Mechteld C de Jong

Maastricht University, Maestricht, Limburg, Netherlands

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Publications (39)156.83 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Background The impact of postoperative complications on long-term outcomes after surgery for colorectal liver metastases (CRLM) remains controversial. During the last decade, advances in surgical as well as non-surgical treatment have increased resectability and altered outcomes. We sought to determine the influence of postoperative morbidity on disease-free (DFS) and overall survival (OS). Methods All patients undergoing liver resection for CRLM for the first time between 2000 and 2011 were retrospectively identified from a prospective database. Postoperative morbidity was classified according to Dindo–Clavien grade. A Dindo–Clavien grade ≥3a was considered a major complication. Primary outcomes were DFS and OS depending on the presence or absence of postoperative morbidity. Results Of the 266 included patients, 97 patients (37 %) developed postoperative complications, of whom 61 (23 %) had major complications. Median DFS and OS (5-year) were 17 and 53 months (42 %). The occurrence of postoperative morbidity did not significantly shorten OS (p = 0.130) and DFS (p = 0.101). However, major morbidity reduced DFS significantly (p
    World Journal of Surgery 10/2014; 39(2). DOI:10.1007/s00268-014-2799-1 · 2.35 Impact Factor
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    ABSTRACT: Currently, resection criteria for colorectal cancer liver metastases (CRCLM) are only limited by remnant liver function. Morbidity and survival after a partial hepatectomy with limited or extended indication criteria were compared. Between 1991 and 2010, patients undergoing a liver resection for CRCLM with limited (n = 169) or extended indication criteria (n = 129) were retrospectively identified in a prospectively collected single-centre database. Limited indication criteria were defined as less than three unilateral, not centrally located liver metastases in the absence of extra hepatic metastases. The extended criteria were only limited by predicted remnant liver volume and patients fitness. Data on co-morbidity, resection margin, short- and long-term morbidity, disease-free (DFS) and overall survival were compared. Patients with limited indications had less major complications (19.5% vs. 33.1%, P < 0.01), longer overall survival of 68.8 months [confidence interval (CI) 46.5-91.1] vs. 41.4 months (CI 33.4-49.0, P ≤ 0.001) and longer median DFS of 22.0 months [confidence interval (CI) 15.8-28.2] vs 10.2 months (CI 8.4-11.9, P < 0.001) compared with the extended indication group. Cure rates, defined as 10-year DFS, were 35.5% and 15.8%, respectively. Fewer patients in the extended indication group underwent an R0 resection (92.9% vs. 77.5%, P < 0.001). Only 17% of all R1 resected patients had recurrences at the transection plane. A partial hepatectomy for CRCLM with extended indications seems justified but is associated with higher complication rates, earlier recurrence and lower overall survival compared with limited indications. However, the median 5-year survival was substantial and a cure was achieved in 15.8% of patients.
    HPB 11/2013; 16(6). DOI:10.1111/hpb.12181 · 2.05 Impact Factor
  • M N Mavros · M de Jong · E Dogeas · O Hyder · T M Pawlik
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    ABSTRACT: BACKGROUND: Postoperative complications may have an adverse effect not only on short-term but also long-term outcome among patients having surgery for cancer. A retrospective series of patients who had surgery for colorectal liver metastases (CLM) was used to assess this association. METHODS: Patients who had surgery with curative intent for CLM from 2000 to 2009 were included. The impact of postoperative complications, patient characteristics, disease stage and treatment on long-term survival was analysed using multivariable Cox regression models. RESULTS: A total of 251 patients were included. The median age was 58 (interquartile range 51-68) years and there were 87 women (34·7 per cent). A minor or major postoperative complication developed in 41 and 14 patients respectively, and five patients (2·0 per cent) died after surgery. The 5-year recurrence-free (RFS) and overall survival rates were 19·5 and 41·9 per cent respectively. Multivariable analysis revealed that postoperative complications independently predicted shorter RFS (hazard ratio (HR) 2·36, 95 per cent confidence interval 1·56 to 3·58) and overall survival (HR 2·34, 1·46 to 3·74). Other independent predictors of shorter RFS and overall survival included lymph node metastasis, concomitant extrahepatic disease, a serum carcinoembryonic antigen level of at least 100 ng/dl, and the use of radiofrequency ablation (RFS only). The severity of complications also correlated with RFS (P = 0·006) and overall survival (P = 0·001). CONCLUSION: Postoperative complications were independently associated with decreased long-term survival after surgery for CLM with curative intent. The prevention and management of postoperative adverse events may be important oncologically. Copyright © 2013 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.
    British Journal of Surgery 04/2013; 100(5). DOI:10.1002/bjs.9060 · 5.21 Impact Factor
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    ABSTRACT: BACKGROUND: Sustainability of hepatic glutathione (GSH) homeostasis is an important cellular defense against oxidative stress. Therefore, knowledge of liver GSH status is important. However, measurement of plasma GSH and tissue is difficult due to its instability. Alternatively, ophthalmate (OPH), an endogenous tripeptide analog of GSH, has been suggested as a potential indicator to assess GSH depletion. AIM: To provide an overview of present knowledge with respect to the usefulness of OPH as a biomarker for oxidative stress and hepatic GSH homeostasis. METHODS: A systematic, computerized search combined with a cross-reference search of the literature described in PubMed (January 1975 to January 2012) was conducted, key words: 'ophthalmate' and 'ophthalmic acid'. RESULTS: Twenty-two articles were included. Hepatic OPH levels increase inversely proportional to a drop in hepatic GSH in mice with paracetamol (PCM) induced hepatotoxicity. Little is known about the stability of OPH in human plasma. To measure the very low physiological concentrations of plasma OPH, liquid chromatography-mass spectrometry techniques can be employed. OPH synthesis can be measured in humans, using stable isotope labeling with a deuterated water ((2)H(2)O) load. CONCLUSION: OPH may be a promising biomarker to indicate hepatic glutathione depletion, but the suggested biological pathways need further unraveling.
    Clinical nutrition (Edinburgh, Scotland) 10/2012; 32(3). DOI:10.1016/j.clnu.2012.10.008 · 3.94 Impact Factor
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    ABSTRACT: Outcomes after operative management of benign hepatic lesions are ill-defined. We sought to define patient-reported quality of life (QOL) postoperatively for benign hepatic tumors. Patients who underwent surgery for benign liver lesions (n = 255) were invited to complete a QOL survey designed using validated assessment tools. Clinicopathologic data were collected from 2 participating hepatobiliary centers and correlated with QOL data. The response rate was 70.2%. Most patients had a benign cystic (41.9%) or solid (47.5%) tumor; 19 (10.6%) patients had an indeterminate lesion. The lesion was most often solitary (71.5%) and median size was 7.5 cm. Most benign lesions were either a simple cyst (35.8%), hemangioma (19.6%), focal nodular dysplasia (19.6%), or hepatic adenoma (16.9%). Presenting symptoms included abdominal pain (70.9%), nausea/vomiting (5.0%), and early satiety (5.0%). Surgery involved less than hemihepatectomy (68.2%); a laparoscopic approach was utilized in 40.8% of patients. Perioperative morbidity was 16%. Postoperatively, the proportion of patients who reported moderate-to-extreme pain decreased from 46.9% to 15.6% and 6.8% at 6 months and 1-year, respectively (P < .001). Patient self-reported mean pain scores also decreased over time (preoperative, 1.65 vs 6 months, 0.63 vs 1 year, 0.28; P < .001). Patients with "moderate-to-extreme" pain preoperatively were more likely to report an improvement in pain scores (odds ratio, 1.96; 95% confidence interval, 1.05-3.66; P = .03). Many patients reported overall improvement in general health (40.5%) and physical health (39.3%; P < .001). Surgery for benign liver lesions is associated with high patient satisfaction and improved QOL. Patients with significant preoperative symptoms derive the most benefit from surgery.
    Surgery 08/2012; 152(2):193-201. DOI:10.1016/j.surg.2012.05.004 · 3.11 Impact Factor
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    ABSTRACT: Based on animal experimentations, ophthalmate (OPH) has recently been suggested as a potential plasma biomarker to probe hepatic GSH homeostasis. Up until now, the inability to accurately determine OPH concentrations in human plasma prohibited further studies of OPH metabolism in humans. This study therefore aimed to study the influence of delayed sample preparation on OPH concentrations using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Venous plasma samples from 5 healthy human volunteers were incubated for varying times (5, 30, 60 and 120 min) at temperatures of 4 °C and 37 °C to investigate potential enzymatic degradation. At 37 °C, the decrease in OPH reached significance after 120 min (74.6% (range: 56.2-100.0%; p<0.0001)). At 4 °C, the same trend was observed but did not reach significance. These findings indicate ongoing enzymatic activity, stressing the need for immediate sample deproteinization to obtain reliable plasma concentrations. To investigate the feasibility of the here developed method, baseline arterial plasma values of 21 patients scheduled for partial liver resection were determined to be 0.06±0.03 μmol/l (mean±s.d.). In addition, in pooled samples from 3 patients, an OPH calibration curve was spiked to arterial plasma, arterial whole blood and liver biopsy material, resulting in a linear calibration curve in all cases. Individual measurements of baseline samples revealed that both arterial whole blood and liver biopsy material contained significant levels of endogenous OPH, namely 16.1 (11.8-16.4) μmol/l and 80.0 (191.8-349.2) μmol/kg, respectively. In conclusion, the present LC-MS/MS assay enables the accurate measurement of OPH in human plasma, whole blood and liver biopsies. Freshly prepared samples and immediate deproteinization are mandatory to block enzymatic degradation.
    Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 06/2012; 903:1-6. DOI:10.1016/j.jchromb.2012.06.023 · 2.69 Impact Factor
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    ABSTRACT: The benefit of pre-operative chemotherapy in patients with resectable colorectal liver metastases (CRLM) remains ill defined. We sought to evaluate the impact of peri-operative systemic chemotherapy timing on outcome following resection of CRLM. 676 patients who underwent surgery for CRLM were identified from two hepatobiliary center databases. Data were collected and analyzed utilizing multivariate, matched, and propensity-score analyses. Median number of metastases was 2 and median tumor size was 3.3 cm. 334 patients (49.4%) received pre-operative chemotherapy while 342(50.6%) did not. Surgical treatment was resection only (n = 555; 82.1%; minor hepatectomy, n = 399; 59.1%). While there was no difference in morbidity following minor liver resection (pre-operative chemotherapy: 17.9% versus no pre-operative chemotherapy: 16.5%; P = 0.72), morbidity was higher after major hepatic resection (pre-operative chemotherapy: 23.1% versus no pre-operative chemotherapy: 14.2%; P = 0.06). Patients treated with pre-operative chemotherapy had worse 5-year survival (43%) as compared to patients not treated with pre-operative chemotherapy (55%)(P = 0.009). Controlling for baseline characteristics, pre-operative chemotherapy was not associated with outcome on multivariate (HR = 1.04, P = 0.87) or propensity-score analysis (HR = 1.40, P = 0.12). Pre-operative chemotherapy was associated with a trend toward increased morbidity among patients undergoing a major hepatic resection. Receipt of pre-operative chemotherapy was associated with neither an advantage nor disadvantage in terms of long-term survival.
    Journal of Surgical Oncology 05/2012; 105(6):511-9. DOI:10.1002/jso.22133 · 2.84 Impact Factor
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    ABSTRACT: Although hepatic metastasectomy is well established for colorectal and neuroendocrine cancer, the approach to hepatic metastases from other sites is not well defined. We sought to examine the management of noncolorectal non-neuroendocrine liver metastases. A retrospective review from 4 major liver centers identified patients who underwent liver resection for noncolorectal non-neuroendocrine metastases between 1990 and 2009. The Kaplan-Meier method was used to analyze survival, and Cox regression models were used to examine prognostic variables. There were 420 patients available for analysis. Breast cancer (n = 115; 27%) was the most common primary malignancy, followed by sarcoma (n = 98; 23%), and genitourinary cancers (n = 92; 22%). Crude postoperative morbidity and mortality rates were 20% and 2%, respectively. Overall median survival was 49 months, and 1, 3, and 5-year Kaplan-Meier survival rates were 73%, 50%, and 31%. Survival was not significantly different between the various primary tumor types. Recurrent disease was found after hepatectomy in 66% of patients. In multivariable models, lymphovascular invasion (p = 0.05) and metastases ≥5 cm (p = 0.04) were independent predictors of poorer survival. Median survival was shorter for resections performed between 1990 and 1999 (n = 101, 32 months) when compared with resections between 2000 and 2009 (n = 319, 66 months; p = 0.003). Hepatic metastasectomy for noncolorectal non-neuroendocrine cancers is safe and feasible in selected patients. Lymphovascular invasion and metastases ≥5 cm were found to be associated with poorer survival. Patients undergoing metastasectomy in more recent years appear to be surviving longer, however, the reasons for this are not conclusively determined.
    Journal of the American College of Surgeons 03/2012; 214(5):769-77. DOI:10.1016/j.jamcollsurg.2011.12.048 · 4.45 Impact Factor
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    ABSTRACT: BACKGROUND. Surgical strategy for hilar cholangiocarcinoma often includes hepatectomy, but the role of portal vein resection (PVR) remains controversial. In this study, the authors sought to identify factors associated with outcome after surgical management of hilar cholangiocarcinoma and examined the impact of PVR on survival. Three hundred five patients who underwent curative-intent surgery for hilar cholangiocarcinoma between 1984 and 2010 were identified from an international, multi-institutional database. Clinicopathologic data were evaluated using univariate and multivariate analyses. Most patients had hilar cholangiocarcinoma with tumors classified as T3/T4 (51.1%) and Bismuth-Corlette type II/III (60.9%). Resection involved extrahepatic bile duct resection (EHBR) alone (26.6%); or hepatectomy and EHBR without PVR (56.7%); or combined hepatectomy, EHBR, and PVR (16.7%). Negative resection (R0) margin status was higher among the patients who underwent hepatectomy plus EHBR (without PVR, 64.2%; with PVR, 66.7%) versus EHBR alone (54.3%; P < .001). The median number of lymph nodes assessed was higher among the patients who underwent hepatectomy plus EHBR (without PVR, 6 lymph nodes; with PVR, 4 lymph nodes) versus EHBR alone (2 lymph nodes; P < .001). The 90-day mortality rate was lower for patients who underwent EHBR alone (1.2%) compared with the rate for patients who underwent hepatectomy plus EHBR (without PVR, 10.6%, with PVR, 17.6%; P < .001). The overall 5-year survival rate was 20.2%. Factors that were associated with an adverse prognosis included lymph node metastasis (hazard ratio [HR], 1.79; P = .002) and R1 margin status (HR, 1.81; P < .001). Microscopic vascular invasion did not influence survival (HR, 1.23; P = .19). Among the patients who underwent hepatectomy plus EHBR, PVR was not associated with a worse long-term outcome (P = .76). EHBR alone was associated with a greater risk of positive surgical margins and worse lymph node clearance. The current results indicated that hepatectomy should be considered the standard treatment for hilar cholangiocarcinoma, and PVR should be undertaken when necessary to extirpate all disease. Combined hepatectomy, EHBR, and PVR can offer long-term survival in some patients with advanced hilar cholangiocarcinoma. Cancer 2012. © 2012 American Cancer Society.
    Cancer 03/2012; 118(19):4737-47. DOI:10.1002/cncr.27492 · 4.90 Impact Factor
  • Journal of Surgical Research 02/2012; 172(2):286. DOI:10.1016/j.jss.2011.11.488 · 2.12 Impact Factor
  • E. Neis · S. Dello · M. de Jong · H. van Eijk · C. Dejong
    Clinical Nutrition Supplements 12/2011; 6(1):36-36. DOI:10.1016/S1744-1161(11)70088-6
  • Skye C Mayo · Mechteld C de Jong · Timothy M Pawlik
    Annals of Surgical Oncology 12/2011; 18 Suppl 3(S3):S220-1; author reply S222-3. DOI:10.1245/s10434-010-1343-2 · 3.94 Impact Factor
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    ABSTRACT: For patients who present with synchronous colorectal carcinoma and colorectal liver metastasis (CRLM), a reversed treatment sequence in which the CRLM are resected before the primary carcinoma has been proposed (liver-first approach). The aim of the present study was to assess the feasibility and outcome of this approach for synchronous CRLM. Between 2005 and 2010, 22 patients were planned to undergo the liver-first approach. Feasibility and outcomes were prospectively evaluated. Of the 22 patients planned to undergo the liver-first strategy, the approach was completed in 18 patients (81.8%). The main reason for treatment failure was disease progression. Patients who completed treatment and patients who deviated from the protocol had a similar location of the primary tumour, as well as comparable size, number and distribution of CRLM (all P > 0.05). Post-operative morbidity and mortality were 27.3% and 0% following liver resection and 44.4% and 5.6% after colorectal surgery, respectively. On an intention-to-treat-basis, overall 3-year survival was 41.1%. However, 37.5% of patients who completed the treatment had developed recurrent disease at the time of the last follow-up. The liver-first approach is feasible in approximately four-fifths of patients and can be performed with peri-operative mortality and morbidity similar to the traditional treatment paradigm. Patients treated with this novel strategy derive a considerable overall-survival-benefit, although disease-recurrence-rates remain relatively high, necessitating a multidisciplinary approach.
    HPB 10/2011; 13(10):745-52. DOI:10.1111/j.1477-2574.2011.00372.x · 2.05 Impact Factor
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    ABSTRACT: To identify factors associated with outcome after surgical management of intrahepatic cholangiocarcinoma (ICC) and examine the impact of lymph node (LN) assessment on survival. From an international multi-institutional database, 449 patients who underwent surgery for ICC between 1973 and 2010 were identified. Clinical and pathologic data were evaluated using uni- and multivariate analyses. Median tumor size was 6.5 cm. Most patients had a solitary tumor (73%) and no vascular invasion (69%). Median survival was 27 months, and 5-year survival was 31%. Factors associated with adverse prognosis included positive margin status (hazard ratio [HR], 2.20; P < .001), multiple lesions (HR, 1.80; P = .001), and vascular invasion (HR, 1.59; P = .015). Tumor size was not a prognostic factor (HR, 1.03; P = .23). Patients were stratified using the American Joint Committee on Cancer/International Union Against Cancer T1, T2a, and T2b categories (seventh edition) in a discrete step-wise fashion (P < .001). Lymphadenectomy was performed in 248 patients (55%); 74 of these (30%) had LN metastasis. LN metastasis was associated with worse outcome (median survival: N0, 30 months v N1, 24 months; P = .03). Although patients with no LN metastasis were able to be stratified by tumor number and vascular invasion (N0; P < .001), among patients with N1 disease, multiple tumors and vascular invasion, either alone or together, failed to discriminate patients into discrete prognostic groups (P = .34). Although tumor size provides no prognostic information, tumor number, vascular invasion, and LN metastasis were associated with survival. N1 status adversely affected overall survival and also influenced the relative effect of tumor number and vascular invasion on prognosis. Lymphadenectomy should be strongly considered for ICC, because up to 30% of patients will have LN metastasis.
    Journal of Clinical Oncology 08/2011; 29(23):3140-5. DOI:10.1200/JCO.2011.35.6519 · 18.43 Impact Factor
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    ABSTRACT: As indications for liver resection expand, objective measures to assess the risk of peri-operative morbidity are needed. The impact of sarcopenia on patients undergoing liver resection for colorectal liver metastasis (CRLM) was investigated. Sarcopenia was assessed in 259 patients undergoing liver resection for CRLM by measuring total psoas area (TPA) on computed tomography (CT). The impact of sarcopenia was assessed after controlling for clinicopathological factors using multivariate modelling. Median patient age was 58 years and most patients (60%) were male. Forty-one (16%) patients had sarcopenia (TPA ≤ 500 mm(2) /m(2) ). Post-operatively, 60 patients had a complication for an overall morbidity of 23%; 26 patients (10%) had a major complication (Clavien grade ≥3). The presence of sarcopenia was strongly associated with an increased risk of major post-operative complications [odds ratio (OR) 3.33; P= 0.008]. Patients with sarcopenia had longer hospital stays (6.6 vs. 5.4 days; P= 0.03) and a higher chance of an extended intensive care unit (ICU) stay (>2 days; P= 0.004). On multivariate analysis, sarcopenia remained independently associated with an increased risk of post-operative complications (OR 3.12; P= 0.02). Sarcopenia was not significantly associated with recurrence-free [hazard ratio (HR) = 1.07] or overall (HR = 1.05) survival (both P > 0.05). Sarcopenia impacts short-, but not long-term outcomes after resection of CRLM. While patients with sarcopenia are at an increased risk of post-operative morbidity and longer hospital stay, long-term survival is not impacted by the presence of sarcopenia.
    HPB 07/2011; 13(7):439-46. DOI:10.1111/j.1477-2574.2011.00301.x · 2.05 Impact Factor
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    ABSTRACT: Management of patients with neuroendocrine liver metastasis (NELM) remains controversial. We sought to examine the relative efficacy of surgical management versus intra-arterial therapy (IAT) for NELM and determine factors predictive of survival. A total of 753 patients who had surgery (n = 339) or IAT (n = 414) for NELM from 1985 to 2010 were identified from nine hepatobiliary centers. Clinicopathologic data were assessed with regression modeling and propensity score matching. Most patients had a pancreatic (32%) or a small bowel (27%) primary tumor; 47% had a hormonally active tumor. There were statistically significant differences in characteristics between surgery versus IAT groups (hormonally active tumors: 28 vs. 48%; hepatic tumor burden >25%: 52% vs. 76%) (all P < 0.001). Among surgical patients, most underwent hepatic resection alone without ablation (78%). The median number of IAT treatments was 1 (range, 1-4). Median and 5-year survival of patients treated with surgery was 123 months and 74% vs. 34 months and 30% for IAT (P < 0.001). In the propensity-adjusted multivariate Cox model, asymptomatic disease (hazard ratio 2.6) was strongly associated with worse outcome (P = 0.001). Although surgical management provided a survival benefit over IAT among symptomatic patients with >25% hepatic tumor involvement, there was no difference in long-term outcome after surgery versus IAT among asymptomatic patients (P = 0.78). Asymptomatic patients with a large (>25%) burden of liver disease benefited least from surgical management and IAT may be a more appropriate treatment strategy. Surgical management of NELM should be reserved for patients with low-volume disease or for those patients with symptomatic high-volume disease.
    Annals of Surgical Oncology 06/2011; 18(13):3657-65. DOI:10.1245/s10434-011-1832-y · 3.94 Impact Factor
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    ABSTRACT: Following resection of pancreatic adenocarcinoma, tumor size has been considered a key prognostic feature; however, this remains controversial. We sought to examine the association of size with outcomes following resection of pancreatic adenocarcinoma. Between 1970 and 2010, 1,697 patients with pancreatic adenocarcinoma at the Johns Hopkins Hospital underwent curative intent pancreaticoduodenectomy. Prognostic factors were identified by univariate and multivariate analyses. Of 1,697 patients, tumor size was ≤ 2 cm in 418 (24.6%) patients, 2-5 cm in 1,070 (63.1%) patients, and ≥ 5 cm in 209 (12.3%) patients. On univariate analyses, 5-year survival was inversely proportional to tumor size (≤ 2 cm: 28.8% vs. 2-5 cm: 19.4% vs. ≥ 5 cm: 14.2%; P < 0.001). Size correlated with the risk of other adverse factors, with larger tumors being more likely to be associated with nodal disease and poor differentiation (both P < 0.05). On multivariate analysis, the 2 cm cut-off was not associated with survival, while nodal disease (HR = 1.59; P = 0.006) and poor differentiation (HR = 1.59; P = 0.04) remained predictive of outcome, regardless of size. The cut-off value of 2 cm is not independently associated with outcome, however, tumor size was strongly associated with the risk of other adverse prognostic factors. The effect of size on prognosis was largely attributable to these other biologic factors rather than tumor size itself.
    Journal of Surgical Oncology 06/2011; 103(7):656-62. DOI:10.1002/jso.21883 · 2.84 Impact Factor
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    ABSTRACT: The American Joint Committee on Cancer staging system for hilar cholangiocarcinoma may be inaccurate because the bile duct lacks discrete tissue boundaries. To examine the accuracy of the American Joint Committee on Cancer staging schemes and to determine the prognostic implications of tumor depth. From January 1, 1987, through December 31, 2009, there were 106 patients who underwent resection of hilar cholangiocarcinoma who had pathologic slides available for re-review. Tumor depth and overall survival. Overall median survival was 19.9 months. The 6th and 7th editions of the T-classification criteria were unable to discriminate among T1, T2, and T3 lesions (P > .05 for all). Median survival was associated with the invasion depth of the tumor (≥5 mm vs <5 mm): 18 months vs 30 months (P = .01). On multivariate analysis, tumor depth remained predictive of disease-specific death (hazard ratio, 1.70; P = .03). The American Joint Committee on Cancer T-classification criteria did not stratify patients with regard to prognosis. Depth of tumor invasion is a better predictor of long-term outcome.
    Archives of surgery (Chicago, Ill.: 1960) 06/2011; 146(6):697-703. DOI:10.1001/archsurg.2011.122 · 4.30 Impact Factor
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    ABSTRACT: In recent years, with a deeper understanding of pathologic changes in hepatolithiasis, more and more attention has been paid to the relationship of postoperative remnant proliferative cholangitis (PC) with stone recurrence and biliary restenosis, but effective management strategies have not yet been developed. Thus, the aim of this study was to determine whether epidermal growth factor receptor inhibitor (AG-1478) could inhibit hyperplasia and lithogenic potentiality of PC. The PC animal model was established via retrograde insertion of a 5-0 nylon thread into the common bile duct through Vater's papilla. The common bile duct in the therapeutic group received a single intraluminal administration of AG-1478, followed by weekly intraperitoneal injections of AG-1478. Subsequently, influence of EGFR inhibitor on hyperplasia, apoptosis, and lithogenic potential of PC were evaluated via histology, expression changes of EGFR, BrdU, Ki-67, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), Fas, mucin 5 AC, and collagen I. EGFR inhibitor AG-1478 was effective not only in inhibiting the mRNA and protein expression of EGFR, BrdU, and Ki-67, but also in increasing Fas mRNA expression and TUNEL-positive cells, as a result leading to the inhibition of hyperplasia of the biliary epithelium, submucosal gland, and collagen fibers in the diseased bile duct. Additionally, collagen I expression and fibrous thickness of the bile duct wall was significantly reduced, thereby reducing the incidence of biliary tract stricture secondary to PC. Also of note, treatment with AG-1478 could efficiently decrease the lithogenic potential of PC via inhibition of mucin 5AC expression and mucoglycoprotein secretion, hereby facilitating prevention of stone recurrence. EGFR antagonist AG-1478 had a potent anti-proliferative and anti-fibrotic effectiveness on PC and, therefore, holds promise as a candidate of PC treatment.
    Journal of Surgical Research 03/2011; 166(1):87-94. DOI:10.1016/j.jss.2009.09.058 · 2.12 Impact Factor
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    ABSTRACT: The management of patients with liver metastasis from a gynecologic carcinoma remains controversial, as there is currently little data available. We sought to determine the safety and efficacy of liver-directed surgery for hepatic metastasis from gynecologic primaries. Between 1990 and 2010, 87 patients with biopsy-proven liver metastasis from a gynecologic carcinoma were identified from an institutional hepatobiliary database. Fifty-two (60%) patients who underwent hepatic surgery for their liver disease and 35 (40%) patients who underwent biopsy only were matched for age, primary tumor characteristics, and hepatic tumor burden. Clinicopathologic, operative, and outcome data were collected and analyzed. Of the 87 patients, 30 (34%) presented with synchronous metastasis. The majority of patients had multiple hepatic tumors (63%), with a median size of the largest lesion being 2.5 cm. Of those patients who underwent liver surgery (n=52), most underwent a minor hepatic resection (n=44; 85%), while 29 (56%) patients underwent concurrent lymphadenectomy and 45 (87%) patients underwent simultaneous peritoneal debulking. Postoperative morbidity and mortality were 37% and 0%, respectively. Median survival from time of diagnosis was 53 months for patients who underwent liver-directed surgery compared with 21 months for patients who underwent biopsy alone (n=35) (p=0.01). Among those patients who underwent liver-directed surgery, 5-year survival following hepatic resection was 41%. Hepatic surgery for liver metastasis from gynecologic cancer can be performed safely. Liver surgery may be associated with prolonged survival in a subset of patients with hepatic metastasis from gynecologic primaries and therefore should be considered in carefully selected patients.
    World Journal of Surgery 03/2011; 35(6):1345-54. DOI:10.1007/s00268-011-1074-y · 2.35 Impact Factor

Publication Stats

951 Citations
156.83 Total Impact Points

Institutions

  • 2011–2014
    • Maastricht University
      • • Department of Surgery
      • • NUTRIM School for Nutrition, Toxicology and Metabolism
      Maestricht, Limburg, Netherlands
  • 2013
    • Maastricht Universitair Medisch Centrum
      • Central Diagnostic Laboratory
      Maestricht, Limburg, Netherlands
  • 2009–2013
    • Johns Hopkins University
      • • Department of Surgery
      • • Department of Medicine
      Baltimore, Maryland, United States
  • 2009–2012
    • Johns Hopkins Medicine
      • Department of Surgery
      Baltimore, Maryland, United States