Eiji Sasaki

Immunohistochemically Demonstrated Lymph Node Micrometastasis and Prognosis in Patients With Gallbladder Carcinoma

Objective:To investigate whether immunohistochemically demonstrated lymph node micrometastasis has a survival impact in patients with advanced gallbladder carcinoma (pT2–4 tumors). Summary Background Data:The clinical significance of immunohistochemically detected lymph node micrometastasis recently has been evaluated in various tumors. However, few reports have addressed this issue with regard to gallbladder carcinoma. Methods:A total of 1476 lymph nodes from 67 patients with gallbladder carcinoma (pN0, n = 40; pN1, n = 27) who underwent curative resection were immunostained with monoclonal antibody against cytokeratins 8 and 18. The results were correlated with clinical and pathologic features and with patient survival. Results:Lymph node micrometastases were detected immunohistochemically in 23 (34.3%) of the 67 patients and in 37 (2.5%) of the 1476 nodes examined. Of the 37 nodal micrometastases, 21 (56.8%) were single-cell events, and the remaining 16 were clusters. Five micrometastases were detected in the paraaortic nodes. Clinicopathologic features showed no significant associations with the presence of lymph node micrometastases. Survival was worse in the 27 patients with pN1 disease than in the 40 with pN0 disease (5-year survival; 22.2% vs. 52.6%, P = 0.0038). Similarly, survival was worse in the 23 patients with micrometastasis than in the 44 without micrometastasis (5-year survival; 17.4% vs. 52.7%, P = 0.0027). Twenty-eight patients without any lymph node involvement had the best prognosis, whereas survival for the 11 patients with both types of metastasis was dismal. The grade of micrometastasis (single-cell or cluster) had no effect on survival. The Cox proportional hazard model identified perineural invasion, lymph node micrometastasis, and microscopic venous invasion as significant independent prognostic factors. Conclusions:Lymph node micrometastasis has a significant survival impact in patients with pN0 or pN1 gallbladder carcinoma who underwent macroscopically curative resection. Extensive lymph node sectioning with keratin immunostaining is recommended for accurate prognostic evaluation for patients with gallbladder carcinoma.

Acid and Duodenogastroesophageal Reflux after Esophagectomy with Gastric Tube Reconstruction

OBJECTIVE:Patients who undergo esophagectomy with gastric tube reconstruction incur increased risk for acid reflux and duodenogastroesophageal reflux. Few postesophagectomy studies of gastroesophageal reflux disease have included simultaneous 24-h pH and bilirubin monitoring. The aim of this study is to evaluate acid reflux and duodenogastroesophageal reflux after esophagectomy with gastric tube reconstruction.METHODS:Reflux symptom evaluation, endoscopy, and simultaneous 24-h pH and bilirubin monitoring in the cervical esophagus were performed in 25 patients who underwent Ivor Lewis esophagectomy, intrathoracic esophagogastrostomy, and digital dilation of the pyloric ring as treatment for esophageal cancer.RESULTS:Reflux symptoms were severe, mild, and absent in 2, 7, and 16 patients, respectively. Reflux esophagitis and Barretts esophagus was observed in 11 and 1 patients, respectively. Elevated acid reflux occurred in 7 patients (28%). Elevated duodenogastroesophageal reflux was recorded in 11 patients (44%). Reflux profile analysis identified three patterns: 4 subjects (16%) with both elevated acid reflux and duodenogastroesophageal reflux; 3 (12%) with only elevated acid reflux; and 7 (28%) with only elevated duodenogastroesophageal reflux. Of 7 patients with only elevated duodenogastroesophageal reflux, 4 developed reflux esophagitis. Although reflux symptoms did not correlate with endoscopic esophagitis, a significant correlation was observed between endoscopic esophagitis and acid reflux and/or duodenogastroesophageal reflux.CONCLUSIONS:Reflux symptoms represented a poor indication of esophagitis in patients with esophagectomy and gastric tube reconstruction. Simultaneous 24-h pH and bilirubin monitoring can help in identifying patients at high risk for reflux esophagitis, as well as indicating the cause of esophagitis.

Nocturnal Knee Pain Increases With the Severity of Knee Osteoarthritis, Disturbing Patient Sleep Quality

Sleep disturbances frequently accompany chronic pain from osteoarthritis (OA). Effective management of sleep disturbances may require successful treatment of chronic pain, a key factor in the clinical evaluation of knee OA. However, the relationship between the severity of knee OA and sleep quality is unclear. Our purpose was to correlate the prevalence of nocturnal knee pain with different OA severity levels and to determine its influence on sleep quality.

Prospective Randomized Study of Objective and Subjective Clinical Results Between Double-Bundle and Single-Bundle Anterior Cruciate Ligament Reconstruction

Background: There is controversy as to whether double-bundle anterior cruciate ligament (ACL) reconstruction with hamstring tendon graft (DB-HT) or single-bundle ACL reconstruction with patellar tendon graft (SB-PT) obtains the best clinical outcomes. Purpose: To compare the short-term clinical outcomes of DB-HT with those of rectangular-tunnel SB-PT (RTSB-PT) at 2-year follow-up and to identify the factors that affect subjective knee functional score. Study Design: Randomized controlled trial. Level of evidence, 1. Methods: Sixty-three male patients (mean age, 26.1 years) and 87 female patients (mean age, 25.8 years) were included in this study and were randomly distributed to either the DB-HT (n = 76) or RTSB-PT (n = 74) group. Clinical outcomes (knee flexion range of motion [ROM], heel-height difference, side-to-side difference in anterior laxity, rotational laxity, and Tegner activity score) were compared between the DB-HT and RTSB-PT groups, and examination of factors affecting subjective outcomes (Knee Injury and Osteoarthritis and Outcome Score [KOOS] results) was performed by multiple linear regression analysis. Results: Fourteen patients (9 DB-HT, 5 RTSB-PT) had secondary ACL injury within 2 years after primary ACL reconstruction and were excluded from analysis. In the examination of 136 patients at the 24-month follow-up, there was no significant difference between the 2 groups in clinical or subjective outcomes. The normalized knee extensor strength of the RTSB-PT group showed negative surgical technique effect in the early postoperative phase (P = .005), but there was no significant difference between the 2 groups at the 24-month follow-up (P = .114). There was no significant difference in change of normalized knee flexor strength between the 2 groups (P = .493). Age, sex, body mass index (BMI), and presence of meniscus injury were the factors that affected KOOS subscale scores. Conclusion: In this prospective randomized controlled study, there was no significant difference in the incidence of secondary ACL injury and no difference in objective or subjective outcomes between the DB-HT and RTSB-PT reconstruction at 24-month follow-up. Age, sex, presence of meniscus injury, and BMI affected subjective KOOS subscale scores, while surgical technique did not.

Effect of glutamine supplementation on neutrophil function in male judoists.

Glutamine is an important amino acid for immune function. Though high intensity and prolonged exercise decreases plasma glutamine concentration and causes immune suppression, the relationship between neutrophil functions and glutamine has not yet been found. The purpose of this study was to investigate the impacts of glutamine supplementation on neutrophil function. Twenty-six male university judoists were recruited. Subjects were classified into glutamine and control groups. The glutamine group ingested 3000 mg of glutamine per day and the control group ingested placebo for 2 weeks. Examinations were performed at the start of preunified loading exercise (pre-ULE), then 1 and 2 weeks after ULE (post-ULE). Reactive oxygen species (ROS) production, phagocytic activity, serum opsonic activity and serum myogenic enzymes were measured. Differences between the levels obtained in pre-ULE and post-ULE for the two groups were compared. In the glutamine group, ROS production activity increased 1 week after ULE, whereas it was not observed in the control group (P < 0.001). Though myogenic enzymes increased significantly after ULE (P < 0.001), the glutamine group remained unchanged by supplementation during ULE. Glutamine supplementation has prevented excessive muscle damage and suppression of neutrophil function, especially in ROS production activity, even during an intensive training period.

Influence of obesity on blood pressure and arterial stiffness in the early teens

PROBLEM We studied the influence of adiposis on the progression of blood pressure and arteriosclerosis in the early teens. METHODS The subjects of this study were 147 boys and girls (72 boys and 75 girls) in junior high school. Height, weight, percentage body fat, blood pressure, brachial-ankle pulse wave velocity (baPWV) and exercise time were measured. All subjects were measured at two points--at 5th grade in elementary school (ages between 10 and 11 years) and 2nd grade in junior high school (8th grade, ages between 13 and 14 years). The relationship between the change values of adiposis over 3 years (from 5th grade to 8th grade) and blood pressure/baPWV at the age of 13-14 were analyzed with multiple regression analysis. RESULTS For boys, the change values in BMI and percentage body fat were correlated positively with systolic blood pressure. For girls, the change values in BMI and percentage body fat were correlated positively with systolic and diastolic blood pressures and baPWV. CONCLUSIONS In conclusion, raised blood pressure was already observed in obese early teens as a result of arteriosclerosis progression regardless exercise habit, and it was more apparent in girls.

Comparison of gastroesophageal reflux in 100 patients with or without prior gastroesophageal surgery

Background and purposeThe role of duodenogastroesophageal reflux (DGER) in gastroesophageal reflux disease (GERD) remains controversial. Few studies of reflux have compared patients with an intact stomach to those without intact stomach after gastroesophageal surgery. This study aimed to investigate differences of the refluxate between patients with and without prior gastroesophageal surgery and to assess the role of DGER in GERD.MethodsOne hundred patients (34% with reflux symptoms) were divided into four groups: 23 with an intact stomach, and 27, 42, and 8 with esophagectomy followed by gastric tube reconstruction, distal gastrectomy, and total gastrectomy, respectively. Reflux symptoms were evaluated, and endoscopy and simultaneous 24-h monitoring of esophageal pH and bilirubin were performed.ResultsOf 44 patients with increased DGER but without increased acid reflux, three had severe reflux esophagitis and seven had Barrett’s esophagus. DGER was most frequent under weakly acidic conditions in the intact stomach, esophagectomy, and distal gastrectomy groups. Pure acid reflux and DGER at any pH were elevated in GERD patients with an intact stomach, while weakly acidic and alkaline DGER were elevated in GERD patients after gastrectomy. Esophagectomy patients had reflux with the combined characteristics of those in the intact stomach and gastrectomy groups. Weakly acidic or alkaline DGER was correlated with symptoms and esophageal mucosal changes in gastrectomy patients.ConclusionThe refluxate causing GERD differed between patients with and without prior gastroesophageal surgery. Weakly acidic or alkaline DGER may cause both symptoms and esophageal mucosal damage.

Changes in neutrophil functions during a 10-month soccer season and their effects on the physical condition of professional Japanese soccer players

We examined changes in neutrophil function of soccer players over a 10-month period and determined its effectiveness as an index for athlete physical condition. Subjects included 21 male professional Japanese soccer players. Data on body composition, myogenic enzymes and neutrophil function were obtained before and after 2 h of training at 3 investigation points: one week before opening season, at season mid-point, and one week before the last game of the season. As a result, change ratios of myogenic enzyme levels before and after the 2-hr training session at the third investigation point were significantly higher compared to the two other points. Reactive oxygen species production and phagocytic activity significantly increased after 2-hr training session at point 1, although the extent of the increase became smaller over time and ROS production capability decreased significantly by point 3 assessment. Fatigue, especially muscle fatigue, chronically accumulated along with a gradual decrease in neutrophil immune function over the 10-month season. Therefore, determination of neutrophil function can be used as a useful index to assess and understand an athletes physical condition.

The Knee injury and Osteoarthritis Outcome Score reflects the severity of knee osteoarthritis better than the revised Knee Society Score in a general Japanese population

PURPOSE The purposes of this study were to examine population-based reference data for sex- and age-related differences between the 2011 revised Knee Society Score (KSS2011) and the Knee injury and Osteoarthritis Outcome Score (KOOS), to assess the correlation between those scores and radiographic knee osteoarthritis (OA), and to validate the use of the scores in a general Japanese population. METHODS This cross-sectional study included 963 volunteers (368 males, 595 females; mean age: 54.7years). Participants were classified into five subgroups by age: under 40, 40s, 50s, 60s, and over 70years old. The KSS2011 and KOOS were determined using self-administered questionnaires. Weight-bearing radiographs of the bilateral knee were taken and graded according to the Kellgren-Lawrence (KL) scale. The mean KSS2011 and KOOS were compared among age groups. Correlations between the severity of knee OA and each score were assessed using multiple regression analysis. RESULTS The overall KSS2011 tended to gradually decrease with age. Most subscales of the KSS2011 did not show sex-related differences. Similarly, the overall KOOS and all its subscales steadily decreased by approximately 20 points per decade with age. Most subscales of the KOOS were significantly decreased in females over 50. The KL grade was significantly related to both the overall KOOS (β=-0.42, p<0.001) and KSS2011 (β=-0.13, p=0.001), though the correlation to the KOOS was stronger. CONCLUSION The overall KSS2011 and KOOS appear to decrease with age. In this population, the KOOS reflects the severity of knee OA better than the KSS2011.

A comprehensive expression analysis of mucins in appendiceal carcinoma in a multicenter study: MUC3 is a novel prognostic factor.

Background Mucins are implicated in survival in various cancers, but there have been no report addressed on survival in appendiceal carcinoma, an uncommon disease with different clinical and pathological features from those of other colon cancers. We aimed to investigate the clinical implications of expression of mucins in appendiceal carcinoma. Methods Expression profiles of MUC1, MUC2, MUC3, MUC4, MUC5AC, MUC6, MUC16 and MUC17 in cancer tissue were examined by immunohistochemistry in 108 cases of surgically resected appendiceal carcinoma. Results The following relationships of mucins with clinicopathologic factors were identified: MUC1 with positive lymphatic invasion (p = 0.036); MUC2 with histological type (mucinous carcinoma, p<0.001), superficial invasion depth (p = 0.007), negative venous invasion (p = 0.003), and curative resection (p = 0.019); MUC3 with non-curative resection (p = 0.017); MUC5AC with histological type (mucinous carcinoma, p = 0.002), negative lymphatic invasion (p = 0.021), and negative venous invasion (p = 0.022); and MUC16 with positive lymph node metastasis (p = 0.035), positive venous invasion (p<0.05), and non-curative resection (p = 0.035). A poor prognosis was related to positive lymph node metastasis (p = 0.04), positive lymphatic invasion (p = 0.02), positive venous invasion (p<0.001), non-curative resection (p<0.001), and positive expression of MUC3 (p = 0.004). In multivariate analysis, positive venous invasion (HR: 6.93, 95% CI: 1.93–24.96, p = 0.003), non-curative resection (HR: 10.19, 95% CI: 3.05–34.07, p<0.001) and positive MUC3 expression (HR: 3.37, 95% CI: 1.13–10.03, p = 0.03) were identified as significant independent prognostic factors in patients with appendiceal carcinoma. Conclusions Expression of MUC3 in appendiceal carcinoma is an independent factor for poor prognosis and a useful predictor of outcome in patients with appendiceal carcinoma after surgery.