Curative Criteria After Endoscopic Resection for Superficial Esophageal Squamous Cell Carcinomas.

BACKGROUND: According to the Japanese Esophageal Society (JES) guidelines, risk factors for lymph node (LN) metastasis in the muscularis mucosa (MM)/submucosa to a depth of up to 200 µm (SM1) in cases of esophageal squamous cell carcinomas (ESCCs) include the presence of lymphatic invasion (ly), venous invasion (v), infiltration pattern (INF)c, and SM1. The long-term prognoses of these patients are unclear, and there are very few reports on the validation of the curative criteria for MM/SM1 ESCCs. AIMS: To examine the long-term prognoses of these patients and the risk factors for LN metastasis of MM/SM1 ESCCs after endoscopic resection (ER). METHODS: This study included patients with MM/SM1 ESCCs who underwent ER at Hiroshima University Hospital from December 1990 to November 2016. We evaluated the clinicopathological characteristics of 98 patients and overall survival, disease-specific survival, recurrence-free survival, and recurrence rates in the e-curative and non-e-curative groups. RESULTS: The mean observation period was 75 months. There was no significant difference in disease-specific survival rate between the e-curative and non-e-curative groups (100 vs. 98%). There was no significant difference in disease-specific survival rates between the groups (100 vs. 98%). In contrast, the LN recurrence-free survival rate in patients with INFa, ly(-), and v(-) was significantly higher than that in patients with INFb/c, ly(+), or v(+) (100 and 87%, P < 0.05). CONCLUSION: Contrary to the JES guidelines, our findings suggest that new criteria (MM/SM1, INFa, negative vertical margin (VM0), ly[-], and v[-]) may be associated with curative ER without additional treatment.

Diagnosis of superficial esophageal squamous cell carcinoma invasion depth before endoscopic submucosal dissection.

Endoscopic submucosal dissection (ESD) is a widely accepted procedure for superficial esophageal squamous cell carcinoma (SESCC) limited to the epithelium or lamina propria mucosae (EP/LPM). We aimed to compare the efficacy of endoscopic ultrasonography (EUS) and magnifying endoscopy with narrow band imaging (ME-NBI) for predicting the tumor invasion depth in patients with SESCC. Specifically, we evaluated the ability of these examinations to distinguish EP/LPM from SESCC invading the muscularis mucosae or superficial submucosa (MM/SM1) and more deeply invasive lesions before ESD.We retrospectively analyzed a database of all patients with SESCC who had undergone both EUS and ME-NBI for pretreatment staging and ESD resection at Hiroshima University Hospital between September 2007 and June 2015. The clinicopathologic characteristics of SESCCs were classified according to the Japanese Classification of Esophageal Cancer.A total of 174 lesions in 174 patients were included: 124 (71%) EP/LPMs, 35 (20%) MM/SM1s, and 15 (9%) SESCCs invading the mid submucosae (SM2). The sensitivity of EUS and of ME-NBI in distinguishing EP/LPM from MM/SM1 and more invasive lesions was 72% and 83%, respectively. The accuracy of EUS and ME-NBI in distinguishing EP/LPM from MM/SM1 and more invasive lesions was 70% and 82%, respectively. Sensitivity and accuracy of ME-NBI in distinguishing EP/LPM from MM/SM1 and more deeply invasive SESCCs is significantly higher than those of EUS (P = 0.048 and P = 0.017, respectively).ME-NBI may be more useful than EUS for the determination of SESCC invasion depth before ESD.

Animal models of cartilage repair.

Cartilage repair in terms of replacement, or regeneration of damaged or diseased articular cartilage with functional tissue, is the 'holy grail' of joint surgery. A wide spectrum of strategies for cartilage repair currently exists and several of these techniques have been reported to be associated with successful clinical outcomes for appropriately selected indications. However, based on respective advantages, disadvantages, and limitations, no single strategy, or even combination of strategies, provides surgeons with viable options for attaining successful long-term outcomes in the majority of patients. As such, development of novel techniques and optimisation of current techniques need to be, and are, the focus of a great deal of research from the basic science level to clinical trials. Translational research that bridges scientific discoveries to clinical application involves the use of animal models in order to assess safety and efficacy for regulatory approval for human use. This review article provides an overview of animal models for cartilage repair. Cite this article: Bone Joint Res 2014;4:89-94.

Anomalous vertebral and posterior communicating arteries as a risk factor in instrumentation of the posterior cervical spine.

We investigated the incidence of anomalies in the vertebral arteries and Circle of Willis with three-dimensional CT angiography in 55 consecutive patients who had undergone an instrumented posterior fusion of the cervical spine. We recorded any peri-operative and post-operative complications. The frequency of congenital anomalies was 30.9%, abnormal vertebral artery blood flow was 58.2% and vertebral artery dominance 40%. The posterior communicating artery was occluded on one side in 41.8% of patients and bilaterally in 38.2%. Variations in the vertebral arteries and Circle of Willis were not significantly related to the presence or absence of posterior communicating arteries. Importantly, 18.2% of patients showed characteristic variations in the Circle of Willis with unilateral vertebral artery stenosis or a dominant vertebral artery, indicating that injury may cause lethal complications. One patient had post-operative cerebellar symptoms due to intra-operative injury of the vertebral artery, and one underwent a different surgical procedure because of insufficient collateral circulation. Pre-operative assessment of the vertebral arteries and Circle of Willis is essential if a posterior spinal fusion with instrumentation is to be carried out safely.

Computed tomographic and histological findings of Hansen type I intervertebral disc herniation in dogs.

OBJECTIVE: To evaluate whether non-contrast-enhanced computed tomography (CT) as a stand-alone imaging modality can be used to define the Hansen type I intervertebral disc herniation (IVDH) lesion and also whether the Hounsfield unit (HU) value of herniated disc is relevant to clinical duration and to histopathological chronicity of extruded disc material. METHODS: Information from a series of CT studies performed on 45 dogs with a presumptive diagnosis of Hansen type I IVDH was used. Clinical duration of IVDH was estimated based on time from onset of signs per owner communication to time of surgical intervention. Hansen type I IVDH was confirmed at surgery. Retrieved herniated disc was histologically examined. The HU values were analyzed to correlate the clinical duration and histopathological chronicity of the disc lesion. RESULTS: Non-contrast-enhanced CT provided sufficient diagnostic information to plan surgery in 42 of 45 dogs (93%). The value of the HU was significantly higher in clinically chronic cases (n = 12) compared to peracute cases (n = 11) (p <0.05). The HU values were significantly correlated with clinical duration (r = 0.482, p = 0.0008) and histopathological chronicity of the herniated disc (r = 0.408, p = 0.0056). CONCLUSION: Consistent with the previous reports, the use of non-contrast-enhanced CT alone was sufficient for the diagnosis and surgical planning in most patients with Hansen type I IVDH in the thoracolumbar spine. In addition, the present study suggested that HU values on CT images may be useful in the evaluation of disease chronicity of IVDH.

Exercise training improves vasoreactivity in the knee artery.

Physical activity has been shown to enhance endothelial function of central and peripheral vascular beds. The primary purpose of the present study was to test the hypothesis that a short-term exercise training program would result in enhanced endothelium-dependent vasorelaxation of a major artery supplying blood flow to the knee joint, the middle genicular artery. Female Yucatan miniature swine were randomly assigned into exercise trained (n=7) or sedentary (n=7) groups. Exercise trained pigs underwent a daily exercise training program on treadmills for 7 days. In vitro assessment of vasorelaxation was determined in a dose response manner by administrating increasing doses of 3 different dilators; adenosine diphosphate, bradykinin, and sodium nitroprusside. The role of nitric oxide synthase and cyclooxygenase pathways in vasomotor responses was evaluated with specific inhibitors using nitro-L-arginine methyl ester and indomethacin incubation, respectively. The results of this investigation indicate that adenosine and bradykinin-induced endothelium-dependent vasorelaxation were significantly enhanced in middle genicular artery from exercise trained pigs (p<0.05). Endothelium-independent vasorelaxation was not altered with exercise training as determined by the response to sodium nitroprusside. The findings of the present investigation indicate that short-term exercise training enhances endothelial function of middle genicular artery through adaptations in the nitric oxide synthase and by non-nitric oxide synthase, non-cyclooxygenase pathways.

Subchondral bone changes in three different canine models of osteoarthritis.

OBJECTIVE: To test the hypothesis that changes in subchondral bone are significantly different among three canine models of osteoarthritis (OA). DESIGN: In 21 purpose-bred mongrel dogs, OA was induced in one knee joint via either anterior cruciate ligament transection (ACLt; n = 5), medial femoral condylar groove creation (GR; n = 6), or medial meniscal release (MR; n = 5). Five dogs that had sham surgery (SH; n = 5) in one knee joint served as controls. Lameness scoring was performed every 4 weeks. Twelve weeks after surgery, the knee joints were examined by histology and histomorphometry. RESULTS: Articular cartilage pathology as determined by Mankin scores was significantly severe in all three OA models compared to SH controls in the medial tibia (P < 0.001 to P = 0.026). ACLt had significantly thinner subchondral plate thickness (Sp.Th) in both the medial and lateral tibias while MR had significantly thicker Sp.Th in the medial tibia compared to SH controls (P < 0.001 to P = 0.011). Trabecular bone volume (BV/TV) and trabecular bone thickness (Tb.Th) for ACLt were significantly less than SH controls in the tibias (P < 0.001 to P = 0.011). Tibial Sp.Th, BV/TV, and Tb.Th were all moderately to strongly correlated with lameness scores obtained throughout the study period (r = -0.436 to r = -0.738, P < 0.001 to P = 0.047) while Mankin scores showed moderate to strong correlations with Sp.Th in each OA model (r = 0.465 to r = 0.816, P < 0.001 to P = 0.033). CONCLUSIONS: Changes in Sp.Th are associated with articular cartilage damage while tibial Sp.Th and BV/TV and Tb.Th appear to be all influenced by joint loading alterations.

Skeletal-extraskeletal angiomatosis in a dog.

An 8-year-old castrated male mixed-breed dog had an ill-defined hemorrhagic and painful lesion in the base of the claw of the second digit of the right forelimb. Radiographically, the expansile and lytic lesion affected the distal phalanx. The digit was amputated and submitted for histologic examination. Histologically, the distal phalanx was largely replaced by a mass composed of variably sized cavernous vascular spaces lined by a single layer of flattened endothelial cells. A similar mass was in the subcutis adjacent to the distal phalanx. The benign vascular proliferation involving the medulla of bone and a second tissue type in this dog is consistent with skeletal-extraskeletal angiomatosis as described in humans. To the authors' knowledge, this is the first report of skeletal-extraskeletal angiomatosis in the veterinary literature.

[Ruptured proximal aorta after operation for type A dissection presenting as opacified left hemothorax; report of a case].

We report an unusual clinical presentation of ruptured proximal aorta as a left hemothorax after operation for type A dissection. A 74-year-old man who had undergone ascending aortic replacement for acute type A dissection 4 months previously developed a loss of consciousness followed by shock state. Both chest X-ray and computed tomography (CT) scan revealed opacified left hemothorax. The patient died during a diagnostic procedure. Post mortem examination showed rupture of proximal aortic dissection extended to the left pleural cavity path through the right atrial wall and the right ventricular wall.

An intensive group therapy programme for smoking cessation using nicotine patch and internet mailing supports in a university setting.

AIMS: Despite the growing literature on workplace tobacco control policies, very few studies have evaluated the role of smoking cessation programme as one of these policies in a university setting. We aimed to investigate the efficacy of intensive cessation programme delivered in a group format using nicotine patch therapy and internet mailing supports for our university employees. METHODS: From January 2003, we conducted the group therapy programme for smoking cession seven times in Okayama University, Japan. This programme consisted of nicotine patch therapy and on-line supporting system. Smoking status was regularly assessed by direct interviews. RESULTS: A total of 102 employees were enrolled in this programme, of whom 101 initiated their smoking cessation. One hundred participants (99%) received nicotine patch therapy, and its toxicities were generally mild. Of the 94 employees who could be follow-up for a year after the cessation, 50 (53%) sustained abstinence for a year. Multivariate analysis revealed that writing and sending e-mail messages within the first 1 week were significant factors affecting long-term cessation. The type of position also affected the cessation rate. CONCLUSION: This study suggests that our programme in a university setting seems to be effective mainly because of peer-supports among the participants through regular face-to-face meetings and their own mailing supports.

Equivalence of the acute cytokine surge and myocardial injury after coronary artery bypass grafting with and without a novel extracorporeal circulation system.

Cardiopulmonary bypass (CPB) contributes to a morbidity-inducing systemic inflammatory response after cardiac surgery. We compared this response in patients receiving coronary artery bypass grafting (CABG) with (CPB group; n = 7) or without (off-pump group; n = 8) the Minimal Extracorporeal Circulation (MECC) system. Serum concentrations of tumour necrosis factor (TNF)-alpha, soluble TNF receptors, pro- and anti-inflammatory interleukins (ILs) and other myocardial injury markers were measured after anaesthetic induction, at 1 h, 4 h and 24 h after completing all anastomoses or serially. Soluble TNF receptor type I (sTNFRI) and IL-8 peaked early after CABG in both groups and did not decline. Serum sTNFRI was significantly higher in the CPB compared with the off-pump group at 1 h, whereas IL-8 was significantly lower in the CPB group throughout. The MECC system, therefore, produces an equivalent acute cytokine response and degree of myocardial injury to off-pump CABG, and may be useful when CABG cannot be performed without CPB.

beta2-adrenergic receptor stimulation-induced immunosuppressive effects possibly through down-regulation of co-stimulatory molecules, ICAM-1, CD40 and CD14 on monocytes.

We examined the effects of beta2-adrenergic receptor (beta2-AR) agonists on the expression of co-stimulatory molecules on lipopolysaccharide (LPS)-stimulated human peripheral blood mononuclear cells. The study found that beta2-AR agonists inhibited the expression of intercellular adhesion molecule-1 (ICAM-1), CD40 and CD14 on monocytes, and that AR agonist activity was antagonized by the selective beta2-AR antagonist, butoxamine. The selective beta2-AR agonists salbutamol and terbutaline induced a similar co-stimulatory molecule expression pattern. The LPS-induced production of tumour necrosis factor-alpha was inhibited by AR agonists, and this was also antagonized by butoxamine, and mimicked by salbutamol and terbutaline. The AR agonists also inhibited T-cell proliferation through beta2-AR stimulation. This study clearly demonstrated that endogenous catecholamines elicited immunosuppressive effects through beta2-AR stimulation, possibly due to down-regulation of the expression of ICAM-1, CD40 and CD14 on monocytes. These results suggested that the sympathetic nervous system might regulate the T-helper cell balance via the peripheral end-effectors of the stress system.

Polymorphisms of human CD19 gene: possible association with susceptibility to systemic lupus erythematosus in Japanese.

CD19 regulates the signaling for B lymphocyte development, activation and proliferation. In mice, CD19 deficiency and overexpression were shown to result in hypogammaglobulinemia and autoantibody production, respectively. In the present study, we screened for the polymorphisms of CD19, and examined the detected polymorphisms for the association with rheumatoid arthritis (RA), Crohn's disease and systemic lupus erythematosus (SLE). Two SNPs, c.705G>T (P235P and IVS14-30C>T, were decreased (P = 0.0096 and P = 0.028, respectively), in SLE. A GT repeat polymorphism, c.*132(GT)(12-18), was detected within the 3'-untranslated region, and individuals with > or =15 times repeat was significantly increased in the independent two groups of Japanese SLE patients (P = 0.011 and P = 0.035, respectively); the overall difference between total SLE and controls was striking (P = 0.0061). No association was observed for RA and Crohn's disease. In addition, no variations other than the common polymorphisms were detected in four patients with common variable immunodeficiency, the phenotype of which resembles CD19 deficient mice. In Caucasian SLE families, this GT repeat polymorphism was rare. CD19 mRNA level in the isolated peripheral blood B lymphocytes was lower in individuals possessing (GT)(15-18) alleles compared with those without these alleles, both in controls and in SLE patients; however, the difference did not reach statistical significance. These results suggested that either the slight reduction in the CD19 mRNA level associated with the elongation of GT repeat, or an allele of another locus in linkage disequilibrium with CD19 (GT)(15-18), may be associated with susceptibility to SLE in Japanese.

[Cardiac surgery for chronic dialysis patients].

Chronic dialysis patients who received open heart surgery were examined, and main concern was perioperative management. There were 12 chronic dialysis patients and open heart surgeries were performed between October 1990 and June 2000. The patients were comprised of 7 men and 5 women with the average age being 64 with plus or minus 7.9. The operative procedure of 6 coronary artery bypass grafting (CABG) [on-pump], 1 CABG + mitral valve replacement (MVR), 3 aortic valve replacement (AVR), 1 mitral valvuloplasty (MVP) and 1 ascending aorta replacement were performed. All patients were discharged from the hospital with good conditions 27.1 days after operation. There were no hospital deaths. One postoperative complication of mediastinitis of the sternum has been found. A conventional dialysis was performed the day before the operation and an intra-operative hemodialysis (HD) was performed, placing a dialyzer into a cardiopulmonary system during the operation. For the perioperative management, HD was started the day or 2 days after the operation with no immediate postoperative hemocatharsis and returned to the normal HD 7 days after the operation. The result of the perioperative management has been good.

[An elderly case of ruptured aortic arch aneurysm 3 years after coronary artery bypass grafting].

We reported a case of trans-aortic endovascular stent grafting (open stent method) for ruptured true aneurysm of the aortic arch. A 83-year-old female, who had suddenly complained back pain and been diagnosed as the ruptured aortic arch aneurysm by computer tomography, was admitted for an emergent surgery. We performed emergent trans-aortic endovascular stent grafting (open stent method). Postoperatively she had no complication and recovered uneventfully.

[Decompressive craniectomy for massive infarction of middle cerebral artery territory].

There is continuing controversy about the benefits of decompressive craniectomy for the treatment of massive infarction of middle cerebral artery (MCA) territory. Under conservative therapy, the mortality rate for this stroke is reported to be up to 80%. So the authors have actively carried out decompressive craniectomy since 1997, and have compared the outcome with patients who were admitted before 1997 and, consequently treated with conservative therapy. Fifteen consecutive victims of massive infarction of MCA territory were studied. Seven patients (male: 1, female: 6, mean age: 79.8 years) were treated with conservative therapy, and 8 patients (male: 3, female: 5, mean age: 71.8 years) were treated with decompressive craniectomy. There were no significant differences in age and consciousness level distribution between the two groups. Mortality rate in the conservative therapy group was 85.7% against 12.5% in the surgery group (p < 0.05). Functional performance, which was evaluated by activity in daily life (ADL), was also better in the surgery group e.g. 3 patients in ADL 3, and 3 in ADL 4 (1 patient died from a non-neurological cause). Even among the patients with speech-dominant hemispheric stroke, all except one were able to communicate in some way and understand language. Even though patients in this study were elderly, decompressive craniectomy reduced mortality and improved functional performance, so it seems that this surgery should be aggressively considered for massive infarction of MCA territory.

[Long distance air transport by helicopter of a patient with severe head damage].

A report of a case of a patient with severe head trauma with pneumonia and cerebral infarction transported by helicopter. An eighty-year-old male was referred to our hospital because of dyspnea after a fall during sightseeing at Hiroshima. He was lucid at first, but, after two days presented restlessness due to brain contusional hemorrhage and edema. Moreover, he developed pneumonia and cerebral infarction during the period of his hospitalization. He was intubated and received central venous routing. While being transported, his consciousness showed moderate disturbance, aphasia and right hemiplegia. His family asked that therapy be continued near his house in Osaka. We selected transport by helicopter because of his bad general condition and because transport time would be much shorter. He was transported by helicopter to Osaka one month after admission. First, he was transported by ambulance to the airport of Hiroshima. He was carried to the helicopter at the airport. An oxygen cylinder was connected to the incubation tube via an ambu bag because direct connection between the oxygen cylinder and the intubation tube was impossible. Just before the take off, O2 saturation was checked by the pulse oximeter of the ambulance. In the helicopter, there were six men; two pilots, two rescue men, one doctor and the patient. Suction was applied only once and there was no trouble during the flight. The weather was fine and the helicopter experienced almost no rolling during the flight. The flight time was only one hour and twenty minutes. The helicopter safely landed at an emergency heliport in Osaka. The patient was carried to a waiting ambulance and transported to the hospital. Total transport time was only two hours and thirty minutes. This is a case showing a helicopter could safely transport a patient with severe brain damage over a long distance in a short time.

Anchoring the Duran flexible annuloplasty ring with continuous sutures.

We practised a deviced method of anchoring the Duran flexible ring with continuous sutures. After passing through 3/0 monofilament sutures at the right and left fibrous trigones, both sutures are passed through the ring between the corresponding ring marker and continuous sutures are placed to attach the ring to the mitral valve annulus. This technique requires less time to anchor the ring than the original method with interrupted sutures and can prevent narrowing the mitral valve annulus following the deformity of the flexible ring. This technique can contribute to extend the indication of the prosthetic ring in mitral valve surgery.