Comparison of preoperative chemotherapy using docetaxel, cisplatin and fluorouracil with cisplatin and fluorouracil in patients with advanced carcinoma of the thoracic esophagus.

We retrospectively compared preoperative docetaxel, cisplatin, and fluorouracil (DCF) with cisplatin and fluorouracil (CF) in patients with esophageal cancer. The study included patients with advanced thoracic esophageal carcinoma (excluding T4 tumors) receiving preoperative chemotherapy. In the DCF group, five patients received two courses of treatment every 4 weeks, and 33 patients received three courses every 3 weeks. In the CF group, 38 patients received two courses of treatment every 4 weeks. Patients underwent curative surgery 4-5 weeks after completing chemotherapy. Patient demographic characteristics did not differ between the two study groups. The incidence of a grade 3 or 4 hematologic toxicity was significantly higher in the DCF group (33 patients) than in the CF group (five patients; P < 0.001). Curative resection was accomplished in 79% of patients in the DCF group and 66% in the CF group (P = 0.305). There were no in-hospital deaths. The incidence of perioperative complications did not differ between the groups. A grade 2 or 3 histological response was attained in a significantly higher proportion of patients in the DCF group (63%) than in the CF group (5%; P < 0.001). Progression-free survival and overall survival were significantly higher in the DCF group (P = 0.013, hazard ratio 0.473; P = 0.001, hazard ratio 0.344). In conclusion, a grade 3 or 4 hematologic toxicity was common in the DCF group but was managed by supportive therapy. Histological response rate, progression-free survival, and overall survival were significantly higher in the DCF group compared with the CF group.

A new operative technique for the resection of gastric tube cancer by means of lifting the anterior chest wall and videoscope-assisted surgery.

The prolonged survival of patients receiving surgery for esophageal cancer has led to an increased incidence of adenocarcinoma arising in the gastric tube used for reconstruction (gastric tube cancer). In patients with advanced gastric tube cancer, resection of the gastric tube should be considered, but currently available procedures are very invasive. In patients undergoing curative surgery for gastric tube cancer that has developed after reconstruction through the retrosternal route, the gastric tube is usually resected through a median sternotomy, followed by reconstruction with the colon. However, postoperative complications often occur and treatment outcomes remain poor. We developed a new surgical technique for gastric tube resection without performing a sternotomy in patients with gastric tube cancer who had previously undergone reconstruction through the retrosternal route. Our technique was used to treat two patients. Two Kirschner wires were passed subcutaneously through the anterior chest; the chest was lifted to extend the retrosternal space and secure an adequate surgical field. The stomach was separated from the surrounding tissue under videoscopic guidance. Total resection of the gastric tube was done. The retrosternal space was used to lift the jejunum. Roux-en-Y reconstruction was performed. Neither patient had suture line failure or surgical site infection. Their recovery was uneventful. Our surgical technique has several potential advantages including (i) reduced surgical stress; (ii) the ability to use the retrosternal space for reconstruction after gastric tube resection; and (iii) a reduced risk of serious infections such as osteomyelitis in patients with suture line failure. Our findings require confirmation by additional studies.

Epigenetic silencing of AXIN2 in colorectal carcinoma with microsatellite instability.

Mutation or epigenetic silencing of mismatch repair genes, such as MLH1 and MSH2, results in microsatellite instability (MSI) in the genome of a subset of colorectal carcinomas (CRCs). However, little is yet known of genes that directly contribute to tumor formation in such cancers. To characterize MSI-dependent changes in gene expression, we have now compared transcriptomes between fresh CRC specimens positive or negative for MSI (n=10 for each) with the use of high-density oligonucleotide microarrays harboring >44,000 probe sets. Correspondence analysis of the expression patterns of isolated MSI-associated genes revealed that the transcriptome of MSI+ CRCs is clearly distinct from that of MSI- CRCs. Such MSI-associated genes included that for AXIN2, an important component of the WNT signaling pathway. AXIN2 was silenced, apparently as a result of extensive methylation of its promoter region, specifically in MSI+ CRC specimens. Forced expression of AXIN2, either by treatment with 5'-azacytidine or by transfection with AXIN2 cDNA, resulted in rapid cell death in an MSI+ CRC cell line. These data indicate that epigenetic silencing of AXIN2 is specifically associated with carcinogenesis in MSI+ CRCs.

Isolated osteochondroma near the mandibular angle.

A benign tumour of osseous and cartilaginous origins, osteochondroma generally develops in osseous tissue and is frequently found near the end of long bones. It is relatively rare in the oral and maxillofacial region but is common in the mandibular condyle and coronoid process in the pediculate form. This is a report on a rare case of osteochondroma in soft tissue near the mandibular angle without pedicle to the bone.

Primary oral KIT-positive tumour consistent with gastrointestinal stromal tumour.

Gastrointestinal stromal tumours are characteristically positive for KIT (reflective of the c-KIT gene). A case is reported of an apparent rapidly growing gastrointestinal stromal tumour, which arose in the floor of the mouth and metastasized to the left neck without evidence of disease elsewhere.

A long-term follow-up study of radiographically evident degenerative changes in the temporomandibular joint with different conditions of disk displacement.

The purpose of this retrospective study is to assess the relationship between an initial and persisting condition of disk displacement (DD) and the long-term course of radiographically evident degenerative changes of the temporomandibular joint (TMJ). Nineteen patients agreed to a radiographic follow-up examination of 29 joints and were included in this study. The joints were radiographically assessed at the first visit and at least 46 months after the first visit (mean 89.3 months). At the time of the follow-up, all subjects had a good clinical course after a favorable response to the treatments. There were significant relationships between the initial diagnosis of DD and the interval change in the morphology of the articular eminence. The articular eminence became flattened or deformed only in the joints with persistent DD without reduction. And there was a tendency that the condyle became smaller in the joints initially with permanent DD and in the joints which show a progression in the disk-condylar relationship. The results of this study suggested that, in the joints with persisting non-reducing disk displacement, flattening and deformation of the articular eminence and regression of the condylar size were likely to happen even after symptoms and signs of TMJ disorders were resolved or reduced.

Nosocomial transmission of methicillin-resistant Staphylococcus aureus via the surfaces of the dental operatory.

OBJECTIVE: We assess the possibility of methicillin-resistant Staphylococcus aureus (MRSA) transmission via the surfaces of the dental operatory. METHODS: A survey of MRSA contamination on the surfaces of the dental operatory, and an analysis of MRSA transmission via the dental operatory between patients was carried out in the department of special dental care and oral surgery. RESULTS: MRSA was observed on the surfaces of dental operatory including the air-water syringe and reclining chair. Nosocomial infection or colonisation of MRSA occurred in eight out of 140 consecutive patients who had no evidence of MRSA at admission. Antibiograms of 30 antibiotics revealed that the isolates from the eight patients were of the same strain as those from the surface of dental operatory. After treating the patients under a revised infection control (IC) protocol including a single use of barrier covers, MRSA was not detected on the surfaces of the dental operatory, and no nosocomial infection or colonisation occurred during hospitalisation (0/117 patients). CONCLUSIONS: These results suggest that MRSA contaminates the surfaces of the dental operatory, and therefore the dental operatory should be considered a possible reservoir of MRSA.

Histological and microradiographic evaluation of hydrated and hardened alpha-tricalcium phosphate/calcium phosphate dibasic mixtures.

Bone tissue response to pre-hardened alpha-tricalcium phosphate (alpha-TCP) and calcium phosphate dibasic (DCPD) mixture by hydration was studied histologically and microradiographically after implanting on the inferior aspect of the mandible in rabbits. In 1-month implants, new bone formation was observed along the surface of the material near the host bone, and connection of new and host bone through thin bone bridges was seen in some places. In 3-month implants, newly formed bone filled the greater part of the gap between material and host bone, and in 6-month implants, it surrounded almost all the surface of the material. New bone was in direct contact with the material in all implant periods. The bone response was essentially consistent with that to hydroxyapatite (HA). Resorption of the material was noticed in 3- and 6-month implants. It was concluded that pre-hardened alpha-TCP/DCPD mixture has good biocompatibility with bone tissue equal to HA and that it resorbs when implanted in rabbit. Further research should be performed to evaluate the material changes of resorption and formation of the white zone.

In vivo study of a calcium phosphate cement consisting of alpha-tricalcium phosphate/dicalcium phosphate dibasic/tetracalcium phosphate monoxide.

Prehardened calcium phosphate cement consisting of alpha-tricalcium phosphate (alpha-TCP), dicalcium phosphate dibasic (DCPD) and tetracalcium phosphate monoxide (TeCP) was implanted in rabbit mandibles and back muscles, and studied histologically and microradiographically. In the mandibles, new bone formation occurred around the implants and increased in quantity the longer the implant period lasted. Histology, microradiography and scanning electron microscopy (SEM) demonstrated direct contact of bone and cement. Bone response to this cement was essentially the same as to hydroxyapatite (HA) ceramics, known as a biocompatible bone substitute. Material resorption was recognized, which increased with the implant period and was greater in the surface bound by soft tissue than the surface bound by bone tissue. In the back muscles, however, no calcified tissue formation occurred. Resorption proved to be faster than in the case of the mandible implants. It was concluded that the cement, in prehardened form, has good biocompatibility and is a promising material as a bone substitute.

Ectopic osteogenesis with biphasic ceramics of hydroxyapatite and tricalcium phosphate in rabbits.

Porous calcium phosphate ceramics consisting of hydroxyapatite (HA) and tricalcium phosphate (TCP) with different HA to TCP ratio were implanted intramuscularly in rabbits for six months in order to carry out a comparative study on osteogenic activity of the ceramics. Bone formation was detected only in HT73 (HA to TCP ratio, 7-3) specimens. Other implants, HT28 (2-8) and HT010 (0-10), could not induce bone. After a six-month period of implantation, HT28 and HT010 implants showed obvious degradation of the implants changing their shape and size macro and microscopically. Microscopically, they showed aggregates of fine particles and appearance of multinucleated cells. However, HT73 implants was less degraded and could maintain their original structure macro and microscopically. This study showed that HT73 ceramics can induce bone in rabbit muscle tissue and it is considered that maintenance of porous structure, that is, degradation rate of the materials may be one of the affecting factors in ceramic-induced osteogenesis.

Osteogenesis in muscle with composite graft of hydroxyapatite and autogenous calvarial periosteum: a preliminary report.

To investigate the bone forming activity of composite grafts of hydroxyapatite (HA) and autogenous calvarial periosteum, porous HA rods with or without the periosteum were implanted into the back muscle of white rabbits. They were harvested 3 and 6 months after implantation and studied histologically and microradiographically. Bone formation in the pores of HA occurred in three out of four composite implants of the 3 month group, and four out of five implants of the 6 month group. The two specimens without bone formation revealed irregular calcified tissue outside the HA implant. No formation of bone and calcified tissue took place in any of the specimens with HA alone. These results indicate the potential of this new experimental system of ectopic osteogenesis and offer the possibility of a new improved bone graft consisting of HA and autogenous periosteum.

In vivo study of calcium phosphate cements: implantation of an alpha-tricalcium phosphate/dicalcium phosphate dibasic/tetracalcium phosphate monoxide cement paste.

alpha-Tricalcium phosphate (alpha-TCP)/dicalcium phosphate dibasic (DCPD)/tetracalcium phosphate monoxide (TeCP) cement was implanted in paste form into soft tissue (rate subcutaneous sockets) and bone tissue (defects in rabbit mandibles) to evaluate the setting behaviour of the cement and tissue responses to the cement. A histological study of the soft tissue implants revealed thin fibrous capsule formation, the appearance of multinucleated giant cells on and close to the cement surface, and small clusters of the cement near the main part of the set cement which were formed by the migration of the paste while setting. X-ray diffraction (XRD) analysis of the implanted cement showed peaks for hydroxyapatite (HA) which increased as the implant period increased. Histology and microradiography of the bone tissue implants showed well-set cement without migration, active bone formation around the cement and direct bone union to it. However, the cement disappeared from the implant site in 4 of 16 specimens where intense bleeding seemed to wash away the implants while setting. From the results of the present study, we concluded that the cement is well tolerated, especially by bone tissue. This may be related to the fact that the cement sets producing HA. The cement is a promising material as a bone substitute; however, there is a problem of migration while setting in soft tissue and of exclusion from the bone defects by intense bleeding.

Reaction of surrounding gingiva to permucosal implants of dense hydroxyapatite in dogs.

Experimental and histological studies on the reaction of surrounding gingiva to permucosal implants of dense calcium hydroxyapatite were carried out in dogs. Epithelial attachment and connection of supra-alveolar collagen fibres to the implant surface seemed to form a biological seal around implants similar to that around natural teeth. However, excellent oral hygiene is very important for the maintenance of this biological seal.

A preliminary study on osteoinduction of two kinds of calcium phosphate ceramics.

With respect to the effect of material factors on calcium phosphate biomaterial-induced osteogenesis, the osteoinductive property of two kinds of porous hydroxyapatite ceramics, which were made by different producers, was investigated in dorsal muscles of dogs. One hydroxyapatite ceramic (S-HA), macroporous implants with rough pore walls containing abundant micropores, was made by Sichuan Union University (Chengdu, China); the other hydroxyapatite ceramic (J-HA), porous implants with smooth macropore walls composed of regularly aligned crystal grains, was provided by Mitsubishi Ceramic Int. (Japan). Different tissue response was detected histologically and microradiographically after the ceramic samples had been implanted in dorsal muscles of dogs for 3 and 6 months. Bone formation was found in S-HA at 3 months, which increased at 6 months. In contrast, no bone formation was detected in J-HA at both 3 and 6 months. These results indicate that with the special architecture, calcium phosphate ceramic can induce bone formation in soft tissue. As both materials were very similar in their chemical and crystallographic structures, but varied in their microstructures, the latter seem to be an important factor affecting the osteoinductive capacity of calcium phosphate ceramics. These data suggest that, by controlling the preparation of calcium phosphate ceramic, bone substitutes with intrinsic osteoinductive property can be developed from calcium phosphates.

Experimental cranioplasty and skeletal augmentation using an alpha-tricalcium phosphate/dicalcium phosphate dibasic/tetracalcium phosphate monoxide cement: a preliminary short-term experiment in rabbits.

Calcium phosphate cement consisting of alpha-tricalcium phosphate (alpha-TCP), dicalcium phosphate dibasic (DCPD) and tetracalcium phosphate monoxide (TeCP) was implanted into surgically created full-thickness defects in the cranial bone (bone defect experiment) and directly onto the cranial bone under the periosteum (augmentation experiment). Three months after the implantation, the implants were retrieved with the surrounding tissues and studied histologically and micrographically to evaluate if the cement can be used as a cranioplasty and skeletal augmentation material. In the bone defect experiment, successful reconstruction of the defect was seen in 8 out of 12 specimens. Four specimens, where bleeding control was difficult at the time of implantation, showed partial loss of the cement. Histological and microradiographic studies of the successfully implanted cement revealed that new bone surrounded the implant nearly completely and united directly with the cement surface. In the augmentation experiment, the augmented area maintained the hemispherical shape and was connected tightly with the host bone. Histology and microradiography demonstrated that new bone formation was seen in the gap between the cement and the host bone, and on the outer surface (periosteum side) of the cement at the edge of the implant. From this preliminary short-term study, it could be concluded that the cement is a promising material for cranioplasty and skeletal augmentation with indications that it has good osteoconductivity.

Transforming growth factor-beta1 incorporation in an alpha-tricalcium phosphate/dicalcium phosphate dihydrate/tetracalcium phosphate monoxide cement: release characteristics and physicochemical properties.

The osteoconductive properties of calcium phosphate cements (CPCs) may be improved by the addition of growth factors, such as recombinant human transforming growth factor-beta1 (rhTGF-beta1). Previously we have shown that rhTGF-beta1 was released from cement enriched with rhTGF-beta1 and subsequently stimulated the differentiation of pre-osteoblastic cells from adult rat long bones. It is unknown whether the addition of rhTGF-beta1 changes the material properties of this alpha-tricalcium-phosphate (alpha-TCP)/tetracalcium-phosphate-monoxide (TeCP)/dicalcium-phosphate-dihydrate (DCPD) cement, and what the characteristics of the release of rhTGF-beta1 from this CPC are. Therefore, in the present study we determined the release of rhTGF-beta1 from cement pellets in vitro. The possible intervening effects of the CPC modification for intermixing rhTGF-beta1 on physicochemical properties were studied by assessing the compressive strength and setting time, as well as crystallinity, calcium to phosphorus ratio, porosity and microscopic structure. Most of the previously incorporated rhTGF-beta1 in the cement pellets was released within the first 48 h. For all concentrations of rhTGF-beta1 intermixed (100 ng-2.5 mg/g CPC), approximately 0.5% of the amount of rhTGF-beta1 incorporated initially was released in the first 2 h, increasing to 1.0% after 48 h. The release of rhTGF-beta1 continued hereafter at a rate of about 0.1% up to 1 week, after which no additional release was found. The initial setting time, nor the final setting time was changed in control cement without rhTGF-beta1 (standard CPC) or in cement modified for rhTGF-beta1 (modified CPC) at 20 degrees C and 37 degrees C. Setting times were more than six times decreased at 37 degrees C compared to 20 degrees C. The compressive strength was initially low for both standard CPC and modified CPC, after which it increased between 24 h and 8 weeks. The compressive strength for the modified CPC was significantly higher compared with standard at 1, 2, and 8 weeks after mixing. X-ray diffraction revealed that both standard and modified CPC changed similarly from the original components into crystalline apatite. The calcium to phosphorus ratio as determined by an electron microprobe did not differ at all time points measured for standard CPC and modified CPC. In both standard CPC and modified CPC the separated particles became connected by crystals, forming a structure in which the particles could hardly be recognised in a densifying matrix with some small pores. The present study shows that the calcium phosphate cement is not severely changed by modification for the addition of rhTGF-beta1. The addition of rhTGF-beta1 in CPC enhances the biologic response as shown in our previous study and did not interfere with the aimed physical and chemical properties as shown in this study. We conclude that the addition of rhTGF-beta1 enlarges the potential of the CPC in bone replacement therapy.

Genetics and obstructive sleep apnea syndrome: a study of human leukocyte antigen (HLA) typing.

To investigate the possible influence of genetics in subjects with obstructive sleep apnea syndrome (OSAS), HLA-A, B, C, and DR antigens were studied in 32 Japanese subjects with OSAS. The frequency of HLA-A2 antigen was markedly increased in the patients with OSAS compared with normal controls (81.3% vs 40.6%) and compared with the Japanese population (40.7%), Pc < 0.035 and Pc < 0.007, respectively. HLA-B39 was found more frequently in OSAS patients than in the Japanese population (Pc < 0.018), but not in the controls. No significant deviation was observed in the frequencies of HLA-C and DR antigens between the OSAS patients and the controls. We conclude that genetics is important in the development of OSAS.

Daytime hypertension and the effects of short-term nasal continuous positive airway pressure treatment in obstructive sleep apnea syndrome.

Daytime blood pressure (BP) in 31 male patients with obstructive sleep apnea syndrome (OSAS) was measured and the effects of nasal continuous positive airway pressure (CPAP) treatment on daytime BP were studied. Subjects were 48 +/- 10 (mean +/- SD) years old and weighed 80 +/- 13 kg. The mean systolic BP and diastolic BP were 135 +/- 15 mmHg and 88 +/- 14 mmHg, respectively and daytime hypertension was present in 12 (38%) subjects. Apnea index (AI) and the lowest oxygen saturation during sleep were significantly more severe in the hypertensive (HT) than in the non-hypertensive (NHT) patients (p < 0.05). AI was significantly correlated with diastolic BP (p < 0.05) and the mean and lowest oxygen saturation during sleep were significantly correlated with both systolic (p < 0.05) and diastolic BP (p < 0.01). After nasal CPAP treatment for two weeks, both systolic and diastolic BP were significantly reduced; the former from 135 +/- 15 mmHg to 126 +/- 10 mmHg (p < 0.005) and the latter from 88 +/- 14 mmHg to 78 +/- 6 mmHg (p < 0.001). These data form direct evidence that daytime hypertension is partially induced by OSAS and is reversible with nasal CPAP treatment.

Resorption of the postero-superior corner of the lateral part of the mandibular condyle correlates with progressive TMJ internal derangement.

The purpose of this study was to test the hypothesis that resorption of postero-superior corner of lateral part of the mandibular condyle (RLC) occurs with the advancement of TMJ internal derangement (ID). One hundred and sixty-seven TMJs in 122 patients were studied. RLC was assessed on plane radiographs of frontal oblique projection. The correlation between the prevalence of RLC and radiological stage of ID was analysed and clinical correlations to the radiological stage of ID and the prevalence of RLC were discussed. The higher prevalence of RLC in joints with advanced ID was statistically significant (Mann-Whitney U-test, P< 0.05). There was no correlation between the prevalence of RLC and neither OA on the articular surface of the condyle nor clinical symptoms/signs. The result of this study suggests that RLC appears to occur in joints with advanced ID as a result of remodelling changes secondary to ID.

Pitfalls in the treatment of delayed lymph-node metastases after control of small tongue carcinomas.

Between 1985 and 1992, 13 patients were treated for delayed lymph-node metastases that developed after obtaining control of primary lesions of the tongue. These lesions were treated primarily by radiotherapy or surgical resection; cervical metastases were treated mainly by delayed radical neck dissection (RND). Seven of the 13 patients survived with no evidence of recurrence. The other six patients developed tumors in the neck, and five of these patients died due to uncontrollable disease. In all but one patient, recurrence appeared between the site of the primary lesion and the region of RND, the oral floor and/or the parapharyngeal space. None of the patients with recurrence received radiotherapy in the area between the primary lesion and the site of RND. In contrast, there was no recurrence in patients who received external irradiation to the primary lesion and upper cervical lymph nodes. This review emphasizes the need to direct more attention to the area between the site of the primary lesion and the regional lymph nodes in patients receiving treatment for delayed metastases associated with small carcinomas of the tongue.