Late anastomotic leakage after low anterior resection in rectal cancer patients: clinical characteristics and predisposing factors.

AIM: The purpose was to examine the clinical characteristics and predisposing factors of late anastomotic leakage following low anterior resection for rectal cancer. METHOD: We retrospectively evaluated the clinicopathological features of patients who experienced anastomotic leakage after low anterior resection for rectal cancer. Patients were divided into two groups according to the time to leakage: early leakage (within 30 days postoperatively) and late leakage (after 30 days postoperatively). Clinicopathological characteristics were compared between the two groups. RESULTS: Anastomotic leakage occurred in 141 patients. Anastomotic leakage was diagnosed at a median of 17 (range 0-886) days postoperatively; 85 (60.3%) and 56 (39.7%) were categorized as the early and late leakage groups, respectively. Radiotherapy (hazard ratio 5.007; 95% CI 2.208-11.354; P < 0.0001) was the only significant independent predisposing factor for late leakage. Diverting stoma did not protect against late leakage. The late leakage group more frequently had the fistula type (46.4% vs. 10.6%; P < 0.001) and less frequently needed laparotomy (55.4% vs. 78.8%; P = 0.001). The rate of long-term stoma over 1 year was greater in the late leakage than the early leakage group (51.8% vs. 29.4%; P = 0.009). CONCLUSION: Late anastomotic leakages that develop after 30 days following low anterior resection are not uncommon and may be associated with the use of radiotherapy. Late leakage should be a different entity from early leakage in terms of the type of leakage, methods of management and subsequent sequelae.

Clinical implications of mucinous components correlated with microsatellite instability in patients with colorectal cancer.

AIM: Colorectal cancer (CRC) with microsatellite instability (MSI) is characterized by frequent poor differentiation or mucinous histology. The purpose of this study was to evaluate the association of MSI with clinicopathological features and the oncological outcome in patients with a mucinous component. METHOD: CRC tissue samples were analysed for histology and MSI. Patients were grouped according to the mucinous content of the tumour, as follows: > 50%, mucinous adenocarcinoma (MA); ≤ 50%, adenocarcinoma with mucinous component (AMC); none, nonmucinous adenocarcinoma (NMA). Clinicopathological parameters and survival were compared between patient groups. RESULTS: Of 2025 patients, 84 (4%) had MA and 124 (6%) had AMC. In addition, 202 (10%) had MSI. Patients with MA and AMC tended to have a younger age of onset, right-colon predilection, large-sized tumour and high frequency of MSI compared with those with NMA (P < 0.001). MA and AMC patients with MSI showed a trend towards right-colon predilection and infrequent lymph-node metastasis compared with those with microsatellite stability (MSS; P = 0.005-0.03). There were no survival differences between the three groups, but patients with MSI-MA demonstrated lower 4-year recurrence and better overall survival rates than those with MSS-MA (P = 0.018 and P = 0.046, respectively). CONCLUSION: Clinicopathological features of AMC and MA were similar and closely associated with MSI status. Although the prognoses of AMC and MA were no different from that of NMA, survival of patients with an MSI-MA tumour was significantly better than for those with MSS-MA tumours.

Feasibility of proposed single-nucleotide polymorphisms as predictive markers for targeted regimens in metastatic colorectal cancer.

BACKGROUND: Surrogate biomarkers for metastatic colorectal cancer (mCRC) are urgently needed to achieve the best outcomes for targeted therapy. METHODS: A clinical association analysis was performed to examine the three single-nucleotide polymorphisms (SNPs) that were previously proposed as markers of chemosensitivity to the cetuximab (124 patients) and bevacizumab regimens (100 patients) in mCRC patients. In addition, biological correlations were examined for the candidate SNPs in terms of their regulatory pathway. RESULTS: For cetuximab regimens, patients homozygous for the wild-type alleles (GG) of LIFR rs3729740 exhibited a 1.9 times greater overall response rate (ORR) and 1.4 months longer progression-free survival (PFS) than those homozygous or heterozygous for the mutant allele (GA and AA; P=0.022 and 0.027, respectively). For bevacizumab regimens, patients homozygous for the minor alleles (TT) of ANXA11 rs1049550 exhibited an ORR twice as high as those homozygous or heterozygous for the ancestral allele (CC and CT; P=0.031). Overall response rate gain was achieved up to 10% in patients with wild-type LIFR rs3729740 patients either with wild-type KRAS or skin toxicity (P=0.001) respectively. Specifically in clones treated with cetuximab and bevacizumab regimens, active p-ERK and MMP-9 expressions were significantly reduced in clones expressing wild-type LIFR rs3729740 (P=0.044) and in those expressing minor-type ANXA11 rs1049550 (P=0.007), respectively. CONCLUSION: LIFR rs3729740 and possibly ANXA11 rs1049550 may be useful as biomarkers for predicting whether mCRC patients are sensitive to relevant target regimens, although further validation in large cohorts is needed.

Molecular response of human cervical and lumbar nucleus pulposus cells from degenerated discs following cytokine treatment.

We investigated the molecular response of degenerated human cervical and lumbar nucleus pulposus (NP) cells following cytokine treatment. Degenerated cervical and lumbar discs (8 each) were obtained from patients who underwent discectomy for degenerative disc disease; NP cells were isolated and cultured. The mRNA expressions of aggrecan, alkaline phosphatase, type I collagen, type II collagen, osteocalcin, and Sox9 in the 2 groups were compared by real-time PCR, before and following treatment with rhBMP-2 and TGF-ß1. Immunoreactivity was analyzed to check protein activity. Type I collagen expression was significantly higher in cervical compared with that in lumbar disc cells. The mRNA expression was significantly increased after rhBMP-2 and TGF-ß1 treatment. After rhBMP-2 treatment, mRNA expression of type I and II collagens increased significantly more in cervical than in lumbar NP cells. Following TGF-ß1 treatment, the increase in mRNA expression was not significantly different between cervical and lumbar disc cells. Protein immunoreactivity, before and after cytokine treatment was similar to mRNA expression data. The matrix-related gene expression of cervical and lumbar NP after rhBMP-2 and TGF-ß1 treatment increased similarly, with the exception of collagen expression.

Preoperative inflammation is a prognostic factor for gallbladder carcinoma.

BACKGROUND: Inflammation frequently accompanies gallbladder carcinoma (GBC), but its impact on outcome is unclear. The present study investigated the impact of concomitant inflammation on survival of patients with GBC. METHODS: All patients undergoing surgery for GBC between October 2003 and May 2009 were identified retrospectively from a prospectively collected database. Patients were classified according to whether preoperative inflammation was present (65 patients) or not (23). RESULTS: A total of 88 patients were enrolled. There were no differences in sex, mean age, tumour node metastasis (TNM) stage and radicality of resection between the two groups. The overall 3-year survival rate was lower in patients with preoperative inflammation than in those without (33 versus 73 per cent; P = 0·001). In univariable analysis, preoperative inflammation, T, N and M category, TNM stage, radicality of surgery and tumour differentiation were significant prognostic factors. The presence of preoperative inflammation (hazard ratio (HR) 2·38, 95 per cent confidence interval 1·04 to 5·43), lymph node metastases (HR 5·23, 1·05 to 26·09) and R1 or R2 resection (HR 3·77, 1·47 to 9·72) were independent prognostic factors for poor survival. CONCLUSION: The presence of preoperative inflammation is an independent prognostic factor for poor survival in patients with GBC.

Validation of the seventh edition of the American Joint Committee on Cancer tumor-node-metastasis (AJCC TNM) staging in patients with stage II and stage III colorectal carcinoma: analysis of 2511 cases from a medical centre in Korea.

AIM: The sixth and seventh editions of the American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) system for patients with stage II and stage III colorectal carcinoma (AJCC-6 and AJCC-7) were compared. METHOD: Between 2000 and 2007, 2511 stage II/III colorectal carcinoma patients received primary surgical resection at the Asan Medical Center (Seoul, Korea). All patients were staged using AJCC-6 and AJCC-7 TNM systems. Patients with synchronous or other cancers, those given preoperative chemotherapy or radiotherapy and those in whom fewer than 12 lymph nodes were resected, were excluded. Overall survival (OS) and disease-free survival (DFS) were compared. RESULTS: Of 2511 patients, 255 (10.2%) had different stages in the AJCC-6 and AJCC-7. For the AJCC-7, the 5-year OS by stage was 94.2% for stage IIA, 88.8% for stage IIB, 83.5% for stage IIC, 91.8% for stage IIIA, 81.8% for stage IIIB and 72.0% for stage IIIC. The OS and the DFS were not significantly different for the new substages IIB (n = 57) and IIC (n = 34) (P = 0.34 and P = 0.87, respectively). For the 187 patients with stage T3N2a cancer, the OS and the DFS were significantly different from stage IIIB other than T3N2a (P = 0.008 and P = 0.01, respectively) and there were no statistically significant differences in OS between the T3N2a group and the IIIC group (P = 0.46). CONCLUSION: The study indicates that AJCC-7 has better prognostic validity than AJCC-6 for staging of patients with stage II and stage III colorectal carcinoma.

Patency of splenic vessels after laparoscopic spleen and splenic vessel-preserving distal pancreatectomy.

BACKGROUND: This study evaluated the short- and long-term patency of preserved splenic vessels after laparoscopic spleen-preserving distal pancreatectomy (SPDP) with preservation of the splenic vessels. METHODS: This single-centre retrospective study included all patients who had undergone splenic vessel-preserving laparoscopic SPDP between 2004 and 2007. The patency of the splenic vessels was assessed by abdominal computed tomography and classified into three grades according to the degree of stenosis. RESULTS: Twenty-two patients were included. The preoperative patency of the splenic artery and vein was normal in 20 and 19 patients respectively. Normal patency of the splenic artery and vein was observed in 16 and five patients respectively within 1 month of surgery, and in 19 and nine patients 6 months or more after operation. Nine of ten patients with complete splenic vein occlusion developed a collateral circulation in the late postoperative phase. Splenic perfusion was well preserved in all patients. CONCLUSION: Splenic vessel-preserving laparoscopic SPDP has the short-term benefit of good perfusion to the spleen. In the long term, there is a risk of left-sided portal hypertension if the splenic vein becomes occluded after surgery. (c) 2009 British Journal of Surgery Society Ltd.

Recollapse of previous vertebral compression fracture after percutaneous vertebroplasty.

UNLABELLED: This study was undertaken to investigate the incidence rate, characteristics, and predisposing factors associated with recollapse of the same vertebrae after percutaneous vertebroplasty (PVP). Recollapse of the same vertebra after PVP is the one of the complications of the procedure, and the incidence rate in our study was 3.21%. The most important predisposing factor was pre-operative osteonecrosis. Recollapse was not related to trauma. INTRODUCTION: PVP using polymethylmethacrylate has become a popular treatment for osteoporotic vertebral compression fracture. Recollapse of the same vertebrae after PVP has rarely been reported. This study was undertaken to investigate the incidence, characteristics, and predisposing factors associated with recollapse of the same vertebrae after PVP. METHODS: Eleven patients (seven females and four males; mean age, 69.91 +/- 5.49 years), out of a total of 343 patients, developed recollapse of the same vertebra after PVP. The 11 patients who developed recollapse comprised the "recollapse group", while the remaining 332 patients comprised the "well-maintained group". RESULTS: Pre-operative magnetic resonance imaging revealed that the incidence of osteonecrosis was significantly higher in the recollapse group than the well-maintained group (p < 0.05). The degree of re-expansion of the compressed vertebral body after PVP was significantly higher in the recollapse group than in the well-maintained group (p < 0.05). CONCLUSIONS: The most important predisposing factor for recollapse was pre-operative osteonecrosis. Recollapse was not related to trauma. Osteoporotic vertebral compression fracture with osteonecrosis or pseudoarthrosis has been regarded as a relative indication for PVP; however, the findings of this study suggest that this disease category may be a relative contraindication for PVP.

Metabolic syndrome and quality of life (QOL) using generalised and obesity-specific QOL scales.

OBJECTIVES: We investigated the association between metabolic syndrome (MS) and health-related quality of life (HRQOL) assessed using generalised and obesity-specific QOL instruments. METHODS: We recruited 456 outpatients [age: 19-81 years, body mass index (BMI): 16.3-36.7 kg/m2] in the primary care division from 12 general hospitals in Korea. HRQOL was measured using EuroQol comprising the health states descriptive system (EQ-5D) and visual analogue scale (EQ-VAS) as a general instrument. The Korean Obesity-related QOL scale (KOQOL) composed of six domains was used as a disease-specific QOL instrument. MS was defined on the basis of International Diabetes Federation (IDF) criteria with Korean-specific waist circumference cutoffs (men: 90 cm, women: 85 cm). RESULTS: Subjects with MS displayed significantly higher impairment of EQ-5D and KOQOL. Binary logistic regression analysis of MS patients with controls for age, gender, smoking, alcohol, exercise, education, income, marital status and medication history disclosed odds ratio (OR) values of 2.13 (1.33-3.41) for impaired total KOQOL, 2.07 (1.31-3.27) for impaired physical health, 1.63 (1.03-2.60) for impaired work-related health, 2.42 (1.45-4.04) for impaired routine life, 2.08 (1.27-3.40) for impaired sexual life and 2.56 (1.59-4.11) for diet distress. Among the EQ-5D dimensions, only pain/discomfort displayed a significantly increased OR of 1.60 (1.01-2.56) in MS group. CONCLUSIONS: Subjects with MS displayed a significantly impaired HRQOL compared with those without MS. MS and HRQOL were more strongly associated in obesity-specific QOL than in generalised QOL.

Predictors of persistent airway stenosis in patients with endobronchial tuberculosis.

SETTING: The university and municipal hospitals in Seoul, Korea. OBJECTIVE: To evaluate the predictors of persistent airway stenosis following anti-tuberculosis chemotherapy in patients with endobronchial tuberculosis (TB). DESIGN: Diagnosis of TB was confirmed by microbiology or histopathology. Bronchoscopic examinations revealed that patients had endobronchial lesions compatible with endobronchial TB. Study subjects had at least one follow-up bronchoscopy to evaluate their treatment response. Treatment response was determined by changes in the degree or extent of airway stenosis between the first and last bronchoscopic examinations. RESULTS: Sixty-seven subjects were recruited retrospectively from Seoul National University Hospital and Seoul National University Boramae Hospital. Persistent bronchostenosis occurred in 41.8% of the patients. In multivariate regression analysis, age >45 years (OR 3.65), pure or combined fibrostenotic subtype (OR 5.54) and duration from onset of chief complaint to the initiation of anti-tuberculosis chemotherapy >90 days (OR 5.98) were identified as independent predictors of persistent airway stenosis. Oral corticosteroids (prednisolone equivalent >or=30 mg/d) did not reduce the frequency of persistent airway stenosis. CONCLUSION: Early diagnosis and early administration of anti-tuberculosis chemotherapy before involvement of the deeper airways is important to prevent the development of unwanted sequelae of bronchostenosis.

Clinical outcomes compared between laparoscopic and open distal pancreatectomy.

BACKGROUND: Laparoscopic surgery for pancreatic disease has gained increasing popularity. A laparoscopic distal pancreatectomy is technically simple and has been adopted as the preferred method in many centers. However, there is limited information on the outcomes of the laparoscopic surgery compared with open surgery. Therefore, this study aimed to investigate the clinical outcomes of laparoscopic distal pancreatectomy and to evaluate its efficacy compared with open distal pancreatectomy. METHODS: From February 1995 to March 2006, 31 patients underwent laparoscopic distal pancreatectomy, and 167 patients underwent open distal pancreatectomy at Seoul National University Hospital and Bundang Seoul National University Hospital. A case-control design was used with 2:1 matching to compare laparoscopic surgery with open surgery. Among 167 patients who underwent open distal pancreatectomy, 62 patients whose age, gender, and pathology were similar to those of patients who underwent laparoscopic surgery were selected for this study. The operation time, intraoperative transfusion requirements, duration of postoperative hospitalization, complications, mortality, recurrence, and hospital charges were analyzed. RESULTS: There were no significant differences in operation time, rate of intraoperative transfusions, complications, recurrence, or mortality between the two groups. Laparoscopic distal pancreatectomy was associated with a statistically significant shorter hospital stay (11.5 days vs 13.5 days; p = 0.049), but with more expensive hospital charges than open distal pancreatectomy (p < 0.01). CONCLUSION: Laparoscopic distal pancreatectomy is a clinically safe and effective procedure for benign and borderline pancreatic tumors.

AAV-GAD gene for rat models of neuropathic pain and Parkinson's disease.

The introduction of therapeutic genes to neurons by genetic modification has potential as an effective treatment for CNS disorders for all that a successful clinical application has not yet been fully implemented. In this paper, we will discussed the role of AAV vectors with the GAD65 gene for animal models of PD and neuropathic pain. AAV vector is one of the most attractive gene delivery vehicles for direct introduction of therapeutic genes into the CNS in the treatment of neurological diseases. GAD65 is present as a membrane-associated form in synapses and is primarily involved in producing synaptic gamma-aminobutyric acid (GABA) for vesicular release. We constructed rAAV-GAD65 expressing rat GAD65 and demonstrated that rat Parkinsonian symptoms can be significantly improved concomitantly with the production of GAD65. We also demonstrated rAAV-GAD65 as a successful gene delivery vehicle in a chronic pain model by administrating rAAV-GAD65 to DRGs because GABA driven by GAD is a major inhibitory neurotransmitter in the dorsal horn of the spinal cord and also plays an important role in the ventral horn. We believe that AAV vectors can be excellent candidates for gene therapy of neurological diseases.

Gamma knife radiosurgery for medically refractory idiopathic trigeminal neuralgia.

Gamma knife radiosurgery (GKS) has been generally considered as a viable therapeutic option for the management of medically refractory idiopathic trigeminal neuralgia (TN). We reviewed our experience with GKS in patients with TN. Between Feb 1996 and May 2006, 77 patients with medical refractory idiopathic TN were treated using GKS. Thirty-six patients who had undergone other previous procedures, previous GKS, or had brain stem lesion, atypical symptoms, were excluded from this study. Pain improvement was achieved in 38 of the patients with TN (pain response rate 92.7%). Twenty-three patients were pain free and 15 had reduced pain. There were no serious complications. We think that GKS is an effective treatment option for patients with medical refractory idiopathic TN.

Pre-operative embolisation of internal carotid artery branches and pial vessels in hypervascular brain tumours.

BACKGROUND: Pre-operative embolisation is an effective method used to reduce intra-operative bleeding and operative difficulty in hypervascular brain tumour surgery. However, embolisation of the internal carotid artery (ICA) and pial tumour feeding branches has certain limitations. METHODS: From March 2000 to November 2006, 8 patients underwent superselective embolisation for hypervascular brain tumour. Seven tumours were extra-axial (6 meningiomas, 1 solitary fibrous tumour) and 1 was intra-axial (metastatic hepatocellular carcinoma). RESULTS: In all patients, feeding vessels from ICA branches or pial arteries were successfully embolised using superselective microcatheterisation. A provocative test was applied in 4 patients who had tumours adjacent to the motor cortex. Angiographic devascularisation was slight to extensive. Mean devascularisation on post-embolisation MRI ranged from 40 to 80% (mean 63.8%). One patient (12.5%) suffered an embolisation-related complication (loss of choroidal brush), but was not clinically worse because of the pre-existing blindness. CONCLUSIONS: Superselective embolisation of ICA branches or pial vessels should be performed if several conditions are met, especially angiographic findings, pre-existing neurologic deficits, provocative test, and technical feasibility. If the ICA embolisation for hypervascular tumour is successfully achieved, the bleeding loss and operative risk can be reduced.

Data on unstable charge/discharge behavior of composite anode composed of Sn compound and multi-walled carbon nanotube.

This data is related to the article entitled "Effect of Composite Structure on Capacity Instability of SnO2-Coated Multiwalled Carbon Nanotube Composite Anode" (Kim et al., 2018) [1]. This data provides the information about capacitance instability of a composite anode material based on multiwalled carbon nanotube (MWCNT) coated with crystalline and amorphous SnO2 and Sn on the inner and outer walls of MWCNT fabricated by a simple wet synthesis method.

Nanomatrix Coated Stent Enhances Endothelialization but Reduces Platelet, Smooth Muscle Cell, and Monocyte Adhesion under Physiologic Conditions.

Cardiovascular disease is presently the number one cause of death worldwide. Current stents used to treat cardiovascular disease have a litany of unacceptable shortcomings: adverse clinical events including restenosis, neointimal hyperplasia, thrombosis, inflammation, and poor re-endothelialization. We have developed a biocompatible, multifunctional, peptide amphiphile-based nanomatrix coating for stents. In this study, we evaluated the ability of the nanomatrix coated stent to simultaneously address the issues facing current stents under physiological flow conditions in vitro. We found that the nanomatrix coated stent could increase endothelial cell migration, adhesion, and proliferation (potential for re-endothelialization), discourage smooth muscle cell migration and adhesion (potential to reduce neointimal hyperplasia and restenosis), and decrease both platelet activation and adhesion (potential to prevent thrombosis) as well as monocyte adhesion (potential to attenuate inflammatory responses) under physiological flow conditions in vitro. These promising results demonstrate the potential clinical utility of this nanomatrix stent coating, and highlight the importance of biocompatibility, multifunctionality, and bioactivity in cardiovascular device design.

Effect of maternally derived antibody on sequential infection with highly virulent bursal disease virus in newly hatched broilers.

Maternally derived antibodies (MDAs) are important for protection against very virulent infectious bursal disease virus (vvIBDV). In this study, 5-day-old commercial broilers with non-uniform MDA titers (with a coefficient of variation of 50%) were challenged with vvIBDV and given free contact with each other during a 2-week period. The chicks were assigned to four MDA-titer subgroups, GI-1 (very low MDA), GI-2 (low MDA), GI-3 (medium MDA), and GI-4 (high MDA). Transient symptoms of infection were observed in 35.7% of challenged birds. Body weight gain was significantly lower in GI-2, GI-3, and GI-4 birds than in an unchallenged control group. Seroconversion was observed in GI-1 birds and some GI-2 birds. The frequency of virus shedding via the cloaca in vvIBDV-challenged birds increased from 7.1% of GI birds at 5 days post inoculation (dpi) to 35.7% at 14 dpi. The timing of virus shedding was progressively later from GI-1 to GI-4. At 14 dpi, significant atrophy of the bursa of Fabricius (BF) was observed in GI birds compared with GII controls; atrophy was most severe in GI-1 birds and least severe in GI-4 birds. BF lesion scores decreased from GI-1 to GI-4. The proportion of birds with IBDV antigen in the BF at 14 dpi was higher in GI-2 and GI-3 than in GI-1 and GI-4, whereas the viral load in positive birds increased from GI-1 to GI-4. Our results indicate that high levels of MDAs would protect chicks from initial vvIBDV infection but that progressive decay of these MDAs would result in delayed infection by virus shedding in initially infected birds with low MDA titers, resulting in continuous circulation of the virus in a flock with non-uniform MDA titers.

A probiotic combination attenuates experimental colitis through inhibition of innate cytokine production.

Inflammatory bowel disease (IBD) is a severe immune cell-mediated syndrome characterised by extensive inflammatory and effector mucosal responses leading to tissue destruction in the colon and small intestine. The leading hypothesis is that dysbiosis of the gut flora causes an excessive immune response and inflammation in the gastrointestinal track. Lactic acid bacteria (LAB) can correct dysbiosis of the normal microbiota. In the current study, the therapeutic potential of seven LAB strains in combination to treat IBD was evaluated using experimental colitis model. This LAB cocktail, designated GI7, includes four strains of Lactobacillus acidophilus, Lactobacillus plantarum, Lactobacillus rhamnosus, Lactococcus lactis, two strains of Bifidobacterium bifidum, Bifidobacterium breve, and one strain of Streptococcus thermophilus. We confirmed that GI7 suppressed pro-inflammatory cytokines in Raw264.7 macrophages. When dextran sulphate sodium-induced colitic mice were treated with GI7, their symptoms of colitis, as assessed by body weight, colon length, myeloperoxidase activity, intestinal bleeding, and histological damage, were reduced compared to untreated mice. In addition, GI7 treatment significantly inhibited the production of innate pro-inflammatory cytokines during colitic progression. Therefore, we suggest that GI7, a combination of seven LAB, has a potential role in the treatment of IBD.