I.H.M. Borel Rinkes

University Medical Center Utrecht, Utrecht, Utrecht, Netherlands

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Publications (316)1107.09 Total impact

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    ABSTRACT: Introduction: Adequate decision-making in elderly colorectal cancer patients requires accurate information regarding risks of treatment. We analysed the outcome and survival of colorectal resections in the oldest old (≥85 years). Methods: An analysis of the 2011-2012 data from two large nationwide registries: the Dutch Surgical Colorectal Audit (DSCA), containing all colorectal cancer resections, and the Netherlands Cancer Registry (NCR), containing survival data for all newly diagnosed malignancies. Results: The study included more than 1200 patients aged ≥85 years (DSCA n = 1232, NCR n = 1206). The postoperative complication rate was 41 % in the oldest old. The frequency of cardiopulmonary complications rose rapidly with age, from 11 % in those <70 years to 38 % for the oldest old (p < 0.001). Postoperative 30-day mortality rate was 10 % in the oldest old. Three-month mortality was 14 % (compared with 3 % of patients <85 years; p < 0.001). One-year mortality was 24 % and 2-year mortality 36 %. After correction for expected mortality in the general population, excess mortality for the oldest old was 12 % in the first year and 3 % in the second year. Conclusions: In this study of more than 1200 colorectal cancer patients aged ≥85 years undergoing surgical resection, we found high rates of cardiopulmonary complications and excess mortality, particularly in the first year after surgery. We propose that these data could be incorporated into individualized treatment algorithms, which also include detailed information regarding the patients' health status.
    No preview · Article · Jan 2016 · Annals of Surgical Oncology
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    ABSTRACT: Purpose Risk stratification after surgery for colorectal cancer liver metastases (CRLM) is achieved using clinicopathologic variables, however is of limited accuracy. We sought to derive and externally validate a multigene expression assay prognostic of overall survival (OS) that is superior to clinicopathologic variables in patients with surgically resected CRLM. Experimental Design We measured mRNA expression in prospectively collected frozen tumor from 96 patients with surgically resected CRLM at Memorial Sloan Kettering Cancer Center (MSKCC, New York). We retrospectively generated a 20-gene molecular risk score (MRS) and compared its prognostic utility for overall survival (OS) and recurrence-free survival (RFS) with three common clinical risk scores (CRSs). We then tested the prognostic ability of the MRS in an external validation cohort (European) of 119 patients with surgically resected CRLM at the University Medical Center Utrecht (Netherlands) and Paul Brousse Hospital (France). Results For OS in the MSKCC cohort, MRS was the strongest independent prognosticator (HR 3.7-4.9, P<0.001) followed by adjuvant chemotherapy (HR 0.3, P≤0.001). For OS in the European cohort, MRS was the only independent prognosticator (HR 3.5, P=0.007). For RFS, MRS was also independently prognostic in the MSKCC cohort (HR 2.4-2.6, P≤0.001) and the European cohort (HR 1.6-2.5, P≤0.05). Conclusion Compared to CRSs, the MRS is more accurate, broadly applicable, and an independent prognostic biomarker of OS in resected CRLM. This MRS is the first externally validated prognostic multigene expression assay after metastasectomy for CRLM, and warrants prospective validation.
    Preview · Article · Jan 2016 · Clinical Cancer Research

  • No preview · Article · Dec 2015 · Endocrine Practice
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    ABSTRACT: Homeostasis of the continuously self-renewing intestinal tract involves cell proliferation, migration, differentiation along the crypt-villus-axis and shedding of cells into the gut lumen. CD95-ligand (FAS-ligand, CD95L) is a cytokine that is known for its capacity to induce apoptosis by binding its cognate receptor, CD95 (Fas). More recently, it was discovered that CD95L can also induce other cellular responses, such as proliferation, differentiation and cell migration. CD95L is highly expressed in Paneth cells of the small intestine which are in close contact with intestinal stem cells. This suggests a potential role for CD95L in controlling stem cell function and, possibly, intestinal homeostasis. We analyzed the intestines of mice deficient for functional CD95L (gld) for potential alterations in the diversity of stem-cell-lineages and parameters of intestinal homeostasis. Stem cell diversity was assessed by analyzing methylation patterns of the non-transcribed mMYOD gene. Proliferation was analyzed by BrdU labeling and differentiation was assessed by immunohistochemistry. Of all parameters analyzed, only epithelial cell proliferation was significantly reduced in the small intestines of gld-mice, but not in their colons which lack CD95L expression. We conclude that CD95L has a proliferation-stimulating role during normal turnover of the small intestine, but has a marginal effect on overall intestinal homeostasis.
    No preview · Article · Dec 2015 · Medical Molecular Morphology
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    ABSTRACT: Robotic surgery has been introduced to overcome the limitations of conventional laparoscopy. A systematic review and meta-analysis were performed to assess the safety and feasibility for three subgroups of robot-assisted laparoscopic liver resection: (i) minor resections of easily accessible segments: 2/3, 4B, 5, 6, (ii) minor resections of difficult located segments: 1, 4A, 7, 8 and (iii) major resections: ≥ 4 segments.
    No preview · Article · Dec 2015 · HPB
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    ABSTRACT: Background: Health-related quality of life (QoL) is of major importance in pancreatic cancer, owing to the limited life expectation. The aim of this prospective longitudinal study was to describe QoL in patients undergoing resection for pancreatic or periampullary malignancy. Methods: QoL was measured on a scale of 0-100 in patients who underwent pancreatic resection for malignancy or premalignancy at the University Medical Centre Utrecht before resection, and 1, 3, 6 and 12 months after surgery. Measures consisted of the RAND-36, the European Organization for Research and Treatment of Cancer (EORTC) core questionnaire (QLQ-C30) and the EORTC pancreatic cancer-specific module (QLQ-PAN26). Results: Between March 2012 and November 2013, 68 consecutive patients with a malignancy (59 patients) or premalignancy (9) were included. Physical role restriction, social and emotional domains showed a significant and clinically relevant deterioration directly after operation in 53 per cent (RAND-36, P < 0·001), 63 and 78 per cent (QLQ-C30 and RAND-36 respectively, P < 0·001) and 37 per cent (RAND-36, P < 0·001) of patients respectively. Most domains demonstrated recovery to preoperative values or better at 3 months, except for physical functioning. Emotional functioning at 3, 6 and 12 months was better than at baseline (P < 0·001). Symptom scores revealed a deterioration in vitality, pain (P = 0·002), fatigue (P < 0·001), appetite loss (P < 0·001), altered bowel habit (P = 0·001) and side-effects (P < 0·001) after 1 month. After 3 months, only side-effects were worse than preoperative values (P < 0·001). Conclusion: QoL after pancreatic resection for malignant and premalignant tumours decreased considerably in the early postoperative phase. Full recovery of QoL took up to 6 months after the operation.
    No preview · Article · Nov 2015
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    ABSTRACT: Objectives: The aim of this study was to determine the prevalence of pancreatic exocrine insufficiency in patients with pancreatic or periampullary cancer, both before and after resection. Methods: Systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA guidelines). We included studies reporting on pancreatic exocrine insufficiency in patients with pancreatic or periampullary cancer. Data on patient demographics, type of pancreatic resection, diagnostic test, and occurrence of pancreatic exocrine insufficiency were extracted. Prevalence of pancreatic exocrine insufficiency was calculated before and after pancreatic resections and in patients with locally advanced pancreatic cancer. Results: Nine observational cohort studies with 693 patients were included. Median preoperative prevalence of pancreatic exocrine insufficiency was 44% (range, 42%-47%) before pancreatoduodenectomy, 20% (range, 16%-67%) before distal pancreatectomy, 63% before total pancreatectomy, and 25% to 50% in patients with locally advanced pancreatic cancer. The median prevalence of pancreatic exocrine insufficiency at least 6 months after pancreatoduodenectomy was 74% (range, 36%-100%) and 67% to 80% after distal pancreatectomy. Conclusion: Pancreatic exocrine insufficiency is diagnosed in approximately half of all patients scheduled to undergo resection for pancreatic or periampullary cancer. The prevalence increases markedly after resection. These data highlight the need of pancreatic enzyme suppletion in these patients.
    No preview · Article · Oct 2015 · Pancreas
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    ABSTRACT: Background: Surgery is the intervention of choice for definitive diagnosis and treatment in women with pathological nipple discharge (PND). Ductoscopy has been reported to improve diagnosis, but as an interventional procedure it may also reduce the need for surgery. This study evaluated interventional ductoscopy in patients with PND. Methods: A prospective study on ductoscopy was conducted in consecutive patients with PND, but without a suspected malignancy on routine diagnostic evaluation. Intraductal lesions were removed by ductoscopic extraction. Surgery was undertaken if there were suspicious ductoscopic findings or at the patient's request. Therapeutic efficacy was determined by cannulation success, detection and removal rates, symptom resolution and avoided surgery. Results: Ductoscope introduction was successful in 71 (87 per cent) of 82 patients, with abnormalities visualized in 53 (65 per cent); these were mostly polypoid lesions (29 patients). The lesion was removed in 27 of 34 attempted ductoscopic extractions. Twenty-six (32 per cent) of the 82 patients underwent surgery, whereas surgery was avoided in 56 (68 per cent). After a median follow-up of 17 (range 3-45) months, 40 patients (49 per cent) no longer experienced symptoms of PND, 13 of 34 patients experienced an insufficient therapeutic effect after attempted ductoscopic extraction, and the outcome was unknown in two (2 per cent). Malignancy was diagnosed in four patients (5 per cent); two had been missed at ductoscopy and two at initial surgery after ductoscopy. Conclusion: Interventional ductoscopy is technically feasible and may help to avoid surgery in the majority of patients. As endoscopic removal of intraductal lesions is not always possible and malignancy can be the underlying cause of PND, ductoscopic instruments should be further optimized to allow definitive histological diagnosis.
    No preview · Article · Oct 2015 · British Journal of Surgery
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    ABSTRACT: Background: Traditionally, nonparasitic hepatic cysts are marsupialized using laparotomy. In the last 2 decades, laparoscopic fenestration has become the preferred treatment for hepatic cysts. However, this technique is limited by 2-dimensional view and the limited mobility of straight laparoscopic instruments. These limitations may be overcome by the use of a robotic system. We describe laparoscopic fenestration of giant hepatic cysts using the da Vinci Si robotic system with the use of the Endowrist One Vessel Sealer. Methods: Our first patient is a 32-year-old female with a solitary hepatic cyst. The second patient is a 51-year-old female with polycystic liver disease. Results: We performed robot-assisted laparoscopic cyst fenestration with good clinical outcome. No intraoperative complications occurred and patients recovered rapidly. Conclusion: These data show that the da Vinci Si robotic system is eminently suited for the laparoscopic fenestration of large hepatic cysts and that this procedure is associated with rapid recovery.
    No preview · Article · Oct 2015 · Surgical laparoscopy, endoscopy & percutaneous techniques
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    ABSTRACT: Background: Active efflux of irinotecan by ATP-binding cassette (ABC)-transporters, in particular ABCB1 and ABCG2, is a well-established drug resistance mechanism in vitro and in pre-clinical mouse models, but its relevance in colorectal cancer (CRC) patients is unknown. Therefore, we assessed the association between ABC-transporter expression and tumour response to irinotecan in patients with metastatic CRC. Methods: Tissue microarrays of a large cohort of metastatic CRC patients treated with irinotecan in a prospective study (CAIRO study; n=566) were analysed for expression of ABCB1 and ABCG2 by immunohistochemistry. Kaplan-Meier and Cox proportional hazard regression analyses were performed to assess the association of ABC transporter expression with irinotecan response. Gene expression profiles of 17 paired tumours were used to assess the concordance of ABCB1/ABCG2 expression in primary CRC and corresponding metastases. Results: The response to irinotecan was not significantly different between primary tumours with positive versus negative expression of ABCB1 (5.8 vs 5.7 months, p=0.696) or ABCG2 (5.7 vs 6.1 months, p=0.811). Multivariate analysis showed neither ABCB1 nor ABCG2 were independent predictors for progression free survival. There was a mediocre to poor concordance between ABC-transporter expression in paired tumours. Conclusion: In metastatic CRC, ABC-transporter expression in the primary tumour does not predict irinotecan response.
    Full-text · Article · Sep 2015 · Journal of Cancer
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    ABSTRACT: An association between ABO blood type and the development of cancer, in particular, pancreatic cancer, has been reported in the literature. An association between blood type O and neuroendocrine tumors in multiple endocrine neoplasia type 1 (MEN1) patients was recently suggested. Therefore, blood type O was proposed as an additional factor to personalize screening criteria for neuroendocrine tumors in MEN1 patients. The aim of this study was to assess the association between blood type O and the occurrence of neuroendocrine tumors in the national Dutch MEN1 cohort. Cohort study using the Dutch National MEN1 database, which includes >90% of the Dutch MEN1 population. Demographic and clinical data were analyzed by blood type. Chi-square tests and Fisher exact tests were used to determine the association between blood type O and occurrence of neuroendocrine tumors. A cumulative incidence analysis (Gray's test) was performed to assess the equality of cumulative incidence of neuroendocrine tumors in blood type groups, taking death as a competing risk into account. ABO blood type of 200 of 322 MEN1 patients was known. Demographic and clinical characteristics were similar amongst blood type O and non-O type cohorts. The occurrence of neuroendocrine tumors of the lung, thymus, pancreas and the gastrointestinal tract was equally distributed across the blood type O and non-O type cohorts (Grays's test for equality; P = 0.72). Furthermore, we found no association between blood type O and the occurrence of metastatic disease or survival. An association between blood type O and the occurrence of neuroendocrine tumors in MEN1 patients was not confirmed. Addition of the blood type to screening and surveillance practice seems for this reason not of additional value for identifying MEN1 patients at risk for the development of neuroendocrine tumors, metastatic disease or a shortened survival.
    No preview · Article · Aug 2015 · The Journal of Clinical Endocrinology and Metabolism
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    ABSTRACT: Background Pancreatic fistula is a potentially life-threatening complication after a pancreatic resection. The aim of this systematic review was to evaluate the role of matrix-bound sealants after a pancreatic resection in terms of preventing or ameliorating the course of a post-operative pancreatic fistula.MethodsA systematic search was performed in the literature from May 2005 to April 2015. Included were clinical studies using matrix-bound sealants after a pancreatic resection, reporting a post-operative pancreatic fistula (POPF) according to the International Study Group on Pancreatic Fistula classification, in which grade B and C fistulae were considered clinically relevant.ResultsTwo were studies on patients undergoing pancreatoduodenectomy (sealants n = 67, controls n = 27) and four studies on a distal pancreatectomy (sealants n = 258, controls n = 178). After a pancreatoduodenectomy, 13% of patients treated with sealants versus 11% of patients without sealants developed a POPF (P = 0.76), of which 4% versus 4% were clinically relevant (P = 0.87). After a distal pancreatectomy, 42% of patients treated with sealants versus 52% of patients without sealants developed a POPF (P = 0.03). Of these, 9% versus 12% were clinically relevant (P = 0.19).Conclusions The present data do not support the routine use of matrix-bound sealants after a pancreatic resection, as there was no effect on clinically relevant POPF. Larger, well-designed studies are needed to determine the efficacy of sealants in preventing POPF after a pancreatoduodenectomy.
    No preview · Article · Aug 2015 · HPB
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    ABSTRACT: Early oral feeding is currently considered the optimal routine feeding strategy after pancreatoduodenectomy (PD). Some have suggested that patients with preoperative symptoms of gastric outlet obstruction (GOO) who undergo PD have such a high risk of developing delayed gastric emptying that these patients should rather receive routine postoperative tube feeding. The aim of this study was to determine whether clinical outcomes after PD in these patients differ between postoperative early oral feeding and routine tube feeding. We analyzed a consecutive multicenter cohort of patients with preoperative symptoms of GOO undergoing PD (2010-2013). Patients were categorized into two groups based on the applied postoperative feeding strategy (dependent on their center's routine strategy): early oral feeding or routine nasojejunal tube feeding. Of 497 patients undergoing PD, 83 (17%) suffered from preoperative symptoms of GOO. 49 patients received early oral feeding and 29 patients received routine tube feeding. Time to resumption of adequate oral intake (primary outcome; 14 vs. 12 days, p = 0.61) did not differ between these two feeding strategies. Furthermore, overall complications and length of stay were similar in both groups. Of the patients receiving early oral feeding, 24 (49%) ultimately required postoperative tube feeding. In patients with an uncomplicated postoperative course, early oral feeding was associated with shorter time to adequate oral intake (8 vs. 12 days, p = 0.008) and shorter hospital stay (9 vs. 13 days, p < 0.001). Also in patients with preoperative symptoms of GOO, early oral feeding can be considered the routine feeding strategy after PD. Copyright © 2015 IAP and EPC. Published by Elsevier B.V. All rights reserved.
    No preview · Article · Jul 2015 · Pancreatology
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    ABSTRACT: The aim of this study was to investigate whether younger age at surgery is associated with the increased incidence of postoperative complications after prophylactic thyroidectomy in pediatric patients with multiple endocrine neoplasia (MEN) 2. The shift toward earlier thyroidectomy has resulted in significantly less medullary thyroid carcinoma (MTC)-related morbidity and mortality. However, very young pediatric patients might have a higher morbidity rate compared with older patients. Hardly any literature exists on complications in the very young. A retrospective single-center analysis was performed on the outcomes of MEN2 patients undergoing a prophylactic total thyroidectomy at the age of 17 or younger. Forty-one MEN2A and 3 MEN2B patients with thyroidectomy after January 1993 and at least 6 months of follow-up were included, subdivided in 9 patients younger than 3 years, 15 patients 3 to 6 years, and 20 patients older than 6 years. Postoperative hypocalcemia and other complications were registered. Twelve (27%) patients developed transient hypocalcemia and 9 (20%) patients suffered from permanent hypocalcemia, with a nonsignificant trend toward higher incidence with decreasing age. Three (7%) patients had other complications, of whom 2 were younger than 3 years. For patients younger than 3 years, the average length of stay (LOS) was 6.7 days, versus 1.7 and 3.5 days, respectively, for the older patient groups (P < 0.05). Patients with complications had a longer LOS compared with patients without (5.0 vs 2.0, P < 0.01). None of the patients had clinical signs of recurrent MTC after a mean follow-up of 10.5 years. Prophylactic thyroidectomy in very young children is associated with a higher rate of complications, causing a significant increased LOS. Irrespective age of surgery, MTC did not recur in any patient. In planning optimal timing of surgery, clinicians should take the risk of complications into account. We advise not to perform total thyroidectomy before the age of 3 for patients defined high risk by the American Thyroid Association guideline.
    Full-text · Article · Jul 2015 · Medicine
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    ABSTRACT: Since the 1950s, preoperative medical preparation has been widely applied in patients with pheochromocytoma to improve intraoperative hemodynamic instability and postoperative complications. However, advancements in preoperative imaging, laparoscopic surgical techniques, and anesthesia have considerably improved management in patients with pheochromocytoma. In consequence, there is no validated consensus on current predictive factors for postoperative morbidity. The aim of this study was to determine perioperative factors which are predictive for postoperative morbidity in patients undergoing laparoscopic adrenalectomy for pheochromocytoma. It is a retrospective analysis of prospectively maintained databases in five medical centers from 2002 to 2013. Inclusion criteria were consecutive patients who underwent non-converted laparoscopic unilateral total adrenalectomy for pheochromocytoma. Two-hundred and twenty-five patients were included. All-cause and cardiovascular postoperative morbidity rates were 16 % (n = 36) and 4.8 % (n = 11), respectively. Preinduction blood pressure normalization after preoperative medical preparation had no impact on postoperative morbidity. However, past medical history of coronary artery disease (OR [CI95 %] = 3.39; [1.317-8.727]) and incidence of intraoperative hemodynamic instability episodes (both SBP ≥ 160 mmHg and MAP < 60 mmHg) (OR [CI95 %] = 3.092; [1.451-6.587]) remained independent predictors for postoperative all-cause morbidity. Similarly, past medical history of coronary artery disease (OR [CI95 %] = 14.41; [3.119-66.57]), female sex (OR [CI95 %] = 12.05; [1.807-80.31]), and incidence of intraoperative hemodynamic instability episodes (both SBP ≥ 200 mmHg and MAP < 60 mmHg) (OR [CI95 %] = 4.13; [1.009-16.90]) remained independent predictors for postoperative cardiovascular morbidity. This study identifies risk factors for cardiovascular and all-cause postoperative morbidity after laparoscopic adrenalectomy in current clinical setting. These data can help physicians to guide intra-operative blood pressure management and have to be taken into account in further studies.
    Full-text · Article · Jun 2015 · Surgical Endoscopy
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    ABSTRACT: Primary hyperparathyroidism is a common endocrine disorder for which the primary treatment is surgery. For minimal invasive parathyroidectomy adequate pre-operative imaging is essential. Conventional imaging is often inconclusive. There are reports that (18)F-fluorocholine PET-CT might be a superior imaging modality, however evidence is still very scarce. This is the first report of a case with negative ultrasound and sestamibi SPECT-CT imaging that underwent successful minimal invasive surgery because of (18)F-fluorocholine PET-CT. A 57 year-old man presented to us with complaints of fatigue. Laboratory results showed a biochemical primary hyperparathyroidism and an additional DEXA-scan revealed osteopenia of the lumbar spine. Conventional imaging consisting of neck ultrasound and Tc-99m-sestamibi SPECT-CT was however unable to localize the pathological gland. Subsequent (18)F-fluorocholine PET-CT did clearly localize an adenoma dorsally of the left thyroid lobe which was removed at that exact location using minimal invasive parathyroidectomy. Histological examination confirmed the diagnosis adenoma and calcium levels remained normal at follow-up. There is clinical need for a superior imaging modality to detect pathological parathyroid glands to enable minimal invasive surgery. (18)F-Fluorocholine is widely available. (18)F-Fluorocholine PET-CT is a promising new imaging modality for localizing parathyroid adenomas and enabling minimal invasive parathyroidectomy when conventional imaging fails to do. Clinicians should consider its use as a second line modality for optimal patient care. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.
    Full-text · Article · Jun 2015 · International Journal of Surgery Case Reports
  • Jakob W Kist · Sjoerd Nell · Bart de Keizer · Gerlof D Valk · Inne H. M. Borel Rinkes · Menno R Vriens

    No preview · Article · Jun 2015 · Endocrine
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    ABSTRACT: 18F-fluorocholine PET-CT is a new imaging modality for the localization of pathological parathyroid glands in patients with primary hyperparathyroidism. The PET-CT is a combination scan that uses both the physiological information from the PET and the anatomical information from the CT. Uptake of the radio-isotope 18F-fluorocholine is increased in pathological parathyroid glands. 18F-fluorocholine PET-CT helps clinicians to localize the pathological parathyroid glands where conventional modalities fail to do so. This enables surgeons to carry out targeted minimal invasive surgery. It may also prevent the patient having to undergo a more extensive exploration, with its associated risks, and alleviate the necessity of taking medications with side effects. Although the literature on this subject is still scarce, preliminary results are promising. As any hospital with a PET-CT can perform the scan, we expect that its use in patients with hyperparathyroidism will increase over the next few years.
    No preview · Article · Jun 2015 · Nederlands tijdschrift voor geneeskunde

  • No preview · Article · Jun 2015 · Pancreatology

  • No preview · Article · Jun 2015 · Pancreatology

Publication Stats

5k Citations
1,107.09 Total Impact Points


  • 1997-2016
    • University Medical Center Utrecht
      • • Department of Surgery
      • • Department of Radiology
      Utrecht, Utrecht, Netherlands
  • 2013
    • Hubrecht Institute
      Utrecht, Utrecht, Netherlands
  • 1996-2008
    • Utrecht University
      Utrecht, Utrecht, Netherlands
  • 1991-1999
    • Erasmus Universiteit Rotterdam
      Rotterdam, South Holland, Netherlands
  • 1997-1998
    • Erasmus MC
      • Department of Oncological Surgery
      Rotterdam, South Holland, Netherlands
  • 1993-1997
    • Leiden University
      Leyden, South Holland, Netherlands
  • 1995
    • Leiden University Medical Centre
      • Department of Surgery
      Leiden, South Holland, Netherlands
  • 1994
    • TNO
      's-Gravenhage, South Holland, Netherlands