OS exceeds by far reported outcome for chemotherapy, which is the only treatment option available for this patient group. Furthermore, OS is comparable with liver resection for resectable CLMs and survival after repeat liver transplantation for nonmalignant diseases. Selection strategies based on prognostic factors may further improve the outcome (ClinicalTrials.gov: NCT01311453).
Background. Surgical resection is the only curative modality for colorectal liver metastases (CLM), and the pattern of recurrences after resection affects survival. In a prospective study of liver transplantation (Lt) for nonresectable CLM we have shown a 5-year overall survival rate of 60 %, but 19 of 21 experienced recurrence. This study reports the pattern of recurrences after Lt for CLM and the effect on survival. Methods. Characterization of metastatic lesions in a prospective study for Lt for nonresectable CLM was performed (n = 21). The study included reexamination of chest computed tomographic scans taken before Lt. Results. At the time of first recurrence, 16 were a single site, and three were multiple sites. Thirteen of the single sites were pulmonary recurrences. The pulmonary recurrences appeared early and were slow growing, and several were accessible to surgical treatment. When chest computed tomographic scans were reexamined, seven patients had pulmonary nodules at the time of Lt without an effect on survival. There was no first single-site hepatic recurrence. Six of the seven patients who developed metastases to the transplanted liver died from metastatic disease. Conclusions. The pulmonary recurrences after Lt for CLM were of an indolent character, even those that were present at the time of Lt. This contrasts with the finding of metastases to the transplanted liver, which was prognostically adverse. The lack of single hepatic first-site recurrences and hepatic metastases only as part of disseminated disease is different from the pattern of recurrence after liver resection. This suggests two distinct mechanisms for hepatic recurrences after resection for CLM.Chemotherapy as the sole treatment of colorectal liver metastases (CLM) is palliative only, and the 5-year overall survival (OS) after the start of first-line chemotherapy is approximately 10 %.1 Surgical treatment of CLM is potentially curative, and the median 5-year OS is 38 %, ranging from 16 to 74 %.2 Recurrence after liver resection for CLM happens in 60-70 % of the patients.3-5 The first site of recurrence is most frequently liver only (28-45 %), followed by lung only (17-27 %), multiple sites (28-30 %), and locoregional or other single sites (9-12 %). 3,4,[6][7][8] Recently there have been several reports on the effect of the pattern of the first site of recurrence on outcome after liver resection for CLM. Not surprisingly, the survival is better for single-site recurrences than for multiple sites. 6,9 In a recent report from Memorial Sloan-Kettering Cancer Center (MSKCC), the best outcome after single-site lung metastases was demonstrated, and survival after single-site hepatic recurrences was placed in between that after pulmonary and multiple-site recurrences. 6 Other reports show no difference in survival between lung and liver recurrences. 7,9 CLM is currently regarded as a contraindication for liver transplantation (Lt). However, in a prospective study on Lt for nonresectable CLM (n = 21), we showed a 5-year OS of 60 % (...
Patients treated by LT for unresectable CLM have a good prognosis following resection of pulmonary metastases. Doubling time did not appear to be worse with the immunosuppression used after LT.
In a pilot phase 1/11 study we have tested synthetic ras peptides used as a cancer vaccine in 5 patients with advanced pancreatic carcinoma. The treatment principle used was based on loading professional antigen-presenting cells (APCs) from peripheral blood with a synthetic ras peptide corresponding to the ras mutation found in tumour tissue from the patient.Peptide loading was performed ex vivo and the next day APCs were re-injected into the patients after washing to remove unbound peptide. Patients were vaccinated in the first and second week and thereafter every 4-6 weeks. In 2 of the 5 patients treated, an immune response against the immunising ras peptide could be induced. None of the patients showed evidence of a T-cell response against any of the ras peptides before vaccination. The treatment was well tolerated and could be repeated multiple times in the same patient. Side effects were not observed even if an immunological response against the ras peptide was evident. We conclude that ras peptide vaccination according to the present protocol is safe and may result in a potentially beneficial immune response even in patients with advanced malignant disease.o 1996 Wiley-Liss, Inc.Pancreatic adenocarcinoma carries a poor prognosis. Most patients are biologically or technically inoperable when diagnosed. For these patients there is no effective radiation or chemotherapy option available, and median survival time is only 3 4 months (Warshaw and Fernandez-del Castillo, 1992). New treatment approaches of advanced pancreatic cancer are urgently needed. Ras genes carrying mutations at specific positions have been identified in up to 90% of pancreatic adenocarcinomas (Alrnoguera et al., 1988). The spectrum of mutations is limited and confined to position 12 of the m s oncogene in pancreatic adenocarcinoma (Capella et al., 1991). The human immune system has the potential to recognise cells expressing such rus mutations (Fossum et al., 1995).We have previously shown that different human lymphocyte antigen (HLA) molecules can bind ras peptides and present them to T cells, thereby initiating an immune response (Fossum et al., 1993;Gedde-Dahl et al., 1994b). T cells from both healthy individuals (Jung and Schluesener, 1991) and cancer patients (Gedde-Dahl et al., 199%;Fossum et al., 1994) specifically recognise mutant p21 ras and corresponding peptides. The effector cells involved in this recognition are T helper (CD4+) and cytotoxic (CD8+) T cells. Both of these T-cell subsets are able to specifically kill or inhibit growth of colon cancer cell lines presenting the corresponding ras mutation (Gedde-Dahl et al., Fossum et al., 1995). Together these findings demonstrate that the T-cell repertoire in both healthy individuals and cancer patients contain T cells capable of recognising the same seh of common mutant ras peptides. The purpose of vaccination is therefore to selectively expand these T cells in cancer patients.These observations formed the basis for the present pilot clinical study, where peptide loaded professi...
Quantitative spirometrically controlled computed tomography (with 1-mm-thick sections) was performed twice (with a 5-minute break) in 24 adult patients with pulmonary disease to objectively evaluate parenchymal changes in the lung. Twelve measurements of attenuation were made on apical, carinal, and basal scans (right, left, total of each level, total right, total left, total of all three scans), obtained at 50% vital capacity. Since differences in measurements between the first and second examination were not significant, the method provides highly reproducible results.
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