Verhoef, C.

KRAS and BRAF mutation status in circulating colorectal tumor cells and their correlation with primary and metastatic tumor tissue (Article)

2013-07-01T00:00:00Z

Although anti-EGFR therapy has established efficacy in metastatic colorectal cancer, only 10-20% of unselected patients respond. This is partly due to KRAS and BRAF mutations, which are currently assessed in the primary tumor. To improve patient selection, assessing mutation status in circulating tumor cells (CTCs), which possibly better represent metastases than the primary tumor, could be advantageous. We investigated the feasibility of KRAS and BRAF mutation detection in colorectal CTCs by comparing three sensitive methods and compared mutation status in matching primary tumor, liver metastasis and CTCs. CTCs were isolated from blood drawn from 49 patients before liver resection using CellSearch™. DNA and RNA was isolated from primary tumors, metastases and CTCs. Mutations were assessed by co-amplification at lower denaturation temperature-PCR (Transgenomic™), real-time PCR (EntroGen™) and nested Allele-Specific Blocker (ASB-)PCR and confirmed by Sanger sequencing. In 43 of the 49 patients, tissue RNA and DNA was of sufficient quantity and quality. In these 43 patients, discordance between primary and metastatic tumor was 23% for KRAS and 7% for BRAF mutations. RNA and DNA from CTCs was available from 42 of the 43 patients, in which ASB-PCR was able to detect the most mutations. Inconclusive results in patients with low CTC counts limited the interpretation of discrepancies between tissue and CTCs. Determination of KRAS and BRAF mutations in CTCs is challenging but feasible. Of the tested methods, nested ASB-PCR, enabling detection of KRAS and BRAF mutations in patients with as little as two CTCs, seems to be superior. What's new? Circulating tumor cells (CTCs) are present in the blood stream of patients with metastatic colorectal cancer and provide the opportunity to characterize tumor cells without biopsy. The authors isolated CTCs to assess the status of KRAS and BRAF mutations, which severely limit effectiveness of anti-EGFR therapies. The analysis was challenged by the presence of more than 1,000 leukocytes in CTC-enriched fractions, but was successful in detecting mutations in as little as two CTCs when a specific, nested Allele-Specific Blocker PCR strategy was employed. These results underscore the potential of CTC analysis as an alternative to commonly used invasive approaches to test patients for mutations repeatedly during the course of the disease and treatment. Copyright

Increased alpha-fetoprotein serum level is predictive for survival and recurrence of hepatocellular carcinoma in non-cirrhotic livers (Article)

2013-04-01T00:00:00Z

Background: Hepatocellular carcinoma (HCC) may be diagnosed in the absence of cirrhosis. However, little is known about prognostic factors for the survival of HCC patients with a non-cirrhotic liver in the absence of well-established risk factors. Method: Survival rates and risk factors for survival and recurrence were analysed in all patients diagnosed between 2000 and 2010 with HCC in a non-cirrhotic liver and in the absence of well-established risk factors. Results: Ninety-four patients were analysed. Treatment with curative intent consisted of surgical resection in 43 patients (46%) and radiofrequency ablation in 4 patients (4%). In patients treated with curative intent and alive 30 days after treatment (n = 40), 1-and 5-year overall survival rates were 95 and 51%, respectively. Patients with a high preoperative α-fetoprotein (AFP) serum level, the presence of microvascular invasion in the resected specimen, a complicated postoperative course and a major resection, due to a greater tumour volume, had a significantly worse outcome and a higher recurrence rate. In multivariate analysis, a high AFP serum level at presentation was significantly associated with recurrence and a worse survival. Conclusion: HCC presenting in a non-cirrhotic liver in the absence of well-established risk factors has a poor prognosis. Increased AFP serum levels are significantly associated with clinical outcome.

Recently introduced biomarkers for screening of hepatocellular carcinoma: A systematic review and meta-analysis (Article)

2013-01-01T00:00:00Z

Purpose: Early detection of hepatocellular carcinoma (HCC) is essential for improved prognosis and long-term survival. To date, screening for HCC depends on serological testing (alpha-fetoprotein, AFP) and imaging (ultrasonography), both of which are not highly sensitive. A meta-analysis was performed to discuss recent developments in biomarkers that may be effective in screening for HCC. Methods: A systematic search of PubMed, Embase, and Web of Science was performed for articles published between January 2005 and October 2010, and focusing on biomarkers for HCC in urine, serum, or saliva. Data on sensitivity and specificity of tests were extracted from each included article and displayed with a summary ROC. A meta-analysis was carried out in which the area under the curve for each biomarker was used to compare the accuracy of different tests. Results: In seven well-defined studies, three biomarkers were identified for potential use, namely, Golgi protein 73 (GP73), interleukin-6 (IL-6), and squamous cell carcinoma antigen (SCCA). Comparison with AFP showed that GP73 was superior (p = 0.006; 95 % CL -0.23, -0.12), IL-6 was similar (p = 0.66; 95 % CL -0.31, 0.25), and SCCA was inferior to AFP (p = 0.001; 95 % CL 0.12, 0.23). Conclusion: GP73 is a valuable serum marker that seems to be superior to AFP and can be useful in the diagnosis and screening of HCC. Although GP73 may improve the detection and treatment of one of the most common malignancies worldwide, additional research is required.

Hepatocellular adenoma as a risk factor for hepatocellular carcinoma in a non-cirrhotic liver: A plea against (Article)

2012-11-01T00:00:00Z

Prognosis in patients with sentinel node-positive melanoma without immediate completion lymph node dissection (Article)

2012-10-01T00:00:00Z

Background: The therapeutic value of immediate completion lymph node dissection (CLND) for sentinel node (SN)-positive melanoma is unknown. The aim of this study was to evaluate the impact of immediate CLND on the outcome of patients with SN-positive melanoma. Methods: Patients with SN metastases treated between 1993 and 2008 at ten cancer centres from the European Organization for Research and Treatment of Cancer Melanoma Group were included in this retrospective study. Maximum tumour size, intranodal location and penetrative depth of SN metastases were measured. Outcome in those who had CLND was compared with that in patients who did not undergo completion lymphadenectomy. Results: Of 1174 patients with SN-positive melanoma, 1113 (94·8 per cent) underwent CLND and 61 (5·2 per cent) did not. Median follow-up for the two groups was 34 and 48 months respectively. In univariable survival analysis, CLND did not significantly influence disease-specific survival (hazard ratio (HR) 0·89, 95 per cent confidence interval 0·58 to 1·37; P = 0·600). However, patients who did not undergo CLND had more favourable prognostic factors. Matched-pair analysis, with matching for age, Breslow thickness, tumour ulceration and SN tumour burden, showed that CLND had no influence on survival (HR 0·86, 0·46 to 1·61; P = 0·640). After adjusting for prognostic factors in multivariable survival analyses, no difference in survival was found. Conclusion: In these two cohorts of patients with SN-positive melanoma and prognostic heterogeneity, outcome was not influenced by CLND. Copyright

Trends in incidence, treatment and survival of patients with stage IV colorectal cancer: A population-based series (Article)

2012-01-01T00:00:00Z

Aim The incidence, patterns of care and survival were determined in patients with stage IV colorectal cancer (CRC) in a population-based series. Method Computer records for patients diagnosed with stage IV CRC diagnosed from 1 January 1995 to 31 December 2007 were retrieved from the Rotterdam Cancer Registry. Surgical resection of the primary tumour, chemotherapy use, hepatic surgery and survival were evaluated according to year of diagnosis, age, gender and primary tumour site. Results In the southwestern part of the Netherlands, 19014 new patients with CRC were diagnosed and synchronous metastatic disease was found in 3482 (18%). This proportion increased during the study period, from 16% to 21%. Surgical resection of the primary tumour was performed in approximately 50% of the patients and did not change over time. Postoperative 30-day mortality was 8%. Chemotherapy use increased from 18% in the first period to 56% in the latest period. Liver surgery increased from 4% in the first period to 10% in the latest period. Median survival increased from 7months to 12months and 2-year survival increased from 14% to 28%. Two-year survival declined with increasing age and was significantly worse for right-sided tumours (14%). Conclusion Survival of patients with stage IV CRC has improved over time and this is probably a result of the increased use of chemotherapy and the increased numbers of patients who underwent hepatic surgery. © 2011 The Authors. Colorectal Disease

Long-term outcome of isolated limb perfusion with tumour necrosis factor-α for patients with melanoma in-transit metastases (Article)

2011-11-01T00:00:00Z

Background: The use of tumour necrosis factor (TNF) α in isolated limb perfusion (ILP) for in-transit melanoma metastasis is not uniformly accepted. This article reports the long-term results of adding TNF-α to standard melphalan-based ILP (TM-ILP) for treatment of melanoma in-transit metastases. Methods: Data for patients treated between 1991 and 2005 were retrieved from a prospectively maintained database. Hyperthermic ILP was performed with 1-4 mg TNF-α. With a median potential follow-up of 13 years, response rates, time to local progression and disease-specific survival were analysed in relation to standard baseline factors. Results: Some 118 TM-ILPs were analysed in 105 patients, 54 for stage IIIA, 50 for stage IIIAB and 14 for stage IV disease. The overall response rate was 93·2 per cent; the response was complete in 67·8 per cent and partial in 25·4 per cent. The response rate was significantly influenced by stage of disease (IIIA versus IIIAB; P = 0·006). The complete response was maintained until the end of follow-up in 35 patients (33·3 per cent), and local control was achieved with one additional intervention in 12 others (11·4 per cent). Local progression occurred after 66 ILPs (55·9 per cent). Number of in-transit metastases (P = 0·008) and complete response after ILP (P < 0·001) were strong prognostic factors for time to local progression. The 5-year disease-specific survival rate was 27·3 per cent; survival was positively influenced by age, stage of disease, previous ILP and complete response after ILP. Conclusion: ILP with TNF-α may obtain long-term local control in selected patients with in-transit metastases from melanoma. Copyright

Long-term results of tumor necrosis factor α- and melphalan-based isolated limb perfusion in locally advanced extremity soft tissue sarcomas (Article)

2011-10-20T00:00:00Z

Purpose: Because there is no survival benefit of amputation for extremity soft tissue sarcomas (STSs), limb-sparing surgery has become the gold standard. Tumor size reduction by induction therapy to render nonresectable tumors resectable or facilitate function-preserving surgery can be achieved by tumor necrosis factor α (TNF) -based and melphalan-based isolated limb perfusion (TM-ILP). This study reports the long-term results of 231 TM-ILPs for locally advanced extremity STS. Patients and Methods: We analyzed 231 TM-ILPs in 208 consecutive patients (1991 to 2005), who were all candidates for functional or anatomic amputation for locally advanced extremity STS. All patients had a potential follow-up of up to 5 years. TM-ILP was performed under mild hyperthermic conditions with 1 to 4 mg of TNF and 10 to 13 mg/L of limb-volume melphalan. Almost all patients (85%) had intermediate- or high-grade tumors. Results: The overall response rate (ORR) was 71% (complete response, 18%; partial response, 53%). Multifocal sarcomas had a significantly better ORR of 83% (P = .008). The local recurrence rate was 30% (n = 70); local recurrence rates were highest for multifocal tumors (54%; P = .001) and after previous radiotherapy (54%; P<.001). Five-year overall survival rate was 42%. Survival was poorest in patients with large tumors (P = .01) and with leiomyosarcomas (P < .001). Limb salvage rate was 81%. Conclusion: We demonstrated that TM-ILP results in a limb salvage rate of 81% in patients with locally advanced extremity STS who would otherwise have undergone amputation. Whenever an amputation is deemed necessary to obtain local control of an extremity STS, TM-ILP should be considered.

Outcome of Microscopic Incomplete Resection (R1) of Colorectal Liver Metastases in the Era of Neoadjuvant Chemotherapy (Article)

2011-10-17T00:00:00Z

Background: Data from patients with colorectal liver metastases (CRLM) who received neoadjuvant chemotherapy before resection were reviewed and evaluated to see whether neoadjuvant chemotherapy influences the predictive outcome of R1 resections (margin is 0 mm) in patients with CRLM. Methods: Between January 2000 and December 2008, all consecutive patients undergoing liver resection for CRLM were analyzed. Patients were divided into those who did and did not receive neoadjuvant chemotherapy. The outcome after R0 (tumor-free margin >0 mm) and R1 (tumor-free margin 0 mm) resection was compared. Results: A total of 264 were eligible for analysis. Median follow-up was 34 months. Patients without chemotherapy showed a significant difference in median disease-free survival (DFS) after R0 or R1 resection: 17 [95% confidence interval (CI) 10-24] months versus 8 (95% CI 4-12) months (P < 0.001), whereas in patients with neoadjuvant chemotherapy the difference in DFS between R0 and R1 resection was not significant: 18 (95% CI 10-26) months versus 9 (95% CI 0-20) months (P = 0.303). Patients without chemotherapy showed a significant difference in median overall survival (OS) after R0 or R1 resection: 53 (95% CI 40-66) months versus 30 (95% CI 13-47) months (P < 0.001). In patients with neoadjuvant chemotherapy, the median OS showed no significant difference: 65 (95% CI 39-92) months for the R0 group versus the R1 group, in whom the median OS was not reached (P = 0.645). Conclusions: In patients treated with neoadjuvant chemotherapy, R1 resection was of no predictive value for DFS and OS.

Is the clinical risk score for patients with colorectal liver metastases still useable in the era of effective neoadjuvant chemotherapy? (Article)

2011-10-01T00:00:00Z

Background: Several clinical risk scores (CRSs) for the outcome of patients with colorectal liver metastases have been validated, but not in patients undergoing neoadjuvant chemotherapy. Therefore, this study evaluates the predictive value of these CRSs in this specific group. Methods: Between January 2000 and December 2008, all patients undergoing a metastasectomy were analyzed and divided into two groups: 193 patients did not receive neoadjuvant chemotherapy (group A), and 159 patients received neoadjuvant chemotherapy (group B). In group B, the CRSs were calculated before and after administration of neoadjuvant chemotherapy. Results were evaluated by using the CRSs proposed by Nordlinger et al., Fong et al., Nagashima et al., and Konopke et al. Results: In groups A and B, the overall median survival was 43 and 47 months, respectively (P = 0.648). In group A, all CRSs used were of statistically significant predictive value. Before administration of neoadjuvant chemotherapy, only the Nordlinger score was of predictive value. After administration of neoadjuvant chemotherapy, all CRSs were of predictive value again, except for the Konopke score. Conclusions: Traditional CRSs are not a reliable prognostic tool when used in patients before treatment with neoadjuvant chemotherapy. However, CRSs assessed after the administration of neoadjuvant chemotherapy are useful to predict prognosis.

Reply to I. Satzger et al (Article)

2011-09-10T00:00:00Z

Treatment of melanoma metastases in a limb by isolated limb perfusion and isolated limb infusion (Article)

2011-09-01T00:00:00Z

In-transit melanoma metastases are often confined to a limb. In this circumstance, treatment by isolated limb perfusion or isolated limb infusion can be a remarkably effective regional treatment option. Copyright

Hepatic steatosis assessment with CT or MRI in patients with colorectal liver metastases after neoadjuvant chemotherapy (Article)

2011-07-01T00:00:00Z

Purpose: Preoperative radiological assessment of hepatic steatosis is recommended in patients undergoing a liver resection, but few studies investigated the diagnostic accuracy after neoadjuvant chemotherapy. The aim of this study was to compare diagnostic accuracy of preoperative CT or MRI measurements of steatosis in patients with colorectal liver metastases after induction chemotherapy. Methods: MRI measurements (relative signal intensity decrease; RSID), N = 36, and CT scan measurements (Hounsfield units; HU), N = 32, were compared with histological steatosis assessment. Diagnostic accuracy was determined for detecting any (>5%) or marked macrovesicular steatosis (>33%). Results: MRI showed the highest correlation with histology (r = 0.82, P < 0.001), compared to CT measurements (r = -0.65, P < 0.001). Based on linear regression analysis, radiological cut-off values for 5% and 33% macrovesicular steatosis, corresponded to 0.7% and 19.2% RSID in the MRI-group, and 60.4 and 54.2 HU in the CT-group, respectively. Sensitivity and specificity for the detection of any and marked macrovesicular steatosis using MRI was 87% and 69%, and 78% and 100%, respectively, and for CT, 83% and 64%, and 70% and 87%, respectively. Conclusion: In patients treated with neoadjuvant chemotherapy MRI measurements of steatosis showed the highest correlation coefficient and the best diagnostic accuracy, as compared to CT measurements.

Prognosis in patients with sentinel node - positive melanoma is accurately defined by the combined Rotterdam tumor load and dewar topography criteria (Article)

2011-06-01T00:00:00Z

Purpose: Prognosis in patients with sentinel node (SN) -positive melanoma correlates with several characteristics of the metastases in the SN such as size and site. These factors reflect biologic behavior and may separate out patients who may or may not need additional locoregional and/or systemic therapy. Patients and Methods: Between 1993 and 2008, 1,080 patients (509 women and 571 men) were diagnosed with tumor burden in the SN in nine European Organisation for Research and Treatment of Cancer (EORTC) melanoma group centers. In total, 1,009 patients (93%) underwent completion lymph node dissection (CLND). Median Breslow thickness was 3.00 mm. The median follow-up time was 37 months. Tumor load and tumor site were reclassified in all nodes by the Rotterdam criteria for size and in 88% by the Dewar criteria for topography. Results: Patients with submicrometastases (< 0.1 mm in diameter) were shown to have an estimated 5-year overall survival rate of 91% and a low nonsentinel node (NSN) positivity rate of 9%. This is comparable to the rate in SN-negative patients. The strongest predictive parameter for NSN positivity and prognostic parameter for survival was the Rotterdam-Dewar Combined (RDC) criteria. Patients with submicrometastases that were present in the subcapsular area only, had an NSN positivity rate of 2% and an estimated 5- and 10-year melanoma-specific survival (MSS) of 95%. Conclusion: Patients with metastases < 0.1 mm, especially when present in the subcapsular area only, may be overtreated by a routine CLND and have an MSS that is indistinguishable from that of SN-negative patients. Thus the RDC criteria provide a rational basis for decision making in the absence of conclusions provided by randomized controlled trials.

Erratum: High tie versus low tie in rectal surgery: Comparison of anastomotic perfusion (Int J Colorectal Dis DOI 10.1007/s00384-011-1188-6) (Article)

2011-06-01T00:00:00Z

Outcome After Therapeutic Lymph Node Dissection in Patients with Unknown Primary Melanoma Site (Article)

2011-05-25T00:00:00Z

Purpose: The aim of this study was to evaluate the incidence and outcome of melanoma of unknown primary site (MUP) after therapeutic lymph node dissection (TLND) of palpable nodal melanoma metastases. Disease-free (DFS) and overall survival (OS) time of MUP patients were analyzed and compared to patients undergoing a TLND for known primary melanomas (MKP). Methods: This single institution retrospective study analyzed 342 consecutive patients who were treated with 415 TLNDs for palpable nodal disease from 1982 to 2009. Univariate and multivariate analyses included: MUP versus MKP, gender, Breslow thickness, ulceration of primary tumor, site of primary tumor, site of dissection, extracapsular extension, number of collected nodes, number of positive nodes and the node positive ratio. Results: A total of 47 MUP were identified in 342 patients (13.7%). In univariate analysis, a trend was seen toward better survival for MUP patients compared to MKP patients having 5-year OS rates of 40% and 27%, respectively (P = 0.06). Multivariate analysis for OS showed two highly significant factors associated with worse prognosis: extracapsular extension and N3 status (both P < 0.001). Two factors were associated with a significant better prognosis: MUP (P = 0.03) and a neck dissection (P = 0.04). Conclusions: Patients with MUP showed a statistically significant better OS compared to patients with melanoma metastases from known primary tumors. Presence of extracapsular extension and an increased number of positive nodes are statistically significantly negative prognostic factors for OS. The absence of a primary melanoma in stage III melanoma patients does not preclude surgery.

Therapeutic Surgical Management of Palpable Melanoma Groin Metastases: Superficial or Combined Superficial and Deep Groin Lymph Node Dissection (Article)

2011-05-03T00:00:00Z

Background: Management of patients with clinically detectable lymph node metastasis to the groin is by ilioinguinal or combined superficial and deep groin dissection (CGD) according to most literature, but in practice superficial groin dissection (SGD) only is still performed in some centers. The aim of this study is to evaluate the experience in CGD versus SGD patients in our center. Methods: Between 1991 and 2009, 121 therapeutic CGD and 48 SGD were performed in 169 melanoma patients with palpable groin metastases at our institute. Median follow-up was 20 and, for survivors, 45 months. Results: In this heterogeneous group of patients, overall (OS) and disease-free survival, local control rates, and morbidity rates were not significantly different between CGD and SGD patients. However, CGD patients had a trend towards more chronic lymphedema. Superficial lymph node ratio, the number of positive superficial lymph nodes, and the presence of deep nodes were prognostic factors for survival. CGD patients with involved deep lymph nodes (24.8%) had estimated 5-year OS of 12% compared with 40% with no involved deep lymph nodes (p = 0.001). Preoperative computed tomography (CT) scan had high negative predictive value of 91% for detection of pelvic nodal involvement. Conclusions: This study demonstrated that survival and local control do not differ for patients with palpable groin metastases treated by CGD or SGD. Patients without pathological iliac nodes on CT might safely undergo SGD, while CGD might be reserved for patients with multiple positive nodes on SGD and/or positive deep nodes on CT scan.

High tie versus low tie in rectal surgery: comparison of anastomotic perfusion (Article)

2011-03-29T00:00:00Z

Purpose: Both "high tie" (HT) and "low tie" (LT) are well-known strategies in rectal surgery. The aim of this study was to compare colonic perfusion after HT to colonic perfusion after LT. Methods: Patients undergoing rectal resection for malignancy were included. Colonic perfusion was measured with laser Doppler flowmetry, immediately after laparotomy on the antimesenterial side of the colon segment that was to become the afferent loop (measurement A). This measurement was repeated after rectal resection (measurement B). The blood flow ratios (B/A) were compared between the HT group and the LT group. Results: Blood flow was measured in 33 patients, 16 undergoing HT and 17 undergoing LT. Colonic blood flow slightly decreased in the HT group whereas the flow increased in the LT group. The blood flow ratio was significantly higher in the LT group (1.48 vs. 0.91; p = 0.04), independent of the blood pressure. Conclusion: This study shows the blood flow ratio to be higher in the LT group. This suggests that anastomoses may benefit from better perfusion when LT is performed.

Anatomical versus nonanatomical resection of colorectal liver metastases: Is there a difference in surgical and oncological outcome? (Article)

2011-03-01T00:00:00Z

Background: The increased use of neoadjuvant chemotherapy and minimally invasive therapies for recurrence in patients with colorectal liver metastases (CLM) makes a surgical strategy to save as much liver volume as possible pivotal. In this study, we determined the difference in morbidity and mortality and the patterns of recurrence and survival in patients with CLM treated with anatomical (AR) and nonanatomical liver resection (NAR). Methods: From January 2000 to June 2008, patients with CLM who underwent a resection were included and divided into two groups: patients who underwent AR, and patients who underwent NAR. Patients who underwent simultaneous radiofrequency ablation in addition to surgery and patients with extrahepatic metastasis were excluded. Patient, tumor, and treatment data, as well as disease-free and overall survival (OS) were compared. Results: Eighty-eight patients (44%) received AR and 113 patients (56%) underwent NAR. NAR were performed for significant smaller metastases (3 vs. 4 cm, P < 0.001). The Clinical Risk Score did not differ between the groups. After NAR, patients received significantly less blood transfusions (20% vs. 36%, P = 0.012), and the hospital stay was significantly shorter (7 vs. 8 days, P < 0.001). There were no significant differences in complications, positive resection margins, or recurrence. For the total study group, estimated 5-year disease-free and OS was 31 and 44%, respectively, with no difference between the groups. Conclusions: Our study resulted in no significant difference in morbidity, mortality, recurrence rate, or survival according to resection type. NAR can be used as a save procedure to preserve liver parenchyma.

Surgical Treatment of Renal Cell Cancer Liver Metastases: A Population-Based Study (Article)

2011-02-25T00:00:00Z

Background: To evaluate outcomes of surgical treatment in patients with hepatic metastases from renal-cell carcinoma in the Netherlands, and to identify prognostic factors for survival after resection. Renal-cell carcinoma has an incidence of 2,000 new patients in the Netherlands each year (12.5/100,000 inhabitants). According to literature, half of these patients ultimately develop distant metastases with 20% involvement of the liver. Resection of renal-cell carcinoma liver metastases (RCCLM) is performed in only a minority of patients. Hence, little is known about outcome of resectable RCCLM. Methods: Patients were retrieved from local databases of theNetherlands Task Force for Liver Surgery (14 centers) and from the Dutch collective pathology database. Survival and prognostic factors were determined by Kaplan-Meier analysis and log rank test. Results: Thirty-three patients were identified who underwent resection (n = 29) or local ablation (n = 4) of RCCLM in the Netherlands between 1990 and 2008. These patients comprise 0.5% to 1% of the total population of patients diagnosed with RCCLM in that period. There was no operative mortality. The overall survival at 1, 3, and 5 years was 79, 47, and 43%, respectively. Metachronous metastases (n = 23, P = 0.03) and radical resection (n = 19, P < 0.001) were statistically significant prognosticators of overall survival. Size < 50 mm (n = 18, P = 0,54), solitary metastases (n = 19, P = 0.93), and presence of extrahepatic metastases (n = 11, P = 0.28) did not have a statistically significant impact on survival. Conclusions: The favorable 5-year survival rate of 43% without operative mortality as found in this nationwide study indicates that selected patients with RCCLM can benefit from surgical treatment.

Chest wall resection for adult soft tissue sarcomas and chondrosarcomas: Analysis of prognostic factors (Article)

2011-01-01T00:00:00Z

Background: Wide resection with tumor-free margins is necessary in soft-tissue sarcomas to minimize local recurrence and to contribute to long-term survival. Information about treatment outcome and prognostic factors of adult sarcoma requiring chest wall resection (CWR) is limited. Methods: Sixty consecutive patients were retrospectively studied for overall survival (OS), local recurrence-free survival (LRFS), and disease-free survival (DFS). Twenty-one prognostic factors regarding survival were analyzed by univariate analysis using the Kaplan-Meier method and the log-rank test. Results: With a median survival of 2.5 years, the OS was 46% (33%) at 5 (10) years. The LRFS was 64% at 5 and 10 years, and the DFS was 30% and 25% at 5 and 10 years. At the end of the study period, 26 patients (43%) were alive, of which 20 patients (33%) had no evidence of disease and 40 patients (67%) had no chest wall recurrence. In the group of 9 patients with a radiation-induced soft-tissue sarcoma, the median survival was 8 months. Favorable outcome in univariate analysis in OS and LRFS applied for the low-grade sarcoma, bone invasion, and sternal resection. For OS only, age below 60 years and no radiotherapy were significant factors contributing to an improved survival. CWR was considered radical (R0) at the pathological examination in 43 patients. There were 52 patients with an uneventful recovery. There was one postoperative death. Conclusions: CWR for soft-tissue sarcoma is a safe surgical procedure with low morbidity and a mortality rate of less than 1%. With proper patient selection acceptable survival can be reached in a large group of patients. Care must be given to patients with radiation-induced soft-tissue sarcoma who have a significantly worse prognosis.

Comparison of Macroscopic Pathology Measurements with Magnetic Resonance Imaging and Assessment of Microscopic Pathology Extension for Colorectal Liver Metastases (Article)

2010-12-23T00:00:00Z

Purpose: To compare pathology macroscopic tumor dimensions with magnetic resonance imaging (MRI) measurements and to establish the microscopic tumor extension of colorectal liver metastases. Methods and Materials: In a prospective pilot study we included patients with colorectal liver metastases planned for surgery and eligible for MRI. A liver MRI was performed within 48 hours before surgery. Directly after surgery, an MRI of the specimen was acquired to measure the degree of tumor shrinkage. The specimen was fixed in formalin for 48 hours, and another MRI was performed to assess the specimen/tumor shrinkage. All MRI sequences were imported into our radiotherapy treatment planning system, where the tumor and the specimen were delineated. For the macroscopic pathology analyses, photographs of the sliced specimens were used to delineate and reconstruct the tumor and the specimen volumes. Microscopic pathology analyses were conducted to assess the infiltration depth of tumor cell nests. Results: Between February 2009 and January 2010 we included 13 patients for analysis with 21 colorectal liver metastases. Specimen and tumor shrinkage after resection and fixation was negligible. The best tumor volume correlations between MRI and pathology were found for T1-weighted (w) echo gradient sequence (rs= 0.99, slope = 1.06), and the T2-w fast spin echo (FSE) single-shot sequence (rs= 0.99, slope = 1.08), followed by the T2-w FSE fat saturation sequence (rs= 0.99, slope = 1.23), and the T1-w gadolinium-enhanced sequence (rs= 0.98, slope = 1.24). We observed 39 tumor cell nests beyond the tumor border in 12 metastases. Microscopic extension was found between 0.2 and 10 mm from the main tumor, with 90% of the cases within 6 mm. Conclusions: MRI tumor dimensions showed a good agreement with the macroscopic pathology suggesting that MRI can be used for accurate tumor delineation. However, microscopic extensions found beyond the tumor border indicate that caution is needed in selecting appropriate tumor margins.

Trends in treatment for synchronous colorectal liver metastases: Differences in outcome before and after 2000 (Article)

2010-10-01T00:00:00Z

Background: The traditional treatment for stage IV colorectal cancer has changed from palliative chemotherapy toward an aggressive multimodality approach. In the current study outcome in patients who underwent surgery for synchronous colorectal liver metastases (CLM) in a single center was evaluated. Methods: From January 1991 to May 2008 all consecutive patients with synchronous CLM who underwent curative resection of both primary and metastatic disease were included. Date of resection was divided into two groups: date of hepatic resection before and after the year 2000. Results: Fifty patients (26%) with synchronous CLM were resected before 2000 and 142 patients (74%) underwent resection after 2000. The estimated 5-year disease-free survival before and after 2000 was 9% and 27%, respectively (P = 0.379). More patients who underwent resection after 2000 were treated with local therapy or underwent resection for intra-hepatic recurrence (62% vs. 28%, P = 0.033). The estimated 5-year survival before and after 2000 was 26% and 44%, respectively (P = 0.001). Conclusion: Survival rates in patients with synchronous CLM have been increased in the past decade. The introduction of new chemotherapeutic drugs and a more aggressive treatment approach in patients with liver recurrence were probably major factors in this progress.

'Staged' liver resection in synchronous and metachronous colorectal hepatic metastases: Differences in clinicopathological features and outcome (Article)

2010-10-01T00:00:00Z

Aim: Approximately 25% of the patients with colorectal cancer already have liver metastases at diagnosis and another 30% will develop them subsequently. The features and prognosis of patients with synchronous and metachronus colorectal liver metastases, treated with primary resection first followed by partial liver resection were analysed. Method: Curative staged resection of liver metastases was performed in 272 consecutive patients. Demographics, characteristics of the primary tumour and metastatic tumours, surgery-related data and outcome were analysed. Results: Synchronous metastases were present in 105 (39%) patients and metachronous metastases in 167 (61%). More patients in the synchronous group had an advanced primary tumour (T3/T4 and/or node positivity), more than three liver metastases and bilobar distribution. A significantly higher percentage of patients in the synchronous group received neoadjuvant chemotherapy. The 5-year survival rate in the group of 272 patients was 38%. Patients with more than three metastases had a significantly worse survival rate. There were no differences in disease-free and overall survival rates between the synchronous and metachronous group. Conclusion: Although patients with synchronous colorectal liver metastases may have poorer biological features, there was no difference in 5-year disease-free and overall survival compared with patients with metachronous metastases. This may be explained by the observation that patients in the synchronous group received significantly more neoadjuvant chemotherapy. © 2010 The Authors. Colorectal Disease

Local excision of rectal cancer afterchemoradiation: Feasibility depends on the primary stage (Article)

2010-09-01T00:00:00Z

EORTC Melanoma Group sentinel node protocol identifies high rate of submicrometastases according to Rotterdam Criteria (Article)

2010-09-01T00:00:00Z

Sentinel node (SN) status is the most important prognostic factor for disease-free survival (DFS) and overall survival (OS) in stages I-II melanoma. We evaluated the positive sentinel node identification rate of the EORTC Melanoma Group (MG) protocol as well as its capacity to identify minimal tumour burden, according to the Rotterdam Criteria in 421 consecutive patients. Correlations between primary tumour characteristics and SN tumour burden were investigated. The same 2 pathologists worked up all SNs according to the EORTC MG protocol and tumour burden was scored according to the Rotterdam Criteria (<0.1 mm, 0.1-1.0 mm and >1.0 mm for the largest diameter of the largest metastasis in the SN). The positive SN detection rate was 28.7% with a false negative rate of 10.4% at a median Breslow thickness of 2.1 mm. The high positive identification rate of about 30% of the EORTC MG protocol has been confirmed in this study. The protocol is sensitive and identifies submicrometastases (<0.1 mm) in a high percentage (18%). The variables SN tumour load, non-SN (NSN) status and ulceration of the primary were independent prognostic factors for DFS and OS in the multivariate analysis. At a median follow-up time of 4.3 years patients with minimal tumour burden (<0.1 mm) had a 5 year OS rate of 91%, virtually identical to 90% for SN-negative patients. The NSN positivity rate of 0% in these patients indicates that they may be spared a completion lymph node dissection (CLND) and its morbidity.

Outcome of esophagectomy for cancer in elderly patients (Article)

2010-09-01T00:00:00Z

Background: This study analyzes the outcome of esophageal resection in patients 70 or more years of age, compared with patients aged less than 70 years and identifies risk factors for worse outcome in the elderly. Methods: Comorbidity, postoperative morbidity, in-hospital mortality and survival rates were compared between 811 patients aged less than 70 years and 250 patients aged 70 years or more who underwent esophagectomy for esophageal cancer in a single high-volume center from 1985 to 2005. Results: Groups were similar regarding surgical approach, resectability, and tumor stage. More patients aged 70 years or more had cardiovascular and respiratory concomitant disease. Among patients aged 70 years or more, the prevalence of adenocarcinoma and Barrett's transformation was higher (67% versus 53% for patients aged less than 70 years, and 22% versus 15%, respectively). There were no differences in surgical complications (20% versus 17%). Nonsurgical complications occurred more in patients aged 70 years or more (35% versus 27%) and operative mortality was higher among elderly patients (8.4 versus 3.8%), as was in-hospital mortality (11.6% versus 5.4%). The disease-specific 5-year survival was lower for patients aged 70 years or more (27% versus 34%). The 1-year survival, reflecting the impact of operative morbidity and mortality, was 58% for patients aged 70 years or more and 68% for the patients aged less than 70 years (p = 0.002). Among patients aged 70 years or more, respiratory comorbidity and thoracoabdominal resection were risk factors for the occurrence of nonsurgical complications and respiratory comorbidity for in-hospital mortality. Conclusions: Older patients have increased operative and in-hospital mortality and decreased 5-year survival after esophageal resection for cancer. Our results indicate that especially thoracoabdominal resection for esophageal carcinoma should be carefully considered for patients older than 70 years who suffer from respiratory disease.

Importance of tumor load in the sentinel node in melanoma: Clinical dilemmas (Article)

2010-08-01T00:00:00Z

There are two hypotheses to explain melanoma dissemination: first, simultaneous lymphatic and hematogeneous spread, with regional lymph nodes as indicators of metastatic disease; and second, orderly progression, with regional lymph nodes as governors of metastatic disease. The sentinel node (SN) has been defined as the first draining lymph node from a tumor and is harvested with the use of the triple technique and is processed by an extensive pathology protocol. The SN status is a strong prognostic factor for survival (83-94% for SN negative, 56-75% SN-positive patients). False-negative rates are considerable (9-21%). Preliminary results of the MSLT-1 trial did not demonstrate a survival benefit for the SN procedure, although a subgroup analysis indicates a possible benefit. A mathematical model has demonstrated 24% prognostic false positivity. SN tumor burden represents a heterogenous patient population and is classified most frequently with the Starz, Dewar or Rotterdam Criteria. A completion lymph-node dissection might not be indicated in all SN-positive patients. Patients classified with metastases <0.1 mm by the Rotterdam Criteria have excellent survival rates. Ultrasound-guided fine-needle aspiration cytology is emerging as a staging tool for high-risk patients, but more research is necessary before this can change clinical practice.

Circulating tumor cells and sample size: The more, the better (Article)

2010-06-10T00:00:00Z

Cervical lymph node dissection for metastatic testicular cancer (Article)

2010-06-01T00:00:00Z

Introduction. Despite high response rates to systemic chemotherapy, 30% of patients with advanced stage testicular carcinoma will have extra- retroperitoneal residual masses that require resection. Most often, these are located in the lungs and mediastinum and neck. Limited data are available concerning the incidence, surgical management, and follow-up of neck metastasis arising from a testicular primary tumor. Methods. We retrospectively reviewed all 665 patients who were referred to a tertiary referral center with the diagnosis of testicular cancer from January 1997 to June 2009 for the presence of cervical metastases. Patients who underwent concomitant surgical therapy were identified and analyzed. Clinical and pathological data were collected from patient records, including radiology and pathology reports. Furthermore, data on primary treatment strategy, chemotherapeutic regimens, timing of surgical procedures, complications, disease recurrence, and follow-up were collected. Results. Twenty-six patients (4%) had cervical lymph node metastasis. The majority (n = 19) had multiple ERP sites. Nine patients (35%) underwent selective neck dissection: in six patients, this was indicated because of residual masses after chemotherapy, and in three patients, cervical masses represented a late and distant relapse of previously treated disease. Viable cancer cells were present in the resected specimen only in these three patients. Seven patients are currently without evidence of disease. Two patients died of disseminated disease. Conclusions. Cervical lymph node metastases originating from testicular cancer are rare but are more commonly observed in patients with advanced stage disease. Selective neck dissection can be safely performed both after chemotherapy and in the case of recurrent disease.

New developments in sentinel node staging in melanoma: Controversies and alternatives (Article)

2010-05-01T00:00:00Z

PURPOSE OF REVIEW: Melanoma incidence is increasing worldwide. Elective lymph node dissections (ELNDs) could not improve survival. The sentinel node is a targeted approach to occult lymph node metastases. There are controversies regarding the sentinel node procedure for melanoma, with regard to false-negative rates, therapeutic benefit and alternatives, such as ultrasound. The clinical relevance of minimal sentinel node tumor burden is unclear. This review analyzes these issues. RECENT FINDINGS: Through the pathological work-up of the sentinel node, the sentinel node has become an independent prognostic factor for survival in melanoma. False-negative rates of the sentinel node procedure are generally an underestimation, due to incorrect calculations. A subgroup analysis of the Multicenter Selective Lymphadenectomy Trial (MSLT)-1 seemed to demonstrate a survival benefit, but is criticized for a number of reasons. Potentially, a subgroup of sentinel node-positive patients is prognostically false-positive, with dormant metastases, which might not become viable disease. SUMMARY: Sentinel node tumor burden is an extra dimension to predict prognosis, although we have not yet identified the correct group to undergo a completion lymph node dissection. The MSLT-2 and MINITUB studies are analyzing this issue. The EORTC recommends the Rotterdam criteria as the most reproducible and accurate measure of sentinel node tumor burden. Ultrasound-guided fine needle aspiration cytology is emerging as a potential cost-effective alternative.

Optimizing the outcome of surgery in patients with rectal cancer and synchronous liver metastases (Article)

2010-03-01T00:00:00Z

Background: This study evaluated the outcome of patients treated tor rectal cancer and synchronous hepatic metastases in the era of effective induction radiotherapy and chemotherapy. Methods: All patients undergoing surgical treatment of rectal cancer and synchronous liver metastases between 2000 and 2007 were identified retrospectively from a prospectively collected database. Three approaches were followed: the classical staged, the simultaneous and the liver-first approach. Results: Of 57 patients identified, the primary tumour was resected first in 29 patients (group 1), simultaneous resection was performed in eight patients (group 2), and 20 patients underwent a liver-first approach (group 3). The overall morbidity rate was 24-6 per cent; there was no in-hospital mortality. Median in-hospital stay was significantly shorter for the simultaneous approach (9 days versus 18 and 15 days for groups 1 and 3 respectively; P < 0.001). The overall S-year survival rate was 38 per cent, with an estimated median survival of 47 months. Conclusion: Long-term survival can be achieved using an individualized approach, with curative intent, in patients with rectal cancer and synchronous liver metastases. Simultaneous resections as well as the liver-first approach are attractive alternatives to traditional staged resections.

Stereotactic body radiation therapy for colorectal liver metastases (Article)

2010-03-01T00:00:00Z

Background: Stereotactic body radiation therapy (SBRT) is a treatment option for colorectal liver metastases. Local control, patient survival and toxicity were assessed in an experience of SBRT for colorectal liver metastases. Methods: SBRT was delivered with curative intent to 20 consecutively treated patients with colorectal hepatic metastases who were candidates for neither resection nor radiofrequency ablation (RFA). The median number of metastases was 1 (range 1-3) and median size was 2-3 (range 0-7-6-2) cm. Toxicity was scored according to the Common Toxicity Criteria version 3.0. Local control rates were derived on tumour-based analysis. Results: Median follow-up was 26 (range 6-57) months. Local failure was observed in nine of 31 lesions after a median interval of 22 (range 12-52) months. Actuarial 2-year local control and survival rates were 74 and 83 per cent respectively. Hepatic toxicity grade 2 or less was reported in 18 patients. Two patients had an episode of hepatic toxicity grade 3. Conclusion: SBRT is a treatment option for patients with colorectal liver metastases who are not candidates for resection or RFA.

Potential cost-effectiveness of US-Guided FNAC in melanoma patients as a primary procedure and in follow-up (Article)

2010-02-01T00:00:00Z

Radiotherapy for Soft Tissue Sarcomas after Isolated Limb Perfusion and Surgical Resection: Essential for Local Control in All Patients? (Article)

2010-01-01T00:00:00Z

Background: Standard treatment for localized soft tissue sarcoma (STS) is resection plus adjuvant radiotherapy (RTx). In approximately 10% of cases, resection would cause severe loss of function or even require amputation because of the extent of disease. Isolated limb perfusion (ILP) with tumor necrosis factor alpha (TNF-α) and melphalan can achieve regression of the tumor, facilitating limb-saving resection. RTx improves local control but may lead to increased morbidity. Methods: In our database of over 500 ILPs, 122 patients with unifocal STS were treated by ILP followed by limb-sparing surgery. All included patients were candidates for amputation. Results: Surgery resulted in 69 R0 resections (57%), and in 53 specimens (43%) resection margins contained microscopic evidence of tumor (R1). Histopathological examination revealed >50% ILP-induced tumor necrosis in 59 cases (48%). RTx was administered in 73 patients (60%). Local recurrence rate was 21% after median follow-up of 31 months (2-182 months). Recurrence was significantly less in patients with >50% ILP-induced necrosis versus ≤50% necrosis (7% vs. 33%, P = 0.001). A similar significant correlation was observed for R0 versus R1 resections (15% vs. 28%, P = 0.04). In 36 patients with R0 resection and >50% necrosis, of whom 21 were spared RTx, no recurrences were observed during follow-up. Conclusions: In patients with locally advanced primary STS, treated with ILP followed by R0 resection, and with >50% ILP-induced necrosis in the resected specimen, RTx is of no further benefit.

Stereotactic Body Radiation Therapy for Liver Tumors: Impact of Daily Setup Corrections and Day-to-Day Anatomic Variations on Dose in Target and Organs at Risk (Article)

2009-11-15T00:00:00Z

Purpose: To assess day-to-day differences between planned and delivered target volume (TV) and organ-at-risk (OAR) dose distributions in liver stereotactic body radiation therapy (SBRT), and to investigate the dosimetric impact of setup corrections. Methods and Materials: For 14 patients previously treated with SBRT, the planning CT scan and three treatment scans (one for each fraction) were included in this study. For each treatment scan, two dose distributions were calculated: one using the planned setup for the body frame (no correction), and one using the clinically applied (corrected) setup derived from measured tumor displacements. Per scan, the two dose distributions were mutually compared, and the clinically delivered distribution was compared with planning. Doses were recalculated in equivalent 2-Gy fraction doses. Statistical analysis was performed with the linear mixed model. Results: With setup corrections, the mean loss in TV coverage relative to planning was 1.7%, compared with 6.8% without corrections. For calculated equivalent uniform doses, these figures were 2.3% and 15.5%, respectively. As for the TV, mean deviations of delivered OAR doses from planning were small (between -0.4 and +0.3 Gy), but the spread was much larger for the OARs. In contrast to the TV, the mean impact of setup corrections on realized OAR doses was close to zero, with large positive and negative exceptions. Conclusions: Daily correction of the treatment setup is required to obtain adequate TV coverage. Because of day-to-day patient anatomy changes, large deviations in OAR doses from planning did occur. On average, setup corrections had no impact on these doses. Development of new procedures for image guidance and adaptive protocols is warranted.

Abdominosacral resection for locally advanced and recurrent rectal cancer (Article)

2009-11-01T00:00:00Z

Background: The results of resection of locally advanced and recurrent rectal cancers, including sacral resection, were analysed critically. Methods: Between 1987 and 2007, 353 patients with locally advanced or recurrent rectal cancer, all treated in a tertiary referral centre, were identified from a prospective database. Twenty-five patients (eight primary and 17 recurrent tumours) underwent en bloc sacral resection. Results: A mid-sacral resection was carried out in 12 patients (level S3) and a low sacral resection in 13 (level S4/S5). Nineteen patients had an R0, four an R1 and two an R2 resection. There was no postoperative mortality. Median follow-up was 32 months. Incomplete resection had an independent negative influence on local control (5-year local recurrence rate 42 versus 0 per cent in those with and without incomplete resection; P < 0.001). The 5-year overall survival rate was 30 per cent. Five patients with recurrent tumour had pathological invasion into the sacral bone and none survived beyond 1 year. Conclusion: Abdominosacral resection can be performed in patients with locally advanced and recurrent rectal cancer. Patients who cannot undergo a complete resection or have clear evidence of cortical invasion have a poor prognosis. Copyright

Radiofrequency ablation in the treatment of hepatocellular carcinoma: The need for centralization (Article)

2009-09-01T00:00:00Z

Isolated limb perfusion with TNF-α and melphalan in locally advanced soft tissue sarcomas of the extremities (Article)

2009-08-21T00:00:00Z

Limb-sparing surgery has become all the more important in soft tissue sarcoma (STS) of the extremities since we learned that amputation does not improve survival of these patients. In bulky tumours, however, preoperative strategies to reduce tumour size are then required. Isolated limb perfusion (ILP) with tumour necrosis factor (TNF) has been developed as a biochemotherapeutic therapy to act both on the tumour-associated vasculature and on the tumour itself. It has shown to be a very potent treatment modality, as in early reports response rates were around 80%. Limb salvage could then be achieved in a quite similar percentage. Many confirmatory studies have been performed since, with consistent results even in patients with multiple tumours, after extensive radiotherapy or with metastatic disease, all at the cost of very limited toxicity. This chapter gives an overview of the ILP studies performed in patients with soft tissue limb sarcoma, discusses the mechanism of TNF-mediated vasculotoxic effects on tumour vasculature, and places TNF-based ILP in the multimodality treatment of these patients with extensive STS of the extremities.

On the origin of (CD105+) circulating endothelial cells (Article)

2009-08-01T00:00:00Z

Cells designated by the CellSearch™ assay as circulating endothelial cells (CEC) (CD146+/CD105+/ CD45- nuclear cells) are thought to derive from damaged vasculature. As CD105 has been suggested to be expressed by endothelial cells from malignant vasculature particularly, it is currently unknown whether this assay is suitable to determine CECs in non-malignant diseases. Also, more insight is needed whether CECs as detected by this assay predominantly measures CECs or also endothelial progenitor cells (EPCs), which originate from the bone marrow and reflect angiogenesis rather than vascular damage. CEC counts were determined in nine patients treated with isolated limb perfusion with tumour necrosis factor (TNF) a and melphalan, and in 10 healthy donors. Given the severe vascular damage caused by venesection and cannulation of the main vessels, we expected a significant increase in CEC counts in case CEC were of vascular rather than of bone marrow origin. Additionally, this finding, as well as the presence of CD105+CEC in the blood of healthy controls, would confirm that healthy endothelial cells express CD105. Numbers of CD146+/CD105+/CD45-nuclear CEC increased significantly after venesection and cannulation. After administration of TNF, a large fraction of non-intact, possibly apoptotic CEC appeared. This study shows that the Cell-Search™ assay detects CECs originating from damaged vasculature. Furthermore, CD105 expression is found on CEC from damaged normal vasculature rendering further exploration of the value of CEC determined by this assay worthwhile not only in malignant diseases but also in non malignant disorders characterised by vascular damage.

Total pelvic exenteration for primary and recurrent malignancies (Article)

2009-07-01T00:00:00Z

Introduction: Complete resection is the most important prognostic factor in surgery for pelvic tumors. In locally advanced and recurrent pelvic malignancies, radical margins are sometimes difficult to obtain because of close relation to or growth in adjacent organs/structures. Total pelvic exenteration (TPE) is an exenterative operation for these advanced tumors and involves en bloc resection of the rectum, bladder, and internal genital organs (prostate/seminal vesicles or uterus, ovaries and/or vagina). Methods: Between 1994 and 2008, a TPE was performed in 69 patients with pelvic cancer; 48 with rectal cancer (32 primary and 16 recurrent), 14 with cervical cancer (1 primary and 13 recurrent), 5 with sarcoma (3 primary and 2 recurrent), 1 with primary vaginal, and 1 with recurrent endometrial carcinoma. Ten patients were treated with neoadjuvant chemotherapy and 66 patients with preoperative radiotherapy to induce down-staging. Eighteen patients received IORT because of an incomplete or marginal complete resection. Results: The median follow-up was 43 (range, 1-196) months. Median duration of surgery was 448 (range, 300-670) minutes, median blood loss was 6,300 (range, 750-21,000) ml, and hospitalization was 17 (range, 4-65) days. Overall major and minor complication rates were 34% and 57%, respectively. The in-hospital mortality rate was 1%. A complete resection was possible in 75% of all patients, a microscopically incomplete resection (R1) in 16%, and a macroscopically incomplete resection (R2) in 9%. Five-year local control for primary locally advanced rectal cancer, recurrent rectal cancer, and cervical cancer was 89%, 38%, and 64%, respectively. Overall survival after 5 years for primary locally advanced rectal cancer, recurrent rectal cancer, and cervical cancer was 66%, 8%, and 45%. Conclusions: Total pelvic exenteration is accompanied with considerable morbidity, but good local control and acceptable overall survival justifies the use of this extensive surgical technique in most patients, especially patients with primary locally advanced rectal cancer and recurrent cervical cancer.

Local treatment for recurrent colorectal hepatic metastases after partial hepatectomy (Article)

2009-05-01T00:00:00Z

Objective: The objective of the study was to identify patients who may benefit from local treatment in recurrent colorectal liver metastases. Materials and methods: A total of 51 consecutive patients were treated for hepatic recurrence(s) after an initial partial hepatic resection. Surgery was considered as the primary treatment option for eligible patients. Patients with a small liver remnant after major hepatectomy were treated with radiofrequency ablation (RFA) or stereotactic body radiation therapy (SRx). SRx was given as an outpatient, emerging local treatment option for patients with intra-hepatic recurrences not eligible for surgery or RFA. Partial liver resection was performed in 36 patients (70%), RFA in ten patients (20%), and SRx in five patients (10%). Results: Median hospital stay was 7 (range, 3-62) days with a morbidity of 16% without in-hospital death. None of the patients received adjuvant chemotherapy. There was no difference in recurrence or survival between the three treatment modalities. Overall 5-year survival was 35% with an estimated median survival of 37 months. Patients with a disease-free interval between first hepatectomy and hepatic recurrence less than 6 months did not survive 3 years. Conclusions: Resection, RFA, and SRx can be performed safely in patients with recurrent colorectal liver metastases and offer a survival that seems comparable to primary liver resections of colorectal liver metastases.

Isolated hypoxic hepatic perfusion with melphalan in patients with irresectable ocular melanoma metastases (Article)

2009-05-01T00:00:00Z

Aim: Ocular melanoma prefers to metastasize to the liver and the liver is the sole site of metastatic disease in 80% of patients. Until now there has been no standard treatment available and these patients have a very poor prognosis (median survival 2-5 months). Isolated hepatic perfusion may be an option in patients with irresectable hepatic ocular melanoma metastases. The aim of this study was to evaluate applicability, toxicity and response in this selected group of ocular melanoma patients by treatment with isolated hypoxic hepatic perfusion with retrograde outflow (IHHP) with melphalan. Methods: From September 2002 until July 2006 eight consecutive patients were included in this study. IHHP was performed with inflow via the hepatic artery and retrograde outflow via the portal vein during 25 min with 1 mg/kg melphalan. The perfusion was followed by a complete wash-out procedure. Results: The median total operation time was 4 h with a median blood/fluid loss of 1100 ml. No postoperative mortality was observed. Median hospital stay was 9.5 days. Toxicity was moderate: WHO grade 3 leukocytopenia in 3 patients, grade 3 hepatic toxicity in 1 patient. In 37% of patients (3/8) a partial response could be demonstrated 3 months after IHHP. Stable disease was found in 3 patients and progressive disease in 2 patients. Median time to local progression was 6 months and the median survival was 11 months. Conclusion: Melphalan-based IHHP with retrograde outflow is a safe treatment option for patients with irresectable ocular melanoma metastases. Survival benefit seems to be comparable to classical IHHP.

The "liver-first approach" for patients with locally advanced rectal cancer and synchronous liver metastases. (Article)

2009-01-01T00:00:00Z

PURPOSE: This study was designed to investigate the outcome of "the liver-first" approach in patients with locally advanced rectal cancer and synchronous liver metastases. METHODS: Patients with locally advanced rectal cancer and synchronous liver metastases were primarily treated for their liver metastases. If successful, patients underwent treatment for the rectal tumor. RESULTS: Twenty-three patients were included. One patient had liver resection without neoadjuvant chemotherapy followed by chemoradiotherapy. All remaining 22 patients underwent laparotomy after chemotherapy. Eighteen patients underwent partial liver resection and subsequent chemoradiotherapy for the rectal cancer. One patient underwent in one session a partial liver resection and a low anterior resection. Six patients were not treated according to protocol because of extensive disease. Sixteen patients (73 percent) completed the full treatment protocol and all are alive after a median period of 19 (range, 7-56) months. CONCLUSIONS: This is the first sizable report on the "liver-first approach" demonstrating that it may be considered the preferred treatment schedule for patients with locally advanced rectal cancer and synchronous liver metastases. It allows most patients to undergo curative resections of both metastatic and primary disease and can avoid useless rectal surgery in patients with incurable metastatic disease.

Systemic treatment in hepatocellular carcinoma; 'A small step for man...' (Article)

2009-01-01T00:00:00Z

Hepatocellular carcinoma (HCC) is the third most common cause of cancer mortality worldwide. In localised disease, orthotopic liver transplantation, surgical resection or local ablations are the mainstay of treatment. In unresectable or metastatic HCC, systemic therapy has unfortunately yielded disappointing results and therefore until recently was generally considered to be ineffective. Most patients with HCC have an underlying liver disease and many drugs may exacerbate the underlying liver disease. Recently, two randomised phase III trials with sorafenib in patients with advanced or metastatic HCC have shown a significant increase in progression free and overall survival of approximately two months, which is an absolute novum for this disease. Sorafenib is therefore now considered a viable treatment option in patients with unresectable or metastatic HCC, a good performance status and Child-Pugh A liver cirrhosis. Despite this very promising result, of major concern is the treatment-related toxicity as observed in these and other trials by sorafenib treatment. However, the important first significant survival benefit by systemic treatment has generated hope for the development of new treatment strategies which will be more efficacious, have favourable toxicity profiles and will further extend survival of this still highly lethal disease.

The 'liver-first approach' for patients with locally advanced rectal cancer and synchronous liver metastases (Article)

2009-01-01T00:00:00Z

PURPOSE: This study was designed to investigate the outcome of ''the liver-first'' approach in patients with locally advanced rectal cancer and synchronous liver metastases. METHODS: Patients with locally advanced rectal cancer and synchronous liver metastases were primarily treated for their liver metastases. If successful, patients underwent treatment for the rectal tumor. RESULTS: Twenty-three patients were included. One patient had liver resection without neoadjuvant chemotherapy followed by chemoradiotherapy. All remaining 22 patients underwent laparotomy after chemotherapy. Eighteen patients underwent partial liver resection and subsequent chemoradiotherapy for the rectal cancer. One patient underwent in one session a partial liver resection and a low anterior resection. Six patients were not treated according to protocol because of extensive disease. Sixteen patients (73 percent) completed the full treatment protocol and all are alive after a median period of 19 (range, 7Y56) months. CONCLUSIONS: This is the first sizable report on the ''liver-first approach'' demonstrating that it may be considered the preferred treatment schedule for patients with locally advanced rectal cancer and synchronous liver metastases. It allows most patients to undergo curative resections of both metastatic and primary disease and can avoid useless rectal surgery in patients with incurable metastatic disease.

The Rotterdam criteria for sentinel node tumor load: the simplest prognostic factor? (Letter To Editor)

2008-12-01T00:00:00Z

Sentinel node tumor burden according to the rotterdam criteria is the most important prognostic factor for survival in melanoma patients: A multicenter study in 388 ratients with positive sentinel nodes (Article)

2008-12-01T00:00:00Z

Summary Background Data: The more intensive sentinel node (SN) pathologic workup, the higher the SN-positivity rate. This is characterized by an increased detection of cases with minimal tumor burden (SUB-micrometastasis <0.1 mm), which represents different biology. Methods: The slides of positive SN from 3 major centers within the European Organization of Research and Treatment of Cancer (EORTC) Melanoma Group were reviewed and classified according to the Rotterdam Classification of SN Tumor Burden (<0.1 mm; 0.1-1 mm; >1 mm) maximum diameter of the largest metastasis. The predictive value for additional nodal metastases in the comple- tion lymph node dissection (CLND) and disease outcome as disease- free survival (DFS) and overall survival (OS) was calculated. Results: In 388 SN positive patients, with primary melanoma, median Breslow thickness was 4.00 mm; ulceration was present in 56%. Forty patients (10%) had metastases <0.1 mm. Additional nodal positivity was found in only 1 of 40 patients (3%). At a mean follow-up of 41 months, estimated OS at 5 years was 91% for metastasis <0.1 mm, 61% for 0.1 to 1.0 mm, and 51% for >1.0 mm (P < 0.001). SN tumor burden increased significantly with tumor thickness. When the cut-off value for SUB-micrometastases was taken at <0.2 mm (such as in breast cancer), the survival was 89%, and 10% had additional non-SN nodal positivity. Conclusion: This large multicenter dataset establishes that patients with SUB-micrometastases <0.1 mm have the same prognosis as SN negative patients and can be spared a CLND. A <0.2 mm cut-off for SUB-micrometastases does not seem correct for melanoma, as 10% additional nodal positivity is found. Copyright

Isolated Hepatic Perfusion for the Treatment of Liver Tumors: Sunset or Sunrise? (Article)

2008-10-01T00:00:00Z

Experience with isolated hepatic perfusion (IHP) is limited to a few centers in the world because of the technical difficulties, surgery-related morbidity, and unproved efficacy in randomized trials. Experimental animal IHP models have led to exploring new ways of improving efficacy, reducing technical difficulties, and minimizing regional and systemic toxicity. Future research should be directed to the identification of suitable biologic or chemotherapeutic agents, defining clinical indications, and development of technical modifications to make it more generally applicable and even repeatable.

Glomus tumor of the mesentery with atypical features: A case report (Article)

2008-10-01T00:00:00Z

Glomus tumors usually occur in the acral soft tissue and rarely in visceral locations, such as the stomach, intestines, mediastinum, lung, pancreas, bladder, and vagina. The authors present a 74-year-old woman with an exceptionally large glomus tumor of the mesentrium with malignant features. Previously reported cases of intraabdominal glomus tumor in the abdominal cavity exhibited benign behavior and few cases with metastatic disease. Criteria for malignancy in acral glomus tumors, such as unusually large size, infiltrative growth, necrosis, nuclear atypia, and mitotic activity, seem not to translate to abdominal glomus tumors. As very few intraabdominal glomus are described, the malignant potential of these tumors stays uncertain for longer period.

Detection of melanoma micrometastases in sentinel nodes - the cons (Article)

2008-09-01T00:00:00Z

The sentinel node (SN) procedure in melanoma patients is important for prognostic information, but has no impact on survival. Micrometastases are identified in approximately 20% of the SNs. When a Completion Lymph Node Dissection (CLND) is performed for positive SN, additional non-SN lymph node involvement is also approximately 20%. Several classification criteria have been proposed to identify patients with SNs without a risk for additional nodes or a good prognosis. Micro anatomic analyses of metastatic SNs suggest that patients with sub-micrometastases (<0.1mm) in the SN may be judged as SN negative. Patients with this limited tumor burden in their SN have an excellent prognosis and are highly unlikely to benefit from CLND. New techniques such as ultrasound of the lymph nodal basin can be promising as an alternative for SN biopsy.

Decrease of CD117 expression as possible prognostic marker for recurrence in the resected specimen after imatinib treatment in patients with initially unresectable gastrointestinal stromal tumors: A clinicopathological analysis (Article)

2008-07-01T00:00:00Z

Gastrointestinal stromal tumors (GIST) are the most common malignant mesenchymal tumors of the gastrointestinal tract. The principal treatment modality for primary GIST is surgery whereas for metastatic GIST, imatinib has an established role. In patients with locally advanced and metastatic GIST, the role of surgery in the imatinib era is still unclear. Fifteen patients with locally advanced (n≤9) and/or metastatic GIST (n≤6) were treated with imatinib followed by resection. Detailed histopathological examination was performed before and after treatment with imatinib, which was given for a median of 11 months before surgery. Ten patients showed a radiographic partial response, four patients had stable disease, and one patient progressed. At the time of surgery, the median tumor diameter was 6.5g cm. In all the nine patients with locally advanced GIST, a R0 resection could be performed. Histopathological examination showed imatinib effects in all tumors, including the case with progressive disease. All patients with locally advanced disease (n≤9) were alive after a median follow-up of 40 months (range: 18g-59), of which seven patients were free of disease. Four of the six patients treated for metastatic GIST died of disease after 30, 45, 50, and 74 months of follow-up. Remarkably, in five of six patients in whom CD117 expression was diminished or lost in the resection specimen, disease recurrence was observed. In patients with retained CD117 expression, one of the nine patients had recurrent disease. In conclusion, preoperative imatinib treatment in patients with locally advanced GIST resulted in a decrease of tumor load in most patients, enabling complete surgical resection. For patients with metastatic GIST, the role of surgery remains less clear. Loss or decrease of CD117 expression in the resected specimen after imatinib treatment may be associated with disease recurrence.

A place for radiofrequency ablation in the treatment of resectable colorectal liver metastases? (Article)

2008-07-01T00:00:00Z

Cutaneous melanoma and sentinel lymph node biopsy (Letter To Editor)

2008-06-01T00:00:00Z

No abstract

Reirradiation, surgery and IORT for recurrent rectal cancer in previously irradiated patients (Article)

2008-06-01T00:00:00Z

A total of 11 patients with recurrent rectal cancer who had been previously irradiated were treated with preoperative reirradiation (median dose 30 Gy), surgery and IORT. This treatment was related with high morbidity, a short pain-free survival (5 months) and poor local control (27% after 3 years), although some patients have long-term distant control and survival.

Isolated tumor cells and long-term prognosis of patients with melanoma (Letter To Editor)

2008-05-01T00:00:00Z

Isolated hypoxic hepatic perfusion with retrograde outflow in patients with irresectable liver metastases; a new simplified technique in isolated hepatic perfusion (Article)

2008-05-01T00:00:00Z

Background: Isolated hepatic perfusion with high-dose chemotherapy is a treatment option for patients with irresectable metastases confined to the liver. Prolonged local control and impact on survival have been claimed. Major drawbacks are magnitude and costs of the procedure. We developed an isolated hypoxic hepatic perfusion (IHHP) with retrograde outflow without the need for a heart-lung machine. Patients and Methods: Twenty-four consecutive patients with irresectable metastases of various origins were treated. IHHP inflow was via the hepatic artery, outflow via the portal vein with occlusion of the retrohepatic caval vein. Radiolabeled albumine was used for leakage monitoring. Melphalan was used at 1-2 mg/kg. A 25-minute perfusion period was followed by a complete washout. Local and systemic melphalan concentrations were determined. Results: Compared with oxygenated classical IHP, the IHPP procedure reduced operation time from >8 h to 4 hours, blood loss from >4000 to 900 cc and saved material and personnel costs. Leakage was 0% with negligible systemic toxicity and 0% perioperative mortality. Tumor response: complete response (CR) in 4%, partial response (PR) in 58%, and stable disease (SD) in 13%. Median time to progression was 9 months (2-24 months); pharmacokinetics demonstrated intrahepatic melphalan concentrations more than 9 fold higher than postperfusion systemic concentrations. Conclusions: IHPP is a relatively simple procedure with reduced costs, reduced blood loss, no mortality, limited toxicity, and response rates comparable to classic IHP. The median duration of 9 months of tumor control should be improved. Hereto, vasoactive drugs, will be explored in further studies.

Sentinel lymph-node false positivity in melanoma (Letter To Editor)

2008-04-01T00:00:00Z

Somatostatin receptor in human hepatocellular carcinomas: Biological, patient and tumor characteristics (Article)

2008-04-01T00:00:00Z

Background/Aim: The evidence on the efficacy of somatostatin analogues in the treatment of hepatocellular carcinoma (HCC) in humans is conflicting. A variety of human tumors demonstrate somatostatin receptors. All subtypes bind human somatostatin with high affinity, while somatostatin analogues bind with high affinity to somatostatin receptor subtype 2 (sst2). We investigated the sst2 expression in HCC and examined whether HCCs expressing sst2 are a distinct subgroup. Patients and Methods: Forty-five human HCCs were tested for sst2 expression and biological alterations. The proliferative capacity was determined with Ki67 immunostaining and the DNA ploidy status was measured by fluorescent in situ hybridization with a chromosome 1-specific repetitive DNA probe. Expression of tumor suppressor genes (p16, p53 and Rb1) was measured by immunohistochemistry. Results: sst2 expression was detected in 30 tumors (67%). No correlation existed between sst2 expression and the immunoprofiles of the tumor suppressor genes, aneuploidy, proliferation, age, gender, α-fetoprotein levels, tumor size, tumor grade and underlying liver disease. Conclusion: In 67% of the patients with HCC, sst2 could be detected in the tumor. No clinical, pathological or biological characteristics were specific for sst2-positive tumors. Copyright

Quality of Life After Stereotactic Body Radiation Therapy for Primary and Metastatic Liver Tumors (Article)

2008-04-01T00:00:00Z

Purpose: Stereotactic body radiation therapy (SBRT) provides a high local control rate for primary and metastatic liver tumors. The aim of this study is to assess the impact of this treatment on the patient's quality of life. This is the first report of quality of life associated with liver SBRT. Methods and Materials: From October 2002 to March 2007, a total of 28 patients not suitable for other local treatments and with Karnofsky performance status of at least 80% were entered in a Phase I-II study of SBRT for liver tumors. Quality of life was a secondary end point. Two generic quality of life instruments were investigated, EuroQol-5D (EQ-5D) and EuroQoL-Visual Analogue Scale (EQ-5D VAS), in addition to a disease-specific questionnaire, the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ C-30). Points of measurement were directly before and 1, 3, and 6 months after treatment. Mean scores and SDs were calculated. Statistical analysis was performed using paired-samples t-test and Student t-test. Results: The calculated EQ-5D index, EQ-5D VAS and QLQ C-30 global health status showed that mean quality of life of the patient group was not significantly influenced by treatment with SBRT; if anything, a tendency toward improvement was found. Conclusions: Stereotactic body radiation therapy combines a high local control rate, by delivering a high dose per fraction, with no significant change in quality of life. Multicenter studies including larger numbers of patients are recommended and under development.

Clinical Aspects of Hepatocellular Carcinoma (Doctoral Thesis)

2008-02-13T00:00:00Z

Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world and the third most common cause of cancer mortality1. Despite the high numbers of patients diagnosed worldwide (the estimated number of people is 0.5 million cases per year), HCC continue to pose challenging clinical problems. The assessment of the tumor and treatment options needs a multi-disciplinary approach in which the surgeon plays a central role. The aim of this thesis is to update on the incidence, etiology, diagnostic and treatment modalities in patients with HCC.

Isolated limb perfusion with melphalan and TNF-α in the treatment of extremity sarcoma (Article)

2007-12-01T00:00:00Z

Isolated limb perfusion (ILP) with chemotherapy alone has uniformly failed in the treatment of irresectable extremity soft tissue sarcomas. The addition of tumor necrosis factor-alpha (TNF-α) to this treatment approach contributed to a major step forward in the treatment of locally advanced extremity soft tissue sarcoma (STS). High response rates and limb salvage rates have been reported in multicenter trials, which combined ILP with TNF-α plus melphalan, which resulted in the approval of TNF-α for this indication in Europe in 1998. Subsequently a series of confirmatory single institution reports on the efficacy of the procedure have now been published. TNF-α has an early and a late effect; it enhances tumor-selective drug uptake during the perfusion and plays an essential role in the subsequent selective destruction of the tumor vasculature. These effects result in a high response rate in high-grade soft tissue sarcomas. This induction therapy thus allows for resection of tumor remnants some 3 months after ILP and thus avoidance of limb amputation. TNF-α-based ILP is a well-established treatment to avoid amputations. It represents an important example of tumor vasculatory-modulating combination therapy and should be offered in large volume tertiary referral centers.

Pelvic exenteration for primary and recurrent gynaecological malignancies (Article)

2007-10-01T00:00:00Z

Objective: Analyse the outcome of pelvic exenteration for gynaecological malignancies in a tertiary referral center. Post-operative in-hospital morbidity, long-term morbidity, disease free and overall survival rates were studied. Study design: Between 1991 and 2004, 42 patients underwent an anterior, total or posterior exenteration for gynaecological malignancies. Follow-up was obtained from patient files; disease free and overall survival were calculated and prognostic factors were studied. Results: A pelvic exenteration was performed in 14 patients for primary and 28 patients for recurrent gynaecological cancers. In-hospital complications occurred in 19 patients (45%) of whom seven patients needed a reoperation (17%). Late complications occurred in 31 patients (75%); 21 reinterventions were performed (50%). Five-year disease free and overall survival was, respectively, 48 and 52%. Age, type of surgery, histology, localisation of the tumour, lateral wall involvement, completeness of resection and primary versus recurrent cancer were not identified as prognostic factors for recurrence or survival. Conclusion: Long-term survival is possible in about 50% of patients after pelvic exenteration for gynaecological cancers, but is associated with significant post-operative morbidity.

Management of locally advanced primary and recurrent rectal cancer (Article)

2007-08-01T00:00:00Z

Treatment for patients with locally advanced and recurrent rectal cancer differs significantly from patients with rectal cancer restricted to the mesorectum. Adequate preoperative imaging of the pelvis is therefore important to identify those patients who are candidates for multimodality treatment, including preoperative chemoradiation protocols, intraoperative radiotherapy, and extended surgical resections. Much effort should be made to select patients with these advanced tumors for treatment in specialized referral centers. This has been shown to reduce morbidity and mortality and improve long-term survival rates. In this article, we review the best treatment options for patients with locally advanced and recurrent rectal cancer. We also emphasize the necessity of a multidisciplinary team, including a radiologist, radiation oncologist, urologist, surgical oncologist, plastic surgeon, and gynecologist in the diagnosis and treatment of patients with these pelvic tumors. Copyright

Total pelvic exenteration for primary locally advanced and locally recurrent rectal cancer (Article)

2007-05-01T00:00:00Z

Aims: To report the role of total pelvic exenteration in a series of locally advanced and recurrent rectal cancers. Methods: In the period 1994-2004, TPE was performed in 35 of 296 patients with primary locally advanced and recurrent rectal cancer treated in the Daniel den Hoed Cancer Center; 23 of 176 with primary locally advanced and 12 of 120 with recurrent rectal cancer. All but one patient received pre-operative External Beam Radiation Therapy (EBRT). After 1997, Intra Operative Radiotherapy (IORT) was performed in case of a resection margin less than 2 mm. Results: Overall major complication rates were not significantly different between patients with primary and recurrent rectal cancer (26% vs. 50%, p = 0.94). The hospital mortality rate was 3%. The 5-year local control and overall survival of patients with primary locally advanced rectal cancer were 88% and 52%, respectively. In patients with recurrent rectal cancer 3-year local control and survival rates were 60% and 32%, respectively. An incomplete resection, preoperative pain and advanced Wanebo stage for recurrent cancer were negative prognostic factors for both local control and overall survival. Conclusion: TPE in primary locally advanced rectal cancer enables good local control and acceptable overall survival, thereby justifying the use of the procedure. Patients with recurrent rectal cancer showed a high rate of major complications, a high distant metastasis rate, and a poor overall survival.

Giant myositis ossificans of the leg (Article)

2007-04-01T00:00:00Z

Neoadjuvant chemotherapy and resection of advanced synchronous liver metastases before treatment of the colorectal primary (Br J Surg 2006; 93: 872-878) [8] (Article)

2007-02-01T00:00:00Z

Randomized clinical trial comparing feeding jejunostomy with nasoduodenal tube placement in patients undergoing oesophagectomy (Article)

2007-01-01T00:00:00Z

Background: Feeding jejunostomy is frequently performed in patients undergoing oesophageal surgery, but can lead to serious complications. This prospective randomized trial compared the efficacy and complications of feeding jejunostomy with those of nasoduodenal tube feeding in oesophageal surgery. Methods: Over an 18-month period, 150 consecutive patients undergoing oesophageal resection were randomized to participate in the trial. Enteral access was by jejunostomy in 79 patients and by nasoduodenal tube in 71. Enteral feeding was started on the first day after surgery. Results: Full enteral feeding took 3 days to be established in both groups. Minor catheter-related complications occurred in 28 patients (35 per cent) in the jejunostomy group, and in 21 (30 per cent) in the nasoduodenal group (P = 0.488). One patient had jejunostomy leakage that required reoperation. Enteral nutrition was given for a median of 11 days in the jejunostomy group and for 10 days in the nasoduodenal group. Nine patients who had a jejunostomy and five with a nasoduodenal tube did not tolerate full enteral feeding (P = 0.411). Conclusion: Nasoduodenal tube feeding is safe and efficient after oesophageal resection. Copyright

Sentinel node biopsy for clear cell sarcoma (Article)

2006-11-01T00:00:00Z

Clear cell sarcoma (CCS), also known as clear cell sarcoma of tendons and aponeuroses or malignant melanoma of soft tissue, is a rare malignant tumor and is histogenitically related to melanoma. The aim of this study was to describe our experience with the sentinel node (SN) procedure for CCS patients and to discuss the potential value of this technique for CCS patients. Five patients with a subcutaneous CCS, who underwent an SN procedure, are described. Two patients had positive SNs, with additional tumor positive nodes in both lymph node dissection specimens. Only the patients with tumor positive SNs developed recurrent disease during an average follow-up of 33 months. None of the negative SN patients developed recurrent disease and all were alive after an average follow-up of 39 months. SN status seems to predict additional nodal involvement and recurrent disease as well as survival. The SN procedure might be a useful and accurate staging procedure in CCS patients, comparable to the situation in melanoma.

Clinical relevance of melanoma micrometastases (<0.1 mm) in sentinel nodes: are these nodes to be considered negative? (Article)

2006-10-01T00:00:00Z

As only about 20% of sentinel node (SN) positive melanoma patients have additional non-SN lymph node involvement in the Completion Lymph Node Dissection (CLND) specimen, we tried to identify a SN positive patient group, which can be spared CLND. Micro anatomic analyses of metastatic SNs were performed to identify patient/tumor and/or SN factors predicting additional non-SN positivity as well as disease-free and overall survival. SN positivity was found in 77 of 262 stage I/II patients, included into a prospective database (10/97-5/04). Of 74 patients pathology material was available for re-evaluation. Micro anatomic analyses categorized topography of SN-metastases, Starz classification and amount of SN tumor burden. Additional non-SN positivity, DFS, OS and was calculated for all analyses. Mean Breslow thickness was 3.5 mm (0.8-12.0); mean FU was 35 (6-81) months. There was no additional non-SN positivity for SN-micrometastases <0.1 mm. Topography of SN involvement had no impact on OS. Estimated 5-year OS rates for the different groups of <0.1 mm, 0.1-1.0 mm and >1.0 mm SN tumor burden were 100%, 63% and 35% respectively. Distant metastases were exceedingly rare (1/16 = 6.3%) in <0.1 mm SN-positive patients. On multivariate analysis the SN tumor burden was the most important prognostic factor for DFS (P = 0.005) and OS (P = 0.03). Distant metastasis-free survival was identical (91%) to the 5-yr OS of SN negative patients, the estimated 5-yr OS was 100% for these patients and additional non-SN positivity was not observed. Therefore, our data suggest that patients with sub-micrometastases (<0.1 mm) in the SN may be judged as SN negative, as non-stage III, and are highly unlikely to benefit from CLND, which we no longer recommend.

High positive sentinel node identification rate by EORTC melanoma group protocol (Article)

2006-02-01T00:00:00Z

Methods to work-up sentinel nodes (SN) vary considerably between institutes. This single institution study evaluated the positive SN-identification rate of the EORTC Melanoma Group (MG) protocol and investigated the prognostic value of the SN status regarding disease-free survival (DFS) and overall survival (OS) and evaluated the locoregional control after the SN procedure. Multivariate and univariate analyses using Cox's proportional hazard regression model was employed to assess the prognostic value of covariates regarding DFS and OS. The positive SN-identification rate was 29% at a median Breslow thickness of 2.00 mm and the false-negative rate was 9.4%. Breslow thickness and ulceration of the primary correlated with SN status. SN status, ulceration and site of the primary tumour correlated with DFS. SN status and ulceration of the primary correlated with OS. The in-transit metastasis rate correlated with SN-positivity, Breslow thickness and ulceration. Projected 3-year OS was 95% in SN-negative and 74% in SN-positive patients. Transhilar bivalving of the SN with step sections from the central planes is simple and had a high SN-positive detection rate of about 30%. The SN status is the most important predictive value for DFS and OS. In-transit metastasis rates correlated with SN-positivity, Breslow thickness and ulceration of the primary.

Schildwachtklierbiopsie bij het melanoom: prognostische betekenis en nadelen bij 300 patienten (Letter To Editor)

2005-11-01T00:00:00Z

De Vries et al. ( 2005:1845-51 ) concluderen dat de uitslag van de schildwachtklier(SWK)-procedure bij melanoompatiënten de belangrijkste prognostische factor is. Tevens concluderen zij, volgens ons ten onrechte, dat de kans op in-transitmetastasen na een SWK-procedure mogelijk toeneemt. Een aantal zeer recente publicaties van grote studies met meer dan 5000 patiënten weerlegt deze opmerking...

Isolated hypoxic hepatic perfusion with orthograde or retrograde flow in patients with irresectable liver metastases using percutaneous balloon catheter techniques: a phase I and II study. (Article)

2004-12-01T00:00:00Z

BACKGROUND: Isolated hepatic perfusion for irresectable metastases confined to the liver has reported response rates of 50% to 75%. Magnitude, costs, and nonrepeatability of the procedure are its major drawbacks. We developed a less invasive, less costly, and potentially repeatable balloon catheter-mediated isolated hypoxic hepatic perfusion (IHHP) technique. METHODS: In this phase I and II study, 18 consecutive patients with irresectable colorectal or ocular melanoma hepatic metastases were included. Two different perfusion methods were used, both with inflow via the hepatic artery, using melphalan 1 mg/kg. In the first eight patients, the portal vein was occluded, and outflow was via the hepatic veins into an intracaval double-balloon catheter. This orthograde IHHP had on average 56% leakage. In next 10 patients, we performed a retrograde outflow IHHP with a triple balloon blocking outflow into the caval vein and allowing outflow via the portal vein. The retrograde IHHP still had 35% leakage on average. RESULTS: Although local drug concentrations were high with retrograde IHHP, systemic toxicity was still moderate to severe. Partial responses were seen in 12% and stable disease in 81% of patients. The median time to local progression was 4.8 months. CONCLUSIONS: We have abandoned occlusion balloon methodology for IHHP because it failed to obtain leakage control. We are presently conducting a study using a simplified surgical retrograde IHHP method, in which leakage is fully controlled, which translates into high response rates.