Stereotactic radiosurgery and radiotherapy for resected brain metastases: current pattern of care in the Radiosurgery and Stereotactic Radiotherapy Working Group of the German Association for Radiation Oncology (DEGRO).

PURPOSE: Preoperative stereotactic radiosurgery (SRS) of brain metastases may achieve similar local control and better leptomeningeal control rates than postoperative fractionated stereotactic radiotherapy (FSRT) in patients treated with elective metastasectomy. To plan a multicentre trial of preoperative SRS compared with postoperative FSRT, a survey of experts was conducted to determine current practice. METHODS: A survey with 15 questions was distributed to the DEGRO Radiosurgery and Stereotactic Radiotherapy Working Group. Participants were asked under what circumstances they offered SRS, FSRT, partial and/or whole brain radiotherapy before or after resection of a brain metastasis, as well as the feasibility of preoperative stereotactic radiosurgery and neurosurgical resection within 6 days. RESULTS: Of 25 participants from 24 centres, 22 completed 100% of the questions. 24 respondents were radiation oncologists and 1 was a neurosurgeon. All 24 centres have one or more dedicated radiosurgery platform and all offer postoperative FSRT. Preoperative SRS is offered by 4/24 (16.7%) centres, and 9/24 (37.5%) sometimes recommend single-fraction postoperative SRS. Partial brain irradiation is offered by 8/24 (33.3%) centres and 12/24 (50%) occasionally recommend whole-brain irradiation. Two centres are participating in clinical trials of preoperative SRS. SRS techniques and fractionation varied between centres. CONCLUSION: All responding centres currently offer postoperative FSRT after brain metastasectomy. Approximately one third offer single-fraction postoperative SRS and four already perform preoperative SRS. With regard to potential co-investigators, 18 were identified for the PREOP­2 multicentre trial, which will randomise between preoperative SRS and postoperative FSRT.

Adjuvant radiochemotherapy in patients with locally advanced high-risk cervical cancer.

BACKGROUND AND PURPOSE: The aim of this retrospective study was to analyze the outcome of patients with locally advanced cervical carcinoma treated by adjuvant radiochemotherapy and to determine risk factors for local and distant relapse. Furthermore, acute and late effects of treatment were recorded. PATIENTS AND METHODS: A total of 72 patients with FIGO stages I-III cervical carcinoma were treated by radical hysterectomy, pelvic lymphadenectomy, and postoperative radiochemotherapy. Only patients with positive pelvic lymph nodes, parametrial involvement, positive margins, or tumor bulk were eligible. Patients were irradiated with a standard pelvic field (50.4 Gy in 28 fractions). The majority of patients received platinum-based chemotherapy. RESULTS: After a median follow-up of 37 months, estimated 1-, 2-, and 4-year disease-free survival (DFS) and overall survival (OS) rates were 89%, 80%, 68% and 95%, 88%, 76%, respectively. Nine of the 72 patients had pelvic recurrences including only 1 isolated local failure; 23 of the 72 patients presented with distant relapse. The majority of relapses occurred within the first 3 years after adjuvant treatment. The number of positive pelvic lymph nodes (> 1) was the strongest prognostic factor for DFS. Treatment was well tolerated with transient acute hematologic (~30%) and gastrointestinal (~30%) grade 3 toxicity. Small bowel obstruction (~6%) was the only important late sequelae. CONCLUSION: Adjuvant radiochemotherapy in patients with advanced cervical cancer and several risk factors is highly effective to prevent local relapse. Future efforts to improve outcome should be placed on improvement of systemic control especially in subgroups with high-risk features for distant relapse. Combined treatment was well tolerated with moderate acute and late toxicity.

Hereditary non-polyposis colorectal cancer: clinical and molecular evidence for a new entity of hereditary colorectal cancer.

BACKGROUND: Hereditary non-polyposis colorectal cancer (HNPCC) is clinically defined by familial clustering of colorectal cancer and other associated tumours. METHODS: By thorough molecular and clinical evaluation of 41 families, two different groups were characterised: group 1, 25 families with truncating mutations in MLH1 or MSH2 (12 novel mutations); and group 2, 16 Amsterdam positive families without mutations in these genes and without microsatellite instability in their corresponding tumours. RESULTS: Significant clinical differences between these two groups were found. Firstly, earlier age of onset for all colorectal cancers (median 41 v 55 years; p < 0.001) and all tumours (median 43 v 56 years; p = 0.022) was observed, comparing groups 1 and 2. Secondly, 68% of the index colorectal cancers were localised proximally of the splenic flexure in group 1 compared with 14% in group 2 (p < 0.010). Thirdly, more synchronous and metachronous colorectal (p = 0.017) and extracolorectal tumours (p < 0.001) were found in group 1. Fourthly, a higher colorectal adenoma/carcinoma ratio (p = 0.030) and a tendency towards more synchronous or metachronous adenomas in group 2 (p = 0.084) was observed, indicating a slower progression of adenomas to carcinomas. As three mutation negative tumours revealed chromosomal instability after comparative genomic hybridisation, these tumours may be caused by one or more highly penetrant disease alleles from the chromosomal instability pathway. CONCLUSION: These data show that HNPCC includes at least two entities with clinical and molecular differences. This will have implications for surveillance programmes and for cancer research.

Cerebral localization and regulation of the cell volume-sensitive serum- and glucocorticoid-dependent kinase SGK1.

The serum- and glucocorticoid-dependent kinase SGK1 is regulated by alterations of cell volume, whereby cell shrinkage increases and cell swelling decreases the transcription, expression and activity of SGK1. The kinase is expressed in all human tissues studied including the brain. The present study was performed to localize the sites of SGK1 transcription in the brain, to elucidate the influence of the hydration status on SGK1 transcription and to explore the functional significance of altered SGK1 expression. Northern blot analysis of human brain showed SGK1 to be expressed in all cerebral structures examined: amygdala, caudate nucleus, corpus callosum, hippocampus, substantia nigra, subthalamic nucleus and thalamus. In situ hybridization and immunohistochemistry in the rat revealed increased expression of SGK1 in neurons of the hippocampal area CA3 after dehydration, compared with similar slices from brains of euvolaemic rats. Additionally, several oligodendrocytes, a few microglial cells, but no astrocytes, were positive for SGK1. The abundance of SGK1 mRNA in the temporal lobe, including hippocampus, was increased by dehydration and SGK1 transcription in neuroblastoma cells was stimulated by an increase of extracellular osmolarity. Co-expression studies in Xenopus laevis oocytes revealed that SGK1 markedly increased the activity of the neuronal K+ channel Kv1.3. As activation of K+ channels modifies excitation of neuronal cells, SGK1 may participate in the regulation of neuronal excitability.

Deep prosthesis infection in incisional hernia repair: predictive factors and clinical outcome.

OBJECTIVE: To evaluate the incidence of prosthetic infection in incisional hernia repairs, to determine whether there are any factors associated with prosthetic infection and to describe the clinical outcome. DESIGN: Retrospective clinical study. SETTING: Teaching hospital, Germany. SUBJECTS: 121 consecutive patients who underwent incisional hernia repair in our department from December 1994 to December 1999. INTERVENTION: Hernia repair by implantation of an alloplastic prosthesis by the Stoppa-Rives technique. MAIN OUTCOME MEASURES: Postoperative deep prosthetic infection and associated factors. RESULTS: All 121 patients had the mesh implanted in the subfascial plane, 77 had a polypropylene mesh (Prolene) (64%), 7 had a polyester mesh (Mersilene) (6%), and 37 patients had a expanded polytetrafluoroethylene patch (ePTFE, Gore-Tex) (31%). Postoperatively the mesh became infected in 8 patients (7%), a mean of 4.5 months (range 0.5-16) after hernia repair. All three infected ePTFE patches had to be removed whereas drainage was sufficient treatment for the infected polypropylene and polyester meshes. CONCLUSION: Once a mesh infection is verified adequate drainage seems to be sufficient for polypropylene and polyester meshes but ePTFE patches should be removed.

[Experiences with reconstruction of large abdominal wall cicatricial hernias using Stoppa-Rives pre-peritoneal mesh-plasty]. / Erfahrungen mit der Rekonstruktion grosser Bauchwandnarbenhernien mittels präperitonealer Netzplastik nach Stoppa-Rives.

BACKGROUND: The observed recurrence-rate up to 20-50% of conventional incisional-hernia repair might be improved by alloplastic hernia repair in "sublay-technique" described by Stoppa and Rives. METHODS: From 12/94 to 12/97 122 pt. underwent surgery of incisional hernia of whom 50 had a very large abdominal wall defect so that hernia repair by alloplastic technique was necessary. All 50 pt. had mesh-implantation in subfascial plane, 28 pt. by ePTFE-patch (Gore-Tex) and 22 pt. by polypropylen-mesh (Prolene). RESULTS: The implantation-procedure required a mean time of 165 min. (range 55-345 min.). There were pulmonary complications in 2 patients (4%) of whom one had to be ventilated over 34 days, prosthesis-infection occurred in 3 pt. (6%). Follow-up on average 19 months (range 5-44 months) postoperatively revealed 5 hernia-recurrences (10.4%) in 48 patients. CONCLUSION: Mesh-implantation for hernia repair in sublay-technique requires intensive preparation of preperitoneal plane. Thus it took approximately 3 hours for mesh-implantation in this study. From our data Stoppa-Rives-procedure seems to be effective for 4-repair of large incisional hernias and allows immediate abdominal wall stress.

[Brief preoperative radiotherapy in surgical therapy of rectal carcinoma. Long-term results of a prospective randomized study]. / Präoperative Kurzzeitstrahlentherapie in der chirurgischen Therapie des Rectumcarcinoms. Langzeitergebnisse einer prospektiv-randomisierten Studie.

To ascertain whether preoperative short-term radiotherapy can improve local tumor control and the long-term survival of patients with operable rectal cancer, a prospective randomised trial was performed from 1988 to 1993. Ninety-three patients with rectal cancer were either directly treated with surgery (n = 46) or underwent preoperative radiotherapy with 5 x 3.3 Gy irradiation and operation within 48 h (n = 47). If indicated (T4, UICC stage III) patients also received postoperative irradiation. Comparison of the methods of operation (abdominoperineal amputation versus anterior resection) revealed no significant difference in 5-year survival rate (P = 0.393). Local control of R0-resected tumors was improved after preoperative irradiation (P = 0.08). The 5-year survival rate was significantly higher after preoperative short-term radiotherapy (P = 0.027). Preoperative radiotherapy is not an independent factor according to overall survival (P = 0.078) and local recurrence (P = 0.07). In agreement with the results of other authors the present study indicates improved local tumor control of rectal cancer after preoperative radiation therapy. The 5-year survival rate was significantly better after preoperative radiotherapy than after surgery alone.

The epidemiology of sarcoidosis in Rochester, Minnesota: a population-based study of incidence and survival.

Using the unique data resources of the Rochester Epidemiology Project, a community-based study of clinically diagnosed sarcoidosis was conducted. In this population-based study, the 75 Rochester, Minnesota, residents with sarcoidosis initially diagnosed between 1946 and 1975 (incidence cohort) were followed through their comprehensive medical records in the community to January 1, 1982. The age- and sex-adjusted incidence of sarcoidosis was 6.1 per 100,000 person-years. The age-adjusted incidence of sarcoidosis was similar in males (5.9) and females (6.3), with a peak incidence in males 30 to 39 years old (18.7) and in females 40 to 49 years old (15.6). A secular increase in sarcoidosis incidence was noted in the period 1946-1975 for females, with a marked increase in the number and percentage of biopsy-documented cases. Seasonal variation in sarcoidosis incidence was minimal, with a seasonal peak of 31% of the Rochester cases being diagnosed during the spring (March-May). Survival, compared with that of the North Central United States, was unimpaired in this sarcoidosis incidence cohort.

[On the precision of copper determination in liver punctates by neutron activation analysis]. / Zur Genauigkeit aktivierungsanalytischer Kupferbestimmungen in Leberpunktaten.

Variation in the copper contents of liver biopsy specimens was determined by destructive activation analysis of 39 punctates of one liver. The error of method was evaluated by repeated analysis of both the NBS standard Bovine Liver material and homogenized liver. The inhomogeneity of the biopsy specimens with regard to their copper concentrations was shown by comparison of the coefficients of variation. Because of the relatively small variability of the copper concentrations, however, the analysis of single liver punctates provides adequate information for the diagnosis and course of Morbus Wilson.