H B Ris

École Polytechnique Fédérale de Lausanne, Lausanne, Vaud, Switzerland

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Publications (138)327.89 Total impact

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    ABSTRACT: Background Low-dose, Visudyne®-mediated photodynamic therapy (photo-induction) was shown to selectively enhance tumor vessel transport causing increased uptake of systemically administered chemotherapy in various tumor types grown on rodent lungs. The present experiments explore the efficacy of photo-induced vessel modulation combined to intravenous (IV) liposomal cisplatin (Lipoplatin®) on rodent lung tumors and the feasibility/toxicity of this approach in porcine chest cavities.Material and Methods Three groups of Fischer rats underwent orthotopic sarcoma (n = 14), mesothelioma (n = 14), or adenocarcinoma (n = 12) implantation on the left lung. Half of the animals of each group had photo-induction (0.0625 mg/kg Visudyne®, 10 J/cm2) followed by IV administration of Lipoplatin® (5 mg/kg) and the other half received Lipoplatin® without photo-induction. Then, two groups of minipigs underwent intrapleural thoracoscopic (VATS) photo-induction (0.0625 mg/kg Visudyne®; 30 J/cm2 hilum; 10 J/cm2 apex/diaphragm) with in situ light dosimetry in combination with IV Lipoplatin® administration (5 mg/kg). Protocol I (n = 6) received Lipoplatin® immediately after light delivery and Protocol II (n = 9) 90 minutes before light delivery. Three additional animals received Lipoplatin® and VATS pleural biopsies but no photo-induction (controls). Lipoplatin® concentrations were analyzed in blood and tissues before and at regular intervals after photo-induction using inductively coupled plasma mass spectrometry.ResultsPhoto-induction selectively increased Lipoplatin® uptake in all orthotopic tumors. It significantly increased the ratio of tumor to lung Lipoplatin® concentration in sarcoma (P = 0.0008) and adenocarcinoma (P = 0.01) but not in mesothelioma, compared to IV drug application alone. In minipigs, intrapleural photo-induction combined to systemic Lipoplatin® was well tolerated with no toxicity at 7 days for both treatment protocols. The pleural Lipoplatin® concentrations were not significantly different at 10 and 30 J/cm2 locations but they were significantly higher in protocol I compared to II (2.37 ± 0.7 vs. 1.37 ± 0.7 ng/mg, P < 0.001).Conclusion Visudyne®-mediated photo-induction selectively enhances the uptake of IV administered Lipoplatin® in rodent lung tumors. Intrapleural VATS photo-induction with identical treatment conditions combined to IV Lipoplatin chemotherapy is feasible and well tolerated in a porcine model. Lasers Surg. Med. © 2015 Wiley Periodicals, Inc.
    No preview · Article · Sep 2015 · Lasers in Surgery and Medicine
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    Preview · Article · Aug 2015 · British Journal of Surgery
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    Full-text · Article · Aug 2015 · British Journal of Surgery
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    ABSTRACT: Background The pre-conditioning of tumor vessels by low-dose photodynamic therapy (L-PDT) was shown to enhance the distribution of chemotherapy in different tumor types. However, how light dose affects drug distribution and tumor response is unknown. Here we determined the effect of L-PDT fluence on vascular transport in human mesothelioma xenografts. The best L-PDT conditions regarding drug transport were then combined with Lipoplatin® to determine tumor response.Methods Nude mice bearing dorsal skinfold chambers were implanted with H-Meso1 cells. Tumors were treated by Visudyne®-mediated photodynamic therapy with 100 mW/cm2 fluence rate and a variable fluence (5, 10, 30, and 50 J/cm2). FITC-Dextran (FITC-D) distribution was assessed in real time in tumor and normal tissues. Tumor response was then determined with best L-PDT conditions combined to Lipoplatin® and compared to controls in luciferase expressing H-Meso1 tumors by size and whole body bioluminescence assessment (n = 7/group).ResultsTumor uptake of FITC-D following L-PDT was significantly enhanced by 10-fold in the 10 J/cm2 but not in the 5, 30, and 50 J/cm2 groups compared to controls. Normal surrounding tissue uptake of FITC-D following L-PDT was significantly enhanced in the 30 J/cm2 and 50 J/cm2 groups compared to controls. Altogether, the FITC-D tumor to normal tissue ratio was significantly higher in the 10 J/cm2 group compared others. Tumor growth was significantly delayed in animals treated by 10 J/cm2-L-PDT combined to Lipoplatin® compared to controls.Conclusions Fluence of L-PDT is critical for the optimal distribution and effect of subsequently administered chemotherapy. These findings have an importance for the clinical translation of the vascular L-PDT concept in the clinics.
    Full-text · Article · Jan 2015 · Lasers in Surgery and Medicine

  • No preview · Article · Jun 2014 · Interactive Cardiovascular and Thoracic Surgery
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    ABSTRACT: Objectives: Therapeutic interventions during normothermic ex vivo lung perfusion (EVLP) provide an opportunity to repair damaged donor lungs. Here we describe an experimental EVLP platform in rodents and assess its effect on variably damaged lungs. Methods: Thirty-one Sprague-Dawley rats assigned in five groups were tested on a customized EVLP circuit. In Groups 1 and 2 cardiac arrest was followed by cold Perfadex® flush, lung heart bloc extraction and 3 h cold preservation inflated with an FiO2 of 0.21 and 0.5, respectively. Groups 3 and 4 were exposed to 1 h warm ischaemia followed by 2 h of cold preservation with an FiO2 of 0.21 and 0.5. Group 5 had 2 h of warm ischaemia followed by 1 h of cold preservation with an FiO2 of 0.21. Dynamic lung compliance (DC), pulmonary vascular resistance (PVR), differential oxygen partial pressures (ΔpaO2) and lung weight gain over 3 h of EVLP were determined. Protein in bronchoalveolar lavage and protein carbonyl in lung tissue were quantified post EVLP. Results: DC increased in Groups 1 and2, remained stable in Groups 3-4 and decreased significantly in Group 5. PVR increased in all groups although no significant differences between the groups were found. ΔpaO2 remained stable over time in Groups 1 to 4 but decreased significantly in Group 5. Lung weight remained stable in Groups 1 and 2, increased non-significantly in Groups 3 and 4 and increased significantly in Group 5. BAL protein was low in Groups 1 and 2, increased non-significantly in Groups 3 and 4 and significantly in Group 5. Protein carbonyl levels were high in all groups but no significant differences were found in between. Conclusions: Our novel rodent EVLP model allowed the assessment of quantitative parameters that reflected the degree of damage to the lung in accordance with the oxidative stress conditions applied. This model could be further exploited for the development of novel EVLP treatment strategies. Disclosure: No significant relationships.
    Preview · Article · Jun 2014 · Interactive Cardiovascular and Thoracic Surgery

  • No preview · Article · Apr 2014 · The Journal of Heart and Lung Transplantation
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    ABSTRACT: Background: Resection of lung metastases (LM) from colorectal cancer (CRC) is increasingly performed with a curative intent. It is currently not possible to identify those CRC patients who may benefit the most from this surgical strategy. The aim of this study was to perform a systematic review of risk factors for survival after lung metastasectomy for CRC. Methods: We performed a meta-analysis of series published between 2000 and 2011, which focused on surgical management of LM from CRC and included more than 40 patients each. Pooled hazard ratios (HR) were calculated by using random effects model for parameters considered as potential prognostic factors. Results: Twenty-five studies including a total of 2925 patients were considered in this analysis. Four parameters were associated with poor survival: (1) a short disease-free interval between primary tumor resection and development of LM (HR 1.59, 95 % confidence interval [CI] 1.27-1.98); (2) multiple LM (HR 2.04, 95 % CI 1.72-2.41); (3) positive hilar and/or mediastinal lymph nodes (HR 1.65, 95 % CI 1.35-2.02); and (4) elevated prethoracotomy carcinoembryonic antigen (HR 1.91, 95 % CI 1.57-2.32). By comparison, a history of resected liver metastases (HR 1.22, 95 % CI 0.91-1.64) did not achieve statistical significance. Conclusions: Clinical variables associated with prolonged survival after surgery for LM in CRC patients include prolonged disease-free interval between primary tumor and metastatic spread, normal prethoracotomy carcinoembryonic antigen, absence of thoracic node involvement, and a single pulmonary lesion.
    Full-text · Article · Oct 2012 · Annals of Surgical Oncology
  • M Gonzalez · S Peters · Y Wang · H B Ris · T Krueger
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    ABSTRACT: Thirty percent of patients suffering from malignant disease will develop pulmonary metastases. Effective chemotherapy is lacking for many of these tumors. Many studies suggest survival benefit in selected patients when pulmonary metastasectomy allows complete resection. Several operative approach may be offered in order to achieve complete resection and maximal lung sparring. Pre-operative workup must assess the control of the primary tumor and the possibility of performing complete resection. Minimally invasive approaches may offer better quality life and equivalent oncologic outcomes than open approach.
    No preview · Article · Jun 2012 · Revue médicale suisse

  • No preview · Article · Apr 2012 · The Journal of Heart and Lung Transplantation
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    ABSTRACT: Resection of lung metastases from colorectal cancer (CRC) is increasingly performed with a curative intent. This strategy was made possible in the 1990s by the development of new chemotherapeutic approaches, improved surgical techniques and better imaging modalities. However, evidence-based data showing clinical benefits of lung metastasectomy in this setting are nonexistent, and there are no prospective randomized trials to support the routine performance of these procedures for stage IV CRC. Current evidence suggests that resection of pulmonary metastases in combination with new cytotoxic agents, such as oxaliplatin, irinotecan and bevacizumab, may result in prolonged survival for many, and cure for a small minority of CRC patients who experienced tumor spread beyond the limits of the abdomen. This review focuses on the results of surgical management of CRC patients with lung metastases: we report the outcome of published series according to the presence or the absence of liver metastasis (and hepatic resection) prior to lung resection.
    Full-text · Article · Apr 2012 · Expert Review of Anti-infective Therapy
  • M. Gonzalez · H.-B. Ris · T. Krueger · P.-Y. Jayet
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    ABSTRACT: The discovery of an anterior mediastinal mass requires careful management with specific consideration of the pathology. More than 50% of all mediastinal masses seen in adults are in the anterior mediastinum. The most frequent diagnoses are thymoma, lymphoma, teratoma and benign thyroid tumours. 60% of cases are malignant. Often the clinical and radiological findings do not allow a definitive diagnosis and a histological diagnosis is often required to select the optimal treatment modality. The choice of biopsy technique depends on the localization of the lesion, clinical factors, and the availability of special techniques and equipment. Biopsy may be obtained by trans-thoracic puncture under computed tomography or ultrasound guidance, or by a surgical approach (mediastinotomy or thoracoscopy).
    No preview · Article · Feb 2012 · Revue des Maladies Respiratoires
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    ABSTRACT: Resection of hepatic metastases is indicated in selected stage IV colorectal cancer (CRC) patients. A minority will eventually develop pulmonary metastases and may undergo lung surgery with curative intent. The aims of the present study were to assess clinical outcome and identify parameters predicting survival after pulmonary metastasectomy in patients who underwent prior resection of hepatic CRC metastases. We performed a retrospective analysis of 27 consecutive patients (median age 62 years; range: 33-75 years) who underwent resection of pulmonary metastases after previous hepatic metastasectomy from CRC in two institutions from 1996 to 2009. All patients underwent complete resection (R0) for both colorectal and hepatic metastases. Median follow-up was 32 months (range: 3-69 months) after resection of lung metastases and 65 months (range: 19-146 months) after resection of primary CRC. Three- and 5-year overall survival rates after lung surgery were 56 and 39%, respectively, and median survival was 46 months (95% CI 35-57). Median disease-free survival after pulmonary metastasectomy was 13 months (95% CI 5-21). At the time of last follow-up, seven patients (26%) had no evidence of recurrent disease and 6 of these 7 patients presented initially with a single lung metastasis. Resection of lung metastases from CRC patients may result in prolonged survival, even after previous hepatic metastasectomy. Yet, prolonged disease-free survival remains the exception, and seems to occur only in patients with a single lung lesion.
    Full-text · Article · Dec 2011 · World Journal of Surgery

  • No preview · Article · Jul 2010 · Transplantation
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    ABSTRACT: The case of a 38-year old man with recurrent adenocarcinoma of the right lung and infiltration of the thoracic wall, who underwent a right pneumonectomy with thoracic wall resection, is described. Dissection of the right pulmonary hilous was extremely difficult due to the previous operations. The superior vena cava (SVC) was accidentally ligated, resulting in profound hypotension and increased venous pressure in the internal jugular vein. Immediate blood aspiration through a 8.5-French introducer sheath lowered the venous congestion. After the SVC was cross-clamped, the Bispectral Index (BIS) acutely decreased to 0 and remained low during the resuscitation. Over the next 5 hours, BIS was directly affected by mean arterial pressure. Four days postoperatively, the patient was neurologically intact.
    No preview · Article · Mar 2010 · Journal of clinical anesthesia
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    ABSTRACT: Chronic obstructive pulmonary disease (COPD) is the primary indication for lung transplantation (LTx), but survival benefit is still under debate. We analysed the survival impact of LTx in COPD with a new approach, using the BODE (body mass index, airway obstruction, dyspnoea, exercise capacity) index. We retrospectively reviewed 54 consecutive lung transplants performed for COPD. The pre-transplant BODE score was calculated for each patient and a predicted survival was derived from the survival functions of the original BODE index validation cohort. Predicted and observed post-transplant survival was then compared. In the subgroups with a BODE score >or=7 and <7, a majority of patients (66% and 69%, respectively) lived for longer after LTx than predicted by their individual BODE index. The median survival was significantly improved in the entire cohort and in the subgroup with a BODE score >or=7. 4 yrs after LTx a survival benefit was only apparent in patients with a pre-transplant BODE score of >or=7. In conclusion, while a majority of COPD patients had an individual survival benefit from LTx regardless of their pre-transplant BODE score, a global survival benefit was seen only in patients with more severe disease. This supports the use of the BODE index as a selection criteria for LTx candidates.
    Full-text · Article · Dec 2009 · European Respiratory Journal
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    ABSTRACT: The treatment of some cancer patients has shifted from traditional, non-specific cytotoxic chemotherapy to chronic treatment with molecular targeted therapies. Imatinib mesylate, a selective inhibitor of tyrosine kinases (TKIs) is the most prominent example of this new era and has opened the way to the development of several additional TKIs, including sunitinib, nilotinib, dasatinib, sorafenib and lapatinib, in the treatment of various hematological malignancies and solid tumors. All these agents are characterized by an important inter-individual pharmacokinetic variability, are at risk for drug interactions, and are not devoid of toxicity. Additionally, they are administered for prolonged periods, anticipating the careful monitoring of their plasma exposure via Therapeutic Drug Monitoring (TDM) to be an important component of patients' follow-up. We have developed a liquid chromatography-tandem mass spectrometry method (LC-MS/MS) requiring 100 microL of plasma for the simultaneous determination of the six major TKIs currently in use. Plasma is purified by protein precipitation and the supernatant is diluted in ammonium formate 20 mM (pH 4.0) 1:2. Reverse-phase chromatographic separation of TKIs is obtained using a gradient elution of 20 mM ammonium formate pH 2.2 and acetonitrile containing 1% formic acid, followed by rinsing and re-equilibration to the initial solvent composition up to 20 min. Analyte quantification, using matrix-matched calibration samples, is performed by electro-spray ionization-triple quadrupole mass spectrometry by selected reaction monitoring detection using the positive mode. The method was validated according to FDA recommendations, including assessment of extraction yield, matrix effects variability (<9.6%), overall process efficiency (87.1-104.2%), as well as TKIs short- and long-term stability in plasma. The method is precise (inter-day CV%: 1.3-9.4%), accurate (-9.2 to +9.9%) and sensitive (lower limits of quantification comprised between 1 and 10 ng/mL). This is the first broad-range LC-MS/MS assay covering the major currently in-use TKIs. It is an improvement over previous methods in terms of convenience (a single extraction procedure for six major TKIs, reducing significantly the analytical time), sensitivity, selectivity and throughput. It may contribute to filling the current knowledge gaps in the pharmacokinetics/pharmacodynamics relationships of the latest TKIs developed after imatinib and better define their therapeutic ranges in different patient populations in order to evaluate whether a systematic TDM-guided dose adjustment of these anticancer drugs could contribute to minimize the risk of major adverse reactions and to increase the probability of efficient, long lasting, therapeutic response.
    No preview · Article · May 2009 · Journal of chromatography. B, Analytical technologies in the biomedical and life sciences

  • No preview · Article · Jan 2008 · European Journal of Cardio-Thoracic Surgery

  • No preview · Article · Sep 2007 · EJC Supplements
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    ABSTRACT: The aim of this multicenter trial was to prospectively evaluate neo-adjuvant chemotherapy followed by extrapleural pneumonectomy (EPP) and radiotherapy, including quality of life as outcome. Eligible patients had malignant pleural mesothelioma of all histological types, World Health Organization performance status of zero to two and clinical stage T1-T3, N0-2, M0 disease considered completely resectable. Neo-adjuvant chemotherapy consisted of three cycles of cisplatin and gemcitabine followed by EPP. Postoperative radiotherapy was considered for all patients. In all, 58 of 61 patients completed three cycles of neo-adjuvant chemotherapy. Forty-five patients (74%) underwent EPP and in 37 patients (61%) the resection was complete. Postoperative radiotherapy was initiated in 36 patients. The median survival of all patients was 19.8 months [95% confidence interval (CI) 14.6-24.5]. For the 45 patients undergoing EPP, the median survival was 23 months (95% CI 16.6-32.9). Psychological distress showed minor variations over time with distress above the cut-off score indicating no morbidity with 82% (N = 36) at baseline and 76% (N = 26) at 3 months after surgery (P = 0.5). The observed rate of operability is promising. A median survival of 23 months for patients undergoing EPP compares favourably with the survival reported from single center studies of upfront surgery. This approach was not associated with an increase in psychological distress.
    Full-text · Article · Aug 2007 · Annals of Oncology

Publication Stats

3k Citations
327.89 Total Impact Points


  • 2015
    • École Polytechnique Fédérale de Lausanne
      Lausanne, Vaud, Switzerland
  • 1997-2015
    • University Hospital of Lausanne
      • • Service de chirurgie thoracique et vasculaire
      • • Service de chirurgie viscérale
      Lausanne, Vaud, Switzerland
  • 2000-2009
    • University of Lausanne
      • Institute of Pathology
      Lausanne, Vaud, Switzerland
    • Schweizerischen Arbeitsgemeinschaft für Klinische Krebsforschung
      Berna, Bern, Switzerland
    • Städtisches Klinikum Solingen Gmbh
      Solingen, North Rhine-Westphalia, Germany
  • 2004
    • Eawag: Das Wasserforschungs-Institut des ETH-Bereichs
      Duebendorf, Zurich, Switzerland
  • 2002
    • University of Zurich
      Zürich, Zurich, Switzerland
  • 2001
    • University of Vienna
      • Department of Cardio-Thoracic Surgery
      Wien, Vienna, Austria
  • 1993-2000
    • Universität Bern
      • Institute of Pathology
      Berna, Bern, Switzerland
    • Spital Limmattal
      Zurich, Switzerland
  • 1992-2000
    • Inselspital, Universitätsspital Bern
      Berna, Bern, Switzerland
    • Imperial College Healthcare NHS Trust
      Londinium, England, United Kingdom
  • 1998
    • Memorial Sloan-Kettering Cancer Center
      New York City, New York, United States
  • 1992-1998
    • Deutsche Gesellschaft für Thorax-, Herz- und Gefäßchirurgie e.V. 
      Farmsen-Berne, Hamburg, Germany