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  • 1
    ISSN: 1433-0415
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Die chirurgische Radikalität bei Entfernung des Primärtumors bzw. isolierter Metastasen unter Einhaltung definierter Sicherheitsabstände und der Dissektion regionärer Lymphabflußgebiete zählt ebenso zum Standardrepertoire der Tumorbehandlung wie die systemische Chemotherapie bei nicht resektablen soliden Tumoren. Während die Radikalität der Chirurgie zu Funktionsverlusten oder hoher postoperativer Morbidität führen kann, sind die alternativen konservativen Therapiemethoden in ihrem Palliativerfolg zeitlich und von dem Anteil profitierender Patienten oft limitiert. Neue chirurgisch-onkologische Behandlungsmethoden und -strategien haben in den letzten Jahren dazu geführt, daß stadienadaptierte Therapien eingesetzt werden können, die die Nachteile der Standards reduzieren und die Grenzen bisheriger Methoden entweder durch den Einsatz neuer Kombinationsschemata oder individualisierter Therapien verschieben.
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  • 2
    ISSN: 1433-0385
    Keywords: Key words: Chronic pancreatitis ; Duodenum-preserving pancreatic head resection. ; Schlüsselwörter: Chronische Pankreatitis ; duodenumerhaltende Pankreaskopfresektion.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung. Bei Patienten mit chronischer Pankreatitis ist der entzündliche Prozeß im Pankreaskopf häufig Schrittmacher der Krankheit; der entzündliche Pankreaskopftumor verursacht das Schmerzsyndrom und führt bei der Hälfte der Patienten zu lokalen Komplikationen. Die duodenumerhaltende Pankreaskopfresektion bietet gegenüber den in der Vergangenheit praktizierten Verfahren den Vorteil der Erhaltung von Magen, Duodenum und Gallenwegen sowie der Erhaltung der Insulinsekretionskapazität. Die duodenumerhaltende Pankreaskopfresektion entspricht einer minimalisierten subtotalen Resektion des Pankreaskopfes. Bei 380 Patienten war die Krankenhausletalität 0,8 %, die Reoperationsfrequenz 5,3 %. Die mittlere postoperative Krankenhausliegezeit war 13,9 Tage. Frühpostoperativ war der Glucosestoffwechsel bei 2 % verschlechtert und bei 9 % verbessert. Nach einer medianen Nachbeobachtungszeit von 6 Jahren sind 88 % der Patienten vollständig schmerzfrei bzw. haben selten Bauchschmerzen; 63 % sind wieder voll berufstätig; die Spätletalität beträgt 8,9 %. Nur 10 % der Patienten erlitten weitere Pankreatitisschübe. Der entscheidende Vorteil der duodenumerhaltenden Pankreaskopfresektion besteht in der Erhaltung der endokrinen Funktion der Bauchspeicheldrüse bei Schonung der Pankreasnachbarorgane.
    Notes: Summary. In patients with chronic pancreatitis the inflammatory process in the pancreatic head is frequently the pacemaker of the disease. In these cases an inflammatory tumor develops which leads to local complications in half of the patients. Duodenum-preserving pancreatic head resection, contrary to procedures used in the past, offers the possibility to preserve stomach, duodenum, biliary tree, and the insulin secretory capacity. Duodenum-preserving pancreatic head resection is a subtotal resection of the pancreatic head. In a series of 380 patients the hospital mortality rate was 0.8 %, the frequency of reoperation 5.3 %, and the median hospitalisation time 13.9 days. The early postoperative glucose metabolism was deteriorated in 2 % and improved in 9 % of cases. After a median follow-up time of 6 years, 88 % of the patients were completely painfree or suffered pain rarely. Sixty-three percent were gainfully employed; the late mortality was 8.9 %. Only 10 % of the patients had further bouts of pancreatitis. The decisive advantage of duodenum-preserving pancreatic head resection over Kausch-Whipple resection is preservation of the endocrine pancreatic function and of neighbouring organs.
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  • 3
    ISSN: 1432-2323
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé Depuis novembre, 1981, dans notre clinique, nous avons traité 50 malades par chimiothérapie régionale isolée, la majorité d'entre eux présentant des métastases de cancer colo-rectal, le traitement ayant été mis en oeuvre 9 mois environ après l'intervention dont la mortalité aviat été de 8 pour cent. Les agents cytostatiques employés isolément ou en combinaison furent le 5-FU (300–1,250 mg), la mitomycine C (5–50 mg), quatre malades ayant été traités par le cisplatinium (50 mg). Chez 41 malades, il fut possible de suivre l'évolution. Le temps médian de survie fut de 14 mois; 11 malades étaient en vie après 24 mois; les patients décédés ont vécu 12.5 mois. Un traitement complémentaire à l'aide de cycles de perfusion intra-artérielle a paru augmenter la survie (sans traitement complémentaire: 7.5 mois, avec traitement complémentaire: 18 mois). Neuf (22%) des 41 malades suivis ont présenté une rémission complète, 28 (68%) une rémission partielle. Chez 40% des malades présentant des métastases hépatiques, des métastases pulmonaires ou des récidives locales se sont développées. Les avantages de la perfusion isolée du foie que nous considérons sont le fait en particulier des concentrations très élevées des drogues cytostatiques perfusées et de la perfusion complémentaire de la veine porte. Ce mode de traitement ne saurait être appliqué q'une fois.
    Abstract: Resumen A partir de noviembre de 1981 se han tratado 50 pacientes con quimioterapia regional aislada en nuestra clínica, predominantemente pacientes con metástasis de carcinomas colorrectales, 9 meses después de la operación primaria, en promedio. La letalidad de la operación es de 8%. Las drogas citostáticas aplicadas como agente único o en combinación fueron 5-FU (300–1,250 mg), mitomicina C (5–50 mg), y también, en 4 casos, el cis-platino (50 mg). En 41 pacientes se pudo estudiar la evolución de la enfermedad. El promedio de supervivencia para la totalidad de los pacientes fue de 14 meses, de 24 meses en 11 pacientes que todavía vivían, y de 12.5 meses para los que murieron. Un tratamiento adicional con ciclos de infusión intraarterial parece extender el tiempo de supervivencia (sin tratamiento adicional: 7.5 meses, con tratamiento adicional: 18 meses). Nueve (22%) de 41 pacientes presentaron remisión completa, 28 (68%) remisión parcial. En 40% de los pacientes con tumores hepáticos secundarios se desarrollaron metástasis pulmonares y/o recurrencias locales del tumor. Consideramos que las ventajas de la perfusión hepática aislada se relaciona especialmente con las muy elevadas concentraciones de droga citostática en el circuito de infusión y la perfusión adicional de la vena porta. Ciertamente este tipo de principio terapéutico puede ser aplicado solamente una vez y la perfusión hepática aislada debe ser completada mediante otras modalidades de tratamiento.
    Notes: Abstract Since Novermber, 1981, 50 patients (predominantly those with metastases of colorectal carcinomas) have been treated in our clinic by an isolated regional chemotherapy on an average of 9 months after the primary operation. The mortality rate was 8%. The cytostatic drugs applied alone or in combination were 5-fluorouracil (5-FU) (300–1,250 mg) and mitomycin C (5–50 mg) in 46 patients, and 5-FU, mitomycin C, and cisplatin (50 mg) in 4 patients. The course of the disease was observed in 41 patients. The median survival was 14 months, 24 months in 11 patients still living, and 12.5 months in those patients who died. An additional treatment with cycles of an intraarterial infusion therapy seeemed to extend the survival time (7.5 months without additional treatment, 18 months with additional treatment). Nine (22%) of 41 patients had a complete remission, and 28 (68%), a partial remission. Lung metastases and/or local tumor recurrences arose in 40% of the patients with secondary liver tumors. We consider the very high cytostatic drug concentrations in the infusion circuit and the additional perfusion of the portal vein to be the advantages of isolated liver perfusion (ILP). Certainly, this therapy can be applied only once, and ILP must be completed by another means of treatment.
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  • 4
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To determine the optimal concentration time factors for the fluoropyrimidines 5-fluorouracil (FU), 5-fluorouridine (FUR), and 5-fluoro-2′-deoxyuridine (FUdR) in regional chemotherapy, we tested these drugs against the colorectal carcinoma cell line HT 29 at various dosages and exposure times. The measure of cytotoxicity used was the degree of inhibition of colony formation in soft agar after drug treatment compared with untreated control cells. Colonies were visible after 6 days of growth in soft agar, so the initial evaluation of toxicity was done at this time. Additional colonies were found 10 and 16 days after the first evaluation, so the dishes containing the treated cells were also evaluated for this delayed growth phenomenon (“regrowth”), which we considered to be due to a cell growth inhibition effect of the drugs rather than a cytocidal effect. Exposure times of the cells to the drugs ranged from 5 min to 24 h and the doses, between 0.01 and 1000 μg/ml. The toxicity of FUdR was concentration-dependent, but its time dependence ceased after a relatively short exposure time. There was a cell population that was not susceptible to FUdR regardless of dose and exposure time; consequently, FUdR treatment was always accompanied by substantial regrowth of colonies. With FU and FUR, conditions could be achieved that resulted in complete cell death (no regrowth), but high concentrations and long exposure times were required with FU. With FUR, on the other hand, both cytostasis and cytoxicity could be achieved with substantially lower doses and shorter exposure times than with FU. These results indicate that FUR has the potential to be an effective drug in chemotherapy protocols not involving systemic administration.
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  • 5
    ISSN: 1435-2451
    Keywords: Chemosensitivity ; Regional chemotherapy ; Colorectal liver metastases ; Chemosensitivität ; Regionale Chemotherapie ; Colorectale Lebermetastasen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Die Aktivität regional chemotherapeutisch einsetzbarer Cytostatica wurde an Zellsuspensionen von insgesamt 47 colorectalen Lebermetastasen im modifizierten Tumorzell-Kolonien-Test (Hamburger/Salmon) im repräsentativen Konzentrationsbereich untersucht. Bei 1 gg/ml (bei 5-FU und ASTA Z 7654 10 pg/ml) war die Aktivitätssequenz wie folgt: Adriamycin (54% der Tests sensitiv), Mitomycin C (51%), Mitoxantron (40%), ASTA Z 7654 (33%), cis-DDP (26%), Melphalan (25%), 5-FU (23%), Epidoxorubicin (14%). Dieses Chemosensitivitätsprofil sollte bei neuen Protokollen berücksichtigt werden.
    Notes: Summary The chemosensitivity of colorectal liver metastases to drugs selective for regional chemotherapy was tested in vitro in a modified soft agar colony assay (Hamburger/Salmon) at a representative concentration range. At I ssg/ml (in 5-FU and ASTA Z 7654 at 10 μg/ml), the sequence of drug activities was as follows: Adriamycin (54% of the biopsies sensitive), mitomycin C (51%), mitoxantrone (40%), ASTA Z 7654 (33%), cis-DDP (26%), melphalan (25%), 5-FU (23%), and Epidoxorubicin (14%).
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  • 6
    ISSN: 1435-2451
    Keywords: Key words Pancreatic cancer ; Adjuvant therapy ; Neoadjuvant therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: To improve the surgical outcome after resection of pancreatic adenocarcinomas, multimodal treatment concepts need to be applied and improved. The controversies among those being pro and contra adjuvant treatment need an up-to-date review of the indications and results achievable with various treatment modalities. Patients/Methods: The literature regarding the indications and results of adjuvant/neoadjuvant therapies in pancreatic cancer was reviewed to provide a solid base for current recommendations and future developments. The biology of the disease in the spontaneous course, after surgery and during/after various palliative and adjuvant/neoadjuvant treatment modalities was focussed on, to characterise the disease for an optimally targeted treatment in conjunction with surgical removal of the tumour. The results of systemic and regional chemotherapy and radiotherapy, either alone or in combination, before, during and after surgery were critically analysed with respect to the oncological possibilities and pitfalls of each treatment method. Results: In two randomised trials, one testing postoperative radiochemotherapy (GITSG), and one postoperative chemotherapy, the adjuvant treatment achieved a significant prolongation of the median survival time. The 5-year and 10-year survival rates were improved in the GITSG study. The EORTC-GITCCG trial could not confirm the benefit of adjuvant radiochemotherapy. This study had a different design than the GITSG trial. Several historical control studies supported the beneficial effect of postoperative radiochemotherapy. In three historical control trials using regional chemotherapy, one with intraoperative radiotherapy , the survival times were improved compared with surgery alone. Intraoperative or postoperative radiotherapy as single modalities might reduce local relapses, but a survival advantage is still debated. Preoperative neoadjuvant radiochemotherapy has several advantages (downstaging, devitalising margins and lymph node metastases, compatibility of treatment vs. postoperative radiochemotherapy), and does not seem to increase the postoperative morbidity. Several trials have confirmed the feasibility of this concept, but no survival advantage has yet been proven. Systemic and regional chemotherapy is able to downstage primarily nonresectable pancreatic cancers. Conclusions: Postoperative adjuvant radiochemotherapy with up-to-date protocols can be recommended for routine treatment, if the surgeon or the patient desires to improve the usually remote prognosis after surgery alone. For those being indecisive or against adjuvant therapy, the participation in trials, e.g. the ESPAC 1 and 2 studies, is strongly recommended. Regarding our own positive experience with adjuvant regional chemotherapy and in view of the postresectional progression pattern, we currently favour adjuvant radiochemotherapy, with the chemotherapy delivered regionally via the celiac axis. This concept will be tested against surgery alone in the ESPAC 2 trial. Neoadjuvant therapies have a great potential, but should be conducted within studies, such as pre-, intra-, or postoperative radiotherapy.
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  • 7
    ISSN: 1435-2451
    Keywords: Key words Colorectal liver metastasis ; Surgery ; Regional chemotherapy ; Hepatic artery infusion ; Review
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Background: Cure is possible by resecting colorectal isolated liver metastases. In non-resectable isolated colorectal liver metastases (CRLM), regional chemotherapy has been advocated to optimize the disease control in the liver in order to improve the results of the alternative, systemic chemotherapy. The drugs are delivered by means of hepatic artery infusion (HAI) via ports or pumps; pharmacological modifications of the hepatic arterial blood-flow-like HAI with starch microspheres or stop-flow and perfusion techniques were applied to improve HAI. Methods: We reviewed the literature and report our progress, up to May 1999, in analyzing the validity of HAI for CRLM therapy. Results: In the majority of phase-II and -III trials, the response rates to HAI were significantly higher than those from systemic chemotherapy, and local disease control could be achieved even when HAI was used second line to systemic chemotherapy. The meta-analysis of randomized trials comparing HAI with either systemic chemotherapy (five trials) or, optionally, either 5-fluorouracil (FU) or symptomatic treatment (two trials) showed a significant advantage of HAI in response (41% vs 14%, P〈10–10) and median survival time (15 months vs 11 months, P〈0.0009). The active anabolite of 5-FU, 5-fluordeoxyuridine (5-FUDR), the drug of choice for HAI in those trials, may cause severe hepatotoxicity. To avoid this toxicity, we developed a HAI protocol using mitoxantrone, 5-FU plus folinic acid (FA) and mitomycin C (MFFM). The response rates of HAI with 5-FU plus FA or MFFM were 45% and 66%, the interim median survival times 19.8 months and 27.4 months. 5-Year survivors were observed in all our protocols. Since no severe hepatotoxicity occurred, 9 of 74 patients were resected after response to HAI with 5-FU plus FA or MFFM, without surgical mortality and with survival times from 2+ months to 58+ months. Conclusion: The high response rates, the long survival times, the possibility of achieving 5-year-survival either by HAI alone or by resection after down staging with HAI all sum up to the evidence that HAI could be the primary choice of treatment for CRLM. Phase-III trials are conducted to compare the protocols with optimal regional versus systemic chemotherapy.
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  • 8
    ISSN: 1435-2451
    Keywords: Key words Rectal cancer ; Local relapse ; Multimodal therapy ; Adjuvant radiotherapy ; Adjuvant radiochemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Local relapse is a major problem after potentially curative rectal cancer surgery. Although the incidence of local recurrences may be reduced by specialized surgical techniques such as total mesorectal excision (TME), local relapse rates of 20% or higher are the surgical reality today. Studies using adjuvant postoperative radiotherapy, chemotherapy, radiochemotherapy or immunotherapy have tried to reduce local relapse rates and distant progression. Postoperative radiochemotherapy has been the recommended standard, after complete resection of Union Internationale Contra la Cancrum (UICC) stages II and III rectal cancers. In view of recent positive results with preoperative radiotherapy of TME without adjuvant therapy, we found it important to review the literature to update the recommendable adjuvant procedure in rectal cancer. Method/Patients: The literature from 1985 to May 1998 was reviewed for studies trying to either confirm or improve adjuvant therapy in rectal cancer. Only randomized controlled trials were analyzed with regard to their effectiveness in reducing the absolute rates of local recurrence and improving survival. Results: Two trials applying adjuvant radiotherapy were able to demonstrate the reduction of local relapse rates, one trial with marginal significance, both without impact on survival. Four trials involving 1104 patients with rectal cancer stages UICC II–III compared postoperative radiochemotherapy with either surgical controls, adjuvant radiotherapy or conventional radiochemotherapy. In these trials, local relapse rates were significantly reduced by 11–18%, and survival rates significantly improved by 10–14%. Severe acute toxicities occurred in 50–61% of the patients, compromising compatibility, and caused death in 0–1%. Small-bowel obstruction leading to surgery was noted in 2–6% and to death in up to 2% of the patients. Intraoperative radiotherapy (IORT) improved local control and survival after surgery of locally advanced disease/local relapse. Conclusion: In view of four trials demonstrating a significant benefit of postoperative radiochemotherapy and with regard to recent still-debatable results of preoperative short-term radiotherapy optimal surgery with lowest local relapse rates plus postoperative radiochemotherapy remains the actual recommendable standard for rectal cancer surgery in R0 resected tumors stages UICC II+III.
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  • 9
    ISSN: 1435-2451
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
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  • 10
    Publication Date: 2018-07-17
    Description: Pancreatic neuroendocrine tumors (PanNETs) are rare in von Hippel–Lindau disease (VHL) but cause serious morbidity and mortality. Management guidelines for VHL-PanNETs continue to be based on limited evidence, and survival data to guide surgical management are lacking. We established the European-American-Asian-VHL-PanNET-Registry to assess data for risks for metastases, survival and long-term outcomes to provide best management recommendations. Of 2330 VHL patients, 273 had a total of 484 PanNETs. Median age at diagnosis of PanNET was 35 years (range 10–75). Fifty-five (20%) patients had metastatic PanNETs. Metastatic PanNETs were significantly larger (median size 5 vs 2 cm; P 〈 0.001) and tumor volume doubling time (TVDT) was faster (22 vs 126 months; P = 0.001). All metastatic tumors were ≥2.8 cm. Codons 161 and 167 were hotspots for VHL germline mutations with enhanced risk for metastatic PanNETs. Multivariate prediction modeling disclosed maximum tumor diameter and TVDT as significant predictors for metastatic disease (positive and negative predictive values of 51% and 100% for diameter cut-off ≥2.8 cm, 44% and 91% for TVDT cut-off of ≤24 months). In 117 of 273 patients, PanNETs 〉1.5 cm in diameter were operated. Ten-year survival was significantly longer in operated vs non-operated patients, in particular for PanNETs 〈2.8 cm vs ≥2.8 cm (94% vs 85% by 10 years; P = 0.020; 80% vs 50% at 10 years; P = 0.030). This study demonstrates that patients with PanNET approaching the cut-off diameter of 2.8 cm should be operated. Mutations in exon 3, especially of codons 161/167 are at enhanced risk for metastatic PanNETs. Survival is significantly longer in operated non-metastatic VHL-PanNETs.
    Print ISSN: 1351-0088
    Electronic ISSN: 1479-6821
    Topics: Medicine
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