Biomedical subjects
Publications and source records attributed to T J M Ruers.
A patient is presented who was treated with neoadjuvant oxaliplatin-based chemotherapy followed by hepatic resection complicated by fatal liver failure. Histopathological examination revealed hepatic veno-occlusive disease, which is an infrequent reported side effect of oxaliplatin.
A patient is presented with massive hematemesis caused by a fistula between the left cardiac atrium and a gastric tube interposition, which was constructed after esophagectomy for esophageal cancer 3 years earlier.
BACKGROUND: Selection of patients for hepatic resection of colorectal liver metastases is still limited. After conventional work up by computed tomography (CT) scan, 60% of patients will develop recurrent disease in the early years after resection. The aim of the present study was to evaluate whether an additional fluorine-18-deoxyglucose positron emission tomography (FDG-PET) improves patient selection and therefore adds value to select patients for curative liver resection. METHODS: Data from 203 patients selected for surgical treatment of colorectal liver metastases between 1995 and 2003 were collected in a prospective database. Group A consisted of 100 consecutive patients selected for hepatic surgery by conventional diagnostic imaging (CT chest and abdomen) only. Group B consisted of 103 consecutive patients selected for hepatic surgery by conventional diagnostic methods plus an additional FDG-PET. RESULTS: The number of patients with futile surgery, in which further treatment was considered inappropriate at laparotomy, was 28.0% in group A and 19.4% in group B. The reason for unresectable disease differed between groups. In group A, 10/100 (10.0%) patients showed extrahepatic abdominal disease versus 2/103 patients (1.9%) in group B (P = .017). In all other cases, resection was not performed because liver disease proved too extensive at laparotomy. For patients ultimately undergoing surgical treatment of the metastases, survival was comparable between groups. Overall survival at 3 years was 57.1% in group A versus 60.1% in group B. Disease-free survival at 3 years was 23.0% in group A and 31.4% in group B. CONCLUSIONS: In patients with colorectal liver metastases, FDG-PET may reduce the number of negative laparotomies. However, the effect size on the selection of these patients seems not sufficient enough to affect the overall and disease-free survival after treatment.
BACKGROUND: For patients with colorectal liver metastases, resection is the treatment of choice. Careful selection of these patients is crucial in order to reduce the chance of unexpected findings at laparotomy and abandoning further surgical intervention. Here, we evaluate the predictive value of CT and FDG-PET of the liver and extrahepatic findings compared to findings during laparotomy and 6 months follow-up. METHODS: 131 consecutive patients, selected for hepatic surgery for colorectal liver metastases by CT and FDG-PET, were evaluated prospectively. During surgery, the liver was assessed by intra-operative ultrasound, palpation and histology. RESULTS: In 127 patients (97%), CT was true-positive for liver metastases. In 3 patients, CT was false-positive and in 1 patient false-negative. In 126 patients (96%), FDG-PET was true-positive for liver metastases, in 2 patients FDG-PET was false-negative, in 3 patients true-negative (negative FDG-PET, false-positive CT). At laparotomy a total of 363 liver metastases was identified: 63 lesions <10 mm [10 (16%) detected by both CT and FDG-PET], 172 lesions of 10-20 mm [123 (72%) CT-positive, 129 (75%) by FDG-PET-positive], and 28 lesions >20 mm [124 (97%) CT-positive, 121 (95%) FDG-PET-positive]. CT and FDG-PET missed approximately 30% of the smaller liver lesions, resulting in a significant change in clinical management during surgery in only nine patients. CONCLUSIONS: CT and FDG-PET have a similar diagnostic yield for the identification of liver metastases; both modalities being adequate on a patient-basis but inadequate to detect the smallest of liver lesions. However, the clinical relevance of the latter is limited.
Dendritic cells (DC) are professional antigen-presenting cells that play a pivotal role in the induction of immunity. Ex vivo-generated, tumour antigen-loaded mature DC are currently exploited as cancer vaccines in clinical studies. However, antigen loading and maturation of DC directly in vivo would greatly facilitate the application of DC-based vaccines. We formerly showed in murine models that radiofrequency-mediated tumour destruction can provide an antigen source for the in vivo induction of anti-tumour immunity, and we explored the role of DC herein. In this paper we evaluate radiofrequency and cryo ablation for their ability to provide an antigen source for DC and compare this with an ex vivo-loaded DC vaccine. The data obtained with model antigens demonstrate that upon tumour destruction by radiofrequency ablation, up to 7% of the total draining lymph node (LN) DC contained antigen, whereas only few DC from the conventional vaccine reached the LN. Interestingly, following cryo ablation the amount of antigen-loaded DC is almost doubled. Analysis of surface markers revealed that both destruction methods were able to induce DC maturation. Finally, we show that in situ tumour ablation can be efficiently combined with immune modulation by anti-CTLA-4 antibodies or regulatory T-cell depletion. These combination treatments protected mice from the outgrowth of tumour challenges, and led to in vivo enhancement of tumour-specific T-cell numbers, which produced more IFN-gamma upon activation. Therefore, in situ tumour destruction in combination with immune modulation creates a unique, 'in situ DC-vaccine' that is readily applicable in the clinic without prior knowledge of tumour antigens.
BACKGROUND: The current study focuses on the prognostic value of pretreatment metabolic activity in metastases as measured with [(18)F]fluorodeoxyglucose positron emission tomography (FDG-PET), as an indicator of survival in colorectal cancer. PATIENTS AND METHODS: In a prospective series of 152 patients with metastatic colorectal cancer, of whom 67 were treated with resection of metastases and 85 with chemotherapy, standardized uptake values (SUV) as measured with FDG-PET, were calculated prior to treatment. Survival probabilities were estimated by Cox proportional regression analysis. For Kaplan-Meier analysis SUV was stratified by the median value. Survival differences were assessed using the log-rank test. RESULTS: SUV in metastases was a significant predictor for overall survival (hazard ratio 1.17, 95% confidence interval 1.06-1.30, P = 0.002), independent of the subsequent treatment. According to the median value of the patient population a low (SUV <4.26) and high uptake group (SUV >4.26) was defined. The median survival and the 2- and 3-year survival rates were 32 months, 59% and 45%, respectively, in the low-uptake group and 19 months, 37% and 28%, respectively, in the high-uptake group (P = 0.017). CONCLUSION: A significant survival benefit was observed in patients with low FDG uptake in metastases of colorectal cancer.
BACKGROUND: The surgical approach to colorectal liver metastases is becoming increasingly aggressive. The aim of this prospective study was to evaluate the impact of surgery on health-related quality of life (HRQoL) of patients with colorectal liver metastases. METHODS: HRQoL data from 97 patients with colorectal liver metastases were analysed. Sixty patients (group 1) had surgical treatment of the liver metastases. Seventeen patients (group 2) were shown to have inoperable disease at laparotomy. Twenty outpatients with inoperable disease were included as a control group (group 3). Two validated HRQoL instruments, the European Organization for Research and Treatment of Cancer Core questionnaire (QLQ C-30) and the EuroQol-5D, were applied. RESULTS: By 2 weeks after operation patients in group 1 showed a clear overall deterioration in HRQoL, but after 3 months most HRQoL scores had returned to baseline levels. At 2 weeks after surgery there was clear deterioration in almost all HRQoL domains in group 2, and several symptoms were still being reported at 3 months. Patients in group 3 showed hardly any deterioration in HRQoL over the 3 months. CONCLUSION: The fast recovery of HRQoL, generally within 3 months, justifies an aggressive surgical approach to colorectal liver metastases. However, careful preoperative evaluation is crucial to avoid needless laparotomy, considering the ongoing deteriorated HRQoL of group 2.
Resection should still be considered the gold standard for many liver tumours. There is, however, growing interest in the use of radiofrequency (RFA) for the treatment of liver tumours. By RFA, tumour tissue can be destructed selectively without significant damage to vascular structures in the remaining liver. The technique is safe and feasible for many types of liver tumours. RFA appears to be beneficial in the treatment of hepatocellular carcinoma. In the Netherlands, single-centre reports suggest that RFA may be used successfully to control hepatocellular carcinoma in those patients awaiting liver transplantation. RFA is being increasingly used for colorectal liver metastases as an adjunct to surgical resection in case of unresectable lesions. However, to date, there are still no data showing that such an approach is beneficial. For this reason, in the Netherlands, RFA for unresectable colorectal liver metastases is mainly used within a clinical trial. Within the multimodality treatment of neuroendocrine metastases, RFA may deserve a place for either intention to cure (rare) or debulking with the aim of reduction of symptoms or prolongation of life.
BACKGROUND: In 50-60 per cent of patients who undergo hepatic resection for metastasis of colorectal cancer the first site of tumour recurrence is extrahepatic, indicating the presence of more extensive disease at the time of resection. The aim of this study was to evaluate whether the presence of disseminated tumour cells in blood and bone marrow could predict extrahepatic tumour recurrence. METHODS: Cytokeratin 20 (CK20) reverse transcriptase-polymerase chain reaction was used to study the presence of tumour cells in preoperative peripheral blood and bone marrow samples from 41 patients with liver metastasis scheduled for surgical resection. RESULTS: CK20 expression was detected in six of 41 peripheral blood samples and in eight of 32 bone marrow samples. There was no correlation between CK20-positive samples and subsequent extrahepatic recurrence. Positive blood samples did, however, correlate with high serum carcinoembryonic antigen level and large tumour volume. None of the 14 patients previously treated with chemotherapy had CK20-positive samples, whereas six of 27 blood and eight of 20 bone marrow samples were positive in the chemotherapy-naive group. CONCLUSION: Although the number of patients in this study is limited, the presence of disseminated tumour cells did not predict subsequent extrahepatic recurrence. The results strongly suggest that the presence of circulating tumour cells in peripheral blood may reflect transient shedding of tumour cells related to large tumour volume.
AIM: We report the value of sentinel lymph node (SLN) biopsy and fluorodeoxyglucose-positron emission tomography (FDG-PET) in relation to SLN biopsy in staging primary cutaneous melanoma. METHODS: Fifty-five patients with primary cutaneous melanoma >1.0 mm. Breslow thickness and no palpable regional lymph nodes underwent a FDG-PET scan before SLN biopsy. RESULTS: SLN's were retrieved in 53 patients. Melanoma metastases were found in the SLN of 13 patients. FDG-PET detected the lymph node metastases in two of the 13 patients with SLN metastases. In five patients FDG accumulation was recorded in a regional lymph node basin, while no tumour positive SLN was found. In eight patients FDG-PET showed increased activity at a site of possible distant metastasis. Metastatic disease was confirmed in one patient. No explanation for the positive FDG-PET result could be found in five cases. CONCLUSION: FDG-PET should not be considered in this group. SLN biopsy reveals regional metastases that are too small to be detected by FDG-PET. The prevalence of distant metastases is too small to justify routine use of FDG-PET.
AIMS: The Mitotic Activity Index (MAI) is a strong prognostic factor for disease free survival in breast cancer. The MAI is lower in screen detected tumours, correlating with less aggressive biological behaviour in this group. In this study the MAI is compared between screen detected, interval and symptomatic breast cancers. METHODS: Between 1991 and 1999, the MAI was determined in 581 breast cancers, 160 were detected by screening, 66 were interval carcinomas, and 355 were symptomatic breast cancers. Other prognostic factors were also registered. RESULTS: The interval group had a significantly higher median MAI (17-18, range 1-134) than the screen detected group (7-8, range 0-94,P <0.0001). There was no difference with the symptomatic group (MAI 15, range 0-149,P =0.92). CONCLUSIONS: Interval cancers had an intermediate outcome when correlated with other prognostic factors, compared to screen detected and symptomatic cancers.
Currently-used systems to predict prognosis in patients with solid epithelial tumours after surgical resection of the tumour do not give any guarantees for the individual patient. In this respect the clinical relevance of the presence of disseminated tumour cells in blood and bone marrow has been frequently studied. Because of growing awareness that information on merely the presence of disseminated tumour cells is not sufficient for prognostic and therapeutic purposes, attention for characterization of disseminated tumour cells has increased. Numerous reviews have already been published on the detection and clinical relevance of disseminated tumour cells. Therefore, this paper will mainly focus on the biological significance of these cells and discusses the (in)efficiency of the metastatic process, the genotypic and phenotypic characteristics of disseminated tumour cells, and their structure of appearance. Despite the fact that information gained on the several individual aspects is substantial, it did not render any solid solutions for individual patient management yet. Hence, a combined approach of several aspects of disseminated tumour cells together with characteristics and behaviour of the primary tumour is needed to substantially improve our knowledge on the role of disseminated tumour cells in the complex process of tumour metastasis.
PURPOSE: The aims of this prospective study were to investigate the potential role of fluorine-18-deoxyglucose (FDG) positron emission tomography (PET) in determining the efficacy of the local tumor ablative process and to determine the added value of FDG-PET in the detection of tumor recurrence during follow-up. PATIENTS AND METHODS: Twenty-three patients with unresectable colorectal liver metastases were followed up after local ablative therapy consisting of a standard protocol including FDG-PET scanning, computed tomography (CT) scanning, and carcinoembryonic antigen measurements. The mean follow-up period was 16 months (range, 10 to 21 months). RESULTS: Ninety-six lesions was treated, 56 by local ablative treatment. Within 3 weeks after local ablative treatment, 51 lesions became photopenic on FDG-PET, while five lesions (in five patients) showed persistent activity on FDG-PET. In four of five FDG-PET-positive lesions, a local recurrence developed during follow-up; one FDG-PET-positive lesion turned out to be an abscess. None of the FDG-PET-negative lesions developed a local recurrence during a mean follow-up period of 16 months. During follow-up, 11 patients showed recurrence in the liver outside of the treated area. In all cases, previously negative FDG-PET scans became positive. Extrahepatic recurrence was encountered in nine patients during follow-up; FDG-PET showed all nine cases of tumor recurrence. There was one false-positive FDG-PET caused by an intra-abdominal abscess. In all patients, the time point of detection of recurrence by FDG-PET was considerably earlier than the detection by CT. CONCLUSION: FDG-PET seems to have a significant impact in measuring treatment efficacy directly after local ablative therapy. Furthermore, FDG-PET has an added value in patient follow-up because it reveals recurrences earlier than conventional diagnostic modalities.
Liver cryosurgery is one of the treatment options for unresectable liver metastases. Indications for the use of this treatment instead of classic surgery are bilobar disease, location of the tumor at an irresectable anatomic site, and comorbid conditions of the patient. Possible complications of cryosurgery are hemorrhage, coagulopathy, pneumonia, pleural effusion, abdominal abscess, and bile fistula. We describe a patient in whom a hepatobronchial fistula developed after cryosurgery. The patient had cryosurgery because of an unresectable liver metastasis in a Dukes' C rectal carcinoma. More details are given in the case report. To our knowledge, a hepatobronchial fistula as a complication of cryosurgery has never been reported. It therefore should be added to the list of possible cryosurgery complications.
PURPOSE: To assess prospectively the value of fluor-18-deoxyglucose (FDG) positron emission tomography (PET), in addition to conventional diagnostic methods (CDM), as a staging modality in candidates for resection of colorectal liver metastases. PATIENTS AND METHODS: In 51 patients analyzed for resection of colorectal liver metastases, clinical management decisions were recorded after a complete work-up with CDM. Afterward, FDG-PET scans were performed and any change of clinical management according to FDG-PET results was carefully documented. Discordances between FDG-PET and CDM results were identified and related to the final diagnosis by histopathology, intraoperative findings, and follow-up. RESULTS: In 10 (20%) out of 51 patients, clinical management decisions based on CDM were changed after FDG-PET findings were known. FDG-PET detected unresectable pulmonary (n = 5) and hepatic metastases (n = 1) and ruled out extrahepatic (n = 2) and hepatic disease (n = 2). Due to FDG-PET, eight patients were spared unwarranted liver resection or laparotomy and two other patients were identified as candidates for liver resection. When the results of FDG-PET were regarded as decisive in a retrospective analysis, potential change of management was 29% (15 patients). FDG-PET and CDM showed discordant extrahepatic results in 11 patients (22%) and discordant hepatic results in eight patients (16%). Compared with CDM, FDG-PET resulted in true upstaging (n = 11), true downstaging (n = 5), false upstaging (n = 1), and false downstaging (n = 2). The detection rate of liver metastases on a lesion basis was generally better for computed tomography than for FDG-PET (80% v 65%); this was related to tumor size. CONCLUSION: FDG-PET as a complementary staging method improves the therapeutic management of patients with colorectal liver metastases, especially by detecting unsuspected extrahepatic disease.
It is the purpose of this study to investigate whether breast cancer in patients with a positive family history is detected at an earlier stage with better prognostic markers than breast cancer in patients without a positive family history. In 481 patients, tumour size, tumour type, lymph vessel invasion, blood vessel invasion, receptor state, lymphatic spread, mitotic activity index (MAI) and survival were measured and compared, according to their family history. No difference was found between patients without a family history, patients with first-degree relatives or patients with second-degree relatives with breast cancer. Tumours were detected in the same stages and prognostic factors, MAI and survival were similar in all groups. A positive family history of breast cancer does not lead to earlier detection of breast cancer or a better survival.
AIMS: Despite informative staging of patients with colorectal cancer, some patients with localised disease at diagnosis will develop recurrence or metastasis. Attempts to improve staging include sensitive detection of disseminated tumour cells in blood and bone marrow by reverse transcriptase polymerase chain reaction (RT-PCR). The results of this study have been considered in relation to the controversial results in the literature to elucidate the usefulness of cytokeratin 20 (CK20) RT-PCR to detect disseminated tumour cells further. PATIENTS/METHODS: Blood and bone marrow samples from 30 patients with colorectal cancer were studied by CK20 RT-PCR. Specificity was evaluated in 47 blood and 15 bone marrow samples from non-cancer controls. In addition, the expression of CK20 mRNA and protein was studied in normal and tumour colon tissue samples. RESULTS: CK20 expression was detected in nine of 30 and nine of 19 of the blood and bone marrow samples from patients with colorectal cancer, respectively. In non-cancer control blood and bone marrow samples, CK20 expression was detected in 10 of 47 and four of 15, respectively. A difference between patient and control samples may be observed in terms of frequency of positive PCR tests. In tissue samples, CK20 mRNA expression was downregulated in tumour compared with normal colon tissue. CONCLUSIONS: CK20 expression was downregulated in tumour tissue compared with normal colon and a background expression of CK20 was seen in some control blood and bone marrow samples. Despite a lack of standardisation (which hampers comparison of studies), these results, together with other reports in the literature, suggest that CK20 may still be a suitable marker, but that background expression and threshold setting should be studied further.
BACKGROUND: In order to develop a multi-marker RT-PCR, which as such may be more sensitive than a single marker assay for the detection of disseminated tumor cells, we evaluated six RT-PCR markers: cytokeratin 20 (CK20), carcinoembryonic antigen (CEA), guanylyl cyclase C (GCC), epidermal growth factor receptor (EGFR), matrilysin (MMP-7) and HeLa metastatic gene (HLM). MATERIALS AND METHODS: The expression was studied in human colon tumor cell lines, in colon cancer tissues, and in blood and/or bone marrow samples of colorectal cancer patients and control subjects. RESULTS: The cell lines showed a differential expression pattern. The expression of all markers was detected in control blood samples with the lowest frequency for CK20 and EGFR. Semiquantitative analysis, which was performed to study threshold setting, demonstrated that GCC expression was elevated in patient compared to control samples. However, the reproducibility was questionable. CONCLUSION: The results presented in this study suggest an enhanced sensitivity for a combination of RT-PCR markers. Due to limited specificity however, the development of a multi-marker RT-PCR by using conventional PCR does not seem feasible. Future studies should focus on the potential of quantitative RT-PCR.