[Neuroendocrine neoplasia of the stomach : What is new?] / Neuroendokrine Neoplasien des Magens : Was ist neu?

INTRODUCTION: Neuroendocrine Neoplasms are classified according to the new WHO classification in (1.) well differentiated neuroendocrine tumors G1 (NET G1, Ki67 ≤ 2 or mitosis count <2) and (2.) well differentiated neuroendocrine tumors G2 (NET G2, Ki67 3-20 or mitosis count 2-20) and (3.) poorly differentiated neuroendocrine carcinomas G3 (NEC G3, Ki67 > 20 or mitosis count >20). MATERIAL AND METHODS: In this study 310 NENs of the Ludwig-Maximilians-University in Munich were reevaluated according to the new WHO classification. RESULTS: 7% of the analyzed NENs were presented as neoplasias of the stomach. In NENs of the stomach three distinct subtypes are recognized: (1) type 1 associated with autoimmune chronic atrophic gastritis (2) type 2, associated with multiple endocrine neoplasia (MEN1) and Zollinger-Ellison Syndrom; and (3) type 3, sporadic tumors. DISCUSSION: Precursor lesions (i. e. hyperplasia of the ECL cells) are found in patients with hypergastrinaemia (type 1 and 2). This article should provide insights into the diagnosis of NENs of the stomach with emphasis on the new international standard.

Risk index for pelvic organ prolapse based on established individual risk factors.

PURPOSE: To identify known risk factors for pelvic organ prolapse (POP) in a hospital cohort and to develop a prolapse risk index (PRI). METHODS: Risk factors for POP were recorded in women who underwent surgery with symptomatic POP (n = 500) or non-POP gynaecological conditions (n = 236). Descriptive statistics were determined by Chi-squared and Mann-Whitney U tests. Stepwise multivariate regression analysis was performed for all patients and subgroups by age (<60 and ≥60 years). Primary outcome measures were variables with the strongest impact on prolapse and PRI development. Secondary: specificity, sensitivity, positive and negative predictive values (PPV and NPV, respectively), and Cohen's kappa statistic (κ). RESULTS: Stepwise multivariate regression analysis (n = 736) showed difficult obstetric history [odds ratio (OR) 10.04], family history of POP (OR 7.28), and ≥10 years since menopause (OR 4.53) were independent risk factors for prolapse (P < 0.001). When one of the three variables with the strongest influence on POP development was present, the PRI for all women showed a PPV of 82%, NPV of 68%, and κ of 0.47 for predicting symptomatic POP requiring treatment. In women under 60 years (n = 349), logistic regression revealed difficult obstetric history (OR 9.108), positive family history (OR 8.016), and body mass index (OR 2.274) as independent risk factors. CONCLUSIONS: Eighty-seven percent of our patient cohort with symptomatic POP requiring therapy could be identified by the PRI, which may be useful for counselling and education.

[Tyrosine kinases in soft tissue tumors]. / Tyrosinkinasen in Weichgewebstumoren.

The development of therapeutic agents that specifically target the molecular alterations critical for tumorigenesis has a tremendous impact on the management of cancer patients. The successful treatment of advanced gastrointestinal stromal tumors (GIST) with receptor tyrosine kinase (RTK) inhibitors has raised the hope that other malignancies could also benefit from a similar treatment. Tyrosine kinase receptors are promising targets for personalized medicine and new drugs are currently in phase 2 and phase 3 clinical trials. We analyzed a large cohort of soft tissue sarcomas for different tyrosine kinase receptors and correlated the results with clinicopathological parameters. A total of 275 soft tissue sarcomas from the Ludwig-Maximilians University (LMU) were revisited and catagorized according to the current World Health Organization (WHO) classification system. Different entities showed distinct survival curves in 10-year long-term survival. Furthermore, different subtypes of sarcomas showed distinct expression profiles at the protein level. The expression of vascular endothelial growth factor (VEGF) receptors is associated with tumor progression. Due to the fact that not all patients respond to RTK inhibitor therapy, protein signatures should be evaluated before targeting therapy to give a rationale for a viable personalized therapy.

[Diagnostic procedures and results in surgical therapy for cholangiocarcinoma]. / Diagnostisches Vorgehen und Ergebnisse in der chirurgischen Therapie von Gallenwegstumoren.

INTRODUCTION: Despite a rising incidence worldwide, cholangiocarcinoma (CCC) is one of the infrequent malignancies of the gastrointestinal tract. The surgical approach depends largely on the location of the tumour. PATIENTS AND METHODS: Since 1995, 425 consecutive patients with cholangiocarcinoma were seen at our hospital; their data were prospectively entered in our cancer registry. Tumour-specific data were now retrospectively analysed for prognostic value. RESULTS: Resection with primarily curative intent was performed in 183 of the 425 patients; resection rates were 36 % for intrahepatic (66 patients), 44 % for hilar (69 patients) and 56 % for distal cholangiocarcinoma (48 patients). R0-resection was achieved in 152 patients (83 %) and was found to be the most important factor determining survival. With respect to intrahepatic cholangiocarcinoma, clinical T3- and T4-categories, lymph node metastases as well as UICC stages III and IV had negative predictive value; in hilar carcinomas, this was only seen for the last two factors. In distal cholangiocarcinoma, a low degree of differentiation was associated with a poor prognosis. No differences in survival were seen in the presence of perineural infiltration, angioinvasion or elevation of tumour marker CA 19 - 9.  Regarding the surgical techniques, we found a survival benefit for limited liver resection in intrahepatic cholangiocarcinomas, which is explained by earlier tumour stages seen in these cases, as well as the performance of trisectionectomy or liver transplantation in hilar carcinomas. CONCLUSIONS: Comparable to other malignant gastrointestinal tumours, radical surgery represents the most important prognostic factor in cholangiocarcinomas; for hilar tumours, a survival advantage is seen after extended resections (trisectionectomy or liver transplantation) if compared to more limited resections. At the time of presentation, however, the stage of disease was incurable in most patients, thus accounting for the low overall resection rates.

[Poorly differentiated neuroendocrine small-cell carcinoma of the gallbladder]. / Schlecht differenziertes neuroendokrines kleinzelliges Karzinom der Gallenblase.

BACKGROUND: Neuroendocrine tumours of the gastroenteropancreatic system (GEP-NETs) are rare, in particular those of the gallbladder. Due to the limited therapeutic options, surgical resection is favoured. CASE REPORT AND METHODS: Described below is the case of a 69-year-old male with a lymphogenically metastasising, poorly differentiated neuroendocrine carcinoma of the gallbladder who presented with unspecific abdominal pain. RESULTS AND CLINICAL COURSE: Following complete surgical resection of the tumour and the lymph node metastases he developed a recurrence 6  weeks post-operatively. The recurrence was treated with chemotherapy. Re-staging after three courses, however, showed further tumour progression. Prior to the start of a second-line treatment the patient died 13  weeks after surgery. CONCLUSIONS: This case demonstrates the complexity of this rare disease with diagnosis in advanced tumour stage and poor prognosis.

Solitary colorectal liver metastasis: overview of treatment strategies and role of prognostic factors.

The following is an overview of the treatment strategies and the prognostic factors to consider in the therapeutic choice of patients characterized by solitary colorectal liver metastasis. Liver resection is the only potential curative option; nevertheless, only 25% of the patients are considered to be eligible for surgery. To expand the potentially resectable pool of patients, surgeons developed multidisciplinary techniques like portal vein embolization, two-stage hepatectomy or associating liver partition and portal vein ligation for staged hepatectomy. Moreover, mini-invasive surgery is gaining support, since it offers lower post-operative complication rates and shorter hospital stay with no differences in long-term outcomes. In case of unresectable disease, various techniques of local ablation have been developed. Radiofrequency ablation is the most commonly used form of thermal ablation: it is widely used for unresectable patients and is trying to find its role in patients with small resectable metastasis. The identification of prognostic factors is crucial in the choice of the treatment strategy. Previous works that focused on patients with solitary colorectal liver metastasis obtained trustable negative predictive factors such as presence of lymph-node metastasis in the primary tumour, synchronous metastasis, R status, right-sided primary colon tumor, and additional presence of extrahepatic tumour lesion. Even the time factor could turn into a predictor of tumour biology as well as further clinical course, and could be helpful to discern patients with worse prognosis.

Sustained renal response to mycophenolate mofetil and CNI taper promotes survival in liver transplant patients with CNI-related renal dysfunction.

AIM: The aim of this trial was to evaluate the impact of conversion from a calcineurin-inhibitor (CNI)-based immunosuppressive regimen to mycophenolate mofetil (MMF) and reduced-dose CNI on long-term renal function and survival in a series of 63 liver transplant patients with CNI-induced renal dysfunction. METHODS: CNI dosage was significantly tapered after introduction of 2,000 mg MMF per day. Renal function was assessed by determination of serum creatinine levels and calculated creatinine clearance (CCl). The impact of relevant clinical parameters on renal function and survival post-conversion was analyzed by univariate and multivariate analysis. RESULTS: At 60 months post-conversion, mean creatinine level had significantly declined from 197.2±58.3 µmol/l at baseline to 160.0±76.5 µmol/l, and mean CCl has significantly increased from 38.4±13.4 ml/min at baseline to 47.9±21.1 ml/min (p<0.001), respectively. Forty-six patients (73.1%) demonstrated sustained renal response to modified immunosuppression. Full-dose MMF medication (p=0.006) and the early conversion (p=0.02) were identified as independent predictors of persistent renal function improvement. Sustained renal response to MMF plus reduced-dose CNI was identified as the most relevant independent promoter of long-term survival (hazard ratio 6.9). Five-year survival rate post-conversion was 93.9% in renal responders and 64.3% in renal non-responders (log rank<0.001). CONCLUSIONS: Sustained renal response to MMF and CNI dose reduction promotes long-term survival in liver transplant patients with CNI-induced renal dysfunction.

[Update from the soft tissue tumour registry in Jena]. / Neues aus dem Jenaer Weichteiltumor-Register.

The Jena Institute of Pathology has been serving as a consultation and reference center for soft tissue tumors in Germany since 1978. The present study provides an overview of the clinicopathological data from a two-year period and an update on diagnostics and research. Retrospectively, 7043 cases sent to the institute in the years 2006 and 2007 were analyzed. The majority of cases (>77.7%) were soft tissue tumors, of which 49% were categorized as malignant, 11.4% as intermediate, 35% as benign and 4.6% as tumors of uncertain biological potential. Neoplasms with fibroblastic differentiation were the most frequent. The mean age of patients with a sarcoma was 63 years. The molecular pathological analysis of soft tissue tumors has attained a major role in diagnosis. This is further advanced at the Jena institute in the context of a German Federal Ministry of Education and Research (BMBF) project for molecular sarcoma diagnosis with the aim of developing and validating DNA probes for in situ hybridization detection of translocations and their associated chromosomal breaks on the one hand, and DNA chips for the detection of fusion transcripts on the other. Research projects relate to the analysis of specific biomarkers in large tumor collectives and the pathomechanisms in several sarcoma entities.

Inverse correlation between urethral length and continence before and after native tissue pelvic floor reconstruction.

Urethral length was evaluated retrospectively in patients with prolapse undergoing anterior native-tissue repair. Effects of age, prolapse stage, defect pattern, urodynamic and clinical stress test findings, and tension-free vaginal tape (TVT) surgery indication were analyzed using Mann-Whitney and Wilcoxon tests and linear and logistic regression. Of 394 patients, 61% had stage II/III and 39% had stage IV prolapse; 90% of defects were central (10% were lateral). Median pre- and postoperative urethral lengths were 14 and 22 mm (p < 0.01). Preoperative urethral length was greater with lateral defects [p < 0.01, B 6.38, 95% confidence interval (CI) 4.67-8.08] and increased stress incontinence risk (p < 0.01, odds ratio 1.07, 95% CI 1.03-1.12). Postoperative urethral length depended on prolapse stage (p < 0.01, B 1.61, 95% CI 0.85-2.38) and defect type (p = 0.02, B - 1.42, 95% CI - 2.65 to - 0.2). Postoperatively, TVT surgery was indicated in 5.1% of patients (median 9 months), who had longer urethras than those without this indication (p = 0.043). Native-tissue prolapse repair including Kelly plication increased urethral length, reflecting re-urethralization, particularly with central defects. The functional impact of urethral length in the context of connective tissue aging should be examined further.

[Influence of bile duct anatomy on biliary complications in hepatic right lobe living donors]. / Einfluss der Gallengangsanatomie auf biliäre Komplikationen bei Lebendspenden des rechten Leberlappens.

Perioperative morbidity in the living donation of partial livers is mainly due to infections and biliary complications. Bile duct anatomy variants, in particular of the right system, are suspected to be causative. We investigated the influence of bile duct variants on the incidence of biliary donor complications in donations of the right liver lobe. We analyzed 103 donors. Twelve patients had a bile leak that required treatment. All of these were treated endoscopically without any residual defect. We did not see a central extrahepatic bile duct lesion Nagano type C. The anatomic variant Huang A3 is a challenge with respect to the surgical technique. Three of 17 patients with biliary anatomy Huang A3 developed leaks. The bile duct anatomy can be carefully evaluated by magnetic resonance cholangiopancreatography (MRCP) and intraoperative cholangiography. The anatomic variant Huang A3 warrants particular attention for the closure of the bile duct orifice.

Validity of eleven prognostic scores with respect to intra- and extrahepatic recurrence of hepatocellular carcinoma after liver transplantation.

INTRODUCTION: Tumor recurrence is the most frequent cause of death after liver transplantation for hepatocellular carcinoma. We selected ten other prognostic classifications to evaluate their potential to predict the risk of recurrence after LT for HCC as compared to the Milan classification. All of the other scores have not been compared with one another in a single cohort. METHODS: Data of 147 consecutive patients transplanted at our department between 1996 and 2014 were analyzed and staged for morphological and functional scores of underlying liver disease. For long-term follow-up, we analyzed intrahepatic (within the liver ± distant metastases) and extrahepatic (distant metastases only) recurrence separately. RESULTS AND CONCLUSIONS: The median survival time for all patients was 106 months. The 5- and 10-year observed survival rates were 61 and 43%, respectively. The observed cumulative 5- and 10-year recurrence rates were 37 and 39%, respectively, 10-year intrahepatic and extrahepatic recurrence rates were 12 and 27%, respectively. Median survival time after diagnosis of first recurrence was 7.5 (0-120) months; 2 and 18 months for all, intra- and extrahepatic recurrence, respectively. UCSF-, up to seven-, Shanghai Fudan- or Duvoux classifications can identify patients with a cumulative 10-year recurrence rate below 20%. The pre-therapeutic AFP level should be considered in addition to the geometry of the intrahepatic lesions.

Partial liver resection results in a significantly better long-term survival than locally ablative procedures even in elderly patients.

PURPOSE: The number of elderly patients with HCC will increase worldwide in the next years. Therefore, surgeons need to reassess clinical algorithms for the treatment of patients with HCC. We reevaluated a cohort of patients treated in the last 10 years at our hospital, with emphasis on long-term results and age. METHOD: A prospectively recorded consecutive series of all patients treated in between January 1995 and December 2014 with curative intent either by partial liver resection or by ablative therapy was analysed. RESULTS: At the time of diagnosis, 232 patients were younger than 70 years and 127 patients were aged 70 years and over. In the latter group, solitary tumours, absence of liver cirrhosis and resection therapy were more frequent compared to younger patients. Charlson index, AFP-negative tumours and CLIP score were equally distributed in both groups. Observed survival of older and younger patients was similar but after partial liver resection, younger patients had a better survival than elderly patients, whereas survival in patients treated with ablation was similar in both groups. In the univariate analysis, long-term survival of patients aged 70 years and over was influenced by treatment procedure, number of lesions, liver cirrhosis, Child's stage and CLIP score. In the multivariate analysis, only treatment procedure and CLIP score were identified as independent predictors of observed survival, and comorbidity was not. CONCLUSION: In patients aged 70 years and over, long-term prognosis is independently influenced by CLIP score and treatment procedure and other findings have only minor influence on long-term survival.

Which factors affect the long-term survival of patients with hepatocellular carcinoma UICC stage IV?

AIM: In the 7th edition of the TNM classification, not only HCC with distant metastases but also those with regional lymph node metastases are classified as stage IV. MATERIALS AND METHODS, RESULTS: From our prospectively recorded tumor registry, 138 patients (17 %) with HCC were in stage IV. Among those were 68 and 70, respectively, in stage IVA (regional lymph node metastases) and IVB (distant metastases). The tumors were less frequently treated with resection or local ablative treatment (chemoembolization, RFA, SIRT, percutaneous radiation) than patients in stage I-III. Ten HCCs were resected. Five of the resected patients were in stage IVA and five in stage IVB. After tumor resection, patients lived longer than those who underwent local or systemic treatment only (p = 0.003 or p = 0.001, respectively). In the univariate survival analysis, the stage IV patients' long-term survival was decreased statistically significantly through elevated bilirubin, low albumin, Okuda stage III and BCLC stage D. Patients' age and sex, pre-treatment AFP level, Child stage and the presence of venous invasion did not influence survival. In the multivariate analysis (Cox regression), tumor resection and BCLC stage were independent prognostic factors. CONCLUSION: Patients with HCC in TNM stage IV have a very poor prognosis. Only few patients are eligible for resection because of the extent of tumor growth, comorbidities and general condition. These, however, benefit markedly from tumor resection with lymph node dissection and possibly resection of distant metastases.

[Selective internal radioembolization in nonresectable hepatocellular carcinoma]. / Selektive interne Radioembolisation beim nichtresektablen hepatozellulären Karzinom.

INTRODUCTION: The role of selective internal radioembolization (SIRT) in the treatment of hepatocellular carcinoma (HCC) is currently unclear. MATERIALS AND METHODS: We investigated 52 patients with nonresectable HCC in cirrhosis who underwent SIRT at the Department of General, Visceral and Vascular Surgery in co-operation with the Department of Nuclear Medicine and the Institute of Diagnostic and Interventional Radiology between April 2011 and October 2015. RESULTS: In five patients, SIRT was employed for bridging to liver transplantation. In patients who had undergone pre-treatment with SIRT, histological examination of the explanted livers showed extensive tumor necrosis in the targeted areas with only minor remnant vital tissue at the margins. Four of the patients who underwent SIRT as local bridging treatment are tumor-free after transplantation. In the 47 palliatively treated patients, a total of 76 radioembolizations were performed. The observed 1­ and 2­year survival rates in these patients were 58 and 29 %, respectively, after the first SIRT. In the multivariate analysis of the observed survival, AFP before the first SIRT >30ng/ml, time interval of <12 months between the initial diagnosis and the first SIRT, largest tumor diameter >5 cm and portal vein thrombosis were independent negative prognostic factors. In the multi-variate analysis, the time to progression was independently influenced only by the AFP level before the first SIRT. In addition to standard treatment with transarterial chemoembolization (TACE), SIRT is feasible in nonresectable HCC, in particular with portal vein thrombosis, with identical results, less interventions and few side effects.

Influence of surgery on metachronous distant metastases and survival in rectal cancer.

PURPOSE: Total mesorectal excision (TME) and other technical surgical factors reduce local recurrence rate in rectal cancer. Scientific evidence of the positive effect of optimal surgery on survival is locking. Whether a reduction in the incidence of distant metastases can be achieved with optimal surgery is uncertain. We examine the effects of the quality of surgery, as reflected by local recurrence rate, on survival and the incidence of initial distant metastases. PATIENTS AND METHODS: Between 1974 and 1991, 1,581 consecutive patients who underwent curative resection (RO) for rectal carcinoma were monitored for recurrence and survival. TME was introduced in 1985. No patient received adjuvant radiotherapy or chemotherapy. The median follow-up time was greater than 13 years. RESULTS: The local recurrence rate decreased from 39.4% to 9.8% during the study period (P < .0001). The observed 5-year survival rate improved from 50% to 71% (P < .0001). Three hundred six patients with local recurrence had a significantly lower observed 5-year survival rate (P < .0001). A total of 1,285 patients had no local recurrence, but 275 of them developed distant metastases (International Union Against Cancer [UICC] stage I, 8%; stage II, 16%; stage III, 40%). Better-quality surgery had no effect on the incidence of initial distant metastases, which remained constant (P = .44). CONCLUSION: Quality of surgery is an independent prognostic factor for survival in rectal cancer, but has no influence on initial occurrence of distant metastases. Local recurrence cannot be considered an outcome criterion of adjuvant treatment without consideration of the surgeon as a risk factor.

[Completeness and quality of baseline data and follow-up in cancer registry--an analysis on the example of colorectal cancer]. / Vollständigkeit und Qualität der Basisdaten und der Nachbeobachtung im Krebsregister--Eine Untersuchung am Beispiel des kolorektalen Karzinoms.

BACKGROUND AND AIM: In Germany, data of cancer patients are recorded not only in epidemiological registers but also in clinical cancer registers. To ensure the networking of all included medical partners, quality control, and clinical research it is necessary that cancer cases are captured more or less completely. The aim of the present study was to compare the data sets of two registers. PATIENTS AND METHODS: Data from patients with colorectal cancer from two large surgical clinics in Magdeburg are recorded in two registers - the Clinical Cancer Registry Magdeburg and the Institute of Quality Assurance in Operative Medicine at the Otto-von-Guericke University Magdeburg. Here we compared the data sets in order to check the completeness of data capturing and to determine factors influencing the degree of completeness. RESULTS: From all patients captured in the Institute of Quality Assurance, 78.9% are found also in the clinical cancer registry. The percentage improves over the course of time, but also depends on diagnostic criteria such as the staging. There are some differences between both registries, explainable by their specific objectives. Particularly, it is demonstrated that incomplete follow-up record may bias estimates of survival rates from registries. CONCLUSION: Ensuring the completeness and correctness of data is a major challenge for cancer registries. It has distinct influence on estimated quality parameters such as survival rates.

Organ-sparing treatment of advanced bladder cancer: a 10-year experience.

PURPOSE: Radical cystectomy is considered as standard therapy for muscle-invasive bladder cancer. We present 10-year results of bladder-sparing treatment by conservative surgery and radiotherapy +/- chemotherapy. METHODS AND MATERIALS: From 1982 through 1991, 245 consecutive patients, mean age 66 years, with invasive bladder cancer (T2-3 or poor prognostic T1, no distant metastases) entered a prospective protocol with the objective of bladder preservation. Treatment consisted of transurethral resection (complete, if possible) and definitive radiotherapy with 56 Gy maximum dose (50.4 Gy minimum target dose) in 28 fractions. Since 1985, 139 patients received a simultaneous chemotherapy on 5 days in the first and fifth treatment week with either 25 mg/m2 cisplatin daily (79 patients) or 65 mg/m2 carboplatin (60 patients). Cystectomy was performed as salvage treatment for residual or recurrent invasive disease. The median follow-up at the date of analysis (12-31-92) was 5.9 years. RESULTS: The overall survival was 47% after 5 years and 26% after 10 years. The 5-year survival according to the initial T-category was 60% for T1 (44 patients), 64% for T2 (47 patients), 43% for T3 (127 patients), and 16% for T4 (23 patients). The most important single prognostic factor was the amount of residual tumor after TUR (5-year survival 80% after R0, 53% after R1, and 31% after R2 resection, p < 0.01). Chemotherapy increased the rate of complete remission, but had no impact on 5-year survival (52% vs. 50%). Fifty-three salvage cystectomies were performed, all without severe complications, and 192 patients (79%) maintained a normal functioning bladder. The bladder preservation rate in 5-year survivors was 83%. CONCLUSIONS: Organ-sparing treatment of advanced bladder cancer by transurethral surgery and definitive radiotherapy or radiochemotherapy is feasible and effective. The survival in this series is as good as in any comparable cystectomy series. Eighty-three percent of long-term survivors maintained their functioning bladders.

Palliative radiotherapy for recurrent and metastatic malignant melanoma: prognostic factors for tumor response and long-term outcome: a 20-year experience.

PURPOSE: Radiotherapy is used as a "last resort" for patients with advanced cutaneous malignant melanoma. We have analyzed our 20-year clinical experience with respect to different endpoints and prognostic factors in patients with locally advanced, recurrent, or metastatic malignant melanoma. METHODS: From 1977 to 1995, 2,917 consecutive patients were entered in the melanoma registry of our hospital. Radiotherapy was indicated in 121 patients (56 females, 65 males) for palliative reasons in advanced malignant melanoma stages UICC IIB/III/IV. The histology of the primary lesion was nodular in 51 patients, superficial spreading in 35, acral-lentiginous in 8, and lentigo maligna melanoma in 4 patients. Eleven patients had primary or recurrent lesions which were either not eligible for surgery or had residual disease (R2) after resection of a primary or recurrent lesion (UICC IIB); 57 patients had lymph node (n = 33) or in-transit metastases (n = 24) (UICC III), and 53 had distant organ metastases (7 M1a; 46 M1b) (UICC IV). Time from first diagnosis to on-study radiotherapy averaged 19 (median: 18; range: 3-186) months. In most cases, conventional RT was applied with 2-6 Gy single fractions up to a median total radiation dose of 48 (mean: 45; range: 20-66) Gy. RESULTS: At 3 months follow-up, complete response (CR) was achieved in 7 (64%) and overall response [complete (CR) and partial response (PR)] in all (100%) UICC IIB patients, in 25 (44%) and 44 (77%) of 57 UICC III patients, and in 9 (17%) and 26 (49%) of 53 UICC IV patients. Tumor progression during radiotherapy occurred in 25 (21%) patients. Patients with CR survived longer (median: 40 months) than those without CR (median 10 months) (p < 0.01). At last follow-up (Dec 31, 1996), 26 patients were still alive: 6 (55%) UICC IIB, 17 (30%) UICC III, and 3 (6%) UICC IV patients (p < 0.01). Univariate analysis revealed the following prognostic factors for complete response and long-term survival: UICC stage (p < 0.001), primary location in the head and neck region, total radiation dose above 40 Gy (all p < 0.05), while age, gender, and histology had no impact. In multivariate analysis, UICC stage was the only independent prognostic factor (p < 0.001). CONCLUSION: External beam radiotherapy can provide long-term local control and effective palliation in malignant melanoma UICC stages IIB-IV. The current UICC staging system is an excellent prognostic factor for initial and long-term tumor response in metastatic melanoma. Therefore, prospective randomized trials using external radiotherapy with or without adjuvant therapy for advanced malignant melanoma are justified.

Radiotherapy with and without cisplatin in bladder cancer.

From October 1985 to December 1988, 67 patients with invasive bladder carcinoma T1-4 N0-2 M0 were treated with irradiation (50.4 Gy in 28 fractions in 6 weeks) and simultaneous cisplatin (25 mg/m2 per day on 5 consecutive days in the first and fifth irradiation week). After transurethral resection and irradiation plus cisplatin, complete remissions were achieved in 8/11 T1-, 14/16 T2-, 27/36 T3- and 1/4 T4-tumors. The complete remission rate 6 weeks after treatment according to the extent of preceeding transurethral surgery (TUR) was: R0: 67% (8/12); R1: 83% (20/24); R2: 70% (21/30); Rx: 1/1. In patients with incomplete TUR (R1-2), the complete remission rate was 76% (41/54). This was superior to the results of a historical control (76% vs. 45%, p less than 0.01). The estimated 3-year survival according to T-stage was: T1: 73%, T2-3: 68%, T4: 25%. The overall 3-year survival was unchanged as compared to our historical control (66% each). Severe complications have not been observed. We conclude that cisplatin will likely increase the local control rate after incomplete transurethral surgery. An improvement of survival seems unlikely.