Impact of genomic stability on protein expression in endometrioid endometrial cancer.

BACKGROUND: Genomic stability is one of the crucial prognostic factors for patients with endometrioid endometrial cancer (EEC). The impact of genomic stability on the tumour tissue proteome of EEC is not yet well established. METHODS: Tissue lysates of EEC, squamous cervical cancer (SCC), normal endometrium and squamous cervical epithelium were subjected to two-dimensional (2D) gel electrophoresis and identification of proteins by MALDI TOF MS. Expression of selected proteins was analysed in independent samples by immunohistochemistry. RESULTS: Diploid and aneuploid genomically unstable EEC displayed similar patterns of protein expression. This was in contrast to diploid stable EEC, which displayed a protein expression profile similar to normal endometrium. Approximately 10% of the differentially expressed proteins in EEC were specific for this type of cancer with differential expression of other proteins observed in other types of malignancy (e.g., SCC). Selected proteins differentially expressed in 2D gels of EEC were further analysed in an EEC precursor lesion, that is, atypical hyperplasia of endometrium, and showed increased expression of CLIC1, EIF4A1 and PRDX6 and decreased expression of ENO1, ANXA4, EMD and Ku70. CONCLUSION: Protein expression in diploid and aneuploid genomically unstable EEC is different from the expression profile of proteins in diploid genomically stable EEC. We showed that changes in expression of proteins typical for EEC could already be detected in precursor lesions, that is, atypical hyperplasia of endometrium, highlighting their clinical potential for improving early diagnostics of EEC.

Differential expression of ANXA6, HSP27, PRDX2, NCF2, and TPM4 during uterine cervix carcinogenesis: diagnostic and prognostic value.

BACKGROUND: Cytology-based diagnostics of squamous cervical cancer (SCC) precursor lesions is subjective and can be improved by objective markers. METHODS: IHC-based analysis of ANXA6, HSP27, peroxiredoxin 2 (PRDX2), NCF2, and tropomyosin 4 (TPM4) during SCC carcinogenesis. RESULTS: Expression of ANXA6, HSP27, PRDX2, and NCF2 in the cytoplasm of dysplastic cells increased from cervical intraepithelial neoplasia 2/3 (CIN2/3) to microinvasive cancer. Invasive SCC showed lower expression of TPM4 than CIN and normal epithelium. CIN2/3 with the highest sensitivity and specificity differed from normal epithelium by cytoplasmic expression of HSP27. Patients with cytoplasmic HSP27 expression in SCC deviating from that observed in normal epithelium had worse relapse-free (P=0.019) and overall (P=0.014) survival. Invasive SCC with the highest sensitivity and specificity differed from normal epithelium by expression of PRDX2 and TPM4 in the cytoplasm, from CIN2/3 by the expression of ANXA6 and TPM4 in the cytoplasm, and from microinvasive SCC by the expression of PRDX2 and ANXA6 in the cytoplasm. The number of sporadic ANXA6+ cells between the atypical cells increased from CIN2/3 to invasive SCC. CONCLUSION: Detection of expression changes of the proteins ANXA6, HSP27, PRDX2, NCF2, and TPM4 in SCC precursor lesions may aid current cytological and pathological diagnostics and evaluation of prognosis.

Timing of radiotherapy in head and neck free flap reconstruction--a study of postoperative complications.

The local treatment protocol of preoperative radiotherapy in head and neck cancer treatment at the Karolinska University Hospital has resulted in a unique cohort of preoperatively high dose-irradiated patients. In total 216 consecutive patients were reviewed, of whom 221 free flaps, for head and neck cancer reconstruction, were operated between 1984 and 2002. In 194 cases radiotherapy was administered preoperatively and 27 operations were performed without prior radiation. The radiation dose was 64 Gy in 147 cases, 54 Gy or less in 45 cases and uncertain in two cases. In order to study whether the time elapsed between the end of radiotherapy and surgery had any significance regarding postoperative events, the cohort was subsequently divided into three groups: patients operated on within 4 weeks (n=27), between 4 and 6 weeks (n=88) and more than 6 weeks (n=78) after the last radiotherapy session. Postoperative complications were analysed in relation to preoperative dose and timing of radiotherapy. Preoperative radiotherapy was related to an increased risk of free flap necrosis as 22 complete and eight partial flap necroses occurred in the group that had received preoperative radiotherapy and none were observed in the non-irradiated group (P<0.05). Furthermore, a linear trend of increased flap loss (P<0.001), infections (P<0.001) and delayed wound healing (P<0.001) was seen when time increased between the last radiotherapy session and surgery. The largest increase in all complication rates was seen when more than 6 weeks elapsed between last radiotherapy session and surgery. Postoperative complications were independent of the radiation dose given. Our data show an increased morbidity in free flap surgery in the head and neck region after preoperative radiotherapy. Furthermore, time elapsed between the last radiotherapy session and surgery is associated with the risk of developing postoperative complications. We strongly suggest that free flap reconstruction should be performed within 6 weeks of the last radiotherapy session.

Deterioration of intraoral recognition of shapes after treatment of oral and pharyngeal cancer.

Thirty patients with diagnosed malignant tumors of the oral cavity or pharynx were tested in regards to intraoral shape recognition at 4 test occasions: before all treatment, after radiotherapy, 6 months after surgery, and 1 year after surgery. They were compared within groups as well as with a group of healthy reference individuals of the same age who underwent the same test procedure at a 2-month interval. The tumor itself did not influence the capability of shape recognition. The reference individuals demonstrated significantly better results on the second test occasion, which is known as a learning effect. Learning improvement was not seen in the patients whose second test occasions were after radiotherapy, implying an impediment amounting to the magnitude of the learning effect. At 6 months after surgery the patients' capabilities of shape recognition had deteriorated significantly with no difference between the oral cancer group and the pharyngeal cancer group. No spontaneous rehabilitation had taken place 1 year after surgery. The presence or absence of surgical lingual nerve damage did not influence the results. The nonoperated side does not compensate for the operated one. It is plausible that decreased oral sensory acuity in recognizing the shape of the bolus contributes to postoperative swallowing problems.

Deterioration of intraoral hole size identification after treatment of oral and pharyngeal cancer.

Thirty-one patients with a diagnosed malignant tumour of the oral cavity or pharynx were tested in hole size identification on four test occasions: before all treatment, after radiotherapy and 6 months and 1 year after surgical treatment. They were compared within groups as well as with a group of healthy reference individuals of the same age who underwent the same test procedure at a 2 months' interval. The oral group did not decline in hole size identification after radiotherapy, but did after surgery. The deterioration was persistent 1 year after surgery. The pharyngeal group did not change performance in hole size identification after radiotherapy, nor after surgery. It is obvious that surgery of the oral structures causes the deterioration. No correlation with damage to the lingual nerve could be registered. The oral cavity reacts as one unit, despite sensory input from two sides. The non-operated side does not compensate for the operated side. It is plausible that decreased oral sensory acuity, in recognizing hole size of the bolus, contributes to postoperative swallowing problems.

Free radial forearm flap reconstruction in surgery of the oral cavity and pharynx: surgical complications, impairment of speech and swallowing.

The first 100 consecutive free radial forearm flaps used in reconstruction for oral and pharyngeal cancer were investigated. Seven re-operations took place due to circulatory impairment of the flap. Two flaps underwent partial, and four total necrosis, one of those patients died of massive haemorrhage. Post-operative infection was significantly correlated to increased time between the last radiotherapy session and surgery. All but eight patients had post-operative impairment of swallowing and all but five patients had impairment of speech articulation or hypernasality. Post-operative time spent in hospital was a range of 12-122 days (mean 37 days). The 2-year survival rate was 70% and the 5-year survival rate was 45%.

A clinical and radiological two-year follow-up study of maxillary overdentures on osseointegrated implants.

In order to satisfy the need to restore the aesthetics, phonetics and comfort and to facilitate optimal hygiene procedures, 20 edentulous patients were treated with a new concept of overdenture therapy on implants and modum Brånemark. After 24 +/- 3.5 months the patients were re-examined. They were asked to answer a questionnaire and use a Visual Analogue Scale (VAS) to give their opinion on the prosthetic treatment. The results indicate that an implant-retained overdenture in the maxilla with this design can satisfy the patients needs in aesthetics, phonetics and comfort and can facilitate oral hygiene measures.

Avulsed human teeth replanted within 15 minutes--a long-term clinical follow-up study.

Twenty-one avulsed human permanent teeth replanted within 15 min after trauma were followed radiographically for an average of 5 years. Seven teeth did not show any root resorption during the observation period. In 8 teeth shallow resorption cavities were observed, but no signs of progression were observed with increased observation time. In 6 teeth some progressive root resorption was observed with increased observation time. The depth of root resorption cavities was assessed using a radiographic index, and the rate of root resorption was defined as the index change over time. The rate of root resorption was determined. It was concluded that teeth replanted within 15 min after the avulsion have a favourable long-term prognosis.

Progression of root resorption following replantation of human teeth after extended extraoral storage.

Avulsed human permanent teeth subjected to a minimum of 1 h dry extraoral storage before replantation were followed radiographically for an average of 4.8 years. The depth of root resorption cavities was assessed using a radiographic index, and the rate of root resorption was defined as the index change over time. The frequency of inflammatory and replacement resorption was determined at each observation time. Replacement resorption increased in frequency with time in all patients. In teeth endodontically treated within 3 weeks of replantation, minimal inflammatory resorption was found regardless of the age of the patients. In teeth where endodontic treatment was performed more than 3 weeks after replantation, the frequency of inflammatory resorption was significantly higher in young patients but not in older patients, up to more than 3 years after replantation. The rate of root resorption was found to be related to age. In patients 8-16 years old at the time of avulsion the rate of root resorption was significantly higher compared with patients 17-39 years old. Age had a higher impact on the rate of root resorption compared with the delay in endodontic treatment after replantation. It was concluded that a tooth replanted with a necrotic periodontal membrane will become ankylosed and resorbed within 3-7 years in young patients, whereas a tooth replanted under similar conditions in older patients may remain in function for a considerably longer time.

Undiagnosed benign cementoblastoma in a patient with a 6-year pain condition. Report of a case.

Symptoms in the lower first molar developed in a 15-year-old girl. The problems started with tenderness during occlusion. The first radiographic examination revealed a radiopacity at the distal root, which was considered in the radiographic report to be a cementoma. Therapy commenced with occlusal adjustment, but this was followed 20 months later by endodontic therapy, which was undertaken because of the suspicion of partial pulpal necrosis with condensing osteitis. A painful condition developed and led first to apicoectomy and then to extraction 2 1/2 years after the start of the endodontic therapy. Light microscopic examination of adjacent hard tissue revealed signs of chronic inflammation on both occasions, and a diagnosis of diffuse sclerosing osteomyelitis was made. The pain was not relieved but remained at a tolerable level for 18 months. Then a reexamination of the first radiographs led to a strong suspicion of a benign cementoblastoma. A thorough third operation revealed a small piece of hard tissue in a lacuna of the lingual part of the mandible covered buccally by granulation tissue and inflammatory affected bone. The final histopathologic diagnosis was benign cementoblastoma combined with chronic inflammation.

Cysts of the nasopalatine duct.

Nasopalatine duct cysts in 70 patients were reexamined clinically and radiographically. 50 of them were also reexamined histopathologically. 20 specimens of normal duct tissue were likewise examined. More than half of the cysts showed clinical symptoms. The form on the radiograph was usually spherical or oval. Only 1 of 5 cysts was heart-shaped; 1 of 10 was unilateral. The mesiodistal width of the cysts ranged from 4-40 mm, with 75% from 6-12 mm. 3 of 4 showed pronounced radiolucency. Every 2nd cyst was completely surrounded by a thin radiopaque border. The histopathological investigation showed small cysts to be present in 1 of 4 clinically and radiographically normal nasopalatine ducts. More than 1 of 4 clinically and radiographically diagnosed cysts lacked histopathological characteristics of a cystic cavity. The type of epithelium in the cysts was independent of the vertical position in the duct.

Diagnosis and treatment of the unicystic ameloblastoma.

Two cases of unicystic ameloblastoma are presented. The lesions were pain-free and expanded the mandible. They were removed by curettage. Recurrent lesions had similar clinical appearances and histological pictures compared to the original lesions. The unicystic ameloblastoma manifested itself as a cystic cavity without solid neoplastic features, which differs from the solid ameloblastoma with regard to the age of the patients and the rate of recurrence. The behavior of the unicystic ameloblastoma was similar to that of the primordial cyst. Despite the obvious risk of recurrence, conservative treatment with enucleation and curettage seemed to be justified in preference to mutilating radical surgery.