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Biomedical subjects

U Fink

Publications and source records attributed to U Fink.

At least 19 recordsLinked to original sources
PubMed2004

Responders benefit from neoadjuvant radiochemotherapy in esophageal squamous cell carcinoma: results of a prospective phase-II trial.

BACKGROUND: We present the results of a prospective phase-II-study of neoadjuvant combined radiochemotherapy followed by surgical resection in patients with histological proven locally advanced squamous cell carcinoma of the esophagus located at or above the level of the tracheal bifurcation. METHODOLOGY: Between February 1995 and March 2000 a total of 76 patients with esophageal squamous cell carcinoma (uT3/4N0/+-categories) received simultaneous combined neoadjuvant radiochemotherapy consisting of a continuous intravenous infusion of 5-fluorouracil (300 mg/m2/day) 7 day per week concurrently with conventional fractioned external beam radiation therapy (2 Gy/day), five fractions per week up to a total dose of 30 Gy. RESULTS: Radiochemotherapy related acute severe toxicity rate (CTC-grade-III) occurred in 34 patients, two patients died. Sixty-four patients underwent surgery with a complete resection in 48 patients. Three patients died during a 90-day post-operative course. The histopathological workup revealed no viable residual tumour cells in eight patients (ypCR) and according to the modified criteria of Mandard in 26 patients a histopathological response. Twenty-two of these patients underwent a R0-resection. The median follow-up time was 5.4 years with an overall median survival time of 20.6 months. The median survival in the 26 responders was 32.3 months versus 19.5 months in 38 non-responders (p=0.03). CONCLUSIONS: Patients with locally advanced squamous cell carcinoma of the esophagus, who respond to preoperative neoadjuvant combined radiochemotherapy, seem to have more benefit from subsequent resection than non-responding patients.

Adult↗
PubMed2003

Recurrent arachnoid cyst of Meckel's cave mimicking a brain stem ischaemia. Report of a rare case.

UNLABELLED: A 44-years old man developed TIA-like symptoms with dysaesthesia around the mouth, vertigo and diplopia. MRI revealed a cystic space-occupying lesion on the right Meckel's cave, which spread out into cerebellopontine angle in a further examination. Therefore surgical exploration was performed using a suboccipital approach. An arachnoidal cyst was found and removed including its wall. About three months later the patient suffered again from dysaesthesias of the right side of the face and a new MRI revealed a recurrence of the lesion, with extension into the cerebellopontine angle, too. Surgical revision was done using the same approach and the recurrent cyst was removed. Postoperatively, there were a transient hypaesthesia in the distribution area of the right trigeminal nerve and a light pulmonary embolism occurred as a complication. No symptoms have returned during an observation period of 15 months. CONCLUSION: An arachnoidal cyst must be considered as a rare cause, when a lesion is found at the Meckel's cave with intermittent clinical symptoms of a trigeminal nerve affection. As surgical treatment we favour fenestration and cyst wall resection.

Adult↗
PubMed2002

[Neoadjuvant therapeutic principles guided by response prediction and evaluation].

Only patients with a clinical and pathohistological response to neoadjuvant therapy have a significantly improved survival. Therefore the identification of predictors for response and procedures for the early identification of nonresponders appear to be mandatory. Preliminary data of biochemical investigations of target enzymes for several cytostatics (e.g. TS, ERCC1) appear to be promising. Early changes of the tumor metabolism in the FDG-PET enable the identification of nonresponders with a negative predictive value of 88-95%. In near future these findings should lead to consequences in the design and realization of clinical studies.

Adenocarcinoma↗
PubMed2001

[Lumbar lateral recess stenosis. Clinical symptoms, diagnostic modalities and surgical management].

BACKGROUND: In spite of its importance for lumbar radicular syndroms only a few reports about lumbar lateral recess stenosis exist in literature. Most important clinical symptom is radicular pain, which may be exercise-dependent. Confirmation of diagnosis and differentiation from disc herniation requires imaging like CT, MRI or post-myelo-CT. Surgical treatment options include selective decompression techniques like foraminotomy, medial facettectomy and undercutting as well as hemilaminectomy, laminotomy and wide laminectomy or fusion. METHOD: We treated 35 patients with selective decompression techniques. RESULTS: In the follow-up 5 up to 18 months after surgery 25 patients for themselves described the results as good or excellent. Therefore, individually tailored selective microsurgical decompression is an appropriate and successful treatment strategy for lumbar lateral recess stenosis, if conservative treatment fails.

Adult↗
PubMed2001

Prediction of response to preoperative chemotherapy in adenocarcinomas of the esophagogastric junction by metabolic imaging.

PURPOSE: Preoperative chemotherapy in patients with gastroesophageal cancer is hampered by the lack of reliable predictors of tumor response. This study evaluates whether positron emission tomography (PET) using fluorine-18 fluorodeoxyglucose (FDG) may predict response early in the course of therapy. PATIENTS AND METHODS: Forty consecutive patients with locally advanced adenocarcinomas of the esophagogastric junction were studied by FDG-PET at baseline and 14 days after initiation of cisplatin-based polychemotherapy. Clinical response (reduction of tumor length and wall thickness by > 50%) was evaluated after 3 months of therapy using endoscopy and standard imaging techniques. Patients with potentially resectable tumors underwent surgery, and tumor regression was assessed histopathologically. RESULTS: The reduction of tumor FDG uptake (mean +/- 1 SD) after 14 days of therapy was significantly different between responding (-54% +/- 17%) and nonresponding tumors (-15% +/- 21%). Optimal differentiation was achieved by a cutoff value of 35% reduction of initial FDG uptake. Applying this cutoff value as a criterion for a metabolic response predicted clinical response with a sensitivity and specificity of 93% (14 of 15 patients) and 95% (21 of 22), respectively. Histopathologically complete or subtotal tumor regression was achieved in 53% (eight of 15) of the patients with a metabolic response but only in 5% (one of 22) of the patients without a metabolic response. Patients without a metabolic response were also characterized by significantly shorter time to progression/recurrence (P =.01) and shorter overall survival (P =.04). CONCLUSION: PET imaging may differentiate responding and nonresponding tumors early in the course of therapy. By avoiding ineffective and potentially harmful treatment, this may markedly facilitate the use of preoperative therapy, especially in patients with potentially resectable tumors.

Adenocarcinoma↗
PubMed2001

Neoadjuvant therapy for patients with locally advanced gastric carcinoma with etoposide, doxorubicin, and cisplatinum. Closing results after 5 years of follow-up.

BACKGROUND: The intent to curatively treat patients with gastric carcinoma is based on complete surgical resection of the primary tumor and its lymphatic drainage. Postoperative adjuvant chemotherapy has failed to show a significant prognostic advantage for these patients. Preoperative chemotherapy, based on promising results in the treatment of patients with disease in primarily unresectable stages, is still being evaluated for those with locally advanced gastric carcinoma. Most published studies still lack adequate staging methods, and long term results of this treatment modality are not known at present. METHODS: In a Phase II study, a series of 42 patients with locally advanced gastric carcinoma (International Union Against Cancer Stages IIIA, IIIB, and IV) initially were staged with endoscopy, with endoscopic ultrasound to establish the clinical tumor classification, with computed tomography scans to rule out tumor infiltration of adjacent organs and to detect distant metastases, and with surgical laparoscopy to exclude occult peritoneal carcinomatosis. Three or four planned cycles of neoadjuvant chemotherapy with etoposide, doxorubicin, and cisplatinum were given prior to total gastrectomy. RESULTS: After a complete follow-up of at least 5 years, there was a median survival of 19.1 months for all patients. Only patients who underwent a complete surgical tumor resection appeared to have a survival benefit, with a median survival of 28.4 months. A superior survival rate was seen in patients who had a major clinical response to chemotherapy, with a median survival of 45 months. CONCLUSIONS: Phase III studies comparing results from patients who undergo neoadjuvant chemotherapy followed by surgery with results from patients who undergo surgery alone should stress the value of adequate pretherapeutic staging and must be accompanied by studies of potential methods for predicting tumor response.

Adolescent↗
PubMed2001

A new method for surgical repair of impression fractures of the cranial vault and frontal sinus with rivet-like titanium clamps.

Conventional methods of stabilizing fragments in cranial impression fracture include the use of threads, wires, plates, etc. A new approach to facilitate this surgery is the use of titanium clamps, presented here in five cases, including one with frontal sinus fracture. Surgery was performed on admission day, with the exception of the sinus fracture. Compared with the use of mini- and microplates, the procedure was simple and short. The fixation was very rigid and the esthetic result excellent in all five cases. Skin irritation was minimal, compared with that from miniplates. Computed tomography and MRI compatibility due to artifacts are identical to those with miniplates.

Adult↗
PubMed2001

[Monitoring of response to neoadjuvant therapy by positron emission tomography (PET)].

Neoadjuvant therapy is frequently hampered by the lack of reliable non-invasive techniques for prediction and assessment of response. Positron emission tomography using the glucose analogue 18F-fluorodeoxyglucose (FDG-PET) provides a unique means of non-invasive assessment of tumor metabolism. Several recent studies have indicated that a reduction of tumor metabolic activity after neoadjuvant therapy is closely correlated with the degree of histopathological tumor regression. The reduction of metabolic activity may also allow one to predict subsequent response early during the course of therapy. Therefore FDG-PET may permit individualized therapy management. However, there is a requirement for larger-scale trials to assess this technique.

Female↗
PubMed2001

Proliferation kinetics and prognosis in gastric cancer after resection.

The influence of proliferation and proliferation kinetics on prognosis in gastric cancer after complete resection are controversial. In a prospective study we investigated the tumour specimens of 111 patients after resection of gastric cancer, who received 200 mg intravenous (i.v.) bromodeoxyuridine (BrdU) pre-operatively. The following biological parameters were analysed in the tumour tissue using flow-cytometry: DNA ploidy, proportion of S-phase cells, BrdU labelling index (LI), DNA synthesis time (T(s)), potential tumour doubling time (T(pot)), proliferating cell nuclear antigen (PCNA) and Ki-67 LI. The median follow-up time was 40 months (range 19-62 months). Besides the established pathohistological prognostic factors, univariate analysis revealed a prognostic influence on survival for BrdU LI, T(pot) and the proportion of S-phase cells. By multivariate Cox analysis of the completely resected cases, only tumour stage and T(pot) had a significant, independent influence on survival. By classification and regression trees (CART) analysis, resection status, tumour stage and T(pot) defined risk groups with significantly different outcomes. A short T(pot) was a predictor of better survival in stage I, II and IIIA tumours. Ploidy and the other investigated proliferation-related parameters failed to demonstrate any influence on prognosis after resection of gastric cancer.

Adenocarcinoma↗
PubMed2001

Neoadjuvant therapy of esophageal squamous cell carcinoma: response evaluation by positron emission tomography.

OBJECTIVE: To evaluate the use of positron emission tomography using [(18)F]-fluorodeoxyglucose (FDG-PET) to assess the response to neoadjuvant radiotherapy and chemotherapy in patients with locally advanced esophageal cancer. SUMMARY BACKGROUND DATA: Imaging modalities, including endoscopy, endoscopic ultrasound, computed tomography, and magnetic resonance imaging, currently used to evaluate response to neoadjuvant treatment in esophageal cancer do not reliably differentiate between responders and nonresponders. METHODS: Twenty-seven patients with histopathologically proven squamous cell carcinoma of the esophagus, located at or above the tracheal bifurcation, underwent neoadjuvant therapy consisting of external-beam radiotherapy and 5-fluorouracil as a continuous infusion. FDG-PET was performed before and 3 weeks after the end of radiotherapy and chemotherapy (before surgery). Quantitative measurements of tumor FDG uptake were correlated with histopathologic response and patient survival. RESULTS: After neoadjuvant therapy, 24 patients underwent surgery. Histopathologic evaluation revealed less than 10% viable tumor cells in 13 patients (responders) and more than 10% viable tumor cells in 11 patients (nonresponders). In responders, FDG uptake decreased by 72% +/- 11%; in nonresponders, it decreased by only 42% +/- 22%. At a threshold of 52% decrease of FDG uptake compared with baseline, sensitivity to detect response was 100%, with a corresponding specificity of 55%. The positive and negative predictive values were 72% and 100%. Nonresponders to PET scanning had a significantly worse survival after resection than responders. CONCLUSION: FDG-PET is a valuable tool for the noninvasive assessment of histopathologic tumor response after neoadjuvant radiotherapy and chemotherapy.

Adult↗
PubMed2001

Histologic tumor type is an independent prognostic parameter in esophageal cancer: lessons from more than 1,000 consecutive resections at a single center in the Western world.

OBJECTIVE: To analyze the changing pattern in tumor type and postoperative deaths at a national referral center for esophageal cancer in the Western world and to assess prognostic factors for long-term survival after resection. SUMMARY BACKGROUND DATA: During the past two decades, the epidemiology and treatment strategies of esophageal cancer have changed markedly in the Western world. The influence of these factors on postoperative deaths and long-term prognosis has not been adequately evaluated. METHODS: Between 1982 and 2000, 1,059 patients with primary esophageal squamous cell cancer or adenocarcinoma had resection with curative intention at a single center. Patient and tumor characteristics and details of the surgical procedure and outcome were documented during this period. Follow-up was available for 95.8% of the patients. Changing patterns in tumor type and postoperative deaths were analyzed. Prognostic factors for long-term survival were assessed by multivariate analysis. RESULTS: The prevalence of adenocarcinoma in patients with resected esophageal cancer increased markedly during the study period. The postoperative death rate decreased from about 10% before 1990 to less than 2% since 1994, coinciding with the introduction of a procedure-specific composite risk score and exclusion of high-risk patients from surgical resection. In addition to the well-established prognostic parameters, tumor cell type "adenocarcinoma" was identified as a favorable independent predictor of long-term survival after resection. The independent prognostic effect of tumor cell type persisted in the subgroups of patients with primary resection and patients with primary resection and R0 category. CONCLUSION: Esophagectomy for esophageal cancer has become a safe procedure in experienced hands. Esophageal adenocarcinoma has a better long-term prognosis after resection than squamous cell carcinoma.

Adenocarcinoma↗
PubMed2001

[How can the effectiveness of multimodality therapy concepts be evaluated? From the viewpoint of the pathologist].

Prognostically relevant histopathological grading of tumor regression (grades I-III) is possible, although laborious. Morphological changes after chemotherapy indicate a specific response to treatment with central fibrosis and residual tumor islands in the periphery. Prognostic factors, such as TNM categories, UICC-R status, tumor size, and lymphangiosis, which are not intrinsic part of regression grading still correlate with patient survival.

Combined Modality Therapy↗
PubMed2000

[New therapy approaches in tumors of the upper gastrointestinal tract (esophagus, stomach)].

Despite numerous phase-II and phase-III studies investigating neoadjuvant treatment in esophageal and gastric cancer, the value of multimodal therapy in these tumors is not clearly defined yet. One reason are the different study entry criteria and different staging modalities in the investigations published so far. Concerning esophageal cancer, neoadjuvant chemotherapy does not yet have a definite role after several phase-III studies. It may be that this treatment should only be inaugurated in innovative protocols. Furthermore, in esophageal cancer it is proven that chemoradiation is superior to radiation alone in the neoadjuvant setting. Following neoadjuvant chemoradiation, there is a distinct trend in favor of multimodal therapy. In the case of locally advanced squamous cell carcinoma of the esophagus, neoadjuvant chemoradiation offers 30%-60% of the patients the possibility for a complete resection (UICC-R0); however, this is accompanied by increased postoperative morbidity and mortality. In gastric cancer, neoadjuvant chemotherapy is still an experimental approach. Intraperitoneal chemotherapy has failed to show any benefit in Western trials. Clinically related research is concentrating on the problem of distinguishing responder from non-responder at the beginning of the therapy. First results indicate that with molecular markers, response might be predicted before therapy. Using 18-FDG PET, it could be possible that the response can be recognized after only 1 week of treatment, opening the door to early response evaluation. New therapeutics like monoclonal antibodies for adjuvant therapy, which is again under discussion in gastric cancer, are only in phase-I studies.

Combined Modality Therapy↗
PubMed2000

Multidisciplinary approach to esophageal and gastric cancer.

Despite marked advances in surgical therapy for patients with esophageal, esophagogastric, and gastric cancers, the overall prognosis of these patients has not markedly improved during the past decades. Multidisciplinary approaches using adjuvant postoperative and neoadjuvant preoperative therapeutic principles have received increasing attention with regard to the management of these patients. A series of randomized, prospective trials has demonstrated that adjuvant postoperative radiation or chemotherapy does not result in a convincing survival advantage after complete tumor resection in esophageal, esophagogastric junction, or gastric cancer. The available data on the role of neoadjuvant preoperative therapy are not yet conclusive. Although neoadjuvant therapy may reduce the tumor mass in many patients, several randomized, controlled trials have shown that, compared with primary resection, a multimodal approach does not result in a survival benefit in patients with locoregional, that is, potentially resectable, tumors. In contrast, in patients with locally advanced tumors, that is, patients in whom complete tumor removal with primary surgery seems unlikely, neoadjuvant therapy increases the likelihood of complete tumor resection on subsequent surgery, but only patients with objective histopathologic response to preoperative therapy seem to benefit from this approach. Consequently, in the future, improvements in the overall survival of patients with esophageal, esophagogastric junction, or gastric cancer most likely will be achieved only by tailored therapeutic strategies that are based on the individual tumor location, tumor stage, and consideration of established prognostic factors. A clear classification of the underlying tumor entity, a profound knowledge of the prognostic factors applicable, a thorough preoperative staging, and identification of parameters that allow for the prediction of response to preoperative therapy will become essential for the selection of the optimal therapeutic modality for individual patients.

Adenocarcinoma↗
PubMed2000

Gemcitabine and cisplatin in the treatment of advanced or metastatic pancreatic cancer.

BACKGROUND: This phase II study was initiated to determine the efficacy and safety of gemcitabine plus cisplatin in patients with pancreatic cancer. PATIENTS AND METHODS: Gemcitabine 1000 mg/m2 was given on days 1, 8, and 15 of a 28-day schedule, and cisplatin 50 mg/m2 on days 1 and 15 to chemonaive patients with locally advanced or metastatic pancreatic cancer. RESULTS: Of the 41 patients enrolled (median age 57, and 61% male), median Karnofsky performance status was 80%. Patients received a median of 4.2 cycles (range 1-11). In 35 evaluable patients, one complete response (CR) and three partial responses (PR) were observed, for an overall response rate of 11% (95% confidence interval (95% CI): 3.2% -26.7%). Stable disease (SD) > 3 months occurred in 20 (57%) patients; 6 survived > or = 1 year. Median time to progressive disease was 4.3 months (95% CI: 3.0-5.7 months). For all patients, median survival was 8.2 months (95% CI: 6.1-10.6 months) with a one-year survival rate of 27%. Therapy was well tolerated. Grade 3-4 neutropenia (no grade 3-4 infection), thrombocytopenia (no bleeding), nausea/vomiting, and alopecia were reported in 29%, 13%, and 2.6% of patients, respectively. CONCLUSIONS: The combination of gemcitabine and cisplatin is a moderately active treatment for patients with locally advanced and metastatic pancreatic cancer without compromising tolerability.

Adult↗
PubMed2000

Multiple molecular marker testing (p53, C-Ki-ras, c-erbB-2) improves estimation of prognosis in potentially curative resected non-small cell lung cancer.

A prospective study was performed in patients with non-small cell lung cancer (NSCLC) to evaluate the prognostic importance of multiple molecular marker (p53, c-Ki-ras, c-erbB-2) testing. 103 patients with potentially curative resections (RO resection) for NSCLC in histopathological stages I-IIIA were included. SSCP analysis and DNA sequencing for p53 and c-Ki-ras genes were performed on paired tumour and normal lung tissue samples and immunohistochemistry (c-erbB-2) was done on frozen tissue sections with a specific anti-c-erbB-2 monoclonal antibody. 46/103 (44.6%) NSCLC showed p53 mutations and 17/103 (16.5%) c-Ki-ras mutations including 12/37 (32.4%) adenocarcinomas. Overexpression of c-erbB-2 (p185) was detected in 56/103 (54.4%) tumours. 24/103 (23.3%) NSCLC were negative for alterations in all 3 parameters (c-Ki-ras, p53 and p185) whereas 79/103 (76.7%) were positive for at least one of the 3 parameters. In a regression model including a multiple molecular marker parameter (negative for all 3 markers versus positive for at least one marker), histopathological stage (P<0.00001), respectively the pT (P<0.01) and pN (P<0.00001) categories and the multiple molecular marker parameter (P<0.01) were of significant prognostic importance. This study demonstrates that testing 3 molecular markers (c-Ki-ras, p53 and c-erbB-2) improves estimation of prognosis compared to single marker testing and appears to define low (82.6%+/-7.9% 5-year survival) and high risk (40.2%+/-5.5% 5-year survival) groups for treatment failure in potentially curative (RO) resected NSCLC.

Adult↗
PubMed2000

Influence of simultaneous neoadjuvant radiotherapy and chemotherapy on bronchoscopic findings and lung function in patients with locally advanced proximal esophageal cancer.

To assess the bronchoscopic and lung function changes induced by preoperative radiochemotherapy (30 Gy radiation and 5-fluorouracil) in patients with proximal esophageal cancer, we prospectively compared the findings in 77 consecutive patients before and after the therapy. All patients completed the radiochemotherapy protocol; toxicity was minimal. Sixty-four patients underwent surgery, 48 had total gross removal of disease, and six had a complete histologic response. Of the 13 patients who developed apparent direct macroscopic signs of tumor invasion into the airways during therapy, histologic proof of cancer was obtained in only one of the abnormalities. Bronchoscopy was falsely negative in six patients in whom airway invasion of the cancer was found at surgery. Neoadjuvant therapy led to no systematic changes in the appearance of the uninvolved tracheal mucosa; microscopically, an increase in postinflammatory changes, hyperplasia, and metaplasia was found. There was no significant change in the values of lung function parameters after the therapy. No patient developed symptoms suggestive of radiation-induced lung changes, although in one of them, subtle radiologic features consistent with radiation pneumonitis were found. No patient died of postoperative pulmonary complications. The interpretation of bronchoscopy in the assessment of airway invasion of esophageal cancer after radiochemotherapy is more difficult than at baseline staging; the positive predictive value of macroscopic abnormalities without microscopic proof of cancer is low, and even with extensive sampling for histology and cytology, the procedure was falsely negative in 9.4%. Neoadjuvant therapy did not induce radiation pneumonitis or changes in lung function that could be of concern at the following operation.

Adult↗