcinoma (ICC) among various populations. Several studies have suggested that hepatitis C virus (HCV) infection may play a role in the development of ICC, whereas the role of hepatitis B virus (HBV) infection is less clear. METHODS: To determine whether HBV or HCV infection is a risk factor of ICC, we compared baseline demographic and clinical factors in 622 patients diagnosed between 2000 and 2004 with histologically confirmed ICC and 2,488 healthy controls, matched 4:1 with ICC patients for sex and year of birth. RESULTS: HBV infection (odds ratio [OR] 2.3, 95% confidence interval [CI] 1.6-3.3), but not HCV infection, was significantly related to ICC. Other significant risk factors for ICC included liver cirrhosis (OR 13.6), heavy alcohol consumption (OR 6.6), diabetes (OR 3.2), Clonorchis sinensis infection (OR 13.6), hepatolithiasis (OR 50.0), and choledochal cysts (OR 10.7). CONCLUSIONS: Our results indicate that development of ICC seems to be more closely related to HBV infection than to HCV infection in Korea, where both HBV and ICC are endemic.

Comparative analysis of clinical outcomes for laparoscopic distal pancreatic resection and open distal pancreatic resection at a single institution.

BACKGROUND: Despite recent advances in laparoscopic pancreatic surgery, few studies have compared laparoscopic distal pancreatic resection (LDPR) with open distal pancreatic resection (ODPR). This study aimed to compare clinical outcomes for LDPR and ODPR performed at a single institution. METHODS: For this study, 93 patients with benign pancreatic disease underwent LDPR, and 35 patients with benign pancreatic disease underwent ODPR. Patient demographic characteristics, operative times, perioperative complications, length of hospital stay, and return to normal diet were compared retrospectively between the two groups. RESULTS: The LDPR and ODPR groups had the same demographic characteristics. The median operative time was 195 min in the LDPR group and 190 min in the ODPR group (p>0.05). The rate of spleen preservation was higher in the LDPR group (40.8%) than in the ODPR group (5.7%) (p<0.05) No operative mortality occurred in either group. The overall complication rate was 24.7% in the LDPR group and 29% in the ODPR group (p>0.05). The rate of pancreas-related complications was 11.8% in the LDPR group and 17.2% in the ODPR group (p>0.05). Pancreatic fistula developed in 8.6% of the LDPR group and in 14.3% of the ODPR group (p>0.05). Bowel movement return to normal and resumption of normal diet were achieved 2.8+/-1.3 days after the operation in the LDPR group and 4.5+/-1.6 days after the operation in the ODPR group (p<0.05). The median duration of hospital stay was 10 days for the LDPR group, which was significantly shorter than the 16 days for the ODPR group (p<0.01). CONCLUSION: The use of LDPR for benign lesions of the distal pancreas is feasible and safe. The LDPR procedure is associated with operative times and complication rates similar to those for ODPR, but LDPR has the advantages of an earlier return to normal bowel movements and normal diet and shorter hospital stays than ODPR.

Trophoblasts regulate natural killer cells via control of interleukin-15 receptor signaling.

PROBLEM: Trophoblasts are known to decrease natural killer (NK) cell cytotoxicity. However, little is known about the interaction between trophoblasts and NK cells during pregnancy. Interleukin-15 (IL-15) is essential for priming NK cells and maximizing their effector functions. We investigated whether trophoblasts regulate NK cell activation via IL-15/IL-2 receptor and its signaling pathways. METHOD OF STUDY: Natural killer-92 cells were primed with human first-trimester trophoblast cells (Sw.71) conditioned medium (CM) and co-cultured with K562 cells. Flow cytometry, Western blot analysis, and real-time PCR were performed to assess NK cell cytotoxicity, IL-15/IL-2 receptor expression, phosphorylation of STAT5 and MAPKs, and mRNA expression of IL-15-related genes. RESULTS: Natural killer-92 cells incubated with Sw.71 CM showed reduced cytotoxicity and IL-15-mediated proliferation, and expression of IL-15/IL-2 receptor subunits. STAT5 phosphorylation, EOMES and T-bet mRNA expressions, and ERK/JNK pathways of NK 92 cells were suppressed by Sw.71 CM. Productions of perforin, granzyme B, and IFN-γ were also downregulated. CONCLUSION: Trophoblasts regulate human NK cell functions via suppression of IL-15/IL-2 receptor expression, transcription factors, and ERK/JNK pathways.

Design and construction of a double inversion recombination switch for heritable sequential genetic memory.

BACKGROUND: Inversion recombination elements present unique opportunities for computing and information encoding in biological systems. They provide distinct binary states that are encoded into the DNA sequence itself, allowing us to overcome limitations posed by other biological memory or logic gate systems. Further, it is in theory possible to create complex sequential logics by careful positioning of recombinase recognition sites in the sequence. METHODOLOGY/PRINCIPAL FINDINGS: In this work, we describe the design and synthesis of an inversion switch using the fim and hin inversion recombination systems to create a heritable sequential memory switch. We have integrated the two inversion systems in an overlapping manner, creating a switch that can have multiple states. The switch is capable of transitioning from state to state in a manner analogous to a finite state machine, while encoding the state information into DNA. This switch does not require protein expression to maintain its state, and "remembers" its state even upon cell death. We were able to demonstrate transition into three out of the five possible states showing the feasibility of such a switch. CONCLUSIONS/SIGNIFICANCE: We demonstrate that a heritable memory system that encodes its state into DNA is possible, and that inversion recombination system could be a starting point for more complex memory circuits. Although the circuit did not fully behave as expected, we showed that a multi-state, temporal memory is achievable.