[Quality of care of acute ischemic stroke in Germany 2018]. / Versorgungsqualität des akuten ischämischen Schlaganfalls in Deutschland 2018.

In this overview the current quality of acute in-hospital care of stroke patients in Germany in 2018 is described based on standardized and evidence-based quality indicators. For this purpose the reports of the regional quality assurance projects for stroke care, which collaborated within the German-speaking Stroke Registers Study Group (ADSR) were analyzed. Overall, more than 280,000 acute admissions of stroke patients were documented in the included quality assurance projects. The results regarding the defined 16 quality indicators comprising diagnostics, acute treatment, rehabilitation and secondary prevention showed a high level of acute inpatient treatment of stroke in Germany. Only a few quality indicators, such as early transfer for thrombectomy indicated a great necessity for process optimization.

Oncological outcome after MRI-based selection for neoadjuvant chemoradiotherapy in the OCUM Rectal Cancer Trial.

BACKGROUND: It is not clear whether all patients with rectal cancer need chemoradiotherapy. A restrictive use of neoadjuvant chemoradiotherapy (nCRT) based on MRI findings for rectal cancer was investigated in this study. METHODS: This prospective multicentre observational study included patients with stage cT2-4 rectal cancer, with any cN and cM0 status. Carcinomas in the middle and lower third that were 1 mm or less from the mesorectal fascia, all cT4 tumours, and all cT3 tumours of the lower third were classified as high risk, and these patients received nCRT followed by total mesorectal excision (TME). All other carcinomas with a minimum distance of more than 1 mm from the mesorectal fascia and those in the upper third were classified as low risk; these patients underwent TME alone (no nCRT). Patients were followed for at least 3 years. Outcomes were the rates of local recurrence, distant metastasis and survival. RESULTS: Among 545 patients included, 428 were treated according to the study protocol: 254 (59·3 per cent) had TME alone and 174 (40·7 per cent) received nCRT and TME. Median follow-up was 60 months. The 3- and 5-year local recurrence rates were 1·3 and 2·7 per cent respectively, with no differences between the two treatment protocols. Patients with disease requiring nCRT had higher 3- and 5-year rates of distant metastasis (17·3 and 24·9 per cent respectively versus 8·9 and 14·4 per cent in patients who had TME alone; P = 0·005) and worse disease-free survival compared with that in patients who did not need nCRT (3- and 5-year rates 76·7 and 66·7 per cent, versus 84·9 and 76·0 per cent in the TME-alone group; P = 0·016). CONCLUSION: Restriction of nCRT to high-risk patients achieved good results.

[Performance Indicators of Hospitals in One Region Between 2006/07 and 2013: a Trend Analysis]. / Trendanalyse der Qualitätsindikatoren der Krankenhäuser einer Region von 2006/07 bis 2013.

BACKGROUND: In spite of a nationwide implementation of performance indicators (PI) for monitoring inpatient medical care, a systematic evaluation of their development over time is still missing. METHODS: A trend analysis of annual rates of PI from 2006/07 to 2013 of Bavarian hospitals was conducted; 123 out of a total of 245 PI selected from 15 distinct clinical fields were available and comparable over the entire period and evaluated. Joinpoint regression was used to estimate annual percentage changes (APC) in regional averages. Individual hospital rates were inspected with box plots for selected indicators. RESULTS: 99 PI (80.5%) showed improvement over time, 67 (54.5% of all PI) were statistically significant. A change from positive to negative trend was found in 15 indicators (12.2%); the negative trend was significant only once. A continuous negative trend was observed in 9 cases (7.3%) (3 significant). Extreme values of hospital rates were present throughout the entire period of observation with results generally far below the national average. CONCLUSION: The majority of indicators improved continuously, which may be interpreted as indicating effectiveness of quality assurance programs, and could also give a strong impetus to further quality improvement measures.

[Quality of Mesorectal Excision ("Plane of Surgery") - Which Quality Targets are Adequate?]. / Qualität der Mesorektumexzision ("plane of surgery") - Welche Qualitätsziele sind angemessen?

Today, the examination of rectal cancer specimens includes the obligate macroscopic assessment of the quality of mesorectal excision by the pathologist reporting the plane of surgery. The frequency of operations in the muscularis propria plane of surgery (earlier described as incomplete mesorectal excision) is essential. The quality of mesorectal excision is important for the prognosis, especially as local recurrences are observed more frequently after operations in the muscularis propria plane of surgery. For the definition of quality targets, data of 13 studies published between 2006 and 2012, each with more than 100 patients and adequate specialisation and experience of the surgeons (5413 patients), data of the prospective multicentric observation study "Quality Assurance - Rectal Cancer" (at the Institute for Quality Assurance in Operative Medicine at the Otto-von-Guericke University at Magdeburg) from 2005 to 2010 (8044 patients) and data of the Department of Surgery, University Hospital Erlangen, from 1998 to 2011 (991 patients) were analysed. The total incidence of operations in the muscularis propria plane of surgery was 5.0 % (721/14 448). Even with adequate specialisation and experience of the surgeon, the frequency of operations in the muscularis propria plane of surgery is higher in abdominoperineal excisions than in sphincter-preserving surgery (8.4 vs. 2.8 %, p < 0.001). Thus, the quality target for the frequency of operations in the muscularis propria plane should be defined as < 5 % for sphincter-preserving procedures and as < 10 % for abdominoperineal excisions.

Prognostic subdivision of ypT3 rectal tumours according to extension beyond the muscularis propria.

BACKGROUND: The subdivision of T3 in rectal carcinoma according to the depth of invasion into perirectal fat has been recommended in the TNM Supplement since 1993. This study assessed the prognostic impact of this pathological staging in tumours removed after neoadjuvant chemoradiotherapy (ypT3). METHODS: Data from patients with ypT3 rectal carcinoma (less than 12 cm from the anal verge) treated with neoadjuvant chemoradiation and total mesorectal excision were analysed. Tumour category ypT3 was subdivided into ypT3a (5 mm or less) and ypT3b (more than 5 mm), based on histological measurements of maximal tumour invasion beyond the outer border of the muscularis propria. RESULTS: Important differences between ypT3a (81 patients) and ypT3b (43) were found in 5-year rates of locoregional recurrence (7 versus 18 per cent; P = 0·049), distant metastasis (20 versus 41 per cent; P = 0·002), disease-free survival (73 versus 47 per cent; P = 0·001), overall survival (79 versus 74 per cent; P = 0·036) and cancer-related survival (81 versus 74 per cent; P = 0·007). In Cox regression analyses, the ypT3 subclassification was identified as an independent prognostic factor for disease-free (ypT3b: hazard ratio (HR) 2·13, 95 per cent confidence interval 1·16 to 3·89; P = 0·014), observed (ypT3b: HR 2·02, 1·05 to 3·87; P = 0·035) and cancer-related (ypT3b: HR 2·46, 1·20 to 5·04; P = 0·014) survival. Extramural venous invasion was found to be an additional prognostic factor, but the pathological node category after chemoradiotherapy (ypN) did not influence survival. CONCLUSION: In ypT3 rectal carcinomas, the proposed subclassification is superior to ypN in predicting prognosis.

[Quality indicators of diagnosis and therapy in MRI-based neoadjuvant radiochemotherapy for rectal cancer - interim analysis of a Prospective Multicentre Observational Study (OCUM)]. / Qualitätsindikaktoren der Diagnose und Therapie bei MRT-basierter neoadjuvanter Radiochemotherapie des Rektumkarzinoms - Interimsanalyse einer prospektiven, multizentrischen Beobachtungsstudie (OCUM).

BACKGROUND: The interim analysis of a prospective multicentre observational study of selective neoadjuvant chemoradiotherapy (OCUM) in patients with rectal cancer should evaluate the quality of diagnosis and therapy as a prerequisite for continuation of the study. PATIENTS AND METHODS: 230 patients with the clinical stage cT2 - 4, each cN, M0 with radical tumour resection were enrolled until now. The values of 13 quality indicators were compared with the target values formulated by the workflow of the Working Group rectal cancer II and the German Cancer Society and were also compared with the results of the certified bowel centres of Germany 2010. RESULTS: The target values were fulfilled to a high degree regardless of caseload. 83 % of parameters have been fully achieved and 14 % nearly achieved. In primary surgery the proportion of patients with 12 or more histologically examined lymph nodes was 99.2 %, after neoadjuvant chemoradiotherapy 90 %. A R0 resection was performed in 98.3 % and a resection of TME in muscularis propria plane only in 2.2 %. The rate of positive circumferential resection margins (pCRM + ) was 5.7 % only. CONCLUSIONS: The high quality of rectal surgery justifies the concept and the continuation of the study.

Individualized magnetic resonance imaging-based neoadjuvant chemoradiation for middle and lower rectal carcinoma.

AIM: In most institutions neoadjuvant chemoradiation for middle and lower rectal carcinoma is currently given to patients with tumours of clinical stages II or III (cT3,4 and/or N1,2). The possibility of a reduction in the use of neoadjuvant chemoradiation by an individualized magnetic resonance imaging (MRI)-based indication for neoadjuvant chemoradiation was analysed. METHOD: Assessment of the pathological and oncological principles indicating for neoadjuvant treatment was used to determine the prognostic importance of the distance between the tumour and the circumferential resection margin and pretherapeutic assessment using modern MRI. RESULTS: Based on the results of pretreatment MRI scanning, a proposal is presented for the treatment of middle and lower rectal carcinoma with neoadjuvant chemoradiation. Adopting this proposal, the frequency of neoadjuvant chemoradiation decreased from 70% to 35% and the early and late adverse effects of this therapy were reduced. In contrast, the expected locoregional recurrence rate increased from 6% to 11% if all quality criteria were met and to 18% if not. CONCLUSION: An MRI-based indication for neoadjuvant chemoradiation is justified only for centres with regular quality assurance of MRI, surgery, radiotherapy and pathology. The proposal needs confirmation by long-term follow up and by prospective studies with larger numbers of patients.

Time to locoregional recurrence after curative resection of rectal carcinoma is prolonged after neoadjuvant treatment: a systematic review and meta-analysis.

AIM: A systematic review of the literature with meta-analysis was performed to evaluate the time to locoregional recurrence after curative resection of rectal carcinoma, assuming that this time is prolonged after neoadjuvant radiochemotherapy and/or present day surgery. METHOD: English and German language peer-reviewed articles published between 1980 and 2007 were selected. Twenty-five of 118 studies fulfilled the defined inclusion and exclusion criteria. For some special questions, data of the Erlangen Registry of Colorectal Carcinoma (ERCRC) from 1985 to 1997 are reported. RESULTS: After conventional surgery of rectal carcinoma, 75% (range 66-84%) of locoregional recurrence presented during the first 2 years after resection. Following the introduction of total mesorectal excision surgery and the use of neoadjuvant treatment, a general reduction of the frequency of local recurrence combined with a prolongation of the time to local recurrence was observed. In the practice of today, in particular after neoadjuvant long-course radiochemo-or radiotherapy, 24% (range 8-40%) of all local recurrences present later than 5 years after primary therapy. In contrast, such late local recurrences are observed in only 8% (range 5-9%) following primary surgery alone. CONCLUSION: For a definite assessment of the therapeutic results regarding local control, a minimal follow up of 7-8 years either after neoadjuvant long-course radiochemo- or radiotherapy and a minimum of 5 years after surgery alone is necessary. For patients with primary surgery followed by adjuvant therapy, it is not possible to make a clear statement.

[Methods of health economic evaluation for health services research]. / Methoden der gesundheitsökonomischen Evaluation in der Versorgungsforschung.

On August 30, 2010, the German Network for Health Services Research [Deutsches Netzwerk Versorgungsforschung e. V. (DNVF e. V.)] approved the Memorandum III "Methods for Health Services Research", supported by the member societies mentioned as authors and published in this Journal [Gesundheitswesen 2010; 72: 739-748]. The present paper focuses on methodological issues of economic evaluation of health care technologies. It complements the Memorandum III "Methods for Health Services Research", part 2. First, general methodological principles of the economic evaluations of health care technologies are outlined. In order to adequately reflect costs and outcomes of health care interventions in the routine health care, data from different sources are required (e. g., comparative efficacy or effectiveness studies, registers, administrative data, etc.). Therefore, various data sources, which might be used for economic evaluations, are presented, and their strengths and limitations are stated. Finally, the need for methodological advancement with regard to data collection and analysis and issues pertaining to communication and dissemination of results of health economic evaluations are discussed.

[Diagnosis of and therapy for gastric cancer--work-flow]. / Diagnostik und Therapie des Magenkarzinoms--Workflow.

AIM: This review comments on the diagnosis and treatment of gastric cancer in the classical meaning--excluding adenocarcinoma of the -oesophagogastric junction. Algorithms of diagnosis and care with respect to tumour stage are presented. PREOPERATIVE DIAGNOSIS: Besides oesophagogastroduodenoscopy, endoscopic ultrasonography is necessary for the accurate diagnosis of T categories and as a selection criterion for neoadjuvant chemotherapy. Computed tomography is recommended for preoperative evaluation of tumours > T1, laparoscopy has become an effective stag-ing tool in T3 and T4 tumours avoiding unnecessary laparotomies and improving the detection of small -liver and peritoneal metastases. TREATMENT: Endoscopic mucosal resection and submucosal dissection are indicated in superficial cancer confined to the mucosa with special characteristics (T1 a / no ulcer / G1, 2 / Laurén intestinal / L0 / V0 / tumour size < 2 cm). In all other cases total gastrectomy or distal subtotal gastric resection are indicated, the latter in cases of tumours located in the distal two-thirds of the stomach. Standard lymphadenectomy (LAD) is the D2 LAD without distal pancreatectomy and splenectomy. The Roux-en-Y oesophagojejunostomy is still the preferred type of reconstruction. An additional pouch reconstruction should be considered in -patients with favourable prognosis, this also -applies for the preservation of the duodenal passage by jejunum interposition. Extended organ resections are only indicated in cases where a R0-resection is possible. Hepatic resection for metachronous or synchronous liver metastases is rarely advised since 50 % of patients with liver metastases show concomitant peritoneal dissemination of the disease. DISCUSSION AND CONCLUSIONS: Undergoing gastrectomy at a high-volume centre is associated with lower in-hospital mortality and a better prognosis, however, clear thresholds for case load cannot be given. Perioperative chemotherapy and postoperative chemoradiotherapy are based on the MAGIC and MacDonald trials. Perioperative chemotherapy should be performed in patients with T3 and T4 tumours with the aim to increase the likelihood of curative R0-resection by downsizing the tumour. Adjuvant postoperative chemotherapy cannot be recommended since its benefit has so far not been proven in randomised trials. In selected patients with incomplete lymph-node dissection and questionable R0-resection postoperative chemoradiotherapy may be debated.

[Problems in the treatment of upper rectal carcinoma]. / Probleme bei der Therapie des oberen Rektumkarzinoms.

In the literature there is some disagreement about the treatment of upper rectal carcinoma (aboral margin 12-16 cm from the anocutaneous line), in particular about the necessary extent of mesorectal excision and the indications for neoadjuvant and adjuvant therapy. The special pathologic features of upper rectal carcinomas (lymphatic spread, distal tumor spread beyond the gross margin) and present clinical experiences are discussed. From it result the following recommendations: partial mesorectal excision, neoadjuvant radiochemotherapy for cT4 tumors only; adjuvant radiochemotherapy in case of intraoperative tumor perforation or incision into/through tumor, incomplete partial mesorectal excision or tumor positive circumferential resection margin (CRM); adjuvant chemotherapy in case of histologically confirmed regional lymph node metastases.

Use of Preoperative Magnetic Resonance Imaging to Select Patients with Rectal Cancer for Neoadjuvant Chemoradiation--Interim Analysis of the German OCUM Trial (NCT01325649).

INTRODUCTION: Introduction of total mesorectal excision (TME) surgery for rectal cancer decreased local recurrence dramatically. Additional neoadjuvant chemoradiation (nCR) is frequently given in UICC II and III tumors based on TNM staging which is of limited accuracy. We aimed to evaluate determination of circumferential margin by magnetic resonance imaging (mrCRM) as an alternative criterium for nCR. METHODS: Multicenter prospective cohort study which enrolled 642 patients in 13 centers with non-metastasized rectal adenocarcinoma. Patients with T4 tumors or patients with a mrCRM of 1 mm or less were treated by neoadjuvant chemoradiation. All others proceeded directly to surgery when inclusion criteria and no exclusion criteria were met. Quality of TME and accuracy of mrCRM determination were assessed during pathology workup. RESULTS: TME was complete in 381 of 389 patients after surgery without nCR (97.9%) and in 245 of 253 patients (96.8%) after nCR. Negative pathology circumferential margins (pCRM) were seen in 97.4% without nCR and in 89% of patients after nCR. Negative pCRM was predicted by negative mrCRM in 98.3% of rectal cancers. NCR was given to 253 of 642 patients (39.5%). Lymph node count was 23 (range 7-79; median/range) for surgery without nCR and 19 (range 2-56) for surgery after nCR. CONCLUSIONS: Surgical quality determined by pathology workup of specimen was very good in this study. Magnetic resonance imaging guided indication for nCR allows to achieve superb results concerning surrogate parameters for good oncological outcome. Thus, use of neoadjuvant chemoradiation with its potential detrimental side effects may be substantially reduced in selected patients.

The Munich Polypectomy Study (MUPS): prospective analysis of complications and risk factors in 4000 colonic snare polypectomies.

BACKGROUND AND STUDY AIMS: Screening colonoscopy with polypectomy has been shown to reduce the morbidity and mortality associated with colorectal cancer. However, there is a lack of large and systematic prospective studies of the complications of polypectomy. PATIENTS AND METHODS: Data on all snare polypectomies performed in 13 institutions (six hospitals and seven gastroenterology offices) were recorded prospectively during a 20-month period, including data on a 30-day follow-up period. The primary end points of the study were polypectomy complications, which were classed as "major" or "minor". Risk factors for complications were analyzed for both patient characteristics and polyp parameters. RESULTS: A total of 3976 snare polypectomies in 2257 patients (mean age 64.5 years) were included in the study. The mean polyp size was 1.1 cm, and 72% were sessile. Complications occurred in 9.7% of patients (6.1% of polyps); 75% of these complications were minor; and the mortality rate was zero. Multivariate regression analysis revealed polyp size as the main risk factor, both for complications overall (odds ratio 6.56, 95%CI 4.45-9.67) and for major complications (odds ratio 31.01, 95%CI 7.53-128.1). Right-sided polyp location was a significant risk factor for major complications (odds ratio 2.40, 95%CI 1.34-4.28). Setting a cut-off value of 3% as an acceptable rate for major complications, polyps larger than 1 cm in the right colon or 2 cm in the left colon, and multiple polyps carried an increased risk. CONCLUSIONS: Colonoscopic polypectomy is associated with a 10% rate of complications, but three-quarters of these are of minor clinical significance. More than 90% of the complications can be managed conservatively if adequate endoscopic expertise is available. Guidelines for intensified follow-up after polypectomy should be based on the size, location, and number of a patient's polyps.

[Lymph node dissection after primary surgery and neoadjuvant radiochemotherapy of rectal cancer. Interim analysis of a multicenter prospective observational study (OCUM)]. / Lymphknotendissektion nach primärer Chirurgie und neoadjuvanter Radiochemotherapie des Rektumkarzinoms. Interimsanalyse einer multizentrischen prospektiven Beobachtungsstudie (OCUM).

INTRODUCTION: The OCUM trial (NCT01325649) aims to clarify whether low rates of local recurrence are also achieved when the indications for neoadjuvant radiochemotherapy are not based on the clinical TNM staging but on preoperative magnetic resonance imaging with measurement of the tumor distance to the circumferential resection margin. In this interim analysis the lymph node status in OCUM patients was investigated as a surrogate parameter for quality of surgery and histopathological work-up. MATERIAL AND METHODS: Until now a total of 560 patients have been included in this study. Total mesorectal excision (TME) without pretreatment was undertaken in 338 patients (60.4 %) and neoadjuvant radiochemotherapy was administered in 222 (39.6 %) patients. The histological work-up was performed according to the guidelines of the German Association of Pathologists. Data are given as median values and ranges in brackets. RESULTS: The lymph node yield was 24 (7-79) in 338 patients undergoing primary TME surgery without pretreatment, while 20 (3-56) lymph nodes were identified in patients after neoadjuvant radiochemotherapy (p = 0.001). A minimum of 12 lymph nodes were analyzed in 335 out of 338 patients (99.1 %) and in 209 out of 222 patients (94.1 %) following neoadjuvant radiochemotherapy (p = 0.001). Lymph node metastasis was identified (p = 0.362) in 116 out of 338 patients without pretreatment (34.3 %) and in 71 out of 222 patients after neoadjuvant radiochemotherapy (32.0 %). Patient age did not influence the number of identified lymph nodes or rate of lymph node metastasis. CONCLUSION: In this trial the number of identified lymph nodes suggests that the quality of surgery and histopathological work-up were adequate compared to the standards defined by national guidelines. Neoadjuvant radiochemotherapy led to a reduced lymph node yield compared to surgery without pretreatment; however, this did not influence the rate of lymph node metastasis.

[Spincter preservation after selective chemoradiotherapy of rectal cancer. Interim results of the OCUM study]. / Spinktererhalt nach selektiver Radiochemotherapie des Rektumkarzinoms. Zwischenergebnisse der OCUM-Studie.

BACKGROUND: In a prospective multicenter observational study (OCUM) neoadjuvant chemoradiotherapy (nRCT) was selectively administered depending on the risk of local recurrence and based on the distance between tumor and mesorectal fascia in pretherapeutic high-resolution magnetic resonance imaging (MRI). OBJECTIVE: Frequency and quality of abdominoperineal excision (APE) and sphincter preserving operations. PATIENTS AND METHODS: Of 642 patients treated in 13 hospitals 389 received surgery alone and 253 nRCT followed by surgery. By univariate and multivariate analysis risk factors for APE were determined. Quality parameters were the quality grade of mesorectal excision, the pathohistological involvement of the circumferential resection margin and intraoperative local dissemination of tumor cells. RESULTS AND DISCUSSION: In 12.8 % of the patients APE was performed. Independent risk factors for APE were tumor location in the lower third of the rectum and the individual hospitals, where APE varied between 0 and 32 %. This variation was chiefly caused by the different case mix. Hospitals with a high APE rate (> 30 %) treated significantly more patients with very low lying carcinomas (< 3 cm above the anal verge) and more advanced tumors. The median height of the tumor in cases of APE was nearly equal in all participating hospitals. Independent on the number of cases the quality of rectal surgery was high. Within the patient groups of primary surgery and nRCT the oncological quality parameter did not significantly differ between sphincter preservation and APE. As far as sphincter preservation is concerned the results justify a selective application of nRCT in patients with rectal carcinoma. The long-term results still have to be awaited.

Testing a new staging system for cutaneous melanoma proposed by the American Joint Committee on Cancer.

The American Joint Committee on Cancer (AJCC) recently proposed a new staging system for cutaneous melanoma. We tested its practicability and its prognostic value was compared with the currently used TNM classification. The data of 1976 melanoma patients were used for the testing. 1218 patients (61.6%) could be assigned to the proposed pT classification, 136 patients (90.1%) with lymph node metastases and/or in-transit metastases to the proposed pN classification and all 14 patients with distant metastases to the proposed pM classification. Proposed pathological staging was possible for 971 patients (49%). The number of pT1 patients (399 versus 230) and stage I patients (544 versus 393) was distinctly higher in the proposed classification. In proposed stage II and III groups, subgroups with different prognosis could be identified. The new staging system includes more detailed information on clinical and pathohistological findings. Nevertheless, it is practicable and enables more patients with excellent prognosis to be identified.

Preliminary results of treatment of invasive bladder carcinoma with radiotherapy and cisplatin.

From October 1985 to February 1988, 41 patients with invasive bladder cancers were treated with transurethral resection (TUR) and radiotherapy with simultaneous cisplatin chemotherapy at the University Hospital in Erlangen. Radiotherapy was performed as primary treatment in case of macroscopic residual tumor after TUR (n = 22) or as adjuvant treatment in patients with macroscopically complete transurethral resection (n = 19). Age ranged from 44 to 77 years. Radiotherapy was given in daily fractions of 1.8 Gy. The pelvis was treated with a box up to 41.4 Gy and the bladder was boosted up to 50.4 Gy by a rotation technique. Cisplatin was administered in the first and fifth treatment week on five consecutive days with 25 mg cisplatin/m2 per day as short infusion. Pathohistologic response was examined by control cystoscopy with biopsies from the deep layers 6 weeks after completing radiochemotherapy. Maximum follow-up is 24 months after control cystoscopy. After TUR plus radiochemotherapy, histologically confirmed complete remission rates according to T-stage were: 7/8 T1-, 26/31 T2-3-, and 2/2 T4-tumors. In patients with macroscopic tumor prior to radiochemotherapy, histological and cytological complete remission was achieved in 2/3 T1-, 14/18 T2-3-, and 1/1 T4-cancers with an overall complete response rate of 77%. In complete responders, 3 isolated local recurrences (2 T1- and one T3-recurrence) and two local recurrences with distant metastases have occurred until now. Six patients had only partial response. Mild to moderate side effects occurred frequently, but overall treatment tolerance was good even in older patients. Complications did not occur. So far, 7 cystectomies have been performed, 6 were a result of persistent or recurrent tumor and one a result of a contracted bladder after multiple TURs. Thirty-four of forty-one patients (83%!) maintained their bladder and normal bladder function. In conclusion, moderate dose radiation therapy (50 Gy) in combination with simultaneous cisplatin chemotherapy is a well-tolerated treatment and highly effective for controlling local disease and preservation of bladder function in invasive bladder cancers.

Prognostic factor research in oncology.

The prognosis of solid tumors is predominantly influenced by the anatomic extent before and after initial treatment. It is defined by the TNM/pTNM system and the residual tumor (R) classification as internationally agreed on and published by the International Union Against Cancer (UICC). However, there are several independent factors effective in prognosis in addition to TNM and R. Their identification is the first objective in prognostic factor research. Correctly applied multivariate methods appropriate for the specific situation play a key role. Cooperation between clinical oncologists and experienced medical statisticians is indispensable. Putative new prognostic factors have to be carefully evaluated before they can be accepted for general use in clinical oncology. In the future, we have to focus on the development of prognostic systems. Such systems integrate multiple independent prognostic factors with present staging (TNM, R) to improve the assessment of prognosis.

Classification and regression trees (CART) for estimation of prognosis in patients with gastric carcinoma.

A total of 961 patients who had received resective surgery for gastric carcinoma were grouped according to prognosis by classification and regression trees (CART). This grouping was compared to the present UICC stage grouping. For patients resected for cure (R0) the CART approach allows a better discrimination of patients with poor prognosis (5-year survival rates 15%-30%) from patients with a 5-year survival of 50%, on the one hand, and from patients with extremely poor prognosis (5-year survival rates below 5%) on the other. In the present investigation CART grouping was not influenced by the differentiation between pT1 and pT2 or between pT3 and pT4.

Reduction of carcinogenicity of N-nitrosomethylurea by indomethacin and failure of resuming effect of prostaglandin E2 (PGE2) against indomethacin.

Nonsteroid antiinflammatory drugs such as indomethacin may play an important role in preventing the development of chemically induced experimental carcinomas of various organs including the large bowel in rats and mice. This effect might correlate with an inhibition of prostaglandin (PG) synthesis by these drugs. Sprague-Dawley rats were given three intrarectal doses of 4 mg N-nitrosomethyl-urea (MNU) within week 1 to induce large-bowel carcinomas. The experimental groups of rats received a 0.001% aqueous solution of indomethacin ad libitum as drinking water for days 1-8 and/or a subcutaneous injection of 500 micrograms/kg body weight of PGE2 immediately before and 2 h after each MNU dose. They were then maintained on basal diet and plain tap water without further treatment. At autopsy at week 31, the tumor incidence and the mean number of tumors per rat were 90% and 1.7 in untreated rats, 67% and 0.8 in indomethacin-treated rats, and 79% and 1.2 in indomethacin + PGE2-treated rats, respectively. The data indicate that indomethacin reduced the number of large-bowel tumors, while pharmacologic doses of PGE2 failed to reestablish the anticarcinogenic activity of indomethacin. It was concluded that a tolerable therapeutic dose of indomethacin can reduce the carcinogenic activity of MNU in the large bowel.