[The radiotherapy satellite in Kristiansand--a model for Norwegian regional hospitals?]. / Stråleterapisatellitten i Kristiansand--en modell for norske regionsykehus?

BACKGROUND: During the first decade of 2000, significant increase of radiotherapy capacity in Norway will take place, as the number of linear accelerators will increase from 24 to 36. In Norway, radiotherapy departments are traditionally located only in university hospitals. However, six of the new accelerators will not be installed in existing radiotherapy centres, but in small, new radiotherapy units, set up in selected county hospitals and organized as satellites of the university hospitals, in order to secure the treatment quality. The university hospital is responsible for both medical and technical standards in the satellite, while the county hospitals have the financial responsibility. RESULTS: The satellite model combines two important aspects of hospital management; treatment is geographically decentralized, while treatment quality is centralized. The first radiotherapy satellite was established in the town of Kristiansand in January 2001. We report our experience with this new concept in radiotherapy. INTERPRETATION: The satellite model should be evaluated also for other medical specialties within the university hospitals.

Reduced expression of p21WAF1 is an indicator of malignant behaviour in anal carcinomas.

AIMS: p21 and p27 protein expression were examined in a comparatively large series of patients with squamous cell carcinoma of the anal canal and compared with clinical and histopathological data (tumour stage, nodal status and differentiation). METHODS AND RESULTS: We analysed the expression of p21 and p27 protein in 94 anal carcinomas by immunohistochemistry. Nuclear p21 and p27 staining were detected in 71% (67/94) and 75% (71/94) of the cases, respectively. There was no significant association between p27 staining and tumour stage, nodal status or overall survival. We observed that negative p21 immunoreactivity was significantly associated with poorly differentiated anal carcinomas. Furthermore, a shorter overall survival for patients with no p21 protein expression was seen. CONCLUSIONS: Our data indicate that p21 levels, but not p27 expression, may be a useful predictor of survival in patients with anal carcinomas.

[Patient treatment in radiation accidents]. / Pasientbehandling ved strålingsulykker.

Accidental human injury due to ionizing radiation is rare. Industrial accidents are comparatively the most common. Life saving procedures should always have priority to any concern about radiation injury or contamination. The personal risks for emergency medical personnel is negligible when simple measures are taken. Repeated clinical examinations and blood lymphocyte counts should be performed on all patients with suspected radiation injury to allow a diagnosis. The radiation syndrome develops within days or weeks depending on total radiation dose, dose rate and dose distribution. Damage to the bone marrow and gut are the most important. Local radiation injuries to the hands are common in industrial accidents. The Norwegian Radiation Protection Authority should always be called when a potential ionizing radiation accident takes place within Norway.

Changes in oxygen tension during radiotherapy of head and neck tumours.

Increased knowledge about changes that occur in tumour oxygenation during radiotherapy and the biological factors causing these changes can be useful in the development of optimal radiation treatments. The aims of this study were a) to study changes in the oxygen tension (pO2) of human head and neck tumours during radiotherapy in relationship to changes in cell density and vascular density, and b) to investigate whether the pO2, measured before or during therapy, can be used to predict the therapeutic outcome. Preliminary data from the first 11 patients included in the study are reported. The pO2 was measured before treatment (11 patients) and once a week during therapy (8 patients), using polarographic needle electrodes. Cell density and vascular density were determined from biopsies taken after each pO2 measurement in 5 patients. Significant fluctuations in pO2 occurred during therapy. Changes in hypoxic fraction; i.e., fraction of pO2 readings below 2.5 mm Hg, 5 mm Hg or 10 mm Hg, coincided with changes in cell density, but not with changes in vascular density, which suggests that the changes in hypoxic fraction were caused by changes in oxygen consumption rather than supply. Response evaluation after a median follow-up time of 19 months showed that progressive disease occurred among the patients with highly hypoxic tumour, regardless of whether hypoxic fraction before treatment or after two weeks of radiotherapy was considered.

Endoluminal radiotherapy for rectal tumors.

The present study was performed to evaluate local tumor control and side effects of endoluminal radiotherapy given to patients with rectal tumors. Twelve patients with adenocarcinoma and 10 patients with villous/adenovillous adenomas were treated with curative intent from 1989 to 1995. The majority of patients were of advanced age and in poor medical condition, and had previously been found unable to undergo radical surgery or colostomy. Three patients had tumor remains following radiotherapy, they successfully received local surgery (n = 2) or an iridium implant (n = 1) as second-line treatment. Two patients (adenomas) later experienced a local relapse. No serious side effects were observed. We conclude that endoluminal radiotherapy is an efficacious option for patients with malignant or premalignant tumors in the lower rectum who are in poor medical condition.

[Endocavitary radiotherapy of distal rectal tumors]. / Endokavitaer strålebehandling ved distale rectumtumorer.

We describe our experience of endocavitary radiotherapy of adenomas and carcinomas of the lower rectum. The method is an alternative for patients who cannot undergo standard surgical procedure or do not want a permanent colostomy. The method is cheap, fast and causes little discomfort to the patients, gives reasonable long-term results and has low morbidity.

Anal carcinoma: a clinical approach to p53 and RB gene proteins.

The role of p53, retinoblastoma (RB) and c-erbB-2 gene proteins in the pathogenesis of anal carcinomas has been examined. A total of 97 patients were included in the study. c-erbB-2, RB and p53 proteins were abnormal in 0, 5 and 34% of the cases, respectively. No correlation was observed between p53 and age, sex, tumour stage, histopathological tumour grading, human papilloma virus (HPV) affection or prognosis. It is concluded that the c-erbB-2 gene is not involved in the development of anal carcinomas; the role of the RB gene is somewhat uncertain, while p53 may be involved in about 1/3 of the cases. However, p53 is not correlated with HPV infection or clinical or histopathological data.

[Anal cancer. A review]. / Analcancer. En oversikt.

The article contains a brief review of anal carcinoma. Biopsy and histopathological examinations are extremely important to ensure correct diagnosis, as there is a great therapeutic difference between squamous cell carcinoma and adenocarcinoma in this region. Primary treatment for squamous cell carcinoma is chemoradiotherapy, while surgery is second line treatment. This regimen gives excellent locoregional tumour control with 70% long-time survival. The most serious problem now is the the development of distant metastases. The main diagnostic procedure, both for primary tumours and local relapses, is well performed digital anal palpitation. A Norwegian standard protocol for anal carcinoma has been prepared to ensure good quality diagnostic procedures, therapy and follow-up in these patients.

Evaluation of the prognostic significance of nm23/NDP kinase and cathepsin D in anal carcinomas. An immunohistochemical study.

Reduced expression of nm23/NDP kinase and increased expression of cathepsin D seem to be correlated with a high metastatic potential for a variety of malignancies. Nm23/NDP kinase and cathepsin D have been correlated with several clinical variables, including survival in 96 patients with squamous cell carcinoma of the anal canal. Immunohistochemical methods were used on paraffin-embedded biopsies. Seventy-six (79%) anal carcinomas were nm23/NDP kinase positive, whereas 35 (36%) and 28 (29%) of the cases were cathepsin D positive in tumor cells and stromal cells, respectively. We have found no indication that the extent of cathepsin D staining has any prognostic significance. The overall survival of patients with tumours positive for nm23/NDP kinase in the cytoplasm was significantly shorter than that of patients with anal carcinomas negative for nm23/NDP kinase.

Skin treatment with bepanthen cream versus no cream during radiotherapy--a randomized controlled trial.

In several radiotherapy departments, dexpanthenol cream (Bepanthen 'Roche') has been used extensively to ameliorate acute radiotherapy skin reactions. The evidence base for this practice is obscure as no randomized trials have been performed. In the present clinical prospective study of 86 patients we have compared Bepanthen cream with no topical ointment at all. The cream was applied on randomly selected parts of treatment fields in laryngeal and breast cancer patients, and so each patient acted as his own control. Seven patients were withdrawn from analysis. Scoring of skin reactions in 16 laryngeal and 63 breast cancer patients was performed without knowledge of which area that had been given cream or not. Endpoints were a modified skin reaction grading according to EORTC/RTOG, and itching/pain in treated fields. The study did not indicate any clinically important benefits of using Bepanthen cream for ameliorating radiogenic skin reactions under the conditions applied.

Prevalence and physical state of human papillomavirus DNA in anal carcinomas.

Epidemiologic studies suggest that human papillomavirus (HPV) plays an important role in the development of squamous cell carcinoma of the anal canal. However, in previous studies the prevalence of HPV found in tumor varied from 0 to 85%. This study was performed to investigate the prevalence and physical state of HPV DNA in anal carcinomas. HPV infection was examined using in situ hybridization and polymerase chain reaction. HPV DNA was detected in 80/99 (81%) of the tumors, including 66/74 (89%) from females and 14/25 (56%) from males. HPV16 was demonstrated in 84% of the females and 52% of the males. HPV18, HPV31, and HPV33 could be demonstrated in 5% or less of the cases. In situ hybridization technique showed that 100% of the virus-infected cases had punctate signal and 67% had in addition a diffuse signal, indicating integrated and episomal virus DNA, respectively. The integrated and episomal HPV DNA coexisted in the majority of the tumor cell nuclei. This study indicates that infection and integration of HPV DNA may play an important role in the pathogenesis of anal canal carcinomas.

Prognostic factors in anal carcinoma.

This study was performed to examine if commonly recorded parameters are of prognostic importance for patients with squamous cell carcinoma of the anal canal. A total of 77 patients received combined chemoradiotherapy and were followed at regular intervals after treatment. Age, sex, performance status, tumour stage, histopathological differentiation and grade, were not found to be of prognostic importance. Most blood tests did not correlate with prognosis, although elevated serum alkaline phosphatase (ALP) and lactate dehydrogenase (LD) proved to be unfavourable prognostic factors. In the present study serum ALP and LD were the only parameters that significantly correlated with development of distant metastases during follow-up.

Chemoradiotherapy of anal carcinoma: tumour response and acute toxicity.

This study was performed to evaluate local tumour control and toxicity of chemoradiotherapy given to patients with primary or recurrent carcinoma of the anal canal. A total of 117 patients were admitted to the Norwegian Radium Hospital during the period of 1983-1989, of which 106 received a combination of radiotherapy (50 Gy to the pelvis) and chemotherapy (mitomycin C + 5-fluorouracil). Sixty-five percent of the patients with primary carcinomas presented with advanced tumours (T3 or T4). Good local tumor control was obtained as only 25% of the patients with advanced tumours (T3 and T4) and 7% of those with smaller tumours (T1 and T2) had a local relapse after treatment. Recurrent tumours following primary surgery did not respond as well; 50% of these patients still had carcinoma 1 month following therapy. All patients experienced acute toxicity (dermatitis/mucositis, diarrhoea and general fatigue), and 50% needed as split course. There was, however, no therapy-related mortality. Survival data seem promising, but further follow-up is necessary to make conclusions. Eight percent of the patients had serious anal insufficiency after treatment. We conclude that the present regimen provides good local tumour control and well-preserved anal function, but has considerable acute toxicity.

Treatment of relapsing anal carcinoma.

Between 1983 and 1989, a total of 94 patients were admitted to the Norwegian Radium Hospital for primary squamous cell carcinoma (including 'basaloid' and 'cloacogenic' carcinomas) of the anal canal. Seven patients with evident distant metastases received chemotherapy, while without known distant metastases received combined chemo- and radiotherapy. Of the latter patients, 17 developed distant metastases and 11 local recurrence later on. Patients with distant metastases had a median survival of 12 months (range 3-54 months) following start of chemotherapy (cisplatin + 5-FU or mitomycin C + 5-FU). An abdominoperineal resection was performed on 9 of the 11 patients with local relapse. Of these, 6 patients were alive without evident disease after 3 years of observation.

[Endocavitary radiotherapy of rectal cancer]. / Endokavitaer strålebehandling ved cancer recti.

Most patients with rectal carcinomas undergo surgery, either a resection with anastomosis or Miles' operation with permanent colostomy. Endocavitary radiotherapy is an alternative to surgery in patients with small carcinomas (Dukes' A) or adenovillous adenomas. The treatment is cheap, simple, gives good local tumour control, has low morbidity and does not require hospitalization. The Norwegian Radium Hospital has recently started to use this method in selected cases of rectal carcinomas.

Diagnosis and treatment of anal carcinoma. An overview.

Squamous cell carcinoma of the anal canal gives early symptoms and is easy to diagnose. However, these patients often present with advanced tumours, probably because of patient's and/or doctor's delay. The diagnosis must be confirmed by a conclusive biopsy as the treatment of ano-rectal tumours is based upon correct histopathological diagnosis. Loco-regional tumour control of squamous cell carcinoma is excellent following radiotherapy or combined chemoradiotherapy as only 10-20% of the patients develop a local recurrence. The great majority of these are cured by abdominoperineal resection. However, this treatment involves considerable acute and chronic toxicity, but mortality is less than 2%. There is no general agreement about how to minimize toxicity without hazarding loco-regional tumour control. One way could be to irradiate only the primary tumour site in patients with early lesions, and reserve radiotherapy of regional lymph nodes for more advanced cases. About 20% of the patients develop distant metastases, which make the disease incurable. Hence, frequent, rectal digital examination is the most important follow-up since early local recurrences can easily be cured. There is no general consensus concerning adjuvant chemotherapy, but its potential should be further explored.

Carcinoembryonic antigen in anal carcinoma.

Patients with squamous cell carcinoma of the anal canal occasionally present with an elevated level of carcinoembryonic antigen (CEA) in serum. The present study was performed to evaluate the clinical importance of this observation. Serum CEA was measured in 106 patients prior to chemo- and radiotherapy and during follow-up. Twenty patients had elevated serum CEA level before treatment. In 6 of 12 cases, serum CEA did not normalize after successful treatment and in 4 of 7 cases it rose no further despite progressive disease. CEA-positive tumours were more often poorly differentiated than CEA-negative tumours. There was no significant correlation between serum CEA, tumour CEA and prognosis. We conclude that measurement of serum CEA and staining of tumour CEA lack clinical importance.

Chemotherapy and radiation therapy for anal carcinoma. Survival and late morbidity.

This study was performed to evaluate the survival and late morbidity rates of a widely used combined chemotherapy and radiation therapy regimen given to patients with carcinoma of the anal canal. One hundred six patients received radiation therapy (5000 cGy given by two anteroposterior-posteroanterior [AP-PA] opposed fields) and chemotherapy (mitomycin C plus 5-fluorouracil [5-FU]) from 1983 to 1989. Patients with primary tumors (n = 86) had a complete response rate of 84% and a 5-year survival rate of 72%. There was no significant difference in survival rate according to tumor stage. Patients with local recurrence (n = 20) after primary surgery had a complete response rate of 50% and a 5-year survival rate of 40%. Fifteen percent of the patients experienced late treatment-related symptoms including anal incontinence, intestinal obstruction, and chronic pelvic pain. The current treatment regimen is effective but carries a considerable risk of complications. As survival rate was independent of tumor stage, the locoregional treatment should probably be less extensive for small tumors than for advanced tumors. This strategy may reduce the late side effects for patients with small tumors without reducing the survival rate.