Perioperative change in white blood cell count predicts outcome of hepatic resection for hepatocellular carcinoma

Background

In spite of improvements in surgical management, hepatocellular carcinoma (HCC) still recurs after operation in 60–70% of patients. Therefore, we investigated the relation between perioperative change in white blood cell count (WBC) and tumor recurrence as well as survival in patients with HCC after hepatic resection.

Methods

Subjects were 53 patients who underwent elective hepatic resection for HCC. We retrospectively examined the relation between perioperative change in WBC and recurrence of HCC as well as overall survival.

Results

Advanced tumor stage and increasing of WBC on postoperative day (POD) 1 were positively associated with worse disease-free survival rate on both univariate and multivariate analysis (P < 0.05). Advanced tumor stage, increasing of WBC on POD 1, and blood transfusion were positively associated with worse overall survival rate on univariate analysis (P < 0.05), while change in WBC was the only independent factor on multivariate analysis (P < 0.05).

Conclusions

Perioperative change in WBC after elective hepatic resection for HCC is positively associated with recurrence and worse survival.     

Involvement of Onuf’s nucleus in Machado–Joseph disease: a morphometric and immunohistochemical study

Machado–Joseph disease (MJD) is an autosomal dominant neurodegenerative disease caused by an expansion of CAG repeats in the MJD1 gene, in which lower urinary tract dysfunction is known to be the most commonly encountered autonomic failure. However, it remains unclear whether Onuf’s nucleus (ON), which plays major roles in the micturition reflex and voluntary continence, degenerates during the disease process. In the present study, we conducted a morphometric and immunohistochemical study of ON, together with the lateral nuclear group (LNG) of the sacral anterior horns, in seven patients with MJD. When compared with controls, the number of lower motor neurons in both ON and LNG was significantly smaller in the MJD patients, the former being inversely correlated with the size of the expanded CAG repeats. Notably, MJD patients with a large CAG-repeat expansion showed an ON-predominant pattern of neuronal loss, while in the remaining patients, ON and LNG were affected to a similar degree, or rather an LNG-predominant pattern of neuronal loss was evident. Moreover, when adjusted for age, the degree of neuronal loss in both ON and LNG was significantly correlated with the extent of expansion of the CAG repeats. In MJD, the remaining lower motor neurons in ON often exhibited ataxin-3- or 1C2-immunoreactive (ir) neuronal intranuclear inclusions, while no pTDP-43-ir neuronal cytoplasmic inclusions were present in these neurons. In conclusion, the present findings strongly suggest that neuronal loss in ON, the degree of which is highly influenced by the extent of expansion of CAG repeats, is a consistent feature in MJD.     

Development of a simple model for predicting need for surgery in patients who initially undergo conservative management for adhesive small bowel obstruction

Background

Among patients with adhesive small bowel obstruction (ASBO) initially managed with a conservative strategy, predicting risk of operation is difficult.

Methods

We investigated ASBO patients at 2 different periods to derive and validate a clinical prediction model for risk of operation.

Results

One hundred fifty-four patients were enrolled into the derivation cohort and 96 into the validation cohort. Based on the derived scoring, including age ≥65 years, presence of ascites, and gastrointestinal drainage volume >500 mL on day 3, each patient was classified into 1 of 4 risk classes from low risk to high risk. When applied to the validation cohort, the positive predictive value (PPV) for operation in the high-risk class was 72%, while the negative predictive value (NPV) in the low-risk class was 100% with high sensitivity (100%) and specificity (96%).

Conclusions

The prediction model performs well for risk stratification of need for surgical intervention following conservative strategy among ASBO patients.     

Lifespan extension in the spontaneous dwarf rat and enhanced resistance to hyperoxia-induced mortality

Lifespan extension has been demonstrated in dwarfism mouse models relative to their wild-type. The spontaneous dwarf rat (SDR) was isolated from a closed colony of Sprague–Dawley (SD) rats. Growth hormone deficiencies have been indicated to be responsible for dwarfism in SDR. Survival time, the markers of oxidative stress, antioxidant enzymes, and resistance to hyperoxia were compared between SDR and SD rats, to investigate whether SDR, a dwarfism rat model, also extends lifespan and has an enhanced resistance to oxidative stress.     

Dental infection of Porphyromonas gingivalis exacerbates high fat diet-induced steatohepatitis in mice

Background

We investigated the effects of dental infection with Porphyromonas gingivalis (P.g.), an important periodontal pathogen, on NASH progression, by feeding mice a high fat diet (HFD)and examining P.g. infection in the liver of NASH patients.

Methods

C57BL/6J mice were fed either chow-diet (CD) or HFD for 12 weeks, and then half of the mice in each group were infected with P.g. from the pulp chamber (HFD-P.g.(?), HFD-P.g.(+), CD-P.g.(?) and CD-P.g.(+)). Histological and immunohistochemical examinations, measurement of serum lipopolysaccharide (LPS) levels and ELISA for cytokines in the liver were performed. We then studied the effects of LPS from P.g. (P.g.-LPS) on palmitate-induced steatotic hepatocytes in vitro, and performed immunohistochemical detection of P.g. in liver biopsy specimens of NASH patients.

Results

Serum levels of LPS are upregulated in P.g.(+) groups. Steatosis of the liver developed in HFD groups, and foci of Mac2-positive macrophages were prominent in HFD-P.g.(+). P.g. was detected in Kupffer cells and hepatocytes. Interestingly, areas of fibrosis with proliferation of hepatic stellate cells and collagen formation were only observed in HFD-P.g.(+). In steatotic hepatocytes, expression of TLR2, one of the P.g.-LPS receptors, was upregulated. P.g.-LPS further increased mRNA levels of palmitate-induced inflammasome and proinflammatory cytokines in steatotic hepatocytes. We demonstrated for the first time that P.g. existed in the liver of NASH patients with advanced fibrosis.

Conclusions

Dental infection of P.g. may play an important role in NASH progression through upregulation of the P.g.-LPS-TLR2 pathway and activation of inflammasomes. Therefore, preventing and/or eliminating P.g. infection by dental therapy may have a beneficial impact on management of NASH.     

Development of an ex vivo cellular model of rheumatoid arthritis: critical role of CD14-positive monocyte/macrophages in the development of pannus tissue

OBJECTIVE: To establish an ex vivo cellular model of pannus, the aberrant overgrowth of human synovial tissue (ST). METHODS: Inflammatory cells that infiltrated pannus tissue from patients with rheumatoid arthritis (RA) were collected without enzyme digestion, and designated as ST-derived inflammatory cells. Single-cell suspensions of ST-derived inflammatory cells were cultured in medium alone. Levels of cytokines produced in culture supernatants were measured using enzyme-linked immunosorbent assay kits. ST-derived inflammatory cells were transferred into the joints of immunodeficient mice to explore whether these cells could develop pannus. CD14 and CD2 cells were depleted by negative selection. RESULTS: Culture of ST-derived inflammatory cells from 92 of 111 patients with RA resulted in spontaneous reconstruction of inflammatory tissue in vitro within 4 weeks. Ex vivo tissue contained fibroblasts, macrophages, T cells, and tartrate-resistant acid phosphatase-positive multinucleated cells. On calcium phosphate-coated slides, ST-derived inflammatory cell cultures showed numerous resorption pits. ST-derived inflammatory cell cultures continuously produced matrix metalloproteinase 9 and proinflammatory cytokines associated with osteoclastogenesis, such as tumor necrosis factor alpha, interleukin-8, and macrophage colony-stimulating factor. More importantly, transferring ST-derived inflammatory cells into the joints of immunodeficient mice resulted in the development of pannus tissue and erosive joint lesions. Both in vitro development and in vivo development of pannus tissue by ST-derived inflammatory cells were inhibited by depleting CD14-positive, but not CD2-positive, cells from ST-derived inflammatory cells. CONCLUSION: These findings suggest that overgrowth of inflammatory cells from human rheumatoid synovium simulates the development of pannus. This may prove informative in the screening of potential antirheumatic drugs.     

Change in acetylcholine release from rat bladder with partial outlet obstruction

OBJECTIVE

To investigate changes in acetylcholine release from the bladder of rats with partial bladder outlet obstruction (BOO), as partial BOO leads to hypertrophy and an alteration in the contractions of the detrusor smooth muscle, and acetylcholine plays an important role in urinary bladder contractions but there is little available information on acetylcholine release after BOO.

MATERIAL AND METHODS

Partial BOO was induced in adult female rats by ligating the proximal urethra over a 1 mm angiocatheter; sham‐operated rats served as controls. The rats were killed 2 weeks, 3 and 6 months after induction of BOO. We investigated the contractions induced by carbachol, KCl (80 mm ), ATP and electrical‐field stimulation (EFS, 2.5–40 Hz), and collected the dialysate obtained from a microdialysis probe inserted into the muscle strips during EFS, and measured the amount of acetylcholine in the dialysate fraction by high‐performance liquid chromatography with electro‐chemical detection. S‐100 immunohistochemical staining of the bladder preparations was used for histological examination in BOO and control rats.

RESULTS

The bladder weight gradually increased after BOO. There were no significant changes in KCl‐induced contractions throughout the experimental period in either group. There were no significant changes in carbachol‐induced contractions until 3 months after BOO but there was a significant reduction at 6 months. ATP‐induced contractions were significantly increased 2 weeks and 3 months after BOO. EFS‐induced contractions were gradually reduced after BOO. Acetylcholine release from the bladder strips was not significantly different between the groups until 2 weeks after BOO. However, acetylcholine release in BOO rats was significantly decreased 3–6 months after BOO, being significantly lower than that of the control rats. In the histological study, the number of nerve fibres in the BOO rats was significantly lower than in the control rats.

CONCLUSIONS

We suggest that the prolonged BOO caused a decrease in EFS‐induced acetylcholine release and the number of nerves in the rat urinary bladder, which might contribute to bladder underactivity in BOO.     

Thrombospondin-1-induced migration is functionally dependent upon focal adhesion kinase

Vascular smooth muscle cell migration is important in vascular disease. Previously, we showed thrombospondin-1 activates focal adhesion kinase in these cells. We hypothesized that focal adhesion kinase is important for thrombspondin-1-induced vascular smooth muscle cell migration. Bovine aortic smooth muscle cells were transfected with FAK397, FAK-wild type, pcDNA, or beta-Gal plasmids. Migration was assessed with thrombospondin-1 or serum-free medium in quiescent transfected cells or quiescent cells pretreated with the focal adhesion kinase inhibitor, geldanamycin. Number of cells migrated per 5 fields (x400) were recorded. Antihemagglutinin immunoprecipitation and Western blot were used to examine thrombospondin-1-induced focal adhesion kinase phosphorylation in transfected cells. FAK397 transfection inhibited thrombospondin-1-induced focal adhesion kinase phosphorylation and migration (P < .05). Geldanamycin inhibited thrombospondin-1-induced smooth muscle cell migration (P < .05). In conclusion, vascular smooth muscle cells transfected with FAK397 inhibited thrombosponin-1-induced migration and tyrosine phosphorylation. Further, geldanamycin also inhibited migration. These results suggest focal adhesion kinase is involved in thrombospondin-1-induced vascular smooth muscle cell migration.     

Sagittal alignment changes after thoracic laminectomy in adults

OBJECT: The increased kyphosis after thoracic laminectomy in adult patients was retrospectively evaluated and various factors affecting this spinal deformity were analyzed. METHODS: The authors conducted a retrospective study of 58 cases in which laminectomy was performed and more than half of the facet joints were left intact. The study group included 44 men (mean age 59 years) and 14 women (mean age 61 years) with thoracic myelopathy due to ossifications of the ligamentum flavum and/or the posterior longitudinal ligament or due to posterior bone spurs. Patients were followed up for a minimum of 2 years. Their neurological condition was evaluated using the Japanese Orthopaedic Association (JOA) scale (a full score is 11), and the magnitude of local kyphosis in the laminectomized area was determined using the Cobb angle method. RESULTS: The mean preoperative JOA score was 5.4; the mean postoperative score was 8.3. No relationship was found between postoperative JOA score and increased kyphotic angle. The mean preoperative kyphotic angle was 7.0 degrees . The mean postoperative kyphotic angle was 10.8 degrees . Thus local kyphosis in the treated area increased by only 3.8 degrees . The mean increase in kyphosis per spinal segment, calculated by dividing the kyphotic angle of the surgically decompressed area by the number of resected laminae, was 1.9 degrees . Female patients with >or= 3-level laminectomies showed a significant increase of kyphosis in both the laminectomized area and each spinal segment. CONCLUSIONS: The increase in kyphosis after thoracic laminectomy is not large and thus spinal fusion is usually not necessary. In cases involving female patients who undergo long-segment laminectomies, however, careful radiographic follow-up is recommended.