[An unusual case of upper GI bleeding: esophageal cancer metastasis at a percutaneous endoscopic gastrostomy site--case report and review of the literature]. / Ungewöhnlicher Fall einer akuten oberen gastrointestinalen Blutung: PEG-Implantationsmetastase eines Osophaguskarzinoms--Fallbericht und Literaturübersicht.

We present the case of a patient with an esophageal squamous cell carcinoma, who was treated primarily by radiotherapy. Due to dysphagia, the patient received a percutaneous endoscopic gastrostomy (PEG) without any sign of tumour at that time. Five months later the patient presented with an upper GI bleeding from a gastric ulcer, which histologically turned out to be a metastasis of the previously diagnosed squamous cell carcinoma. So-called "implantation metastases" at the percutaneous endoscopic gastrostomy site are rare and most of the cases have been described in patients with head and neck tumours. Moreover, the presentation as an upper GI bleed is very uncommon and needs the attention of both endoscopists as well as gastrointestinal oncologists. Clinicopathological features of this case with a brief review of the literature are presented.

Oesophageal squamous cell neoplasia in head and neck cancer patients: upregulation of COX-2 during carcinogenesis.

Patients with (previous) head and neck cancer (HNC) are at high risk for developing second squamous cell cancer of the oesophagus. The role of cyclooxygenase-2 (COX-2) in oesophageal squamous carcinogenesis has not yet been investigated in this high-risk group. Therefore, this study examined COX-2 mRNA and protein expression in oesophageal biopsies and resected tissues of 44 HNC patients. The evaluation covered 55 oesophageal tissue samples (18 invasive oesophageal squamous cell cancers, four high- and eight low-grade dysplasias, 25 normal squamous epithelia) from the 44 patients. mRNA levels of COX-2 were measured by real-time PCR using a LightCycler. COX-2 protein expression was studied immunohistochemically and graded by a staining score. COX-2 mRNA was detected in all samples, and its levels correlated positively with the immunohistochemical staining score (P<0.05). COX-2 expression was upregulated during oesophageal squamous carcinogenesis in HNC patients, that is COX-2 expression increased significantly from normal oesophageal squamous epithelium to low- and high-grade dysplasia and finally to invasive squamous cell cancer (P<0.001). Our findings suggest that COX-2 upregulation contributes to oesophageal squamous carcinogenesis in HNC patients. Prospective studies are needed to evaluate the chemopreventive potential of COX-2 inhibitors in this high-risk group.

Prognostic value of nuclear survivin expression in oesophageal squamous cell carcinoma.

Survivin, a new member of the family of apoptosis inhibitors, is expressed almost exclusively in proliferating cells, above all in cancers. Subcellular localisation and prognostic implications of the survivin protein have not yet been determined in oesophageal squamous cell carcinoma. The survival of 84 patients with oesophageal squamous cell carcinomas was correlated with the extent of immunohistochemical survivin expression in tumour cell nuclei. Tumours were scored positive when >5% cells stained positive. Patients were followed up for at least 5 years or until death. In normal oesophageal squamous cell epithelium, some cytoplasmic survivin expression was detected in the basal cells, whereas proliferating cells showed nuclear staining of survivin. Nuclear expression of survivin was also detected in 67 cancers (80%). The mean survival for patients of this group (28 months, range 20-36) was significantly less than that for patients without survivin expression in the tumour cell nuclei (108 months, range 62-154, P=0.003). Using univariate analysis, nuclear survivin expression (P=0.003), tumour depth (P=0.001), lymph node metastasis (P=0.003) and stage (P<0.001) were the best predictors of survival. In contrast, cytoplasmic survivin staining was noted in 53 (63%) tumours and had no prognostic relevance. In conclusion, the analysis of nuclear survivin expression identifies subgroups in oesophageal squamous cell cancer with favourable (survivin(-)) or with poor prognosis (survivin(+)). We suggest that the determination of nuclear survivin expression could be used to individualise therapeutic strategies in oesophageal squamous cell cancer in the future.

The bridge graft: a new concept for infrapopliteal surgery.

BACKGROUND: The long-term results of ePTFE grafts are particularly poor in crural reconstructions. We report on a novel surgical technique, whereby both run-off and anastomotic mismatches are concomitantly addressed. PATIENTS AND METHODS: Short segments of vein grafts (5-15 cm in length) were used to bridge two crural artery segments. Subsequently, a femoro-distal ePTFE graft was anastomosed to the bridge graft. Venous valves were made incompetent to allow bi-directional flow. In a retrospective series of 45 patients with crural bridge grafts, 12 patients were in stage III and 33 in stage IV. In 18 patients the reconstruction was the first procedure and in the remaining 28 patients it was the first or second re-operation. RESULTS: The primary patency rate at 1, 2, 3 and 4 years was 53, 44, 35 and 26% respectively. The secondary patency rate was 67, 53, 49 and 39% respectively. The corresponding limb salvage rate was 70, 61, 56 and 45%. In a small subgroup of patients, in which the crural bridge was the first reconstructive procedure, the primary patency was 76 at 1 year and 64 at 4 years. CONCLUSION: convincing long-term crural bridge grafts should be considered in those patients who have more than one crural or pedal artery available for grafting and an insufficient length of saphenous vein.

Telomerase is a strong indicator for assessing the proneness to progression in neuroblastomas.

BACKGROUND: As traditional parameters do not ensure completely accurate prognostic grouping in neuroblastoma (NB), new molecular markers are needed for assessing the individual patient's prognosis more precisely. PROCEDURE, RESULTS, AND CONCLUSIONS: Based on 133 NB, we show that telomerase activity (TA) is a powerful, independent prognostic marker for all stages and is capable of differentiating between good and poor outcome in putative 'favorable' clinical or biological subgroups of NB patients. Analysis of gene and protein expression of telomerase subunits suggests that the presence or absence of TA in NB is strongly correlated with expression levels of both the catalytic subunit hTERT and the internal RNA component (hTR).

Redo surgery for carotid artery stenosis: when and how?

PURPOSE: We analyzed operations performed at our institution retrospectively for recurrent carotid artery stenosis to assess the indication for surgery. We also assessed the techniques used for these operations. PATIENTS AND METHODS: From January 1992 to December 1998 1210 carotid endarterectomies were performed. Forty two (3.4%) of these were for recurrent stenosis. A new vein patch was implanted in 27 cases, PTFE patches were used in nine cases. In six cases an interposition with the great saphenous vein was performed. RESULTS: The mean interval between primary and secondary procedure was 60. 2months (3months to 23yr). Twenty five of our 41 patients had had ipsilateral neurologic symptoms before redo surgery, the remainder were free of symptoms. The grade of stenosis was over 90% in 22 cases, between 75 and 90% in 11 cases and below 75% in nine cases, two cases had aneurysmatic lesions. None of the patients died in the 30day observation period. One patient had a stroke with a permanent neurological deficit. In two cases postoperative bleeding occurred requiring reexploration. Two patients developed hypoglossal neurapraxia and in four patients the recurrent laryngeal nerve was injured. One patient had an apneic episode in the recovery room. CONCLUSION: The reported incidence of recurrent carotid artery stenosis surgery ranges from 3 to 36% and our incidence is at the lower end of this range. The surgical results of reoperating are acceptable with a low incidence of complications.

Telomerase expression in uveal melanoma.

BACKGROUND/AIMS: Accumulating evidence indicates that telomerase activity is repressed in normal human somatic cells but reactivated in cancers and immortal cells, suggesting that activation of telomerase activity has a role in carcinogenesis and immortalisation. To date, telomerase in uveal melanoma and, whether, it may have a role in the development or progression of these tumours has not been described. The expression patterns and the activity of telomerase were investigated in 14 uveal melanoma and these results were correlated with histological and immunohistological features of these tumours. METHODS: A modified PCR based telomeric repeat amplification protocol (TRAP) assay was used to demonstrate telomerase activity in 14 uveal melanomas. In addition, in situ hybridisation was used to demonstrate the expression pattern of the telomerase RNA component (hTR) at the single cell level in eight of these globes. RESULTS: The TRAP assay revealed moderate telomerase activity in all uveal melanomas examined. In situ hybridisation visualised a moderate to high upregulation of hTR in the melanoma cells but not in the admixed reactive cells. There was no correlation among tumour location, cell type, or growth fraction and the amount of telomerase activity. In addition, the cells of the germinative zone of the lens demonstrated a strong hTR expression. CONCLUSION: Telomerase activity is upregulated in uveal melanomas. The expression of hTR was located to the tumour cells and not the reactive tumour infiltrating cells. Strong telomerase expression was also demonstrated in cells of the germinative zone of the lens.

[Abdominal actinomycosis after stomach surgery in a patient with long-term rheumatoid arthritis treated with methotrexate]. / Abdominelle Aktinomykose nach Magenoperation bei einer Patientin mit langjähriger rheumatoider Arthritis unter Methotrexat-Therapie.

HISTORY AND ADMISSION FINDINGS: A 78-year-old woman had a 30-year history of rheumatoid arthritis, of late treated with prednisolone and methotrexate. A week before admission she had first noticed a mass about 3 cm in diameter, at the lower end of a scar from a Billroth II gastric resection for gastric ulcer, performed 4 months before. She reported to have lost 6.5 kg in weight. On admission a moderately mobile, hard mass was palpated on the abdomen. INVESTIGATIONS: Ultrasound and computed tomography revealed a superficial, inhomogenous space-occupying lesion with poorly circumscribed margins. TREATMENT AND COURSE: After two days the skin over the mass became reddened and a laparotomy was performed because an incarcerated herniation was suspected. An abscess and inflammatory adhesions were found in the area of the transverse colon, histologically shown to be a chronic purulent abscess with granular clusters of pathogens indicating actinomycosis. After 3 weeks' treatment with imipenem i.v. the patient became free of symptoms, oral doxycyclin was continued for a further 6 months. CONCLUSION: Actinomycosis should be considered in the differential diagnosis of a tumour of undetermined benignity in the region of the head, chest or abdomen in immunosuppressed patients. This bacterial infection should be thought of especially if the gastrointestinal mucosa has been penetrated by invasive procedures.

Hodgkin and Reed-Sternberg cells of classical Hodgkin's disease overexpress the telomerase RNA template (hTR).

There is accumulating evidence to suggest that Hodgkin and Reed-Sternberg (HRS) cells represent the malignant cell population in Hodgkin's disease (HD). A recent report that HD tissue is in most instances devoid of telomerase activity was therefore unexpected. Since telomerase activity was determined in whole tissue extracts and HRS cells comprise only a small minority of the cells in the affected tissue, the telomerase activity of the HRS cells might have escaped detection. To test this possibility and to clarify whether HRS cells contain the enzyme telomerase, 13 cases of classical HD were analysed by three different methods. The presence of telomerase was studied at the single cell level by a sensitive radioactive in situ hybridization method employing a probe specific for the telomerase RNA template (hTR). In addition, tissue extracts were studied for telomerase activity by a modified TRAP assay and for hTR by reverse transcription-polymerase chain reaction (RT-PCR). The extractive methods revealed telomerase activity in eight and hTR in all of the 13 HD cases studied. In situ hybridization located large amounts of hTR in the HRS cells of all 13 HD cases and low to medium amounts in some of the non-malignant lymphoid bystander cells. These results indicate that HRS cells constitutively overexpress telomerase and thus use this enzyme for stabilizing their telomeres. This substantiates the malignant nature of HRS cells. Furthermore, the results confirm that normal lymphoid cells can express telomerase. In consequence, methods of measuring telomerase in tissue extracts are not suitable for determining the presence of this molecule in lymphoma cells, since the vast majority of lymphoid neoplasms contain significant amounts of non-neoplastic lymphoid cells.

Demonstration of constant upregulation of the telomerase RNA component in human gastric carcinomas using in situ hybridization.

Upregulation of the ribonucleoprotein telomerase seems to be a prerequisite for immortality, a feature of malignant cells. Using a polymerase chain reaction (PCR)-based assay, it is possible to demonstrate telomerase activity (TA) in specimens of most human malignancies, whereas it is absent from most normal tissues. It remains unclear, however, why between 5 and 50 per cent of various malignant tumour samples give negative results when TA is measured by the telomeric repeat amplification protocol (TRAP). The expectation that reverse transcription (RT)-PCR for detection of the telomerase RNA component (hTR) would be able to complement or to replace the TRAP assay failed, since malignant as well as non-malignant tissue samples gave positive results in most instances. In the present study, in situ hybridization (ISH) was developed to demonstrate the RNA component of human telomerase at the single cell level. With this method, 13 specimens of fresh frozen gastric carcinoma and four of normal, dysplastic, or inflamed gastric mucosa were investigated and the results were compared with those obtained by RT-PCR and the TRAP assay. In addition, ISH was performed on formalin-fixed sections of the same cases. The TRAP assay revealed positive results in 8 out of 13 gastric carcinomas and was negative in all non-malignant tissues. RT-PCR led to amplification of the telomerase RNA component in all specimens tested, irrespective of the presence or absence of malignant cells. By ISH, all gastric carcinomas showed strong telomerase RNA component-specific signals over malignant cells, whereas only a few grains were detectable over some types of normal somatic cells, including activated lymphocytes. In conclusion, high expression of the telomerase RNA component was restricted to the malignant cells of all the gastric carcinomas investigated, as shown by ISH. This indicates that the absence of TA in a proportion of carcinomas is due to methodological problems of the TRAP assay and is not caused by biological factors. The detection of high levels of the telomerase RNA component by ISH is thus a useful technique for demonstrating malignant cells in frozen and formalin-fixed pathological specimens.

Non-radioactive measurement of telomerase activity in human bladder cancer, bladder washings, and in urine.

Early diagnosis is still the most important prerequisite for successful cancer treatment and this holds true for bladder cancer. Urine cytology is commonly used as a non-invasive screening procedure for the detection of bladder carcinoma, but this method is labour-intensive and often generates false-negative results. The ribonucleoprotein telomerase appears to be promising new cancer marker, since its activity has been reported to correlate with indefinite growth. The aim of this study was to investigate whether telomerase activity can be detected in bladder cancer and in corresponding bladder washings. For this purpose, a sensitive non-radioactive TRAP (telomeric repeat amplification protocol) detection system was developed. With this technique, telomerase activity was found in 95 per cent of the carcinomas (n = 20), in 70 per cent of the corresponding bladder washings, but in none of the urine samples obtained from patients with bladder carcinoma. No telomerase activity was detectable in normal urothelium or in samples from dysplastic urothelium. The data obtained from bladder washings show that superficial carcinoma cells released into the bladder still harbour telomerase activity. The absence of telomerase activity in voided urine is thus most likely due to degradation or inactivation under these conditions. The high rate of telomerase activity in bladder carcinoma indicates that the activation of telomerase in a common step in the tumourigenesis of bladder cancer.

[Telomerase as a tumor marker?]. / Die Telomerase als Krebsmarker?

The maintenance of the length of chromosomes (telomeres) is the prerequisite of unlimited malignant growth of cells. In normal cells the telomeres will be shortened by each cell division finally leading to cell senescence. Unlimited growing cells possess an enzyme, the telomerase, which is able to maintain the length of the telomeres by de novo synthesis of the telomeric repeats. In consequence the telomerase is detectable in nearly all malignant tumours and cell lines. However, in addition to malignant cells some type of non-malignant cells such as germ cells, activated lymphocytes and basal epithelial cells contain significant amounts of telomerase activity. Therefore, the detection of telomerase activity by extractive procedures such as TRAP assay is not sufficient to determine malignant nature of tissue samples.

Bilateral oral melanoacanthoma.

A case of bilateral oral melanoacanthoma involving the buccal mucosa is reported. This rare lesion, most often found in young black persons, is suggested here to be reactive in nature.

Telomerase activity in bladder cancer, bladder washings and in urine.

With only a few exceptions, the ribonucleoprotein telomerase has been found in malignant, but not in benign tissues. Telomerase is thus a potentially new diagnostic marker. Carcinoma of the urinary bladder is the most frequent malignant tumor of the urinary tract and, after prostatic carcinoma, the second most common malignancy of the genitourinary system. In order to evaluate the diagnostic capabilities of telomerase in bladder carcinomas, four cell lines derived from human urothelial carcinomas of the bladder, 75 tissue samples from bladder carcinomas, eight tissue samples of normal bladder urothelium, 40 bladder washings and 30 urine samples were examined for telomerase activity. The four cell lines derived from urothelial carcinoma of the bladder (F975, 582, SCaBER, UM-UC-3) all exhibited high telomerase activity and were thus used as positive controls. Telomerase activity was found in nearly all (96%) tissue samples obtained from histologically confirmed urothelial carcinoma of the bladder. None of the normal tissue samples examined showed telomerase activity. Telomerase activity was similarly found in 73% of bladder washings in patients with histologically confirmed bladder carcinoma. There were no false positive results. The determination of telomerase activity in bladder washing samples thus represents a new diagnostic method for detection of tumor cells in rinsing media. Because of the early inactivation or degradation of telomerase there was no detection of the enzyme in native urine in the present study.