Table S1. The biomarker serum phospholipid fatty acids in wt% and quartiles (P25‚ 75), n = 49. Ta... more Table S1. The biomarker serum phospholipid fatty acids in wt% and quartiles (P25‚ 75), n = 49. Table S2. Spearman correlation coefficients (ρ) for selected fatty acids from supplements, n = 49. (DOCX 55 kb)
Sentinel lymph node biopsy is an integral part of the management of breast cancer and malignant m... more Sentinel lymph node biopsy is an integral part of the management of breast cancer and malignant melanoma. The concept is now being applied to colorectal cancer. We publish two papers which discuss sentinel node biopsy in terms of the advantages and disadvantages of this approach which is a refinement of staging. Lymph node staging in colorectal cancer has been a quest bedevilled by the inability of external imaging to deliver sensitivity and specificity sufficient to be of clinical value. Perhaps this may change although much needs to be done to establish the accuracy of the investigation and to convince surgeons and oncologists that the technical requirements to obtain the information are worth the effort. The whole question of lymph node staging in colorectal cancer is coming into focus. Magnetic resonance and more recently PET, are beginning to deliver information which has the potential to influence management policy. Sentinel node status may or may not stand the test of time, but it is something that is a part of the present discussion.
Malignant melanoma is the most common metastatic lesion of the intestine, found at autopsy in app... more Malignant melanoma is the most common metastatic lesion of the intestine, found at autopsy in approximately 60% of patients who die from melanoma. Common symptoms include bleeding, perforation and ileus/subileus. Patients with such symptoms should be operated on immediately, if they are not too reduced because of advanced disease. Long-term survival (five years) has been achieved in 34 of 179 (19%) of stage IVA melanoma patients after a radical operation procedure. Surgical removal of gastrointestinal metastases provides effective palliation in 80-95% of patients, who undergo laparotomy. We describe two patients with gastrointestinal metastases from malignant melanoma. A 33 year-old man had a large melanoma metastasis removed (non-radically) from the small intestine. He recovered rapidly, and experienced good palliative effect for three months, but died from a recurrence of the disease six months after operation. The other patient had a melanoma metastasis in the right lobe of the liver, which was treated by right hemihepatectomy. There has been no recurrence ten months after operation. We recommend surgical removal of abdominal melanoma metastasis if the surgery can be performed without unacceptable risk.
Pseudomembranous colitis is an inflammatory intestinal disease that is usually secondary to antib... more Pseudomembranous colitis is an inflammatory intestinal disease that is usually secondary to antibiotic treatment. The disease upsets the normal bacterial flora of the large intestine. Therapy consists of fluid replacement, discontinuation of broad-spectrum antibiotics and treatment with vancomycin or metronidazole. In severe or resistant cases surgical treatment is required. We describe one case history and give some guidelines for surgical treatment.
Despite the fact that a prognosis in 1991 predicted a surplus of ten gastroenterological surgeons... more Despite the fact that a prognosis in 1991 predicted a surplus of ten gastroenterological surgeons in 1994, several hospitals are now experiencing a lack of applicants. In order to define the scope of this problem, the Norwegian Gastroenterological Society and The Specialty Committee for Gastroenterological Surgery sent a questionnaire and made a telephone query to all Norwegian Surgical Departments in autumn 1995. There were 21 vacant posts and 27 specialists are still needed to carry out the tasks the hospitals are instructed to perform. An initiative must be taken to increase the capacity and geographical distribution of the education and improve the working conditions, and thereby job satisfaction, of gastroenterological surgeons.
One of the disadvantages of breast conserving treatment compared with mastectomy is the higher ra... more One of the disadvantages of breast conserving treatment compared with mastectomy is the higher rate of local recurrence. Even though a local recurrence has no influence on survival, it is a psychological trauma for the woman it affects. Breast conserving treatment has been practised at Ullevaal Hospital since 1986. This study is based on data from 216 consecutive cases of breast conserving surgery, from January 1986 to March 1996. Mean observation time was 29 months. Nine (4.2%) patients experienced a local recurrence. Age, histological grade, and the size of the tumor were identified as risk factors, whereas there was no correlation between histology, axillary node involvement, and surgical margins.
The vasodilator bradykinin (Bk) has long been though to participate in shock induced by endotoxem... more The vasodilator bradykinin (Bk) has long been though to participate in shock induced by endotoxemia, anaphylaxis and acute pancreatitis. Recently developed kinin antagonists have made it possible to test this hypothesis. We studied the effect of two of them. DArg0Hyp3-Thi5.8-DPhe7-Bk (45 and 220 micrograms/kg/min) and Lys-Lys-Hyp2-Thi5.8-DPhe7-Bk (100 micrograms/kg/min) on the early hypotensive response to Escherichia coli lipopolysaccharide (LPS). Rats infused with the antagonist vehicle were used as controls. At 45 micrograms/kg/min, DArg0-Hyp3-Thi5.8-dPhe7-Bk prevented the hypotensive response to high doses of Bk; however, neither antagonist prevented the hypotensive response to LPS. Circulating kinins measured 3 min after injecting LPS or vehicle were similar (16.3 +/- 1.4 vs. 26.0 +/- 7.2 pg/ml; P greater than .23). In allergically sensitized rats, 500 micrograms/kg/min DArg0-Hyp3-Thi5.8-DPhe-7-Bk did not alter the hypotensive (anaphylactic) response to antigen challenge (P greater than .38). Similarly, hypotension caused by development of acute pancreatitis in rats was not prevented by infusion of DArg0-Hyp3-Thi5.8-DPhe7-Bk at 200 micrograms/kg/min, 10 min) (P greater than .69). These results indicate that in the rate formation of kinins is not a major contributor to the hypotensive response observed in early endotoxemia, anaphylaxis and acute pancreatitis.
Inflammatory bowel disease (ulcerative colitis and Crohn's disease) is a chronic illness, often a... more Inflammatory bowel disease (ulcerative colitis and Crohn's disease) is a chronic illness, often affecting people of reproductive age. Treatment involves drugs which have potential side effects and because of this pregnancy causes considerable concern. The course of the disease is not much affected by pregnancy. The relapse rate is only slightly increased when the disease is active at the time of conception. Relapses during pregnancy should be treated in the usual manner. Surgical intervention should be carried out on the same indications as in those who are not pregnant. Frequency of complications is not increased during pregnancy, at delivery or post partum. Sectio may be necessary in perianal disease. With few exceptions, drug treatment should be continued throughout pregnancy. No adverse effects are seen with normal doses of sulfasalazine, 5-amino-salicylic acid and steroids. Planned pregnancies should be started in periods of quiescent disease.
177 Background: We have investigated whether the introduction of organized mammography screening ... more 177 Background: We have investigated whether the introduction of organized mammography screening in Norway led to less aggressive breast cancer surgery in the invited age group. Methods: We obtained aggregate incidence and surgical treatment data for women treated for ductal carcinoma in situ or invasive breast cancer from the Norwegian Cancer Registry. Rates of breast operations (mastectomy plus breast conserving therapy) and rates of mastectomy only for three age groups; women aged 40-49, 50-69 and 70-79 years were calculated. Changes in rates from a pre-screening period (1993-95) to a screening introduction phase (1996-2004) and then to a screening period (2005-08) are presented as hazard ratios comparing invited and non-invited women. Results: From the pre-screening period (1993-95) to the screening period (2005-08) the annual breast operation rate increased by 70% (HR=1.70 95% CI 1.62 to 1.78), from 180 to 305 per 100 000 women in the invited age group (50-69 years). In contras...
Multiple organ failure may develop as a consequence of defective tissue oxygenation, particularly... more Multiple organ failure may develop as a consequence of defective tissue oxygenation, particularly in the gut. Measurements of intramucosal pH (pHi), accomplished by means of a tonometer placed in the stomach or in the sigmoid colon, seem to monitor the degree of mucosal oxygenation very good. The tonometer technique is noninvasive and easy to perform. pHi may be useful as an index to guide therapeutic interventions in critically ill patients.
Background: Sentinel lymph node (SN) biopsy is a technique for identifying axillary metastases fr... more Background: Sentinel lymph node (SN) biopsy is a technique for identifying axillary metastases from primary breast cancer. The present paper reports our results with the method. Material and methods: SN biopsies have been routinely performed at Ullevål University Hospital since 2000 and the results have been prospectively recorded. 1409 patients with breast cancer or ductal carcinoma in situ grade 3, were injected with peritumoral radiocolloid the day before the biopsy and with blue dye per-operatively to detect the SN. Results: The SN was detected in 90 % of the operations. Metastases to SN were detected in 25 % of the patients and 52 % of these had no further positive nodes in the axilla. Thus, axillary lymph node clearance was omitted in 948 patients. Three patients had local recurrence in the axilla within one year after the successful SN procedure. Ductal carcinoma in situ grade 3 was diagnosed preoperatively in 162 patients (cytology); 88 had the diagnosis after histology and the rest had invasive cancer or combinations with in situ lesions of other grades. Axillary metastases were found in 4.8 % of these patients. Isolated tumour cells (< 0.2 mm diameter) were found in 9 patients for whom axillary clearance has not been performed. Interpretation: SN biopsy has replaced routine axillary clearance as a routine operation in breast cancer. The method is safe when performed correctly, as metastases in the axilla after a negative SN rarely occur.
Introduction: A sentinel lymph node (SN) is the primary node draining the tumor and is assumed to... more Introduction: A sentinel lymph node (SN) is the primary node draining the tumor and is assumed to be affected early in the metastatic process. Detection of metastases in SN is a standard procedure in breast cancer diagnostics based on microscopic evaluation (morphology and immunohistochemistry), determining the need for removal of all axillary glands for inspection which again is crucial for tailoring adjuvant therapy. The identification by microscopy is time-consuming and has a risk for false negative results. We hypothesize that the immune profile of SN changes with the presence of tumor cells, even at very low frequencies (micrometastases). By using a multi marker approach to characterize millions of cells from sentinel lymph nodes with and without metastases we aimed at identifying both tumor cells but also characterize a tumor specific immune response. This dual approach might provide an opportunity for a more sensitive test for SN diagnostics. Material and Methods: We established a mass cytometry assay containing 38 markers (antibodies) using CyTOF technology to combine immune profiling with identification of breast cancer cells. Cell suspensions from 14 metastatic axillary lymph nodes (ALNmet), 16 metastatic sentinel lymph nodes (Snmet) and 14 non-metastatic sentinel lymph nodes (SN) from breast cancer patients from the clinical observational trial Oslo2 (early, operable breast cancer patients representing all subtypes) were successfully analyzed by the multimarker panel (single cell resolution). Results: By using mass cytometry, we detected tumor cells (gated as PanKeratin+/CD45- cells) in 86% (26/30) metastatic lymph nodes (ALNmet and Snmet) and in 14% (2/14) non-metastatic lymph nodes (SN). Further, the leukocyte population, identified as CD45+ cells, was gated into 15 subpopulations, mainly comprising different subsets of B and T cells, monocytes and NK cells. By comparing the leukocyte composition in the ALNmet with those in SN samples we identified a significant increase in the abundance of CD8+ memory phenotype, TFH and TCRγδ cells and a decrease in the CD4+ subpopulation in ALNmet compared to the SN samples. The Snmet samples had smaller deposits of tumor cells than the ALNmet samples, and we found no significant differences in leukocyte composition between Snmet and SN samples. Interestingly, when looking at the activation marker CD56, we observed a significant higher expression in the CD4RO, CD8RO, TFH and Treg subpopulations of Snmet samples compared to SN samples. Conclusion: In this study we identified a significant difference in immune cell composition in lymph nodes with and without metastases (ALNmet compared to SN samples). We also identified activation markers unique for subpopulations of lymphocytes in Snmet, but not in negative lymph nodes (SN). We were also able to detect and identify micrometastases in most lymph nodes where morphological examination had identified them, but in addition found tumor cells in two samples scored as negative. The results will be validated in a larger sample series. Citation Format: Russnes HG, Rye IH, Huse K, Schlichting E, Garred O, Mykelbust JH. Tumor cell detection and immune profiling of lymph nodes from breast cancer patients by mass cytometry [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-03-19.
Background: Increased focus on Quality Indicators and Clinical quality registries shows higher co... more Background: Increased focus on Quality Indicators and Clinical quality registries shows higher compliance to recommended therapy and increased survival. Furthermore, a clinical registry offers an ideal infrastructure for enrolling and following patients in randomized clinical trials. To achieve EUSOMA certification of a Breast Cancer Unit, list of 14 Quality Indicators selected for certification purposes are mandatory. The Norwegian Breast Cancer Group (NBCG) wants a tool for evaluating compliance and results of recommended treatment in breast cancer care on a regular basis utilising the Norwegian Clinical Registry for Breast Cancer run by the Cancer Registry of Norway. The main objective of this study is to describe the development and practise of the Norwegian Clinical Registry for Breast Cancer and to facilitate EUSOMA approval for breast cancer unites on a national level. Report can be given for every institution treating breast cancer in Norway. Methods: To provide researchers with high quality cancer data as well as for the purpose of national cancer statistics, the Cancer Registry of Norway (CRN) employs a cancer registry system to 1) longitudinal collection of data from all patients from all medical entities that diagnosis and/or treat cancer patients (e.g., pathology laboratories and clinic hospitals) in Norway; 2) validate the correctness of collected data, and 3) assemble the validated cancer data as cancer cases. Results: All hospitals currently operating breast cancer patients provides data for the EUSOMA criteria. Data from pathology and surgery are of high quality, However, data from oncologic departments are lacking, but improving. We are however confident that these data will be reported regularly within the next years. We can now provide 8 of 14 mandatory Quality Indicators. Selection of quality indicators used in the annual report for breast cancer in Norway. From year 2016 covering the whole country. 8 of 14 Eusoma Mandatory Quality Indicators for Breast Center Certification are fulfilledCoverage of patients reported to the breast cancer registry99.9% Proportion with reports on diagnosis (TNM stage)90% Proportion with reports on surgical treatment89% Proportion with reports regarding radiology treatment37% 5-years relative survival. Estimated with patients who lived in 2014-201690.4% Proportion with preoperativ diagnosis confirmed with bipsy or cytology98%EusomaProportion with DCIS where grading is reported98.9%EusomaProportion of patients with invasive cancer and axillary clearance with at last 10 lymph nodes examined77%EusomaProportion of patients with invasive cancer not grater than 3 cm who underwent BCT (Neoadjuvant excluded)81.5%EusomaProportion of patients with non invasive breast cancer not grater than 2 cm who underwent BCT90.6%EusomaProportion of patients with DCIS who do not undergo axillary clearance100%EusomaProportion of patients (DCIS) who received just one operation95.5%EusomaProportion of invasive breast cancer patients with pN0 who do not undergo axillary clearance98.2%Eusoma Conclusion: The NBCR promises to deliver all 14 EUSOMA criteria to all hospitals in Norway on a regular annual basis, thus facilitating EUSOMA approval for breast cancer unites. Citation Format: Hartmann-Johnsen OJ, Schlichting E, Kåresen R, Nygård JF. Development of a clinical registry for breast cancer in Norway [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-08-27.
Table S1. The biomarker serum phospholipid fatty acids in wt% and quartiles (P25‚ 75), n = 49. Ta... more Table S1. The biomarker serum phospholipid fatty acids in wt% and quartiles (P25‚ 75), n = 49. Table S2. Spearman correlation coefficients (ρ) for selected fatty acids from supplements, n = 49. (DOCX 55 kb)
Sentinel lymph node biopsy is an integral part of the management of breast cancer and malignant m... more Sentinel lymph node biopsy is an integral part of the management of breast cancer and malignant melanoma. The concept is now being applied to colorectal cancer. We publish two papers which discuss sentinel node biopsy in terms of the advantages and disadvantages of this approach which is a refinement of staging. Lymph node staging in colorectal cancer has been a quest bedevilled by the inability of external imaging to deliver sensitivity and specificity sufficient to be of clinical value. Perhaps this may change although much needs to be done to establish the accuracy of the investigation and to convince surgeons and oncologists that the technical requirements to obtain the information are worth the effort. The whole question of lymph node staging in colorectal cancer is coming into focus. Magnetic resonance and more recently PET, are beginning to deliver information which has the potential to influence management policy. Sentinel node status may or may not stand the test of time, but it is something that is a part of the present discussion.
Malignant melanoma is the most common metastatic lesion of the intestine, found at autopsy in app... more Malignant melanoma is the most common metastatic lesion of the intestine, found at autopsy in approximately 60% of patients who die from melanoma. Common symptoms include bleeding, perforation and ileus/subileus. Patients with such symptoms should be operated on immediately, if they are not too reduced because of advanced disease. Long-term survival (five years) has been achieved in 34 of 179 (19%) of stage IVA melanoma patients after a radical operation procedure. Surgical removal of gastrointestinal metastases provides effective palliation in 80-95% of patients, who undergo laparotomy. We describe two patients with gastrointestinal metastases from malignant melanoma. A 33 year-old man had a large melanoma metastasis removed (non-radically) from the small intestine. He recovered rapidly, and experienced good palliative effect for three months, but died from a recurrence of the disease six months after operation. The other patient had a melanoma metastasis in the right lobe of the liver, which was treated by right hemihepatectomy. There has been no recurrence ten months after operation. We recommend surgical removal of abdominal melanoma metastasis if the surgery can be performed without unacceptable risk.
Pseudomembranous colitis is an inflammatory intestinal disease that is usually secondary to antib... more Pseudomembranous colitis is an inflammatory intestinal disease that is usually secondary to antibiotic treatment. The disease upsets the normal bacterial flora of the large intestine. Therapy consists of fluid replacement, discontinuation of broad-spectrum antibiotics and treatment with vancomycin or metronidazole. In severe or resistant cases surgical treatment is required. We describe one case history and give some guidelines for surgical treatment.
Despite the fact that a prognosis in 1991 predicted a surplus of ten gastroenterological surgeons... more Despite the fact that a prognosis in 1991 predicted a surplus of ten gastroenterological surgeons in 1994, several hospitals are now experiencing a lack of applicants. In order to define the scope of this problem, the Norwegian Gastroenterological Society and The Specialty Committee for Gastroenterological Surgery sent a questionnaire and made a telephone query to all Norwegian Surgical Departments in autumn 1995. There were 21 vacant posts and 27 specialists are still needed to carry out the tasks the hospitals are instructed to perform. An initiative must be taken to increase the capacity and geographical distribution of the education and improve the working conditions, and thereby job satisfaction, of gastroenterological surgeons.
One of the disadvantages of breast conserving treatment compared with mastectomy is the higher ra... more One of the disadvantages of breast conserving treatment compared with mastectomy is the higher rate of local recurrence. Even though a local recurrence has no influence on survival, it is a psychological trauma for the woman it affects. Breast conserving treatment has been practised at Ullevaal Hospital since 1986. This study is based on data from 216 consecutive cases of breast conserving surgery, from January 1986 to March 1996. Mean observation time was 29 months. Nine (4.2%) patients experienced a local recurrence. Age, histological grade, and the size of the tumor were identified as risk factors, whereas there was no correlation between histology, axillary node involvement, and surgical margins.
The vasodilator bradykinin (Bk) has long been though to participate in shock induced by endotoxem... more The vasodilator bradykinin (Bk) has long been though to participate in shock induced by endotoxemia, anaphylaxis and acute pancreatitis. Recently developed kinin antagonists have made it possible to test this hypothesis. We studied the effect of two of them. DArg0Hyp3-Thi5.8-DPhe7-Bk (45 and 220 micrograms/kg/min) and Lys-Lys-Hyp2-Thi5.8-DPhe7-Bk (100 micrograms/kg/min) on the early hypotensive response to Escherichia coli lipopolysaccharide (LPS). Rats infused with the antagonist vehicle were used as controls. At 45 micrograms/kg/min, DArg0-Hyp3-Thi5.8-dPhe7-Bk prevented the hypotensive response to high doses of Bk; however, neither antagonist prevented the hypotensive response to LPS. Circulating kinins measured 3 min after injecting LPS or vehicle were similar (16.3 +/- 1.4 vs. 26.0 +/- 7.2 pg/ml; P greater than .23). In allergically sensitized rats, 500 micrograms/kg/min DArg0-Hyp3-Thi5.8-DPhe-7-Bk did not alter the hypotensive (anaphylactic) response to antigen challenge (P greater than .38). Similarly, hypotension caused by development of acute pancreatitis in rats was not prevented by infusion of DArg0-Hyp3-Thi5.8-DPhe7-Bk at 200 micrograms/kg/min, 10 min) (P greater than .69). These results indicate that in the rate formation of kinins is not a major contributor to the hypotensive response observed in early endotoxemia, anaphylaxis and acute pancreatitis.
Inflammatory bowel disease (ulcerative colitis and Crohn's disease) is a chronic illness, often a... more Inflammatory bowel disease (ulcerative colitis and Crohn's disease) is a chronic illness, often affecting people of reproductive age. Treatment involves drugs which have potential side effects and because of this pregnancy causes considerable concern. The course of the disease is not much affected by pregnancy. The relapse rate is only slightly increased when the disease is active at the time of conception. Relapses during pregnancy should be treated in the usual manner. Surgical intervention should be carried out on the same indications as in those who are not pregnant. Frequency of complications is not increased during pregnancy, at delivery or post partum. Sectio may be necessary in perianal disease. With few exceptions, drug treatment should be continued throughout pregnancy. No adverse effects are seen with normal doses of sulfasalazine, 5-amino-salicylic acid and steroids. Planned pregnancies should be started in periods of quiescent disease.
177 Background: We have investigated whether the introduction of organized mammography screening ... more 177 Background: We have investigated whether the introduction of organized mammography screening in Norway led to less aggressive breast cancer surgery in the invited age group. Methods: We obtained aggregate incidence and surgical treatment data for women treated for ductal carcinoma in situ or invasive breast cancer from the Norwegian Cancer Registry. Rates of breast operations (mastectomy plus breast conserving therapy) and rates of mastectomy only for three age groups; women aged 40-49, 50-69 and 70-79 years were calculated. Changes in rates from a pre-screening period (1993-95) to a screening introduction phase (1996-2004) and then to a screening period (2005-08) are presented as hazard ratios comparing invited and non-invited women. Results: From the pre-screening period (1993-95) to the screening period (2005-08) the annual breast operation rate increased by 70% (HR=1.70 95% CI 1.62 to 1.78), from 180 to 305 per 100 000 women in the invited age group (50-69 years). In contras...
Multiple organ failure may develop as a consequence of defective tissue oxygenation, particularly... more Multiple organ failure may develop as a consequence of defective tissue oxygenation, particularly in the gut. Measurements of intramucosal pH (pHi), accomplished by means of a tonometer placed in the stomach or in the sigmoid colon, seem to monitor the degree of mucosal oxygenation very good. The tonometer technique is noninvasive and easy to perform. pHi may be useful as an index to guide therapeutic interventions in critically ill patients.
Background: Sentinel lymph node (SN) biopsy is a technique for identifying axillary metastases fr... more Background: Sentinel lymph node (SN) biopsy is a technique for identifying axillary metastases from primary breast cancer. The present paper reports our results with the method. Material and methods: SN biopsies have been routinely performed at Ullevål University Hospital since 2000 and the results have been prospectively recorded. 1409 patients with breast cancer or ductal carcinoma in situ grade 3, were injected with peritumoral radiocolloid the day before the biopsy and with blue dye per-operatively to detect the SN. Results: The SN was detected in 90 % of the operations. Metastases to SN were detected in 25 % of the patients and 52 % of these had no further positive nodes in the axilla. Thus, axillary lymph node clearance was omitted in 948 patients. Three patients had local recurrence in the axilla within one year after the successful SN procedure. Ductal carcinoma in situ grade 3 was diagnosed preoperatively in 162 patients (cytology); 88 had the diagnosis after histology and the rest had invasive cancer or combinations with in situ lesions of other grades. Axillary metastases were found in 4.8 % of these patients. Isolated tumour cells (< 0.2 mm diameter) were found in 9 patients for whom axillary clearance has not been performed. Interpretation: SN biopsy has replaced routine axillary clearance as a routine operation in breast cancer. The method is safe when performed correctly, as metastases in the axilla after a negative SN rarely occur.
Introduction: A sentinel lymph node (SN) is the primary node draining the tumor and is assumed to... more Introduction: A sentinel lymph node (SN) is the primary node draining the tumor and is assumed to be affected early in the metastatic process. Detection of metastases in SN is a standard procedure in breast cancer diagnostics based on microscopic evaluation (morphology and immunohistochemistry), determining the need for removal of all axillary glands for inspection which again is crucial for tailoring adjuvant therapy. The identification by microscopy is time-consuming and has a risk for false negative results. We hypothesize that the immune profile of SN changes with the presence of tumor cells, even at very low frequencies (micrometastases). By using a multi marker approach to characterize millions of cells from sentinel lymph nodes with and without metastases we aimed at identifying both tumor cells but also characterize a tumor specific immune response. This dual approach might provide an opportunity for a more sensitive test for SN diagnostics. Material and Methods: We established a mass cytometry assay containing 38 markers (antibodies) using CyTOF technology to combine immune profiling with identification of breast cancer cells. Cell suspensions from 14 metastatic axillary lymph nodes (ALNmet), 16 metastatic sentinel lymph nodes (Snmet) and 14 non-metastatic sentinel lymph nodes (SN) from breast cancer patients from the clinical observational trial Oslo2 (early, operable breast cancer patients representing all subtypes) were successfully analyzed by the multimarker panel (single cell resolution). Results: By using mass cytometry, we detected tumor cells (gated as PanKeratin+/CD45- cells) in 86% (26/30) metastatic lymph nodes (ALNmet and Snmet) and in 14% (2/14) non-metastatic lymph nodes (SN). Further, the leukocyte population, identified as CD45+ cells, was gated into 15 subpopulations, mainly comprising different subsets of B and T cells, monocytes and NK cells. By comparing the leukocyte composition in the ALNmet with those in SN samples we identified a significant increase in the abundance of CD8+ memory phenotype, TFH and TCRγδ cells and a decrease in the CD4+ subpopulation in ALNmet compared to the SN samples. The Snmet samples had smaller deposits of tumor cells than the ALNmet samples, and we found no significant differences in leukocyte composition between Snmet and SN samples. Interestingly, when looking at the activation marker CD56, we observed a significant higher expression in the CD4RO, CD8RO, TFH and Treg subpopulations of Snmet samples compared to SN samples. Conclusion: In this study we identified a significant difference in immune cell composition in lymph nodes with and without metastases (ALNmet compared to SN samples). We also identified activation markers unique for subpopulations of lymphocytes in Snmet, but not in negative lymph nodes (SN). We were also able to detect and identify micrometastases in most lymph nodes where morphological examination had identified them, but in addition found tumor cells in two samples scored as negative. The results will be validated in a larger sample series. Citation Format: Russnes HG, Rye IH, Huse K, Schlichting E, Garred O, Mykelbust JH. Tumor cell detection and immune profiling of lymph nodes from breast cancer patients by mass cytometry [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-03-19.
Background: Increased focus on Quality Indicators and Clinical quality registries shows higher co... more Background: Increased focus on Quality Indicators and Clinical quality registries shows higher compliance to recommended therapy and increased survival. Furthermore, a clinical registry offers an ideal infrastructure for enrolling and following patients in randomized clinical trials. To achieve EUSOMA certification of a Breast Cancer Unit, list of 14 Quality Indicators selected for certification purposes are mandatory. The Norwegian Breast Cancer Group (NBCG) wants a tool for evaluating compliance and results of recommended treatment in breast cancer care on a regular basis utilising the Norwegian Clinical Registry for Breast Cancer run by the Cancer Registry of Norway. The main objective of this study is to describe the development and practise of the Norwegian Clinical Registry for Breast Cancer and to facilitate EUSOMA approval for breast cancer unites on a national level. Report can be given for every institution treating breast cancer in Norway. Methods: To provide researchers with high quality cancer data as well as for the purpose of national cancer statistics, the Cancer Registry of Norway (CRN) employs a cancer registry system to 1) longitudinal collection of data from all patients from all medical entities that diagnosis and/or treat cancer patients (e.g., pathology laboratories and clinic hospitals) in Norway; 2) validate the correctness of collected data, and 3) assemble the validated cancer data as cancer cases. Results: All hospitals currently operating breast cancer patients provides data for the EUSOMA criteria. Data from pathology and surgery are of high quality, However, data from oncologic departments are lacking, but improving. We are however confident that these data will be reported regularly within the next years. We can now provide 8 of 14 mandatory Quality Indicators. Selection of quality indicators used in the annual report for breast cancer in Norway. From year 2016 covering the whole country. 8 of 14 Eusoma Mandatory Quality Indicators for Breast Center Certification are fulfilledCoverage of patients reported to the breast cancer registry99.9% Proportion with reports on diagnosis (TNM stage)90% Proportion with reports on surgical treatment89% Proportion with reports regarding radiology treatment37% 5-years relative survival. Estimated with patients who lived in 2014-201690.4% Proportion with preoperativ diagnosis confirmed with bipsy or cytology98%EusomaProportion with DCIS where grading is reported98.9%EusomaProportion of patients with invasive cancer and axillary clearance with at last 10 lymph nodes examined77%EusomaProportion of patients with invasive cancer not grater than 3 cm who underwent BCT (Neoadjuvant excluded)81.5%EusomaProportion of patients with non invasive breast cancer not grater than 2 cm who underwent BCT90.6%EusomaProportion of patients with DCIS who do not undergo axillary clearance100%EusomaProportion of patients (DCIS) who received just one operation95.5%EusomaProportion of invasive breast cancer patients with pN0 who do not undergo axillary clearance98.2%Eusoma Conclusion: The NBCR promises to deliver all 14 EUSOMA criteria to all hospitals in Norway on a regular annual basis, thus facilitating EUSOMA approval for breast cancer unites. Citation Format: Hartmann-Johnsen OJ, Schlichting E, Kåresen R, Nygård JF. Development of a clinical registry for breast cancer in Norway [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-08-27.
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