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.

Impact of revisions of the JSCCR guidelines on the treatment of T1 colorectal carcinomas in Japan.

PURPOSE: In 1977, the Japanese Society for Cancer of the Colon and Rectum (JSCCR) published the first edition of the general guidelines that described how to record clinical and histopathological findings of colorectal carcinomas (CRCs) and how to treat these cancers, and since then, the guidelines were revised several times. The aim of this study was to examine the impact of the revisions of the JSCCR guidelines on the treatment of submucosal CRCs (T1-CRCs) in Japanese clinical settings. METHODS: Questionnaires were sent to all 391 member institutions of the JSCCR. The questionnaires consisted of 2 parts: details of the institutions and treatment strategies for T1-CRCs. RESULTS: 73 (19 %) institutions responded to the survey. The number of treated T1-CRCs has increased year by year, and the rate of endoscopic resection for T1-CRCs has significantly increased with revisions of the guidelines (1417 [47 %] of 2985 T1-CRCs in 2003 - 2005, 2110 [50 %] of 4212 in 2006 - 2008, and 2546 [54 %] of 4686 in 2009 - 2011, P<.05). CONCLUSION: The revisions of the JSCCR guidelines have influenced the treatment of T1-CRCs in Japanese clinical settings. There is room to revise the criteria for curative endoscopic resection to avoid unnecessary surgeries.

Does shoulder impingement syndrome affect the shoulder kinematics and associated muscle activity in archers?

BACKGROUND: Archery related injuries, such as shoulder impingement syndrome are caused by repeated motion of the shoulder. The aim of this study was to analyze differences in the shoulder kinematics and the associated muscle activity between archers with shoulder impingement and uninjured archery players. METHODS: Thirty male archers, who were divided into an impingement group and an uninjured group, were included in this study. The angle of scapular elevation, shoulder joint abduction, horizontal extension, and elbow joint flexion as well as the electromyographic activity of the upper trapezius, lower trapezius, deltoid middle, deltoid posterior, biceps brachii, and triceps brachii muscles at the point of stabilization during shooting were measured. Variables differing between impingement and uninjured groups were identified, and a stepwise regression analysis was performed to identify a combination of variables that effectively impingement syndrome. RESULTS: The results indicated that the angle of scapular elevation was significantly greater than that uninjured group (P<0.05). The angle of horizontal extension in the impingement group was significantly smaller than that in the uninjured group (P<0.05). The angle of elbow flexion in the impingement group was significantly smaller than that in the uninjured group (P<0.05). The levels of upper trapezius and deltoid middle muscle activity were significantly higher in the impingement group, while the level of lower trapezius muscle activity was significantly lower (P<0.05) when compared to the uninjured group. The impingement group had a greater angle of scapular elevation, smaller angle of horizontal extension, smaller angle of elbow flexion, higher the levels of upper trapezius, lower the levels of lower trapezius, higher deltoid middle muscle activity and higher UT/LT ratio (all differences were significant). A logistic model for predicting impingement syndrome showed that UT/LT ratio was significantly related impingement syndrome (P<0.05). CONCLUSION: The authors concluded that archers with shoulder impingement syndrome exhibit different kinematics and muscle activity compared to uninjured archers. Therefore, in order to prevent shoulder joint impingement during archery, training is necessary what can make lower trapezius muscle activity increased to decrease the UT/LT ratio.

Examination of micro-superficial lesions of up to 5 mm in size in the pharyngolaryngeal region.

OBJECTIVE: For low-grade intraepithelial neoplasia cases, pharyngolaryngeal lesions equal to or less than 5 mm in size do not generally progress to invasive carcinoma. However, micro-superficial lesions equal to or less than 5 mm that showed rapid growth have been recently encountered. This study aimed to identify the characteristics of preferential progression of lesions equal to or less than 5 mm in size. METHOD: Gross findings, endoscopic findings and pathological results of 55 lesions measuring equal to or less than 5 mm in diameter were retrospectively reviewed to identify factors that distinguish squamous cell carcinoma or high-grade intraepithelial neoplasia from low-grade intraepithelial neoplasia or non-atypia lesions. RESULTS: The overall sensitivity, specificity, accuracy, and positive and negative predictive value of background colouration and intrapapillary capillary loop pattern in differentiation of squamous cell carcinoma or high-grade intraepithelial neoplasia from low-grade intraepithelial neoplasia or non-atypia lesions were all 100 per cent. CONCLUSION: Diagnosis based on background colouration and the intrapapillary capillary loop pattern on narrow-band imaging facilitates the pathological examination of lesions measuring equal to or less than 5 mm.

Prospective study of kinesthesia after ACL reconstruction.

Previous studies used a variety of methods to assess kinesthesia, thus no consensus exists regarding kinesthetic adaptation after anterior cruciate ligament (ACL) reconstruction. This study prospectively examined whether kinesthesia is adapted after ACL reconstruction, and then discussed the actual angular velocity required to properly assess kinesthesia in ACL-reconstructed patients. 31 patients were evaluated using the threshold to detect passive motion (TTDPM) test, which was applied preoperatively, and at 3, 6, and 12 months following surgery. TTDPMs were measured at 15° or 45° of knee flexion toward both extension and flexion with angular velocities of 0.1°/s or 0.2°/s. ACL-reconstructed knees showed significantly impaired TTDPMs compared to healthy knees before the operation at 15° of knee flexion toward extension and at 45° of knee flexion toward both extension and flexion at 0.2°/s (15° of knee flexion toward extension, P=0.036; 45° of knee flexion toward extension, P=0.015; 45° of knee flexion toward flexion, P=0.030). However, there were no significant differences after 3 months of follow-up. On the basis of these results, applying 0.2°/s seems appropriate to assess TTDPM for patients with an ACL reconstruction, and kinesthesia is adapted within 12 months after the operation. Sensory function and biomechanical stability are also adapted following ACL reconstruction.

The common mechanisms of anterior cruciate ligament injuries in judo: a retrospective analysis.

BACKGROUND: Although high prevalence of anterior cruciate ligament injuries (ACL) in judokas has been reported, there has been very little research concerning events preceding the injury. OBJECTIVE: To determine the common situations and mechanisms of ACL injury in judo. METHODS: A total of 43 cases of ACL injuries that had occurred during judo competition or practice were investigated, using questionnaires with interviews conducted by a single certified athletic trainer who has 20 years of judo experience to obtain information regarding the situation and mechanism in which the ACL injury occurred. RESULTS: The number of ACL injuries when the participant's grip style was different from the style of the opponent (ie, kenka-yotsu style) (28 cases) was significantly greater than when the participant's grip style was the same as that of the opponent (ie, ai-yotsu style) (15 cases; p<0.001). The number of ACL injuries was significantly higher when the participant was attacked by the opponent than when counterattacked or when attempting the attack (p<0.001). In addition, being attacked with osoto-gari was revealed as the leading cause of ACL injury incidence among the participants (16.8%). CONCLUSIONS: Grip style may be associated with ACL injury occurrence in judo. In addition, direct contact due to the opponent's attack may be a common mechanism for ACL injuries in judo.

Metachronous multiple esophageal squamous cell carcinomas and Lugol-voiding lesions after endoscopic mucosal resection.

BACKGROUND AND STUDY AIMS: Endoscopic mucosal resection (EMR) has been applied to the treatment of superficial esophageal squamous cell carcinoma (SCC). The incidence and characteristics of metachronous multiple esophageal SCCs and Lugol-voiding lesions (LVLs) were investigated in a retrospective study in patients who had undergone EMR for superficial esophageal SCC. PATIENTS AND METHODS: 96 patients with esophageal SCC who had been treated by EMR were followed up by endoscopy for 12 months or longer. Clinicopathologic parameters such as tumor size and location and presence of LVLs were examined. RESULTS: 10 patients (10 %) had synchronous multiple SCCs, and 12 (13 %) developed metachronous multiple SCCs. The mean annual incidence of newly diagnosed tumor was 4.4 %. The incidence of a speckled pattern of LVLs was 20/74 (27 %) in patients with solitary SCC, 5/10 (50 %) in synchronous multiple SCC, and 10/12 (83 %) in metachronous multiple SCC. The incidence of the presence of speckled pattern of LVLs was significantly higher in patients with multiple SCCs than in those with solitary SCC (68 % vs. 27 %, P = 0.0004). CONCLUSIONS: Patients who have undergone EMR for esophageal SCC, especially those with metachronous multiple LVLs in the background mucosa, should undergo follow-up with close endoscopic observation using Lugol staining.

Development of porosity in carbons from yeast grains by activation with alkali metal carbonates.

Cellular structured activated carbon samples were prepared with the aid of alkali carbonates X2CO3 (X = Li, Na, K, Rb, or Cs) from dry bread yeast with a milling procedure. The resultant carbon possesses a very large adsorption amount even for supercritical methane. The activation with Cs2CO3 gave the greatest surface area of 2420 m2 g(-1) from the subtracting pore effect method. The activation efficiency of X2CO3 (X = Li, Na, K, Rb, and Cs) was associated with the order of Gibbs free energy of X2O (X = Li, Na, K, Rb, and Cs) which should play an important role in the gasification. The carbon activated with Rb2CO3 gave the greatest adsorption amount of supercritical methane of 90 mg g(-1) at 0.9 MPa at 303 K.

Olefin hydrosilylation catalyzed by cationic nickel(ii) allyl complexes: a non-innocent allyl ligand-assisted mechanism.

The arene-supported cationic nickel allyl complexes serve as good catalysts for olefin hydrosilylation at room temperature. Detailed mechanistic studies based on experiments and DFT calculations support the novel mechanism, which includes the facile Si-H bond cleavage and Si-C bond formation, assisted by a non-innocent allyl ligand.

Apical segmental dysfunction in hypertrophic cardiomyopathy: subgroup with unique clinical features.

A segmental wall motion abnormality is an unusual finding in patients with hypertrophic cardiomyopathy. To clarify its clinical significance, 48 patients with hypertrophic cardiomyopathy were analyzed. Eight patients (Group A) had apical segmental dysfunction; 40 (Group B) had normal wall motion. No patient in either group had coronary artery stenosis on selective coronary arteriography. In all patients in Group A, apical segmental dysfunction was revealed by left ventriculography; however, it could be detected by echocardiography in only two patients in Group A. Left ventricular hypertrophy by electrocardiogram (ECG) was more common in Group B (p less than 0.05). Abnormal Q waves were more frequently discovered in Group A (p less than 0.005) and were recognized predominantly in the lateral leads. On serial ECGs, a gradual development of abnormal Q waves was noted in six of eight patients in Group A. Malignant arrhythmias were more common in Group A (p less than 0.001). In two patients in Group A, left ventricular dilation and congestive heart failure developed during the follow-up period. Thus, the presence of a Q wave in the lateral leads on an ECG in patients with hypertrophic cardiomyopathy may indicate the presence of apical segmental dysfunction. Left ventriculography should be performed to examine the presence of this abnormality and 24 h ambulatory ECG monitoring should be done to detect malignant arrhythmias in patients who have abnormal Q waves in the lateral leads. Patients with this unique type of hypertrophic cardiomyopathy need careful follow-up evaluation.

Homogeneous distribution and pressure dependent reduction of coronary blood flow in right ventricular free wall during coronary hypoperfusion in anaesthetised open chest dogs.

Relationship of coronary perfusion pressure with total and regional myocardial blood flow in right ventricular free wall was studied in 10 anaesthetised open chest dogs. The right coronary artery was perfused by an autoperfusion system from the carotid artery. Total coronary blood flow into the perfused area was measured by an extracorporeal electromagnetic flow probe. Critical perfusion pressure of the right coronary artery, defined as the lowest pressure level below which the regional wall motion deteriorated, was 39(SEM1) mm Hg. Reactive hyperaemia was noted at 60(2) mm Hg, a level well above the critical perfusion pressure. There was an inverse linear relation between the level of reactive hyperaemia and perfusion pressure. Regional myocardial blood flow was measured by a tracer microsphere technique at control condition, just above and below the critical perfusion pressures and during coronary occlusion. This correlated closely with values obtained by an electromagnetic flow probe (r = 0.94, p less than 0.001) and both values were dependent on the level of perfusion pressure. Endocardial to epicardial flow ratio remained at unity at any level of coronary perfusion pressure. Thus the level of coronary perfusion pressure was a major determinant of the regional myocardial blood flow into the right coronary artery, and autoregulation of the regional myocardial blood flow was not apparent across the wall, despite the presence of a reactive hyperaemia.

Beneficial effects of a serine protease inhibitor in peripheral vascular disease.

Kallikrein, a serine protease known to generate bradykinin (a vasodilating peptide) in alkaline conditions, also generates angiotensin II (a vasoconstricting peptide) in weak acidic conditions. Based on this previous observation, the present study was performed to determine whether ischemic muscle tissue, in which the regional pH must decrease, produces angiotensin II by kallikrein or a similar enzyme, and whether nafamostat (NAF), a serine protease inhibitor, improves local hemodynamics under ischemic conditions caused by exercise in patients with ischemic peripheral vascular disease. NAF was administered intravenously to 20 patients with peripheral vascular disease. Lower-limb thermograms and blood flow were measured before and after exercise. Femoral venous blood of affected limbs was obtained to measure viscosity and humoral variables (i.e., pH, lactate, angiotensin II and bradykinin). Walking distance and subjective symptoms were also recorded. As a control, the same patients repeated this test with saline infusion on a separate day. NAF significantly increased maximal walking distance, improved subjective symptoms during exercise, and attenuated exercise-induced venous lactate and blood viscosity increases, and pH reduction. The blood viscosity increase correlated with the lactate increase. Pretreatment with NAF also resulted in a higher lower-limb skin temperature, and a greater increase of blood flow in the lower limbs after exercise than did pretreatment with saline. The results suggest that kallikrein-like serine protease may exacerbate ischemic symptoms. Changes in plasma bradykinin and angiotensin II in the femoral vein were not detectable, probably because of the lower levels of these peptides in the peripheral circulation.

Development of a new drug delivery system for protein drugs using silicone (II).

In order to achieve a zero-order release of protein drugs, we have developed a new drug delivery system using silicone, which is named the covered-rod-type formulation. Preparation of the covered-rod-type formulation was conducted under mild conditions without heat treatment or the use of organic solvents. The covered-rod-type formulation released human serum albumin (HSA) or interferon (IFN) at a constant rate for 30-100 days in vitro without significant initial burst. When the IFN covered-rod-type formulation was implanted in nude mice, the serum IFN concentration was maintained at a constant level during the period of observation, i.e., 28 days. The covered-rod-type formulation enabled precise control of the release of the protein drugs and would be expected to increase the duration of the drug effect and to reduce the frequency of administration and side effects.

Development of new drug delivery system for protein drugs using silicone (I).

A novel technique, by which protein drugs effective in small doses can be released over a long period, was developed using silicone and a water-soluble substance. In this study, interferon (IFN) was used as a model of the protein drugs. The IFN-silicone formulation released IFN over long periods of time in vitro and suppressed tumor growth in nude mice for about 100 days after a single administration. This indicates that physiologically active IFN is released over a prolonged period of time from the IFN-silicone formulation in vivo. Silicone formulations are expected to be a practically feasible sustained-release formulation.

Effects of intracoronary infusion of atrial natriuretic peptide on pacing-induced myocardial ischemia in patients with effort angina pectoris.

BACKGROUND: Atrial natriuretic peptide (ANP) has been shown to dilate the coronary artery. The aim of this study was to determine whether, in patients with effort angina pectoris, intracoronary infusion of ANP attenuates pacing-induced myocardial ischemia either by dilating the stenotic lesion in a large coronary artery or by dilating collateral vessels. METHODS: We studied six patients who had total or subtotal occlusion in one coronary artery and well-developed, angiographically visible collateral vessels (group A) and five patients who had a significant stenosis in a large coronary artery with no visible collateral vessels (group B). Their heart rate was increased by atrial pacing both before and after intracoronary infusion of ANP (0.03 microgram/kg/min for 15 min) into the donor artery of collateral vessels in group A or into the stenotic artery in group B. RESULTS: Before ANP infusion, all patients of both groups developed an ischemic ST-segment depression (> or = 0.1 mV) and angina-like chest pain from pacing tachycardia. After ANP infusion, significant ST-segment depression was induced by rapid pacing in only one out of six patients of group A, whereas it was noted in all patients of group B (P < 0.01). After ANP infusion, chest pain developed in one out of six patients in group A, whereas it appeared in four out of five patients in group B (P < 0.05). ANP significantly dilated the angiographically normal segment of the epicardial coronary artery, but it did not significantly change the severity of the stenotic lesion in either group. ANP did not change the basal arterial pressure or heart rate, nor did it change their response to pacing tachycardia. CONCLUSION: Infusing ANP into the donor artery of collateral vessels, but not into the artery with culprit stenotic lesion, attenuated pacing-induced myocardial ischemia. Therefore, the beneficial effects of ANP in reducing pacing-induced myocardial ischemia may result from the increase in myocardial perfusion to the ischemic area caused by dilating the collateral vessels.

Dissociation of vascular tolerance and plasma norepinephrine adjustment during long-term nitrate therapy in human coronary arteries.

OBJECTIVE: We examined whether changes in plasma norepinephrine (NE) concentration contribute to the development of nitrate tolerance in human coronary arteries. METHODS: Patients with stable angina were randomized to receiving nitrate (isosorbide dinitrate: ISDN or nitroglycerin: TNG) infusion for 30 minutes (group A), 48 hours (group B), or 78 hours (group C). Coronary diameters were measured angiographically at baseline (CT), during maximum dilation by ISDN (N1), at the end of nitrate infusion (N2) and after additional ISDN (1 mg) injection (N3). RESULTS: In groups A and B, N1, N2, and N3 were greater than CT, and there was no significant difference between N1, N2, and N3 for each group. In group C, N1 and N3 were greater than CT, but there was no difference between CT and N2, in the development of nitrate tolerance. In group A, NE increased significantly during nitrate infusion (304+/-163 vs. 418+/-273 pg/ml). NE did not change in groups B and C. CONCLUSION: The change in NE concentration is not a primary contribution to the development of nitrate tolerance.

Retrospective analysis of the multidisciplinary treatment for 534 hepatocellular carcinoma patients over a 12-year period.

Multidisciplinary treatments for 534 patients with hepatocellular carcinoma (HCC) over a 12-year period from 1981 to 1992 were retrospectively studied. Cumulative survival curve of all patients showed a fine hyperbolic curve, and 1-year, 3-year-, 5-year survivals were 66, 33, and 18%, respectively. Survival of female patients was better than male patients, and survival of HBsAg-negative patients was better than that of HBsAg-positive patients. Several background factors such as the Child-Pugh classification, liver function tests or factors, number of tumors, and the size of the main tumor were analyzed, and each factor was related to survival. Survival curves of 3 treatments, hepatectomy, percutaneous ethanol injection (PEI), and transcatheter arterial embolization (TAE)+PEI, overlapped to a large degree. Also the survival curve of the more recent 6-year period from 1987 to 1992 was better than that of the earlier 6-year period from 1981 to 1986.

Proliferating cell nuclear antigen and grade of malignancy in small hepatocellular carcinoma--evaluation in US-guided specimens.

BACKGROUND/AIMS: We investigated the value of the proliferating cell nuclear antigen labeling index ratio (PCNA-LI ratio: PCNA-LI of cancer/PCNA-LI of surrounding non-cancerous liver tissue) to clarify the prognosis of the patients bearing small hepatocellular carcinomas (HCC) less than 20 mm in diameter and treated by percutaneous ethanol injection therapy (PEIT). MATERIAL AND METHODS: Twenty eight HCC patients who had received PEIT were divided into 3 groups. The non-recurrence (NR) group in which no new lesions were observed for at least 18 months after PEIT (13 patients), the early recurrence group (ER) in which lesions recurred within one year (6 patients), and the late recurrence group (LR) in which lesions recurred more than one year after PEIT (9 patients). Immunohistochemical staining of PCNA was done using biopsied specimens. RESULTS: The PCNA-LI ratio in 37 well differentiated, 13 moderately differentiated, 11 poorly differentiated HCC were 1.86 +/- 0.55, 3.33 +/- 0.51, and 4.75 +/- 0.81 (mean +/- SD), respectively. The ratio in ER group (4.57 +/- 0.57) was significantly higher than that in LR (2.04 +/- 0.61) and NR group (1.87 +/- 0.62) and the PCNA-LI ratio tended to correlate with the periods until the development of recurrent lesions in cases of ER group. CONCLUSIONS: These results indicate the PCNA-LI ratio, in conjunction with the histological grade, is a useful marker for evaluating the grade of malignancy, and for predicting the period until recurrence after treatment of small HCC.