Markus Zuber

Cantonal Hospital of Schwyz, Schwyz, Schwyz, Switzerland

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Publications (113)333.26 Total impact

  • Cancer Research 08/2015; 75(15 Supplement):1275-1275. DOI:10.1158/1538-7445.AM2015-1275 · 9.33 Impact Factor
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    ABSTRACT: Small nodal tumor infiltrates (SNTI)-defined as isolated tumor cells and micrometastases-are associated with worse disease-free and overall survival in stage I and II colon cancer patients. Their detection, however, remains challenging. The objective of the present study was to evaluate whether there is a correlation between the location of SNTI and phagocytosed carbon dye particles in sentinel lymph nodes (SLN) of colon cancer patients. Isosulfan blue and carbon dye were injected intraoperatively near the tumor to mark the SLN. Serial sections of SLN were stained with hematoxylin-eosin and immunohistochemistry. Intranodal distribution of phagocytosed carbon particles was compared to the presence of SNTI. Of a cohort of 159 patients, 24 patients had SNTI in their lymph nodes (LN). SNTI were found in a total of 116 LN of which 66 were SLN and 50 were non-SLN. In 59, these 116 LN with SNTI phagocytosed carbon dye were found (50.9 %). Phagocytosed carbon dye was identified significantly more often in SLN (49 of 66 SNTI positive SLN) compared to 10 of 50 SNTI positive non-SLN (p < 0.001). In 52 out of 59 LN (88.1 %), phagocytosed carbon dye was in close proximity to SNTI. In the majority of patients, SNTI are located in the same SLN compartment as phagocytosed carbon dye particles. Our investigation provides evidence that the use of carbon dye facilitates SNTI detection and improves LN staging in colon cancer. Therefore, the concept of intranodal mapping-which has been previously described for melanoma-can be extended to colon cancer patients.
    World Journal of Surgery 07/2015; 39(10). DOI:10.1007/s00268-015-3130-5 · 2.64 Impact Factor
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    ABSTRACT: The sentinel lymph node (SLN) procedure for colon cancer patients has been increasingly performed over the past decade and has shown advantages regarding lymph node staging. However, there are concerns that the manipulation of the colon, particularly the blue dye injection, results in isolated tumor cell dissemination to lymph nodes. Therefore, the objective of the present study was to evaluate whether the blue dye injection during the SLN procedure for colon cancer induces epithelial cell dissemination to the regional lymph nodes using a fake SLN procedure as a model. One hundred seventy-four colon cancer patients underwent open oncologic colon resection and SLN procedure according to a standardized protocol. For the fake SLN procedure, blue dye was injected ex vivo, into the subserosa of a nontumor-bearing segment of the resected colon in 37 unselected patients. Three levels of each SLN were stained with H&E and with the pancytokeratin marker AE1/AE3 and were analyzed for the presence of cytokeratin positive cells. Identification of fake SLN was successful in 32 of the 37 patients (86 %). Seventy fake SLN were histologically confirmed. The median number of fake SLN was 2 per patient (range 1-8). None of the fake SLN showed any disseminated epithelial cells. The present prospective study provides compelling evidence that blue dye injection during sentinel lymph node procedure for colon cancer does not induce epithelial cell dissemination to the sentinel lymph nodes. Therefore, isolated tumor cells in sentinel lymph nodes result from a true metastatic process.
    International Journal of Colorectal Disease 04/2014; 29(6). DOI:10.1007/s00384-014-1853-7 · 2.45 Impact Factor
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    ABSTRACT: Background: Current histopathological staging procedures in colon carcinomas depend on midline division of the lymph nodes with one section of haematoxylin & eosin (H&E) staining only. By this method, tumour deposits outside this transection line may be missed and could lead to understaging of a high-risk group of stage UICC II cases, which recurs in ∼20% of cases. A new diagnostic semiautomated system, one-step nucleic acid amplification (OSNA), detects cytokeratin (CK) 19 mRNA in lymph node metastases and enables the investigation of the whole lymph node. The objective of this study was to assess whether histopathological pN0 patients can be upstaged to stage UICC III by OSNA. Methods: Lymph nodes from patients who were classified as lymph node negative after standard histopathology (single (H&E) slice) were subjected to OSNA. A result revealing a CK19 mRNA copy number >250, which makes sure to detect mainly macrometastases and not isolated tumour cells (ITC) or micrometastases only, was regarded as positive for lymph node metastases based on previous threshold investigations. Results: In total, 1594 pN0 lymph nodes from 103 colon carcinomas (median number of lymph nodes per patient: 14, range: 1–46) were analysed with OSNA. Out of 103 pN0 patients, 26 had OSNA-positive lymph nodes, resulting in an upstaging rate of 25.2%. Among these were 6/37 (16.2%) stage UICC I and 20/66 (30.3%) stage UICC II patients. Overall, 38 lymph nodes were OSNA positive: 19 patients had one, 3 had two, 3 had three, and 1 patient had four OSNA-positive lymph nodes. Conclusions: OSNA resulted in an upstaging of over 25% of initially histopathologically lymph node-negative patients. OSNA is a standardised, observer-independent technique, allowing the analysis of the whole lymph node. Therefore, sampling bias due to missing investigation of certain lymph node tissue can be avoided, which may lead to a more accurate staging.
    British Journal of Cancer 04/2014; 110(10). DOI:10.1038/bjc.2014.170 · 4.84 Impact Factor
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    ABSTRACT: To compare long-term results of Lichtenstein's operation versus mesh plug repair for open inguinal hernia repair. The technique of best choice in open prosthetic inguinal hernia repair remains a subject of ongoing debate. In this prospective, randomized controlled multicenter trial, patients with primary or recurrent inguinal hernias were randomized to undergo either Lichtenstein's operation or mesh plug repair. The primary endpoint was the long-term recurrence rate. Secondary endpoints included chronic pain, sensibility disorders, and reoperation rate. In total, 697 hernias in 594 patients were randomized (297 patients per group). At a median follow-up of 6.5 years, 528 (76%) operated hernias in 444 (75%) patients were clinically evaluated. The recurrence rate was similar in both groups [mesh plug: 21/268 hernias = 7.8%; Lichtenstein: 21/260 hernias = 8.1%; adjusted odds ratio (OR): 0.92; 95% confidence interval (CI): 0.51, 1.68; P = 0.795]. We did not find a significant difference for chronic pain (Visual Analog Scale score >3) (OR: 0.58; 95% CI: 0.31, 1.09; P = 0.088) and sensory testing (17% vs 20% of patients; OR: 0.53; 95% CI: 0.21, 1.37; P = 0.190) between the 2 groups. There were less reoperations in the mesh plug than in the Lichtenstein's operation group (OR: 0.43; 95% CI: 0.22, 0.85; P = 0.016). The long-term results of this trial indicate not enough evidence for differences in recurrence, chronic pain, and sensibility disorders between mesh plug repair and Lichtenstein's operation but a lower likelihood for reoperation for mesh plug repair. Estimates for all endpoints were statistically not significant or based on large CIs. Identifier: NCT01637818.
    Annals of surgery 10/2013; 259(5). DOI:10.1097/SLA.0000000000000297 · 8.33 Impact Factor
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    ABSTRACT: Colorectal cancer (CRC) infiltration by adaptive immune system cells correlates with favorable prognosis. The role of the innate immune system is still debated. Here we addressed the prognostic impact of CRC infiltration by neutrophil granulocytes (NG). A TMA including healthy mucosa and clinically annotated CRC specimens (n = 1491) was stained with MPO and CD15 specific antibodies. MPO+ and CD15+ positive immune cells were counted by three independent observers. Phenotypic profiles of CRC infiltrating MPO+ and CD15+ cells were validated by flow cytometry on cell suspensions derived from enzymatically digested surgical specimens. Survival analysis was performed by splitting randomized data in training and validation subsets. MPO+ and CD15+ cell infiltration were significantly correlated (p<0.0001; r = 0.76). However, only high density of MPO+ cell infiltration was associated with significantly improved survival in training (P = 0.038) and validation (P = 0.002) sets. In multivariate analysis including T and N stage, vascular invasion, tumor border configuration and microsatellite instability status, MPO+ cell infiltration proved an independent prognostic marker overall (P = 0.004; HR = 0.65; CI:±0.15) and in both training (P = 0.048) and validation (P = 0.036) sets. Flow-cytometry analysis of CRC cell suspensions derived from clinical specimens showed that while MPO+ cells were largely CD15+/CD66b+, sizeable percentages of CD15+ and CD66b+ cells were MPO-. High density MPO+ cell infiltration is a novel independent favorable prognostic factor in CRC.
    PLoS ONE 05/2013; 8(5):e64814. DOI:10.1371/journal.pone.0064814 · 3.23 Impact Factor
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    ABSTRACT: Background: Programmed cell death 1 (PD-1) receptor triggering by PD ligand 1 (PD-L1) inhibits T cell activation. PD-L1 expression was detected in different malignancies and associated with poor prognosis. Therapeutic antibodies inhibiting PD-1/PD-L1 interaction have been developed. Materials and methods: A tissue microarray (n=1491) including healthy colon mucosa and clinically annotated colorectal cancer (CRC) specimens was stained with two PD-L1 specific antibody preparations. Surgically excised CRC specimens were enzymatically digested and analysed for cluster of differentiation 8 (CD8) and PD-1 expression. Results: Strong PD-L1 expression was observed in 37% of mismatch repair (MMR)-proficient and in 29% of MMR-deficient CRC. In MMR-proficient CRC strong PD-L1 expression correlated with infiltration by CD8(+) lymphocytes (P = 0.0001) which did not express PD-1. In univariate analysis, strong PD-L1 expression in MMR-proficient CRC was significantly associated with early T stage, absence of lymph node metastases, lower tumour grade, absence of vascular invasion and significantly improved survival in training (P = 0.0001) and validation (P = 0.03) sets. A similar trend (P = 0.052) was also detectable in multivariate analysis including age, sex, T stage, N stage, tumour grade, vascular invasion, invasive margin and MMR status. Interestingly, programmed death receptor ligand 1 (PDL-1) and interferon (IFN)-γ gene expression, as detected by quantitative reverse transcriptase polymerase chain reaction (RT-PCR) in fresh frozen CRC specimens (n = 42) were found to be significantly associated (r = 0.33, P = 0.03). Conclusion: PD-L1 expression is paradoxically associated with improved survival in MMR-proficient CRC.
    European journal of cancer (Oxford, England: 1990) 03/2013; 49(9). DOI:10.1016/j.ejca.2013.02.015 · 5.42 Impact Factor
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    ABSTRACT: Background: The sentinel lymph node (SLN) procedure has the potential to provide relevant improvement in nodal staging in colon cancer patients. However, there remains room for improvement for SLN identification and sensitivity. Therefore, the objective of the present investigation was to analyze factors influencing the success of the SLN procedure in colon cancer patients. Methods: One hundred seventy-four consecutive colon cancer patients were prospectively enrolled in this multicenter study and underwent in vivo SLN procedure with isosulfan blue 1 % followed by open standard oncologic colon resection. Several patient-, tumor-, and procedure-related factors possibly influencing the SLN identification and sensitivity were analyzed. Results: Sentinel lymph node identification rate and accuracy were 89.1 and 83.9 %, respectively. Successful identification of SLN was significantly associated with the intraoperative visualization of blue lymphatic vessels (p < 0.001) and with female gender (p = 0.024). True positive SLN results were significantly associated with higher numbers of SLN (p = 0.026) and with pN2 stage (p = 0.004). There was a trend toward better sensitivity in patients with lower body mass index (BMI) (p = 0.050). Conclusions: The success of the SLN procedure in colon cancer patients depends on both procedure-related factors (intraoperative visualization of blue lymphatic vessels, high number of SLN identified) and patient factors (gender, BMI). While patient factors can not be influenced, intraoperative visualization of blue lymphatics and identification of high numbers of SLN are key for a successful SLN procedure.
    World Journal of Surgery 01/2013; 37(4). DOI:10.1007/s00268-013-1910-3 · 2.64 Impact Factor
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    ABSTRACT: BACKGROUND A new diagnostic system, called one-step nucleic acid amplification (OSNA), has recently been designed to detect cytokeratin 19 mRNA as a surrogate for lymph node metastases. The objective of this prospective investigation was to compare the performance of OSNA with both standard hematoxylin and eosin (H&E) analysis and intensive histopathology in the detection of colon cancer lymph node metastases. METHODS In total, 313 lymph nodes from 22 consecutive patients with stage I, II, and III colon cancer were assessed. Half of each lymph node was analyzed initially by H&E followed by an intensive histologic workup (5 levels of H&E and immunohistochemistry analyses, the gold standard for the assessment of sensitivity/specificity of OSNA), and the other half was analyzed using OSNA. RESULTS OSNA was more sensitive in detecting small lymph node tumor infiltrates compared with H&E (11 results were OSNA positive/H&E negative). Compared with intensive histopathology, OSNA had 94.5% sensitivity, 97.6% specificity, and a concordance rate of 97.1%. OSNA resulted in an upstaging of 2 of 13 patients (15.3%) with lymph node-negative colon cancer after standard H&E examination. CONCLUSIONS OSNA appeared to be a powerful and promising molecular tool for the detection of lymph node metastases in patients with colon cancer. OSNA had similar performance in the detection of lymph node metastases compared with intensive histopathologic investigations and appeared to be superior to standard histology with H&E. Most important, the authors concluded that OSNA may lead to a potential upstaging of >15% of patients with colon cancer. Cancer 2012. © 2012 American Cancer Society.
    Cancer 12/2012; 118(24). DOI:10.1002/cncr.27667 · 4.89 Impact Factor
  • Pamela Meiers · Tulin Cil · Ulrich Guller · Markus Zuber ·
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    ABSTRACT: Purpose: The objective of this review is to summarize the evidence demonstrating that the sentinel lymph node (SLN) procedure is not only associated with significantly less morbidity compared to the axillary dissection, but may also result in better staging and improved patient outcomes. Methods: A search of MedLine and PubMed articles using the terms "sentinel lymph node biopsy", "breast cancer", "staging", "morbidity", "survival", and "outcomes" was conducted. Results: Breast cancer staging includes axillary evaluation as an integral component. Over the past two decades, sentinel lymph node biopsy has evolved as a technique that has an improved morbidity over traditional axillary dissection. The sentinel node(s) undergo a more intensive pathologic examination than traditional axillary contents. In the node-negative group of patients, this may have led to stage migration and potentially improved disease-free and overall survival. Conclusion: The SLN procedure is not only associated with significantly less morbidity compared to the axillary lymph node dissection, it may also result in more accurate staging, better axillary tumor control and improved survival.
    Langenbeck s Archives of Surgery 12/2012; 398(5). DOI:10.1007/s00423-012-1037-2 · 2.19 Impact Factor
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    ABSTRACT: An overview of colorectal cancer discussed (Philip Paty) the good outcome after primary management with local control in 90-95 % of colon and 85 % in rectal cancer patients with major progression to metastases and to death related to hematogenous dissemination. The major disease pathways include the APC, aneuploid pathway involving mutations of P53, KRAS, SMAD 4, or the CMP/MSI pathway, mismatched repair defect as characterized by Lynch syndrome, the major hereditary form which may also have KRAS and P53 mutations. The common sporadic colorectal cancers are MS1 high, with many patients having BRAF and KRAS mutations. The sentinel node biopsy in colorectal cancer surgery may provide more definitive staging and perhaps modification of the extent of resection with better outcome as suggested by Dr. Saha. The identification of sentinel lymph nodes outside of the planned bowel resection may increase the resection biologically indicated by the sentinel lymph node location leading to better outcome. In a small study by Dr. Saha, the operation was enhanced in 21 % by extending the length of bowel resection, which increased node recovery to 18.5 nodes versus 12 nodes with the more conventional resection, increasing nodal recovery, and positivity to 60 % with reduction to five year recurrence rate to 9 % versus 27 % with the conventional resection. A new (Swiss) technique for pathologic node examination, the OSNA (the One Step Nucleic Acid diagnostic system), was presented which demonstrated increased detection of micro-metastases in a focused pathology study of 22 patients (Zuber) to 11 out of 15 patients versus the 7 micro-metastases identified by the standard single slide per node, and compared to 14 out of 15 with an intensive multi-slide technique. This suggests value in pursuing OSNA study by other centers with relevant clinical trials to establish its true value. An analysis of liver resection for metastatic colorectal cancer (CRC) emphasized the value of 10-year follow-up (DeAngelica). The 10-year survival of 102 patients among 612 patients was 17 % (Memorial Sloan Kettering data). At the five-year point 99 of 102 survivors were NED and 86 have been free of disease since the resection. The usual five-year figure after hepatic resection reveals that one-third of five-year survivors die from recurrence of distant disease suggesting the value of longer term follow-up in these patients. An additional question reviewed related to the role of neoadjuvant systemic chemotherapy (with response rates in the 50 % range) to produce down staging of the hepatic metastases and allow one to retrieve these patients with possible residual disease. In a series of 116 patients who had hepatic resection of CRC metastases in presence of regional node metastases, post neoadjuvant chemotherapy (normally not candidates for resection) these patients were demonstrated to have a 95 % recurrence at median time of 9 months. This raises a cautionary note to the literature report of five-year survivals in the 20-30 % range for hepatic metastases in presence of extra hepatic disease. Such may reflect patient selection rather than a true measure of the biology of disease, and warrant clinical trial evaluation. Lastly, regional therapy and overall systemic therapy were addressed by Dr. Kemeny. The CALGB study of hepatic artery infusion (HAI) with FUDR, dexamethasone versus 5FU leucovorin showed an overall survival of 24.4 months with HAI versus 20 months with systemic therapy (P = 0.0034). An adjuvant trial of HAI at MSK in 156 patients showed an overall survival benefit at 2 year and recent long term 10yr follow-up showing a significant overall survival of 41 % with HAI versus 27 % with systemic therapy (5FU leucovorin). In the neoadjuvant Nordlinger trial for hepatic metastases, there was a significant outcome differences-the preoperative therapy group had 9.2 % increase of progression free survival versus the surgery alone group which suggests the value of combining neoadjuvant surgery in good risk liver resection candidates. Conclude the final lesson from this well presented mini symposium confirms the need for continued evaluation of the numerous discussion points by clinical trial.
    Clinical and Experimental Metastasis 10/2012; 29(7). DOI:10.1007/s10585-012-9517-x · 3.49 Impact Factor
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    Urs von Holzen · Andre Gehrz · Lukas Meier · Markus Zuber ·
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    ABSTRACT: To ensure a high quality of care in surgery, many surgical departments in Switzerland are members of the working group for quality assurance in surgery (AQC). The purpose of this study was to assess the value of the AQC database as a tool for quality assurance and a source for scientific studies. We had two hypotheses. Firstly that the percentage of laparoscopic appendectomies would have increased over time without an increase in the complication rate and secondly that these procedures would primarily have been performed by residents. All appendectomies performed at the Kantonsspital Olten between 2001 and 2006 were prospectively recorded in the AQC database. 684 appendectomies were performed. We recorded a clear increase in the use of laparoscopic interventions from 51 to 81%. Ninety three percent of these appendectomies were performed by residents or junior faculty members. The main complication were surgical site infection in 3.6% of the open procedures as compared to none in laparoscopic procedures (p <0.001). Intra-abdominal abscess formation was recorded in 2.7% of laparoscopic procedures as compared to 1.8% in open surgery (p = 0.608). The overall complication rate in the study was 5.4% with no statistical difference between open (6.5%) and laparoscopic (4.7%) surgery (p = 0.305). The study clearly shows that the AQC-database offers a wide variety of possibilities for quality assurance and scientific analyses. Our data demonstrate that laparoscopic procedures clearly increased from 2001 to 2006. Appendectomies were mainly performed by residents and junior faculty members. Laparoscopic appendectomy is a safe procedure with a low complication rate and should be applied as a teaching operation during the surgical training.
    Schweizerische medizinische Wochenschrift 07/2012; 142:w13617. DOI:10.4414/smw.2012.13617 · 2.09 Impact Factor

  • Cancer Research 06/2012; 72(8 Supplement):3546-3546. DOI:10.1158/1538-7445.AM2012-3546 · 9.33 Impact Factor

  • Cancer Research 06/2012; 72(8 Supplement):1491-1491. DOI:10.1158/1538-7445.AM2012-1491 · 9.33 Impact Factor
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    ABSTRACT: Vital tissue provided by fresh frozen tissue banking is often required for genetic tumor profiling and tailored therapies. However, the potential patient benefits of fresh frozen tissue banking are currently limited to university hospitals. The objective of the present pilot study-the first one in the literature-was to evaluate whether fresh frozen tissue banking is feasible in a regional hospital without an integrated institute of pathology. Patients with resectable breast and colon cancer were included in this prospective study. Both malignant and healthy tissue were sampled using isopentan-based snap-freezing 1 h after tumor resection and stored at -80 °C before transfer to the main tissue bank of a University institute of pathology. The initial costs to set up tissue banking were 35,662 US$. Furthermore, the running costs are 1,250 US$ yearly. During the first 13 months, 43 samples (nine samples of breast cancer and 34 samples of colon cancer) were collected from 41 patients. Based on the pathology reports, there was no interference with standard histopathologic analyses due to the sample collection. This is the first report in the literature providing evidence that tissue banking in a regional hospital without an integrated institute of pathology is feasible. The interesting findings of the present pilot study must be confirmed by larger investigations.
    World Journal of Surgery 05/2012; 36(10):2300-4. DOI:10.1007/s00268-012-1656-3 · 2.64 Impact Factor
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    ABSTRACT: The value of the sentinel lymph node (SLN) procedure in colon cancer patients remains a matter of debate. The objective of this prospective, multicenter trial was 3-fold: to determine the identification rate and accuracy of the SLN procedure in patients with resectable colon cancer; to evaluate the learning curve of the SLN procedure; and to assess the extent of upstaging due to the SLN procedure. One hundred seventy-four consecutive colon cancer patients were enrolled onto this prospective trial. They underwent an intraoperative SLN procedure with isosulfan blue 1% injected peritumorally followed by open standard colon resection with oncologic lymphadenectomy. Three levels of each SLN were stained with hematoxylin and eosin (H&E) and immunostained with the pancytokeratin marker AE1/AE3 if H&E was negative. SLN identification rate and accuracy were 89.1% and 83.9%, respectively. SLN were significantly more likely to contain tumor infiltrates than non-SLN (P < 0.001). Both SLN identification rate (P = 0.021) and the sensitivity of the procedure (P = 0.043) significantly improved with experience. The use of immunohistochemistry in SLN resulted in an upstaging of 15.4% (16 of 104) stage I and II patients considered node-negative in initial H&E analysis. The SLN procedure for colon cancer has good identification and accuracy rates, which further improve with increasing experience. Most importantly, the SLN procedure results in upstaging of >15% of node-negative patients. The potential advantage of performing the SLN procedure appears to be particularly important in these patients because they may potentially benefit from adjuvant therapy.
    Annals of Surgical Oncology 02/2012; 19(6):1959-65. DOI:10.1245/s10434-012-2233-6 · 3.93 Impact Factor
  • Alex Ochsner · Markus Zuber · Carsten T Viehl ·
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    ABSTRACT: Surveillance programs have been recommended for colorectal and breast cancer patients in several countries, and appropriate surveillance guidelines have been issued by various societies. The Swiss Society of Gastroenterology consensus paper recommends a surveillance program for patients after curative resection of colorectal cancer (CRC), and the respective guidelines are updated regularly. Early detection of recurrent disease from CRC allows treatment with intention to cure. Five year survival rates after treatment for recurrent CRC can reach up to 50 % or more. Therefore tumor surveillance in CRC is important, and there is compelling evidence that patients benefit from intensive surveillance. In addition to clinical controls, measurements of carcinoembryonal antigen, colonoscopies and thoraco-abdominal CT scans should be performed on a regular basis. For surveillance of breast cancer (BC) patients, a regular schedule is recommended as well. However, this surveillance program is more focussing on the detection of possible loco-regional tumor relapse, as curative therapy of BC metastases is much less frequently possible than in CRC patients. Irrespective of the underlying tumor entity, surveillance is an important and challenging process that should be coordinated by one single physician. It is crucial that all involved physicians are aware of their responsibility and that they are informed about the respective surveillance program and its benefit to the patient.
    Therapeutische Umschau 01/2012; 69(1):49-55. DOI:10.1024/0040-5930/a000250
  • M. Zuber · C. T. Viehl · I. Langer · A. Zettl · U. Guller ·

    European Journal of Cancer 09/2011; 47. DOI:10.1016/S0959-8049(11)70533-0 · 5.42 Impact Factor
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    ABSTRACT: The prognostic significance of macrophage and natural killer (NK) cell infiltration in colorectal carcinoma (CRC) microenvironment is unclear. We investigated the CRC innate inflammatory infiltrate in over 1,600 CRC using two independent tissue microarrays and immunohistochemistry. Survival time was assessed using the Kaplan-Meier method and Cox proportional hazards regression analysis in a multivariable setting. Spearman's rank correlation tested the association between macrophage and lymphocyte infiltration. The Basel study included over 1,400 CRCs. The level of CD16+ cell infiltration correlated with that of CD3+ and CD8+ lymphocytes but not with NK cell infiltration. Patients with high CD16+ cell infiltration (score 2) survived longer than patients with low (score 1) infiltration (p = 0.008), while no survival difference between patients with score 1 or 2 for CD56+ (p = 0.264) or CD57+ cell (p = 0.583) infiltration was detected. CD16+ infiltrate was associated with improved survival even after adjusting for known prognostic factors including pT, pN, grade, vascular invasion, tumor growth and age [(p = 0.001: HR (95% CI) = 0.71 (0.6-0.9)]. These effects were independent from CD8+ lymphocyte infiltration [(p = 0.036: HR (95% CI) = 0.81 (0.7-0.9)] and presence of metastases [(p = 0.002: HR (95% CI) = 0.43 (0.3-0.7)]. Phenotypic studies identified CD16+ as CD45+CD33+CD11b+CD11c+ but CD64- HLA-DR-myeloid cells. Beneficial effects of CD16+ cell infiltration were independently validated by a study carried out at the University of Athens confirming that patients with CD16 score 2 survived longer than patients with score 1 CRCs (p = 0.011). Thus, CD16+ cell infiltration represents a novel favorable prognostic factor in CRC.
    International Journal of Cancer 06/2011; 128(11):2663-72. DOI:10.1002/ijc.25609 · 5.09 Impact Factor
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    ABSTRACT: The validation of sentinel lymph node (SLN) concept in melanoma and breast cancer has established a new paradigm in cancer metastasis that, in general, cancer cells spread in a orderly fashion from the primary site to the SLNs in the regional nodal basin and then to the distant sites. In this review article, we examine the development of SLN concept in penile carcinoma, melanoma and breast carcinoma and its application to other solid cancers with emphasis of the relationship between micrometastasis in SLNs and clinical outcomes.
    Journal of Surgical Oncology 05/2011; 103(6):518-30. DOI:10.1002/jso.21815 · 3.24 Impact Factor

Publication Stats

3k Citations
333.26 Total Impact Points


  • 2005-2013
    • Cantonal Hospital of Schwyz
      Schwyz, Schwyz, Switzerland
  • 1994-2011
    • Universität Basel
      • • Institute of Geology and Paleontology
      • • Department of Chemistry
      Bâle, Basel-City, Switzerland
  • 2008
    • Schweizerischen Arbeitsgemeinschaft für Klinische Krebsforschung
      Berna, Bern, Switzerland
  • 1996-2000
    • Universitätsspital Basel
      • Institut für Pathologie
      Bâle, Basel-City, Switzerland