Stability of cervical esophagogastrostomy via hand-sewn anastomosis after esophagectomy for esophageal cancer.

The aim of the present study is to evaluate the outcome of hand-sewn esophagogastric anastomosis during radical esophagectomy for esophageal cancer. The outcomes of 467 consecutive esophageal cancer patients who underwent cervical esophagogastric anastomosis using interrupted and double-layered sutures after radical esophagectomy via right thoracotomy or thoracoscopic surgery were retrospectively reviewed. Anastomotic leakage, including conduit necrosis, occurred in 11 of 467 patients (2.4%); 7 of 11 (63.6%) cases experienced only minor leakage, whereas the other four (36.4%) patients had major leakage that required surgical or radiologic intervention, including two patients of conduit necrosis. Anastomotic leakages were more frequently observed after retrosternal reconstruction compared with the posterior mediastinal route (P < 0.0001). The median time to healing of leakage was 40 days (range: 14-97 days). Two patients (2/467, 0.4%) died in the hospital due to sepsis caused by the leakage and conduit necrosis. Twelve patients (2.6%) developed anastomotic stenosis, which was improved by dilatation in all patients. Hand-sewn cervical esophagogastric anastomosis is a stable and highly safe method of radical esophagectomy for esophageal cancer.

Locomotive Syndrome: Operational Definition Based on a Questionnaire, and Exercise Interventions on Mobility Dysfunction in Elderly People.

The increasing elderly population has a great impact on public health, and it is important to understand the progression of musculoskeletal disorders seen in this population. To establish useful preventative methods for such locomotive disorders, we must detect early changes in these individuals and identify those at risk in order to implement early interventions. The purpose of this review was: (1) to introduce an operational definition of locomotion dysfunction to prevent a care-need condition, and to verify its validity through a prospective cohort study, and (2) to review the indication of exercise intervention for multiple musculoskeletal involvements from the preceding literature. We developed a measurement scale called the Geriatric Locomotive Function Scale (GLFS)-25, which clearly reflects the degree of functional deterioration. We used it in a prospective cohort study of 314 patients recruited from 5 clinics or nursing care facilities and investigated the relationship of the GLFS-25 with 46 variables covering various clinical manifestations. The results clearly revealed that the change in the GLFS-25 classification reflected a common pattern seen in those with locomotive dysfunction. Recently, several important movements regarding physical activity and its public promotion have been advocated by international health organizations and journal publishers. Though it has not been confirmed yet that complex musculoskeletal diseases can be treated using therapeutic exercise, the promotion of physical activity appears promising. The degree of activity limitation in aged individuals with locomotive disorders can be evaluated using this scale, which may be useful in predicting the effectiveness of future interventions.

Intestinal epithelial culture under an air-liquid interface: a tool for studying human and mouse esophagi.

This study investigated whether an intestinal epithelial culture method can be applied to mouse and human esophageal cultures. The esophagi harvested from 1-day-old mice and adult humans were maintained in collagen gels. A commercially available culture medium for human embryonic stem cells was used for the human esophageal culture. We discovered that the intestinal epithelial culture method can be successfully applied to both mouse and human esophageal cultures. The long-term cultured esophageal organoids were rod-like luminal structures lined with myofibroblasts. We discovered that regeneration of the esophageal mucosal surface can be almost completely achieved in vitro, and the advantage of this method is that organoid cultures may be generated using host-derived fibroblasts as a niche. This method is a promising tool for mouse and human research in intestinal biology, carcinogenesis, and regenerative medicine.

Soft-plastic brace for lower limb fractures in patients with spinal cord injury.

STUDY DESIGN: Retrospective study at a rehabilitation center. OBJECTIVES: Patients with spinal cord injury, even if they are wheelchair users, sometimes suffer from fractures of the lower limb bones. As their bones are too weak to have surgery, and because a precise reduction is not required for restoration, such patients are often indicated for conservative treatment. This case series study investigated the use of a hinged, soft-plastic brace as a conservative approach to treating fractures of the lower extremities of patients with spinal cord injury. SETTING: National Rehabilitation Center, Japan. METHODS: Fifteen patients (male, n=10; female, n=5; average age, 52.7 years) with 19 fractures of the femur or the tibia who were treated with a newly-developed hinged, soft-plastic brace were studied. All of them used wheelchairs. We analyzed the time taken for fracture union and for wearing orthotics, degree of malalignment, femorotibial angle and side effects. RESULTS: The fractures in this series were caused by relatively low-energy impact. The average time taken for fracture union was 80.1 (37-189) days, and the average amount of time spent wearing orthotics was 77.9 (42-197) days. On final X-ray imaging, the average femorotibial angle was 176.9° (s.d. ±8.90), and 15° of misalignment in the sagittal plane occurred in one patient. CONCLUSION: A hinged, soft-plastic brace is a useful option as a conservative approach for treating fractures of the lower extremities in patients with spinal cord injury.

Aberrant maspin expression in gallbladder epithelium is associated with intestinal metaplasia in patients with cholelithiasis.

OBJECTIVE: Aberrant expression of maspin protein related to DNA hypomethylation in the promoter region is frequently observed in gallbladder carcinomas, whereas the non-tumorous gallbladder epithelium is maspin negative. We investigated maspin expression in non-tumorous gallbladder epithelium in patients with cholelithiasis. METHODS: An immunohistochemical study of maspin expression was performed in 69 patients with cholelithiasis and 30 patients with gastric cancer without cholelithiasis. RESULTS: Immunoreactivity for maspin was observed in focal and patchy regions of the gallbladder epithelium. Positive immunoreactivity for maspin was significantly associated with the presence of intestinal metaplasia in patients with cholelithiasis (p<0.05). CONCLUSION: The high incidence of aberrant maspin expression in both intestinal metaplasia and carcinoma of the gallbladder supports the assumption that intestinal metaplasia of the gallbladder may predispose to gallbladder carcinoma.

Cardiorespiratory responses during passive walking-like exercise in quadriplegics.

STUDY DESIGN: Cross-sectional and comparative investigation using quadriplegics (QP) and nondisabled subjects (ND). OBJECTIVE: To evaluate cardiorespiratory responses during passive walking-like exercise (PWE) in QP. SETTING: National Rehabilitation Center for Persons with Disabilities in Japan. METHOD: The subjects were seven male QP with complete lesion (age: 27.0 +/- 5.4, injured level: C6-C7) and six male ND (age: 26.3 +/- 4.5). Cardiorespiratory responses were measured until voluntary fatigue during PWE, the rhythmical activity of paralyzed lower limbs synchronized with arm movements. RESULTS: There were no significant differences in oxygen consumption (VO(2)), pulmonary ventilation (VE), heart rate (HR) and oxygen pulse (O(2) pulse) between QP and ND during PWE. ND showed increased ventilatory equivalent for oxygen (VE/VO(2) ratio) during exercise, while QP showed a significantly greater respiratory rate (RR) during exercise than ND (P < 0.05). CONCLUSION: PWE elicited an increase in VO(2) with workload increment in QP similar to ND. However, higher RR suggested the intrinsic dysfunction of RR control during submaximal exercise in QP. From these results, it was thought that respiratory response would be the restriction factor of efficient oxygen transportation during PWE in QP.

True carcinosarcoma of the esophagus.

Most esophageal carcinosarcomas are diagnosed as so-called carcinosarcoma, in which individual elements may be derived from a single common ancestor cell, and there have been a few reports describing true carcinosarcoma originating from two individual stem cells. We describe a case of esophageal carcinosarcoma exhibiting neoplastic osteoid formation. Immunoreactivity for vimentin and p53 was limited to only the sarcomatous component and was absent in the carcinomatous component. Furthermore, a point mutation in exon 7 of the p53 gene was observed only in the sarcomatous component. Both sarcoma and carcinoma cells distinctively metastasized to different lymph nodes. These observations led us to diagnose the esophageal tumor as a true carcinosarcoma.

A search for calcium, magnesium and zinc levels in fingernails of 135 patients with osteogenesis imperfecta.

Calcium (Ca), magnesium (Mg) and zinc (Zn) levels of fingernails were measured in 135 patients with osteogenesis imperfecta (OI) and compared with the sex- and age-matched healthy controls. Zinc levels in OI nails were significantly higher than that in normal subjects, but in cases and controls Ca and Mg levels were not significantly different. The ratios of Ca/Zn and Mg/Zn in OI nails differed significantly from those in controls, but a similar Ca/Mg ratio was found in nails of both groups. These results suggest that Zn levels in fingernails may reflect abnormal Zn metabolism in OI. To determine Zn metabolism changes in OI, further studies are needed.

Time-course action analysis of daily life investigations in the Welfare Techno House in Mizusawa.

In this study, we have examined the possibility of non-intrusive monitoring at home. We describe the experimental results of the relation between an individual's recorded behavior and the actions detected by the sensors during the course of the subject's daily life. Infrared sensors and the opening of doors and windows and the use of appliances were used. In this paper, it is assumed that the subjects were sleeping when there were no responses by the infrared sensors or when only the bedroom sensor was responding. The sensors were able to detect excretion by using the outputs of the infrared sensor and the water valve of the lavatory, even if a subject did not record it in the time-course of daily life during the investigation. Our findings show that the actions of subjects who stayed at Welfare Techno House (WTH) in Mizusawa could be estimated from outside the house, especially for sleeping and excretion.

Chemoradiotherapy followed by surgery for thoracic esophageal cancer potentially or actually involving adjacent organs.

The objective of this study was to evaluate the therapeutic usefulness of chemoradiotherapy (CRT) followed by surgery in patients with clinically T4 (cT4) esophageal cancer involving adjacent organs such as the trachea, main bronchi, and large vessels. Thirty-seven patients with cT4 squamous cell carcinoma of the thoracic esophagus were enrolled in this study. The CRT regimen comprised cisplatin (70 mg/m2) on day 1, 5-fluorouracil (700 mg/m2) on days 1-4 and external irradiation (200 cGy/day, total 30 Gy) on either days 8-26 (sequential schedule, n=15) or days 1-19 (concurrent schedule, n022). Two courses of CRT were given. The results of CRT were complete response in nine patients, partial response in 19, no change in three (minor response in two), and progressive disease in six patients. The median response duration in all responders was 172 days (range: 56-2469, n=19). After CRT, 13 patients received surgery. In 12 of these patients, tumors were completely resected. Histopathologic examination of the resected specimen revealed a discrepancy between clinical response and histopathologic effect. The median duration of survival and the 1-, 2- and 5-year survival rates were 304 days (84-3155), 45%, 35% and 23% in all patients, respectively, 866 days (190-3155), 83%, 83% and 57% in the 13 patients whose tumors were resected, and 187 days (84--2630), 25%, 5% and 5% in the 24 patients whose tumors were not resected. Grade 3 toxicity, especially hematological reactions, was noted in 13.5% (5/37) of the patients. There was one toxicity-related death (sepsis). A good outcome may be obtained with CRT, followed by surgery when feasible. However, CRT can cause toxic reactions, and close monitoring of patients is required.

[SIRS in surgical stress].

It has been suggested that SIRS are triggered by superfluous pro-inflammatory cytokine production, and that organ injury is caused by uncontrolled inflammatory responses. However, the results of clinical studies, on the usefulness of specific cytokine antagonists and anti-TNF antibodies for the treatment of septic shock, have been unsatisfactory. The reason for this might have been that when uncontrolled inflammatory reactions progressed locally, anti-inflammatory reactions were elevated in the circulated blood by way of CARS, thus the timing of administration and pharmacokinetics did not match clinical course. Recent research has shown that SIRS is always accompanied by CARS, and since it seems to do the amplitude of SIRS and CARS to each other so that there may be a deep valley, if there is a high mountain. We introduce the recent knowledge which indicates that SIRS is a preliminary alert for not only organ dysfunction but also immunosuppression after severe injury or major surgery.

Mutations in mitochondrial control region DNA in gastric tumours of Japanese patients.

The non-coding control region of mitochondrial DNA (mtDNA), containing the hypervariable regions HV1 and HV2 and the D-loop region, was screened for mutations in 45 gastric tumours (15 tumours each of adenoma, differentiated adenocarcinoma and undifferentiated carcinoma). We found mutations in two of the 45 tumours (4%); a 1 bp A deletion at nucleotide position 248 in a differentiated adenocarcinoma and a G to A transition at nucleotide position 16,129 in an adenoma. We also observed 10 polymorphisms, four of which were not previously recorded. Both mtDNA mutations were present in replication error negative (RER-) tumours. Short mono- or dinucleotide repeats in the control region, such as (C)7, (A)5 or (CA)5, were not altered regardless of nuclear genetic instability. In summary, mtDNA is mutated in a subset of benign and malignant gastric tumours, but, disruption of the mtDNA repair system appears not to be significantly involved in gastric tumours of Japanese patients.

Spondylo-epi-metaphyseal dysplasia with normal stature: a case followed from infancy to skeletal maturity.

Spondylo-epi-metaphyseal dysplasia is a rare skeletal dysplasia showing radiographic abnormalities in the epiphyses and metaphyses of the long and short tubular bones, and in the spine. There are very few reports of a case followed throughout the entire growth period. Here we report the case of a Japanese girl followed from 1 month old to skeletal maturity at 16 years old. She developed progressive kyphoscoliosis at 7 years old, and underwent a surgical correction of the spine at 14 years old. The diagnosis of spondylo-epi-metaphyseal dysplasia was made from examining all the follow-up radiographs showing abnormalities in the spine, long bones and hands involving epiphyses and metaphyses. She had normal stature--a rare finding in this condition.

Problems in neoadjuvant chemoradiotherapy preceding surgery for advanced squamous cell carcinoma of the thoracic esophagus.

The adverse effect of neoadjuvant chemoradiotherapy on the postoperative course in esophageal cancer was studied in 9 patients undergoing neoadjuvant chemoradiotherapy preceding surgery for thoracic esophageal carcinoma possibly involving adjacent organs (neoadjuvant group), and 13 patients undergoing surgery without neoadjuvant therapy for same disease (control group). The two groups were compared for volume of intraoperative hemorrhage, surgical duration, frequency of postoperative morbidity, and for postoperative changes in blood platelet counts, and serum thrombopoietin and interleukin-6 levels. Mean intraoperative blood loss was 1121 g (580-1,662 g) in the neoadjuvant group and 546.5 g (274.7-778.3 g) in controls group (Student's T test: p < 0.01). No significant difference was seen found between the two groups in the degree of postoperative deterioration in cardiopulmonary function or in interleukin-6 levels. Blood platelet counts decreased in both groups until postoperative day 7, but recovery on postoperative day 14 was significantly depressed in the neoadjuvant group compared to controls. Serum thrombopoietin levels were higher in the neoadjuvant group than in controls (Mann-Whitney U-test: p < 0.05). We found that neoadjuvant chemoradiotherapy induces latent postoperative myelosuppression and may lead to intractable infection.

New brittle bone disorder: report of a family with six affected individuals.

We report on a family in which four females and two males in three generations had a previously undescribed brittle bone disorder that was dominantly transmitted through a maternal line. The cardinal manifestations of the disorder comprised dolichocephaly with frontal bossing, hypoplasia of the midface, postpubertal prognathism, micromelic short stature, coarse trabeculae of the entire skeleton, and bone fragility of variable degrees. Mild spondylar modification and iliac hypoplasia were other hallmarks that were recognized in childhood. The proband, a 19-year-old male, was most severely affected with multiple wormian bones in the calvaria, repetitive fractures, intractable bowing of the legs and forearms, and pseudofractures of the long bones with metaphyseal narrowing. His male cousin was next severely affected with angular deformity restricted to the forearm. The four females were much less affected without angular deformity. The mode of inheritance was thus consistent with either an autosomal dominant trait with sex-influence or an X-linked semidominant trait. Histological bone examination in the proband showed atrophy and fibrous degeneration of the lamellar trabeculae and disorganized chondro-osseous junction, which implied that the disorder involved both intramembranous and enchondral ossifications.

Relationship between stride length and walking rate in gait training for hemiparetic stroke patients.

Sixty-three male hemiparetic patients in the recovery stage were examined to investigate the relationship between stride length and walking rate during computer-assisted gait training during a period of 4 wk. The maximum walking speed for 10 m was significantly increased from 32.3 to 53.2 m/min on average, and the stride length and walking rate also increased. However, the ratio of stride length to walking rate did not change significantly in 4 wk, with the mean value being 0.0068 m/steps/min, approximately one-half that of healthy adults based on data from previous reports. The ratio of stride length to walking rate for hemiplegic gait was invariant during the 4 wk of computer-assisted gait training, which is also true at different speeds for healthy adults. These results indicate that the maximum walking speed was significantly improved, with an invariant relationship between stride length and walking rate, and suggest that the ratio could be used as an index for gait training.

Determinants and predictors of the maximum walking speed during computer-assisted gait training in hemiparetic stroke patients.

OBJECTIVE: To investigate biomechanical determinants and predictors of walking speed in early gait training after stroke. DESIGN: Prospective. SETTING: Physical therapy room of Tohoku University Hospital. PARTICIPANTS: Thirty-four male hemiparetic stroke patients received 8 weeks of computer-assisted gait training (CAGT), which was initiated within approximately 3 months after stroke onset. MAIN OUTCOME MEASUREMENTS: The time and the number of steps required to walk 10m at the fastest possible speed (maximum walking speed [MWS]), the sway path of the center of feet pressure (CFP) in the upright posture, the change in CFP when shifting the body weight either left to right or back and forth, and the maximal isokinetic muscle strength during extension of both knees were measured at the start and at 4 and 8 weeks. Stepwise regression procedures were performed to analyze determinants and predictors of the MWS using the MWS as the dependent variable and personal characteristics, standing balance, and the muscle strength of both knees as the independent variables. RESULTS: The MWS significantly increased from 40.4 to 76.5m/min on average after 8 weeks. The determinant of MWS at the start was the postural control of shifting to the left and right (coefficient of determination of 45.4%). The determinant of MWS at 4 and 8 weeks was the muscle strength during knee extension on the affected side (coefficient of determination of 62.9% and 54.5%, respectively). The predictors of MWS at 4 weeks were the MWS at the start of CAGT, followed by muscle strength during knee extension on the affected side and the time from stroke onset to the start of CAGT (total variance of 84.3%). The predictors at 8 weeks were the MWS at the start, followed by the muscle strength during knee extension on the affected side (total variance of 73.4%). CONCLUSIONS: After 4 weeks, the biomechanical determinant of MWS had changed from the postural control of weight-shifting from left to right to the muscle strength during knee extension on the affected side. The MWS at 4 and 8 weeks could be predicted by the initial MWS, the initial muscle strength during knee extension on the affected side, and the time since stroke onset, with high coefficients of determination.

Infrequent frameshift mutations of polynucleotide repeats in multiple primary cancers affecting the esophagus and other organs.

Frequent frameshift mutations of simple nucleotide repeats in the protein-encoding regions, as well as replication errors (RERs) at microsatellite loci, have recently been demonstrated in gastrointestinal tumors. These genetic instabilities have been considered indicative of an increased risk of accumulating mutations in cancer-associated genes and of developing multiple cancers. We studied frameshift (or insertion/deletion) mutations of simple nucleotide repeats in five genes (TGFbeta type II receptor [TGFbetaRII], E2F4, MSH2, MSH3, and MSH6) in 23 tumors from 12 patients who had synchronous cancers of the esophagus and other organs. Genetic instability at four microsatellite loci, as well as mutations in the TP53, APC, and KRAS2 genes, were also studied. No frameshift mutations were observed in the TGFbetaRII, MSH3, and MSH6 genes. RER and a deletion mutation of BAT26 in MSH2 were present in one (1/23; 4%) gastric cancer. This tumor also carried a deletion mutation in the serine (AGC) repeat of the E2F4 gene. Mutation screening of the TP53, APC, and KRAS2 genes revealed that the synchronous cancers did not carry the same mutations. Our results suggested that genetic instability, such as insertion/deletion mutations in simple nucleotide repeats, is not significantly associated with the development of multiple primary cancers of the esophagus and other organs, and that these synchronous cancers developed independently according to their different environmental factors.

Tylosis esophageal cancer locus on chromosome 17q25.1 is commonly deleted in sporadic human esophageal cancer.

BACKGROUND & AIMS: Tumor-suppressor genes found in inherited cancer predisposition syndromes are also responsible for sporadic cancers of the same type. Recently, the tylosis oesophageal cancer (TOC) gene locus has been mapped to 17q25 by linkage analyses of pedigrees with focal nonepidermolytic palmoplantar keratoderma associated with a high risk of esophageal cancer development. The aim of this study was to clarify whether the TOC locus is affected in sporadic esophageal cancers. METHODS: We investigated loss of heterozygosity (LOH) on 17q in 58 sporadic esophageal squamous cell carcinomas (ESCs) using 20 microsatellite markers focusing on the TOC locus. RESULTS: LOH on 17q was observed in 37 of 52 (71%) informative cases at one or more loci, 80% (33/37) of which included the TOC locus. The smallest common deleted region was at D17S1839 within the TOC locus. CONCLUSIONS: The constructed deletion map revealed that the TOC locus is commonly deleted in sporadic ESCs, suggesting that a tumor-suppressor gene responsible for ESC is contained within this locus.

Pharmacokinetics of cisplatin in combined cisplatin and 5-fluorouracil therapy: a comparative study of three different schedules of cisplatin administration.

BACKGROUND: Cisplatin is widely used in combination chemotherapy against a variety of tumors; however, the optimal administration schedule of cisplatin is still controversial. To clarify the pharmacokinetic differences according to the administration schedules of cisplatin, we compared three different administration schedules of cisplatin such as single short-term infusion, daily short-term infusion and daily continuous infusion in combination with 5-fluorouracil. Preliminary clinical responses and toxicities were also investigated. METHODS: A total of 12 courses in combination of cisplatin and 5-fluorouracil therapy was studied. The schedules of cisplatin tested were as follows: single short-term infusion (80 mg/m2, day 1,2 h div., n = 4), daily short-term infusion (20 mg/m2, days 1 to 5, 2 h div., n = 4), daily continuous infusion (100 mg/m2, 120 h, n = 4). In all schedules, 5-fluorouracil was continuously administered at a dose of 800 mg/m2/day on days 1 to 5. The area under the time-concentration curve (AUC) and the maximum concentration (Cmax) of total and free Pt were investigated. RESULTS: The highest AUC of total and free Pt and the lowest Cmax of free Pt were observed in the daily continuous infusion (total AUC; 162.53 +/- 18.39 micrograms h/ml, free AUC; 5.50 +/- 0.9 micrograms h/ml, free Cmax; 0.07 +/- 0.01 microgram/ml, mean +/- SEM). Two patients in the single short-term infusion and one patient in the daily continuous infusion indicated partial responses clinically. No nephrotoxicity or ototoxicity was observed. All toxicities were mild and tolerable in all regimens; however, the incidence of GI toxicity in daily continuous infusion seemed to be relatively higher. CONCLUSIONS: Daily continuous infusion of cisplatin gave the best pharmacokinetic results and to evaluate the clinical advantage of this schedule a prospective randomized trial should be conducted with sufficient numbers of patients.