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Biomedical subjects

N Willich

Publications and source records attributed to N Willich.

At least 55 records · Page 3Linked to original sources

Radiotherapy in Ewing's sarcoma and PNET of the chest wall: results of the trials CESS 81, CESS 86 and EICESS 92.

PURPOSE: Treatment results and the pattern of relapse were evaluated in the multimodal treatment of Ewing's sarcomas of the chest wall. METHODS AND MATERIALS: In a retrospective analysis, 114 patients with non-metastatic Ewing's sarcoma of the chest wall were evaluated. They were treated in the CESS 81, CESS 86, or EICESS 92 studies between January 1981 and December 1993. The treatment consisted of polychemotherapy (VACA, VAIA, or EVAIA) and local therapy, either surgery alone (14 patients), radiotherapy alone (28 patients) or a combination of both (71 patients). The median follow-up was 46.6 months (range 5-170). A relapse analysis for all patients with local or combined relapses was performed. RESULTS: Overall survival was 60% after 5 years, event-free survival was 50%. Thirty-seven patients had a systemic relapse (32.4%), 11 patients had a local relapse alone (9.6%), and 3 patients had a combined local and systemic relapse (2.6%). The risk to relapse locally after 5 years was 0% after surgery alone, 19% after radiation alone, and 19% after postoperative irradiation. None of the 8 patients with preoperative irradiation have failed locally so far. With the introduction of central radiotherapy planning in CESS 86, local control of irradiated patients improved. Ten of 14 patients with local failure could be evaluated in the relapse analysis: 3 patients had an in-field relapse, 4 patients had a marginal relapse, 2 patients had a relapse outside the radiation fields, and 1 patient failed with pleural dissemination. Six treatment deviations were observed. CONCLUSION: Local control was best after surgery alone in a positively selected group of patients. Local control after radiation or combined radiation and surgery was good. With diligent performance of radiotherapy, it will be possible to further improve the results in the radiotherapy group.

Antineoplastic Combined Chemotherapy Protocols↗

External beam irradiation inhibits neointimal hyperplasia after injury-induced arterial smooth muscle cell proliferation.

PURPOSE: Restenosis after catheter-based revascularization has been demonstrated to be primarily caused by smooth muscle cell proliferation. This study examines the effects of external beam irradiation on neointimal proliferation after external injury to the central artery of the rabbit ear. METHODS AND MATERIALS: Thirty male New Zealand White rabbits were used in this study. Crush lesions were performed on each ear under general anesthesia and bilateral auricular nerve blockade. A single dose of 1200 cGy (n = 10), 1600 cGy (n = 10), or 2000 cGy (n = 10) gamma radiation was delivered to the left or right central artery of the ear 24 hours after injury; the contralateral central artery served as control. All rabbits were sacrificed after 21 days and the central arteries of both ears were fixed for morphometric measurements. RESULTS: Mean (+/-SD) neointimal area was 0.062 +/- 0.005 mm2 (1200 cGy), 0.022 +/- 0.005 mm2 (1600 cGy), and 0.028 +/- 0.006 mm2 in irradiated arteries compared with 0.081 +/- 0.009 mm2 in the control group. Mean (+/-SD) luminal area was 0.049 +/- 0.004 mm2 (1200 cGy), 0.059 +/- 0.002 mm2 (1600 cGy), and 0.072 +/- 0.006 mm2 (2000 cGy) in irradiated arteries compared with 0.043 +/- 0.008 mm2 in the control group. The differences in neointimal and luminal area between control and irradiated arteries were significant (p < 0.05) for the 1600 and 2000 cGy group only. CONCLUSION: We conclude that in this model, external beam X-ray irradiation was successful in reducing neointimal proliferation after injury of the central artery of the rabbit ear. Marked reductions in neointimal proliferation were demonstrated in vessels subject to 1600 and 2000 cGy radiation; a less prominent effect was noted for 1200 cGy. Whether this approach can be used successfully to inhibit restenosis in the clinical setting requires further investigation.

Animals↗

Surgical management of intraosseous skull base tumors with aid of Operating Arm System.

Invasion of bone and critical neurovascular structures often impedes complete resection of intraosseous skull base neoplasms, and these lesions tend to recur unless all infiltrated bone is removed. Evolving experience with image guidance over the past few years indicates the potential value of neuronavigation in skull base lesions diffusely infiltrating or fixed to bone structures. We report our early experience with the Radionics Operating Arm System (OAS), specifically emphasizing its utility as an adjunct in the treatment of intraosseous skull base tumors, mainly meningiomas. In April 1995 the OAS was introduced into clinical use at the neurosurgical university clinic in Münster, Germany. Since then, the system's utility has been explored in 10 patients out of the total neuronavigation series presenting with intraosseous skull base tumors (nine females and one male, mean age 47 years; nine meningiomas, one chordoma). For navigational planning, both 3-mm computed tomography scans and a set of 3-mm fat-suppression magnetic resonance images were chosen. At least four adhesive skin markers were used for system calibration. The system was technically usable in all cases in this small series. Because of the relative immobility of the bone structures and/or the tumor, no significant deviation from the preoperative registration accuracy was noted at the end of the procedures. The main advantages were easier localization and resection of infiltrated bone, which is often not grossly identifiable, even under the microscope. Our preliminary experience with the OAS suggests that image guidance is helpful in this type of lesion, providing better anatomical orientation during surgery and delineating tumor margins and their relation to critical neurovascular structures. The problem of a possible intracranial tumor and brain shift can be neglected in these lesions. The system facilitates resection by volumetric contour information, allowing more aggressive and complete resection.

Adult↗

[Lymphedema after breast carcinoma. A study of 5868 cases].

BASIC PROBLEM AND OBJECTIVE: According to published reports, the incidence of lymphoedema of the arm in patients with cancer of the breast, treated by either surgery or radiotherapy, varies widely. We obtained basic data on the treatment of breast cancer in a large number of patients in order to determine the relationship between the incidence of lymphoedema and the radical nature of the primary treatment. PATIENTS AND METHODS: Data were collected on all women with lymphoedema of the arm after treatment for breast cancer between 1972 and 1995. The increase in arm circumference was measured by a standardised method. Only those patients were included in the final analysis whose arm circumference had increased by at least 2 cm. The type of operation and(or) radiotherapy, tumor histology and TNM classification were recorded. RESULTS: There were 1405 cases of arm lymphoedema after treatment of 5868 cases of breast cancer (24%). 2515 breast cancers had been treated surgically. 3353 surgically and by radiotherapy. Lymphoedema occurred in 22.3% after radical mastectomy without radiotherapy and in 44.4% with it; after modified radical mastectomy without radiotherapy in 19.1%, in 28.9% with radiotherapy; after breast-preserving operation without radiotherapy in 6.7%, with radiotherapy in 10.1%. Until the 1970s radical mastectomy with conventional postoperative radiotherapy has been the treatment of choice, with 38% cases of lymphoedema. This incidence gradually decreased to 16% in subsequent years. CONCLUSION: The incidence of lymphoedema of the arm depends on the radical nature of the primary treatment. The quality of life could be easily improved through minimising the incidence of lymphoedema if current standards of breast-preserving surgery were generally practised.

Adult↗

[The demonstration of the radiation-induced production of tumor necrosis factor-alpha in Ewing's sarcoma RM 82 in vitro and in vivo].

AIM: The expression of cytokines plays an important role in the transmission of the effects of ionizing radiation to tumor cells and normal tissue. Tumor necrosis factor alpha (TNF alpha), a pleiotropic monokine, is of special interest because of its cytotoxic effect on tumor cells and the induction of hemorrhagic necrosis in tumors. We examined the influence of ionizing radiation on TNF alpha production in a human Ewing's sarcoma cell line in vitro and in vivo. METHODS: The protein and mRNA levels of the Ewing's sarcoma cell line RM 82 were examined in vitro with "Enhanced Amplified Sensitivity Immunoassay" (EASIA) and semiquantitative RT-PCR before and after treatment with single doses of 2 to 40 Gy, 1 to 72 hours after irradiation. After successful transplantation to nude mice, the time and dose correlation of TNF alpha mRNA production was examined in vivo. RESULTS: In vitro, RM 82 had a basal protein level of TNF alpha of 20.1 +/- 4.3 pg/ml/10(6) cells. We observed a time- and dose-dependent increase of TNF alpha expression with a maximum of 125 pg/ml/10(6) (5.9 fold) 24 hours after irradiation with 20 Gy. At the mRNA level, the maximal up-regulation occurred 6 to 12 hours after 10 Gy. In vivo, the xenograft tumor maintained the capacity of TNF alpha expression. Time- and dose-dependency in mRNA production showed a maximum increase 6 hours after treatment with 10 Gy. CONCLUSIONS: The presented experiments show in vitro a dose- and time-dependent up-regulation of TNF alpha in the Ewing's sarcoma cell line RM 82 on protein and mRNA level. For the first time this phenomenon was also observed in vivo in a human xenograft tumor. This tumor model could be used for further experiments to examine the role of TNF alpha as a biologic radiation response modifier in human tumors.

Animals↗

[Results of the treatment with fast neutrons (d.T 13 MeV) in recurrent rectal carcinoma].

PURPOSE: In spite of improved surgical techniques and the use of multiple modality treatment schemes the local recurrence rate of colorectal carcinomas could not be successfully reduced up to now. Besides surgical treatment of local recurrences in some cases radiation therapy may be indicated. PATIENTS AND METHOD: In the Department of Radiotherapy of the University of Münster 37 patients with recurrent rectal carcinoma were treated between the end of 1985 and September 1992 either with fast neutrons alone or with a combined photon-neutron therapy. Eighteen patients received radiotherapy with fast neutrons (14 MeV d,T) alone; the tumor dose was between 10 and 15 Gy neutrons. Nineteen patients were irradiated with a mixed-beam schedule consisting of 30 to 45 Gy photons (X 10 MV) and neutron doses ranging from 5 to 10 Gy. RESULTS: In 30 patients a good or complete pain relief could be observed immediately after the last irradiation. Sixteen out of 37 patients had local tumor regrowth during the follow-up period. The median survival for all 37 patients was 15.9 months. The probability for survival was 86% after 6 months and 61% after 12 months (Kaplan-Meier). The side effects were slight to moderate (EORTC/RTOG I-II). CONCLUSIONS: This therapy showed good results concerning a fast and effective pain relief. Additionally the results seem to show a good effect concerning local control and overall survival in this negatively selected patients.

Adenocarcinoma↗

[Primary radiotherapy of laryngeal carcinoma. An analysis of the therapeutic results and of the the relapse behavior in 283 patients].

PURPOSE: In the treatment of laryngeal carcinoma definitive radiotherapy results in a similar outcome as surgical treatment in the early stages with a lower morbidity rate and good functional results. In fact no randomized studies exist, so far, and the optimal treatment concept for the different stages is not well defined. The following study analyses retrospectively the treatment results and the recurrence data in patients with a squamous cell carcinoma of the larynx treated with definitive radiotherapy. PATIENTS AND METHOD: Two hundreds and eighty-three patients with carcinoma of the larynx were treated with radiation therapy in the department of radiology of the LMU München between September 1971 and June 1986. Twenty-six patients (9.2%) were female and 257 (73.1%) male. The median age was 68.5 years, respectively 70 years. All patients had a histologically confirmed squamous cell carcinoma of the larynx. No true subglottic cases were observed. Forty-one (14.5%) tumors were localized supraglottically, 207 (73.1%) glottically. Thirty-five patients had a T4 tumor with glottic and supraglottic involvement. In 147 patients the histopathological grading was evaluable: 32 tumors were classified as G1, 95 as G2, 15 as G3 and 5 as G4. According to the UICC classification of 1979 25 patients had a carcinoma in situ (Tis), 93 patients had a stage T1, 90 stage T2, 40 stage T3 and 35 stage T4. Two hundreds and thirty-three of 283 (82.3%) had no lymph node involvement. In 50 patients clinically a lymph node involvement was observed. 22 patients had a stage N1, 5 patients stage N2 and 23 patients stage N3. An external beam radiation mostly with cobalt-60 was performed with a mean dose of 61.9 Gy. RESULTS: The 5-years relapse-free survival for the whole group was 61.7%. The probability for "no evidence of disease" (NED) depended on tumor stage and localisation (glottic tumors: Tis/T1 90.5%: T2 59.4%: T3 39.6%: [5-year NED]; supraglottic tumors T1 64.2%: T2/3 28.6%: T4/N3 24.7% [3-year NED]). Other significant prognostic factors besides T-stage were N-stage (NO vs. N1-3: 3-year recurrence-free survival 68% vs. 37.2%, p < 0.001) and histopathologic grading (G1 vs. G3/4: 3-year recurrence-free survival 74% vs. 37.1%, p < 0.01). One hundred and twenty-two (43.1%) patients had a recurrence, which occurred in 75.4% local, in 12.3% loco regional, in 8.2%, with distant metastases and 4.1% combined. In 50 patients with a recurrent disease a salvage therapy was carried out. Thereby 17 patients achieved a complete response. CONCLUSION: Even for the here described negatively selected patient group with a high median age and multimorbidity, good local control rates could be achieved especially in early stages with definitive radiation therapy. In more advanced stages even in elderly patients a combined surgical-radiotherapeutic treatment should be performed.

Aged↗

Combined modality treatment with accelerated radiotherapy and chemotherapy in patients with locally advanced inoperable carcinoma of the pancreas: results of a feasibility study.

Between July 1990 and September 1993, 32 patients with locally advanced irresectable adenocarcinoma of the pancreas, histologically proven by laparotomy, were involved in our study. Patients were treated with hyperfractionated, accelerated radiotherapy and simultaneous application of 5-fluorouracil and folinic acid. Chemotherapy was given on days 1,2 and 3. Determination of the target volume for radiotherapy was carried out by computerized axial tomography. The total tumour dose of 44.8 Gy was applied relative to the 90% isodose in two daily fractions of 1.6 Gy, resulting in ten fractions per week. On the first three days of radiotherapy, 600 mg m-3 of 5-fluorouracil and 300 mg m-3 of folinic acid were given i.v. According to response, chemotherapy was repeated in 4-week intervals. The median survival time for all patients was 12.7 months, compared with 3-7 months after palliative surgery (historical control). The median progression-free interval was 6.6 months. Toxicity and therapy-induced morbidity were recorded according to WHO criteria. Nausea and vomiting of WHO grade I and II occurred in 72.1% and of grade III and IV in 27.9% of the patients. WHO grade I and II diarrhoea was seen in 11 patients. The overall incidence of leucopenia and thrombocytopenia was 37.4%; severe side-effects (WHO III-IV) occurred in 9.3% of all patients. One patient experienced a severe mucositis (WHO III). This combined modality treatment consisting of accelerated hyperfractionated radiotherapy and chemotherapy turned out to be feasible for patients with locally advanced, irresectable pancreatic cancer. The therapy could be applied in a short period of time, approximately half the time used in conventional therapy schemes.

Adenocarcinoma↗

Primary lymphoma of the stomach: three-year results of a prospective multicenter study. The German Multicenter Study Group on GI-NHL.

BACKGROUND: In October 1992, an ongoing prospective study on primary gastrointestinal (GI) lymphoma was initiated to evaluate histological features, sites of involvement, and management. PATIENTS AND METHODS: Until May 1996, 352 patients were enrolled, with 279 being evaluable for clinical features (208 patients presented with primary gastric lymphoma). Standardized diagnostic workup included central histologic review and endoscopic and radiologic evaluation of the complete GI tract. Primary surgery or conservative management depended on the physician's decision, followed by radiotherapy with or without chemotherapy. Treatment outcome is evaluable in 122 patients with gastric lymphoma. RESULTS: In 279 evaluable patients, the distribution of NHL was as follows: stomach 74.6%, small bowel 8.6%, ileocoecal region 6.5%, multilocal GI involvement 6.8%. In gastric lymphoma, low-grade NHLs accounted for 39%. Of the remaining high-grade NHLs, 36.1% showed simultaneous low-grade components, thus being also of MALT origin. Of 208 patients with gastric NHL, 71.1% were classified as stage I and II1. CCR rate in stomach lymphoma is significantly higher compared to those of the small bowel, whereas involvement of multiple GI organs has the worst prognosis. So far only 7 patients with gastric NHL in stages I and II presented with progressive disease or relapse. Over all stages there seems to be no difference in therapeutic outcome in surgically or conservatively treated patients. Even after R0-resection in limited stages patients appear to have no better outcome. CONCLUSION: The value of surgery in treatment of primary gastric lymphoma--as favored by most authors--should be reexamined.

Adult↗

[The results of primary radiotherapy in vaginal carcinoma].

BACKGROUND: Cancer of the vagina is the least frequent primary malignant tumor of the female genital tract except carcinoma of the fallopian tube. Radiation therapy is the preferred treatment in most cases. PATIENTS AND METHOD: Between 1965 and 1991, 39 patients (median age 66 years) with primary carcinoma of the vagina were treated with radiation therapy at our clinic. The mean observation period was 37 months. Classification according to the FIGO yielded a stage I in 43%, stage II in 24%, stage III in 22% and stage IV in 11%. Histological differentiation resulted in 35 squamous cell carcinomas and 4 adenocarcinomas. In 69%, the tumor was found on the posterior or lateral wall of the vagina, in 43% it arose from the upper third of the vagina. Standard therapy consisted of combined brachy- and teletherapy. Most of the brachytherapy applications were performed with a radium source. RESULTS: Median survival was 37 months, calculated according to the Kaplan-Meier method. The 5-year actuarial survival rate for all stages was 41% (stage 1: 62%, stage II: 44%, stage III: 25%). Sixty-eight percent of all patients achieved a complete remission, 19% a partial response. Significant prognostic factors were stage of disease and histological grading. CONCLUSION: Our results demonstrate the value of radiation therapy for the treatment of primary carcinoma of the vagina. Combined treatment with both external beam radiation and brachytherapy should be preferred.

Adenocarcinoma↗