[Show abstract][Hide abstract] ABSTRACT: Colorectal cancer (CRC) infiltration by CD16+ myeloid cells correlates with improved prognosis. We addressed mechanistic clues, and gene and protein expression of cytokines potentially associated with macrophage polarization.
GM-CSF or M-CSF stimulated peripheral blood CD14+ cells from healthy donors were co-cultured with CRC cells. Tumor cell proliferation was assessed by 3H-Thymidine incorporation. Expression of cytokine (CK) genes in CRC and autologous healthy mucosa (HM) was tested by quantitative, real-time PCR. A tumor microarray (TMA) including >1200 CRC specimens was stained with GM-CSF and M-CSF specific antibodies. Clinic-pathological features and overall survival were analyzed.
GM-CSF induced CD16 expression in 66±8% of monocytes, as compared to 28±1% in cells stimulated by M-CSF (P=0.011). GM-CSF but not M-CSF stimulated macrophages significantly (P<0.02) inhibited CRC cell proliferation. GM-CSF gene was expressed to significantly (n=45, P<0.0001) higher extents in CRC than in HM whereas M-CSF gene expression was similar in HM and CRC. Accordingly, IL-1β and IL-23 genes, typically expressed by M1 macrophages, were expressed to significantly (P<0.001) higher extents in CRC than in HM. TMA staining revealed that GM-CSF production by tumor cells is associated with lower T stage (p=0.02), "pushing" growth pattern (P=0.004) and significantly (P=0.0002) longer survival in mismatch-repair proficient (MMRp) CRC. Favorable prognostic effect of GM-CSF production by CRC cells was confirmed by multivariate analysis and was independent from CD16+ and CD8+ cell CRC infiltration. M-CSF expression had no significant prognostic relevance.
GM-CSF production by tumor cells is an independent favorable prognostic factor in CRC.
Clinical Cancer Research 04/2014; · 8.19 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The few long-term follow-up data for sentinel lymph node (SLN) negative breast cancer patients demonstrate a 5-year disease-free survival of 96-98%. It remains to be elucidated whether the more accurate SLN staging defines a more selective node negative patient group and whether this is associated with better overall and disease-free survival compared with level I & II axillary lymph node dissection (ALND).
Three-hundred and fifty-five consecutive node negative patients with early stage breast cancer (pT1 and pT2< or =3 cm, pN0/pN(SN)0) were assessed from our prospective database. Patients underwent either ALND (n=178) in 1990-1997 or SLN biopsy (n=177) in 1998-2004. All SLN were examined by step sectioning, stained with H&E and immunohistochemistry. Lymph nodes from ALND specimens were examined by standard H&E only. Neither immunohistochemistry nor step sections were performed in the analysis of ALND specimen.
The median follow-up was 49 months in the SLN and 133 months in the ALND group. Patients in the SLN group had a significantly better disease-free (p=0.008) and overall survival (p=0.034). After adjusting for other prognostic factors in Cox proportional hazard regression analysis, SLN procedure was an independent predictor for improved disease-free (HR: 0.28, 95% CI: 0.10-0.73, p=0.009) and overall survival (HR: 0.34, 95% CI: 0.14-0.84, p=0.019).
This is the first prospective analysis providing evidence that early stage breast cancer patients with a negative SLN have an improved disease-free and overall survival compared with node negative ALND patients. This is most likely due to a more accurate axillary staging in the SLN group.
European journal of surgical oncology: the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 12/2008; 35(8):805-13. · 2.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The perioperative use of a single course adjuvant portal vein infusion chemotherapy in patients with potentially curable colorectal cancer has been shown to significantly improve overall survival but did not reduce the occurrence of liver metastases (SAKK 40/81) [Swiss Group for Clinical Cancer Research (SAKK) Lancet 345(8946):349-353, 1995]. The objective of the present prospective, three-arm randomized multicenter trial was to assess whether peripheral venous administration of adjuvant chemotherapy regimen based on 5-fluorouracil (5-FU) and mitomycin C decreases the occurrence of liver metastases as well as prolongs disease-free and overall survival.
Stages I-III colorectal cancer patients (n = 753) were randomized to receive either surgery alone (control arm), surgery plus postoperative portal venous infusion of 5-FU 500 mg/m(2) plus heparin given for 24 hours for seven consecutive days plus mitomycin C 10 mg/m(2) given on the first day (arm 2), or surgery and the same chemotherapy regimen administered by peripheral venous route (arm 3).
The 5-year disease-free survival for the three treatment groups were 65% (control group), 60% (portal vein infusion, hazard ratio 1.18, p = 0.23), and 64% (intravenous infusion, hazard ratio 1.04, p = 0.76); the 5-year overall survival was 72% (control group), 69% (portal vein infusion, hazard ratio 1.21, p = 0.2), and 74% (intravenous infusion, hazard ratio 1.03, p = 0.86), respectively. A significant accumulation of early deaths were observed in the portal vein infusion group (p = 0.015).
The present prospective randomized multicenter trial provides compelling evidence that short-term perioperative chemotherapy does not improve disease-free and overall survival in patients with potentially curative colorectal cancer. In contrary, the chemotherapy regimen administered in the present investigation seems to have potentially harmful effects, a finding which should be carefully considered in the planning of future trials. Postoperative short-term administration of 5-FU plus mitomycin C either through portal infusion or a central venous catheter is not recommended for routine use in patients with potentially curable colorectal cancer.
International Journal of Colorectal Disease 09/2008; 23(12):1233-41. · 2.42 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Two of the most commonly used open prosthetic tension-free techniques for inguinal hernia repair are Lichtenstein's operation and the mesh plug repair. The technique of choice remains a subject of ongoing debate. The objective of the present investigation was to compare the two surgical procedures with respect to associated morbidity and recurrence rates.
Five hundred and ninety-five patients with 700 primary or recurrent inguinal hernias were randomized to undergo either Lichtenstein's operation or mesh plug repair. The primary endpoint of the investigation was the recurrence rate 1 year after surgery. Secondary endpoints were perioperative complications and reoperation rates.
At 12-month follow-up, 597 hernia repairs (85.3 per cent) were evaluated. There were no significant differences regarding recurrence rates and perioperative complications. However, there was a significant difference in the overall reoperation rate between the two treatment groups, with 13 reoperations (4.2 per cent) in the Lichtenstein group and four (1.4 per cent) in the mesh plug group (P = 0.047).
Lichtenstein's operation and the mesh plug repair are comparable with respect to perioperative complications and recurrence rates.
British Journal of Surgery 02/2007; 94(1):36-41. · 5.21 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Reports on long-term outcomes after endoscopic axillary lymph node dissection (ALND) of breast cancer patients are still lacking in the medical literature. The objective of this prospective study was to assess the oncological and functional outcomes in breast cancer patients after endoscopic ALND.
Fifty-five breast cancer patients were prospectively enrolled, of whom 52 were available for follow-up with a median of 71.9 months (range 11-96). The following oncological and functional endpoints were evaluated during follow-up at several time points: occurrence of local, axillary and distant metastases, seroma or infection, shoulder mobility (range of motion), numbness, pain, presence of lymphoedema as well as restriction in activities of daily living.
In 52 patients endoscopic ALND of level I and II was successfully performed. Two port-site metastases (2/52, 4%) occurred, one of which in a patient with negative axillary lymph nodes. The same patient suffered from the only axillary recurrence (1/52, 2%). Three patients (3/52, 6%) developed lymphoedema. No other functional adverse events (shoulder mobility, pain, numbness, hypertrophic scar) were noticed at the end of the observation period.
The present investigation with long-term follow-up after endoscopic ALND--the first one in the literature--reveals minor morbidity, good functional and cosmetic results. In contrary to conventional surgery, the endoscopic procedure is associated with the occurrence of port-site metastases, not seen in the open approach. Axillary recurrences do not appear more frequently when compared with results after conventional ALND. In the meantime the less invasive sentinel lymph node (SLN) biopsy is the established standard technique in evaluating the axillary lymph node status.
Breast Cancer Research and Treatment 04/2005; 90(1):85-91. · 4.20 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We report a case of a 31-year-old male drug addict with acute ischaemia of the right hand after inadverted intraarterial injection of suspended tablets into brachial artery. He was successfully treated with intraarterial administration of urokinase (250'000 IU as bolus, then continuous infusion of 250'000 IU per 12 hours), papaverin (40 mg i.v. 3 x every 4 hours), systematic heparinisation and with axillary plexus anesthesia (Bupivacain 0.25%, 10 ml/h). Treatment options are discussed reviewing recent publications. Early onset of treatment is mandatory for a good outcome.
[Show abstract][Hide abstract] ABSTRACT: Advances in genomics and proteomics are dramatically increasing the need to evaluate large numbers of molecular targets for their diagnostic, predictive or prognostic value in clinical oncology. Conventional molecular pathology techniques are often tedious, time-consuming, and require a lot of tissue, thereby limiting both the number of tissues and the number of targets that can be evaluated. Here, we demonstrate the power of our recently described tissue microarray (TMA) technology in analyzing prognostic markers in a series of 553 breast carcinomas. Four independent TMAs were constructed by acquiring 0.6 mm biopsies from one central and from three peripheral regions of each of the formalin-fixed paraffin embedded tumors. Immunostaining of TMA sections and conventional "large" sections were performed for two well- established prognostic markers, estrogen receptor (ER) and progesterone receptor (PR), as well as for p53, another frequently examined protein for which the data on prognostic utility in breast cancer are less unequivocal. Compared with conventional large section analysis, a single sample from each tumor identified about 95% of the information for ER, 75 to 81% for PR, and 70 to 74% for p53. However, all 12 TMA analyses (three antibodies on four different arrays) yielded as significant or more significant associations with tumor-specific survival than large section analyses (p < 0.0015 for each of the 12 comparisons). A single sample from each tumor was sufficient to identify associations between molecular alterations and clinical outcome. It is concluded that, contrary to expectations, tissue heterogeneity did not negatively influence the predictive power of the TMA results. TMA technology will be of substantial value in rapidly translating genomic and proteomics information to clinical applications.
American Journal Of Pathology 12/2001; 159(6):2249-56. · 4.60 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Cecal volvulus represents a rare disease which causes acute or chronic intermittent mechanical obstruction. Diagnosis of the acute form of cecal volvulus is often established too late with resulting high morbidity and mortality. This study characterizes the typical clinical symptoms, radiological signs and the frequent concomitant diseases, based on a rather large number of patients. We specifically evaluated possible differences concerning clinical presentation, therapy and postoperative course of patients with vital bowel as opposed to necrotic cecum.
26 consecutive patients hospitalised with cecal volvulus from January 1984 until February 2000 were retrospectively evaluated. Patients with vital intestine (n = 14) were compared to those with necrotic cecum (n = 12).
38% of patients underwent previous abdominal surgery, 34% suffered from other acute disease, in 38% cecal volvulus was associated with a neuropsychiatric disorder. 58% of the patients showed symptoms of intestinal obstruction. The clinical pattern of patients with necrotic cecum was not significantly different from those of patients with vital intestine. Diagnosis of cecal volvulus could be established in 77% by plain abdominal X-ray alone or by an additional contrast enema.
Knowledge of the characteristic pattern of history, physical findings, plain abdominal X-ray and the frequently with cecal volvulus associated diseases most often allows to establish diagnosis of cecal volvulus without delay and other diagnostic procedures. Astonishingly we found no major difference between vital and necrotic cecum with regard to clinical presentation and postoperative course.