Publications by authors named "Michał Jankowski"

20 Publications

  • Page 1 of 1

Fallen dogmas - recent advances in locoregionally advanced melanoma.

Pol Arch Intern Med 2021 Apr 14. Epub 2021 Apr 14.

Last decade brought new achievements in the melanoma research, which resulted in an important changes in the clinical management of stage III melanoma. The article summarizes recent updates with particular focus on practical aspects. Results from surgical studies, Multicenter Selective Lymphadenectomy Trial II (MSLT-II) and German Dermatologic Cooperative Oncology Group (DeCOG-SLT) proved that surgical dogmatic approach that all sentinel node melanoma metastasis warrants completion lymphadenectomy is no longer valid; omission of completion lymphadenectomy in large proportion of sentinel node positive melanoma patients has no negative impact on survival rates. Moreover oncological trials (COMBI-AD, EORTC 1325/KEYNOTE-054 and CheckMate 238) showed that in stage III melanoma patients' chances of recurrence-free survival can be improved by 10-20% by modern immunotherapy and/or molecular targeted therapy. These findings led to fall of another dogma in oncology: lack of effective adjuvant therapy for stage III melanoma at acceptable toxicity. At the end of the day in 2021 modern multidisciplinary approach incorporating newest findings offer stage III melanoma patients less surgical complications of better tailored surgery and longer survival in result of efficient adjuvant therapy.
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http://dx.doi.org/10.20452/pamw.15936DOI Listing
April 2021

Clinical Reality and Treatment for Local Recurrence of Rectal Cancer: A Single-Center Retrospective Study.

Medicina (Kaunas) 2021 Mar 19;57(3). Epub 2021 Mar 19.

Department of Surgical Oncology, Ludwik Rydygier's Collegium Medicum, Bydgoszcz, Nicolaus Copernicus University, 85-067 Torun, Poland.

Despite advances in treatment, local recurrence remains a great concern in patients with rectal cancer. The aim of this study was to investigate the incidence and risk factors of local recurrence of rectal cancer in our single center over a 7-year-period. Patients with stage I-III rectal cancer were treated with curative intent. The necessity for radiotherapy and chemotherapy was determined before surgery and/or postoperative histopathological results. Of 365 rectal cancer patients, 76 (20.8%) developed recurrent disease. In total, 27 (7.4%) patients presented with a local tumor recurrence (isolated in 40.7% of cases). Radiotherapy was performed in 296 (81.1%) patients. The most often used schema was 5 × 5 Gy followed by immediate surgery ( = 214, 58.6%). Local recurrence occurred less frequently in patients treated with 5 × 5 Gy radiotherapy followed by surgery ( = 9, 4%). Surgical procedures of relapses were performed in 12 patients, six of whom were operated with radical intent. Only two (7.4%) patients lived more than 5 years after local recurrence treatment. The incidence of local recurrence was associated with primary tumor distal location and worse prognosis. The median overall survival of patients after local recurrence treatment was 19 months. Individualized rectal cancer patient selection and systematic treatment algorithms should be used clinical practice to minimize likelihood of relapse. 5 × 5 Gy radiotherapy followed by immediate surgery allows good local control in resectable cT2N+/cT3N0 patients. Radical resection of isolated local recurrence offers the best chances of cure.
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http://dx.doi.org/10.3390/medicina57030286DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8003449PMC
March 2021

Fear of Cancer Progression and Health Behaviors in Patients with Colorectal Cancer.

Am J Health Behav 2021 01;45(1):138-151

Wojciech Zegarski, Professor, Chair of Surgical Oncology, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Poland and Nicolaus Copernicus University in Torué, Oncology Center, Bydgoszcz, Poland, and Department of Surgical Oncology, Oncology Center - Professor Franciszek Lukaszczyk Memorial Hospital, Romanowskiej, Bydgoszcz, Poland.

Preparation of patients for colon tumor resection, which involves giving up smoking, reducing alcohol intake, having a proper diet, and increasing physical activity, significantly shortens the hospitalization period. In this study, we aimed at determining the relationship between the fear of cancer progression (FoP) and health behaviors among people with colon cancer. Participants were patients a week before a colon tumor surgery and 6 months after. Measured variables included smoking, alcohol intake, anti-health products intake (anti-health behaviors), physical activity, pro-health products intake (pro-health behaviors), and fear of progression cancer. Comparing the week before the surgery and 6 months after revealed a decrease in smoking (η² = .02), alcohol intake (η² = .03), anti-health products intake (η² = .06) and physical activity (η² = .06). A higher level of fear of cancer progression is related to decrease in anti-health behaviors, but does not affect the change in health-promoting behaviors among patients with colorectal cancer. FoP is an important factor facilitating the limitation of anti-health behaviors such as alcohol and anti-health products intake. Symptoms of colorectal cancer have negative influence on physical activity and intake of pro-health products.
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http://dx.doi.org/10.5993/AJHB.45.1.11DOI Listing
January 2021

The analysis of 3-year adjuvant therapy with imatinib in patients with high-risk molecular profiled gastrointestinal stromal tumors (GIST) treated in routine practice.

Eur J Surg Oncol 2020 Aug 16. Epub 2020 Aug 16.

Iagiellonian University, Cracow, Poland.

Introduction: The real-world data on adjuvant imatinib therapy in high-risk primary GIST are scarce.

Methods: We have analysed the data of 107 consecutive patients with gastrointestinal stromal tumour (GIST) after resection treated with adjuvant imatinib (for planned 3 years with initial dose 400 mg daily, started not later than 4 months after operation) in 6 oncological centres in 2013-2018. All patients were required to have high risk of recurrence (at least 50% according to NCCN/AFIP criteria), known mutational status to exclude PDGFRA D842V mutants and KIT/PDGFRA-wild type cases from therapy without any further selection. Median follow-up time was 27 months.

Results: The most common primary localization of GIST was small bowel (63 patients; 59%), followed by the stomach (40 patients; 37%). The majority of GIST cases harboured exon 11 KIT mutations (88 cases, 82%), 11 cases had exon 9 KIT mutations (10%), 8 had other KIT/PDGFRA mutations potentially sensitive to imatinib. Forty patients (37%) finished 3-year adjuvant imatinib therapy as planned, 48 (45%) still continue therapy, 5 (4.5%) patients had finished adjuvant therapy prematurely due to toxicity, 6 (6%) due to disease progression on treatment and 8 (7.5%) due to other reasons. The disease relapse was detected in 19 patients, of them in 5 cases in exon 9 KIT mutants (45%), and 14 cases in patients with exon 11 KIT mutations (11%) [p < 0.01]. Estimated 4-year relapse-free survival (RFS) rate is 78%.

Conclusions: The early results of adjuvant therapy with imatinib in routine practice outside clinical trials in high-risk mutation-driven GIST patients only confirm high efficacy of this therapy with better tolerability than in clinical trials. We found overrepresentation of exon 9 KIT mutants and ruptured tumors in a group of patients with disease relapse.
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http://dx.doi.org/10.1016/j.ejso.2020.08.004DOI Listing
August 2020

Overall treatment outcome - analysis of long-term results of rectal cancer treatment on the basis of a new parameter.

Arch Med Sci 2020 8;16(4):825-833. Epub 2020 Apr 8.

Chair of Surgical Oncology, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Poland.

Introduction: Outcomes of rectal cancer treatment depend on preoperative staging and the effectiveness of treatments. According to disease staging, different variants of combined therapy (surgery, chemo- and radiotherapy) are used. Available parameters such as overall survival rates and disease- free survival rates as well as the presence of recurrence are inaccurate and should be jointly considered.

Material And Methods: Data from 138 patients with rectal cancer (I-III WHO), who were radically operated on in the period 2001-2004 in Bydgoszcz Oncology Centre were analysed. Among this group 84 patients were radically operated on one week after preoperative radiotherapy 5 × 5 Gy (sRT). We established a new parameter, the overall treatment outcome (OTO), based on the finding that there was no recurrence (local recurrence, distant metastases) of the disease within 5 years, which is generally considered a good result for the treatment of rectal cancer.

Results: Among all patients ( = 138) and patients following sRT ( = 84) 7.4%...5.9% local recurrence and 24%...29% distant metastases were observed in 5-year follow-up. Recurrence was found in 30% and 31% of patients, respectively. Analysis of results on the basis of the OTO parameter demonstrated that among all groups of patients a worse treatment outcome is related to the number of lymph nodes involved, pN, pT, cancer stage (WHO) and to pN and patient age in the sRT group ( < 0.005).

Conclusions: In using a combined therapy, it is possible to optimise rectal cancer treatment outcomes. The OTO parameter is a useful tool for defining these results of cancer combination treatment.
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http://dx.doi.org/10.5114/aoms.2020.94330DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7286345PMC
April 2020

Prospective evaluation of muscle strength and spine joint motility of patients who underwent surgery for colorectal cancer by open and laparoscopic methods.

Wideochir Inne Tech Maloinwazyjne 2020 Mar 29;15(1):49-57. Epub 2019 Apr 29.

Department of Surgical Oncology, Collegium Medicum in Bydgoszcz, the Nicolaus Copernicus University in Torun, Poland.

Introduction: The current trend in oncological surgery is to minimize its degree of invasiveness while maintaining a satisfactory survival rate. Surgical treatments within the large intestine are applied through traditional open surgery (OS) or laparoscopic surgery (LS).

Aim: The purpose of this nonrandomized, prospective, single-centered clinical examination was to compare motility within the spine joints and evaluate abdominal muscle strength of patients who underwent LS or OS for colorectal cancer.

Material And Methods: Seventy-two patients were included in the study. Open surgery was applied to 35 patients and LS was applied to 37 patients. Motility range of the thoracic and lumbar spine, muscle strength of abdominal muscles, and pain evaluation by the Visual Analogue Scale (VAS) of the studied group were evaluated twice (on the day of admission to the ward and on the fifth day after the surgery).

Results: Both types of surgical intervention resulted in a decrease of the rectus abdominis and abdominal oblique muscle strength as well as a decrease of the range of thoracic and lumbar spine joint motility (p < 0.001). In the first research period, no statistically significant differences of tested parameters between the groups were found. In the second period, patients who underwent LS achieved better results within the extension of lumbar spine section (p = 0.0339), rectus abdominis strength (p = 0.0105), and left abdominal oblique muscles (p = 0.004).

Conclusions: Both types of surgical intervention (LS and OS) result in reduction of spine joint motility range and abdominal muscle strength. Laparoscopic surgery disrupts the spine joint motility and abdominal muscle strength to a lesser extent than OS.
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http://dx.doi.org/10.5114/wiitm.2019.84762DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7020713PMC
March 2020

Prospective evaluation of the quality of life of patients undergoing surgery for colorectal cancer depending on the surgical technique.

Int J Colorectal Dis 2019 Sep 8;34(9):1601-1610. Epub 2019 Aug 8.

Department of Laser Therapy and Physiotherapy, Ludwik Rydygier's Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Bydgoszcz, Poland.

Purpose: Monitoring of the quality of life of patients in addition to satisfactory survival indexes in order to choose an optimal treatment method is a trend in contemporary oncological surgery. The goal of the study was to prospectively evaluate the quality of life of patients treated for colorectal cancer depending on the type of surgical technique (open surgery (OS) vs. laparoscopic surgery (LS)).

Methods: The quality of life was evaluated thrice in the study groups (on the day of admission to the ward (I), 6 months (II), and 18 months after the procedure (III)). The following questionnaires were used in this evaluation: QLQ-C30 European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, QLQ-CR29 Quality of Life Questionnaire (module-colorectal cancer), and Acceptance of Illness Scale (AIS).

Results: Sixty-seven patients completed this prospective clinical cohort study (LS-32; OS-35). The QLQ-C30 questionnaire demonstrated improvement in functional scales among patients treated with LS technique (p < 0.05) as well as with regard to overall quality of life 6 months after surgery (p < 0,001), while at 18 months postsurgery, statistically significant differences were noted for physical function (p = 0.001) and overall quality of life (p < 0.0001). AIS scale analysis demonstrated that patients treated with laparoscopy were characterized by better acceptance of illness (p < 0.05). Statistically significant differences between OS and LS groups were noted based on the QLQ-CR29 questionnaire with regard to the following scales: body image (p = 0.041) and body mass problem (p = 0.024)-patients treated with LS technique had better scores.

Conclusions: Laparoscopic surgery gives patients a chance for better quality of life.
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http://dx.doi.org/10.1007/s00384-019-03357-4DOI Listing
September 2019

Contemporary enteral and parenteral nutrition before surgery for gastrointestinal cancers: a literature review.

World J Surg Oncol 2018 May 16;16(1):94. Epub 2018 May 16.

Surgical Oncology, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Oncology Centre, Bydgoszcz, 2 Romanowskiej Str, 85-796, Bydgoszcz, Poland.

Background: Gastrointestinal cancers are among the most recognised oncological diseases in well-developed countries. Tumours located in the digestive tract may cause the fast occurrence of malnutrition.

Main Text: The perioperative period is a special time for systemic metabolism. Thanks to published guidelines, early universal control nutritional status before treatment, patients may have a chance to get suitable nutritional intervention. Although the first line of the intervention-nutritional consultation as well as the fortification of a diet and oral nutritional support (ONS)-is not debatable, in a case of inability of undergoing an oral feeding, the choice of the way of administration in patients before a surgery may represent a serious clinical obstacle.

Conclusions: Although there is broad agreement in the staging, classification, and role of surgery and nutritional status for outcomes of treatment of gastrointestinal cancers, there the way of nutritional intervention in patients with gastrointestinal cancer are still discussed.
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http://dx.doi.org/10.1186/s12957-018-1393-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5956927PMC
May 2018

Gastric cancer increases transmigratory potential of peripheral blood monocytes by upregulation of β1- and β2-integrins.

Contemp Oncol (Pozn) 2018 Mar 5;22(1A):33-37. Epub 2018 Mar 5.

Department of Regenerative Medicine and Immune Regulation, Medical University of Bialystok, Poland.

Introduction: Immune responses within the tumor depend on the ability of leukocytes to migrate from peripheral circulation into the local microenvironment. This process is controlled by mechanisms that guide leukocytes to the side of inflammation, allowing them to cross vascular endothelial barrier. Monocytes/macrophages are the predominant population of leukocyte infiltrate of many tumors, including, gastric cancer. However, to date mechanisms that control monocyte trafficking to the side of tumor growth are not fully elucidated.

Aim Of The Study: It this study we aimed to evaluate transmigratory potential of peripheral blood monocytes from gastric cancer patients.

Material And Methods: By using multicolor flow cytometry we assessed expression of β1- and β2-integrins on peripheral blood monocytes from gastric cancer patients.

Results: We found increased frequencies of VLA-4 and VLA-6 expressing monocytes and increased expression of analyzed β2-integrins in gastric cancer patients when compared to age matched controls.

Conclusions: In summary, this study revealed that gastric cancer increases transmigratory potential of peripheral blood monocytes.
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http://dx.doi.org/10.5114/wo.2018.73881DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5885073PMC
March 2018

Keratin 7 expression in lymph node metastases but not in the primary tumour correlates with distant metastases and poor prognosis in colon carcinoma.

Pol J Pathol 2016;67(3):228-234

Department of Pathomorphology, Medical University of Gdańsk, Gdańsk, Poland.

Colorectal carcinoma (CRC) is one of the leading causes of cancer-related deaths worldwide. Alterations in keratin expression, including keratin 7 (K7), are frequent findings in multiple cancers, and they constitute a prognostic factor. The aim of our study was to evaluate the prognostic significance of K7 in the primary tumour and lymph node metastases in two separate cohorts of patients: the first one with lymph node involvement (LN+, 129 cases) and the second one free of LN metastases (LN-, 85 cases). Keratin 7 expression in CRC was analysed on tissue microarrays with immunohistochemistry and evaluated using the h-score. In the LN+ group K7 positivity was identified in 7/129 (5.4%) of primary tumours (PT) and lymph node metastases (LNM); concordance between them was 94% ( 0.396). Keratin 7 was expressed in 8/85 cases (9.4%) in the LN- group. K7 expression in LNM of the LN+ cohort correlated with shorter overall survival (OS) (p = 0.047) and presence of distant metastases at diagnosis (p = 0.005). Expression of K7 in the primary tumour in both cohorts did not correlate with survival. We conclude that the status of K7 expression in metastatic lymph nodes from CRC is a poor prognostic factor.
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http://dx.doi.org/10.5114/pjp.2016.63774DOI Listing
June 2017

Prognostic value of 5-microRNA based signature in T2-T3N0 colon cancer.

Clin Exp Metastasis 2016 12 2;33(8):765-773. Epub 2016 Aug 2.

Department of Oncology and Radiotherapy, Medical University of Gdansk, 7 Dębinki St., 80-211, Gdańsk, Poland.

The role of adjuvant chemotherapy in stage T2-T3N0 colon cancer (CC) is controversial and there are currently no reliable factors allowing for individual selection of patients with high risk of relapse for such therapy. We searched for microRNA-based signature with prognostic significance in this group. We assessed by qRT-PCR expression of 754 microRNAs (miRNAs) in tumour samples from 85 stage pT2-3N0 CC patients treated with surgery alone. MiRNA expression was compared between two groups of patients: 40 and 45 patients who did and did not develop distant metastases after resection, respectively. Additionally, miRNA expression was compared between CC and normal colon mucosa samples and between the mismatch repair (MMR) competent and deficient tumours. Low expression of miR-1300 and miR-939 was significantly correlated with shorter distant metastasis-free survival (DMFS) in Cox univariate analysis (p.adjusted = 0.049). The expression signature of five miRNAs (miR-1296, miR-135b, miR-539, miR-572 and miR-185) was found to be prognostic [p = 1.28E-07, HR 8.4 (95 % CI: 3.81-18.52)] for DMFS and cross-validated in a leave-one-out analysis, with the sensitivity and specificity of 74 and 78 %, respectively. The expression of miR-592 was significantly associated with the MMR status (p.adjusted <0.01). The expression of several novel miRNAs were found to be tumour specific, e.g. miR-888, miR-523, miR-18b, miR-302a, miR-423-5p, miR-582-3p (p < 0.05). We developed a miRNA expression signature that may be predictive for the risk of distant relapse in early stage CC and confirmed previously reported association between miR-592 expression and MMR status.
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http://dx.doi.org/10.1007/s10585-016-9810-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5110606PMC
December 2016

Signatures of post-zygotic structural genetic aberrations in the cells of histologically normal breast tissue that can predispose to sporadic breast cancer.

Genome Res 2015 Oct;25(10):1521-35

Department of Immunology, Genetics and Pathology and SciLifeLab, Uppsala University, 715 85 Uppsala, Sweden;

Sporadic breast cancer (SBC) is a common disease without robust means of early risk prediction in the population. We studied 282 females with SBC, focusing on copy number aberrations in cancer-free breast tissue (uninvolved margin, UM) outside the primary tumor (PT). In total, 1162 UMs (1-14 per breast) were studied. Comparative analysis between UM(s), PT(s), and blood/skin from the same patient as a control is the core of the study design. We identified 108 patients with at least one aberrant UM, representing 38.3% of cases. Gains in gene copy number were the principal type of mutations in microscopically normal breast cells, suggesting that oncogenic activation of genes via increased gene copy number is a predominant mechanism for initiation of SBC pathogenesis. The gain of ERBB2, with overexpression of HER2 protein, was the most common aberration in normal cells. Five additional growth factor receptor genes (EGFR, FGFR1, IGF1R, LIFR, and NGFR) also showed recurrent gains, and these were occasionally present in combination with the gain of ERBB2. All the aberrations found in the normal breast cells were previously described in cancer literature, suggesting their causative, driving role in pathogenesis of SBC. We demonstrate that analysis of normal cells from cancer patients leads to identification of signatures that may increase risk of SBC and our results could influence the choice of surgical intervention to remove all predisposing cells. Early detection of copy number gains suggesting a predisposition toward cancer development, long before detectable tumors are formed, is a key to the anticipated shift into a preventive paradigm of personalized medicine for breast cancer.
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http://dx.doi.org/10.1101/gr.187823.114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4579338PMC
October 2015

Post-zygotic and inter-individual structural genetic variation in a presumptive enhancer element of the locus between the IL10Rβ and IFNAR1 genes.

PLoS One 2013 4;8(9):e67752. Epub 2013 Sep 4.

Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.

Although historically considered as junk-DNA, tandemly repeated sequence motifs can affect human phenotype. For example, variable number tandem repeats (VNTR) with embedded enhancers have been shown to regulate gene transcription. The post-zygotic variation is the presence of genetically distinct populations of cells in an individual derived from a single zygote, and this is an understudied aspect of genome biology. We report somatically variable VNTR with sequence properties of an enhancer, located upstream of IFNAR1. Initially, SNP genotyping of 63 monozygotic twin pairs and multiple tissues from 21 breast cancer patients suggested a frequent post-zygotic mosaicism. The VNTR displayed a repeated 32 bp core motif in the center of the repeat, which was flanked by similar variable motifs. A total of 14 alleles were characterized based on combinations of segments, which showed post-zygotic and inter-individual variation, with up to 6 alleles in a single subject. Somatic variation occurred in ∼24% of cases. In this hypervariable region, we found a clustering of transcription factor binding sites with strongest sequence similarity to mouse Foxg1 transcription factor binding motif. This study describes a VNTR with sequence properties of an enhancer that displays post-zygotic and inter-individual genetic variation. This element is within a locus containing four related cytokine receptors: IFNAR2, IL10Rβ, IFNAR1 and IFNGR2, and we hypothesize that it might function in transcriptional regulation of several genes in this cluster. Our findings add another level of complexity to the variation among VNTR-based enhancers. Further work may unveil the normal function of this VNTR in transcriptional control and its possible involvement in diseases connected with these receptors, such as autoimmune conditions and cancer.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0067752PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3762855PMC
April 2014

Evaluation of FLT-PET/CT usefulness in diagnosis and qualification for surgical treatment of gastric cancer.

Contemp Oncol (Pozn) 2013 29;17(2):165-70. Epub 2013 Apr 29.

Oncology Centre - Prof. Lukaszczyk Memorial Hospital, Bydgoszcz, Poland.

Aim Of The Study: Evaluation of FLT/PET/ CT usefulness in diagnosis and qualification for surgical treatment of gastric cancer.

Material And Methods: The FLT/PET/CT test was carried out in a group of 50 gastric cancer patients. Based on the test result, a decision followed about the therapeutic procedure to be applied. A comparison was made with regards to the consistency of the cancer growth advancement degree evaluation in the initial preoperative FLT/PET/CT test against the evaluation of postoperative degree of cancer advancement in histopathology.

Results: In the group of 50 diagnosed patients a surgical treatment was used for 37 patients. 21 resections were performed out of which 19 operations were radical In the group of 16 non-resective operations 2 post-laparotomic patients were selected for inductive treatment. In the group of 13 patients who did not undergo any surgery, 10 were directed to palliative care and 3 for inductive treatment. In the group of 50 patients, the applied FLT-PET/CT test confirmed presence of primary tumor in 49 patients. The presence of increased uptake of FLT in the local lymph nodes during the preoperative FLT-PET/CT test was confirmed in 22 cases. In 14 patients with FLT-PET/Ct N(+) with the M(-) feature resection surgery was performed. The increased uptake of FLT in localizing metastases (nodal and non-nodal) FLT-PET/CT (M+) was detected in 22 patients. The presence of nodal metastases in the postoperative histopathology examination (hpN+) was detected in 14 cases. In these cases preoperative FLT-PET/CT test proved the N(+) feature in 11 patients. The result FLT-PET/CT N(-) was truly negative in 2 patients, and false negative in 1 patient. In the group of 7 operated hpN(-) patients, in 3 patients a preoperative result FLT-PET/ CT N(+) (false positive result) was obtained. The consistency (positive) of nodal metastases identification in FLT-PET/CT as compared to post-surgical histopathology examination scored 11/15, which equals 73.3%. In the group of patients in whom resection surgery was performed, 4 false negative results were obtained [hp(N+), FLT-PET/CT (N-)] and 3 false positive results [hp(N-), FLT-PET/CT N(+)].

Conclusions: The initial test results indicate that FLT-PET/CT is an effective method in evaluating the primary tumor and the regional lymph nodes and is useful and beneficial in the diagnosis and further treatment evaluation of gastric cancer. FLT-PET/CT examination facilitates making proper therapeutic decisions - it allows the number of unnecessary laparotomies to be lowered.
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http://dx.doi.org/10.5114/wo.2013.34621DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3685381PMC
June 2013

Neoadjuvant treatment for unresectable rectal cancer: an interim analysis of a multicentre randomized study.

Radiother Oncol 2013 May 13;107(2):171-7. Epub 2013 Apr 13.

Department of Radiotherapy II, M. Sklodowska-Curie Memorial Cancer Centre, Warsaw, Poland.

Purpose: To present an interim analysis of the trial comparing two neoadjuvant therapies for unresectable rectal cancer.

Methods: Patients with fixed cT3 or cT4 or locally recurrent rectal cancer without distant metastases were randomized to either 5 × 5 Gy and 3 courses of FOLFOX4 (schedule I) or 50.4 Gy delivered in 28 fractions given simultaneously with 5-Fu, leucovorin and oxaliplatin (schedule II). Surgery in both groups was performed 12 weeks after the beginning of radiation and 6 weeks after neoadjuvant treatment.

Results: 49 patients were treated according to schedule I and 48 according to schedule II. Grade III+ acute toxicity was observed in 26% of patients in group I and in 25% in group II. There were two toxic deaths, both in group II. The microscopically radical resection (primary endpoint) rate was 73% in group I and 71% in group II. Overall and severe postoperative complications were recorded in 27% and 9% of patients vs. 16% and 7%, respectively. Pathological complete response was observed in 21% of the patients in group I and in 9% in group II.

Conclusions: The interim analysis revealed no major differences in acute toxicity and local efficacy between the two evaluated strategies.
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http://dx.doi.org/10.1016/j.radonc.2013.03.001DOI Listing
May 2013

Collaborating with the enemy: function of macrophages in the development of neoplastic disease.

Mediators Inflamm 2013 17;2013:831387. Epub 2013 Mar 17.

Chair of Immunology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University of Torun, Bydgoszcz, Poland.

Due to the profile of released mediators (such as cytokines, chemokines, growth factors, etc.), neoplastic cells modulate the activity of immune system, directly affecting its components both locally and peripherally. This is reflected by the limited antineoplastic activity of the immune system (immunosuppressive effect), induction of tolerance to neoplastic antigens, and the promotion of processes associated with the proliferation of neoplastic tissue. Most of these responses are macrophages dependent, since these cells show proangiogenic properties, attenuate the adaptive response (anergization of naïve T lymphocytes, induction of Treg cell formation, polarization of immune response towards Th2, etc.), and support invasion and metastases formation. Tumor-associated macrophages (TAMs), a predominant component of leukocytic infiltrate, "cooperate" with the neoplastic tissue, leading to the intensified proliferation and the immune escape of the latter. This paper characterizes the function of macrophages in the development of neoplastic disease.
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http://dx.doi.org/10.1155/2013/831387DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3613099PMC
August 2013

Frequent genetic differences between matched primary and metastatic breast cancer provide an approach to identification of biomarkers for disease progression.

Eur J Hum Genet 2010 May 6;18(5):560-8. Epub 2010 Jan 6.

Department of Genetics, University of Alabama at Birmingham, Birmingham, AL, USA.

Breast cancer is a major cause of morbidity and mortality in women and its metastatic spread is the principal reason behind the fatal outcome. Metastasis-related research of breast cancer is however underdeveloped when compared with the abundant literature on primary tumors. We applied an unexplored approach comparing at high resolution the genomic profiles of primary tumors and synchronous axillary lymph node metastases from 13 patients with breast cancer. Overall, primary tumors displayed 20% higher number of aberrations than metastases. In all but two patients, we detected in total 157 statistically significant differences between primary lesions and matched metastases. We further observed differences that can be linked to metastatic disease and there was also an overlapping pattern of changes between different patients. Many of the differences described here have been previously linked to poor patient survival, suggesting that this is a viable approach toward finding biomarkers for disease progression and definition of new targets useful for development of anticancer drugs. Frequent genetic differences between primary tumors and metastases in breast cancer also question, at least to some extent, the role of primary tumors as a surrogate subject of study for the systemic disease.
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http://dx.doi.org/10.1038/ejhg.2009.230DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2987320PMC
May 2010

Chromosome 22 array-CGH profiling of breast cancer delimited minimal common regions of genomic imbalances and revealed frequent intra-tumoral genetic heterogeneity.

Int J Oncol 2006 Oct;29(4):935-45

Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, 75185 Uppsala, Sweden.

Breast cancer is a common malignancy and the second most frequent cause of death among women. Our aim was to perform DNA copy number profiling of 22q in breast tumors using a methodology which is superior, as compared to the ones applied previously. We studied 83 biopsies from 63 tumors obtained from 60 female patients. A general conclusion is that multiple distinct patterns of genetic aberrations were observed, which included deletion(s) and/or gain(s), ranging in size from affecting the whole chromosome to only a few hundred kb. Overall, the analysis revealed genomic imbalances of 22q in 22% (14 out of 63) of tumors. The predominant profile (11%) was monosomy 22. The smallest identified candidate region, in the vicinity of telomere of 22q, encompasses approximately 220 kb and was involved in all but one of the tumors with aberrations on chromosome 22. This segment is dense in genes and contains 11 confirmed and one predicted gene. The availability of multiple biopsies from a single tumor provides an excellent opportunity for analysis of possible intra-tumor differences in genetic profiles. In 15 tumors we had access to two or three biopsies derived from the same lesion and these were studied independently. Four out of 15 (26.6%) tumors displayed indications of clonal intra-tumor genotypic differences, which should be viewed as a high number, considering that we studied in detail only a single human chromosome. Our results open up several avenues for continued genetic research of breast cancer.
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October 2006

Microarray-based survey of CpG islands identifies concurrent hyper- and hypomethylation patterns in tissues derived from patients with breast cancer.

Genes Chromosomes Cancer 2006 Jul;45(7):656-67

Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, 751 85 Uppsala, Sweden.

Maintenance of CpG island methylation in the genome is crucial for cellular homeostasis and this balance is disrupted in cancer. Our rationale was to compare the methylation of CpG islands in tissues (tumor, healthy breast and blood) from patients with breast cancer. We studied 72 genes in 103 samples using microarray hybridization and bisulfite sequencing. We observed tumor specific hyper- or hypomethylation of five genes; COL9A1, MT1A, MT1J, HOXA5 and FLJ45983. A general drop of methylation in COL9A1 was apparent in tumors, when compared with blood and healthy breast tissue. Furthermore, one tumor displayed a complete loss of methylation of all five genes, suggesting overall impairment of methylation. The downstream, evolutionary conserved island of HOXA5 showed hypomethylation in 18 tumors and complete methylation in others. This CpG island also displayed a semimethylated state in the majority of normal breast samples, when compared to complete methylation in blood. Distinct methylation patterns were further seen in MT1J and MT1A, belonging to the metallothionein gene family. The CpG islands of these genes are spaced by 2 kb, which shows selective methylation of two structurally and functionally related genes. The promoters of FLJ45983 and MT1A were methylated above 25% in 18 primary and metastatic tumors. Concurrently, there was also >10% methylation of healthy breast tissue in 11 and 5 samples, respectively. This suggests that the methylation process for the latter two genes takes place already in normal breast cells. Our results also point to a considerable heterogeneity of epigenetic disturbance in breast cancer. This article contains Supplementary Material available at http://www.interscience.wiley.com/jpages/1045-2257/suppmat.
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http://dx.doi.org/10.1002/gcc.20331DOI Listing
July 2006

[Evaluation of usefulness of faecal occult blood test. Prospective screening study in patients with colorectal neoplasia].

Pol Merkur Lekarski 2004 Dec;17(102):579-82

Klinika Chirurgii Ogólnej Akademii Medycznej w Bydgoszczy.

Unlabelled: High incidence of colorectal cancer (CRC), good treatment outcome in case of surgery performed at an early stage of the disease, and a simple, low cost and quick diagnostic test, encourage the common use of screening for CRC. The aim of the study was to examine the efficacy of immunochromatographic faecal occult blood (FOB) testing in screening for early colorectal cancer.

Material And Methods: A total of 346 subjects with abdominal symptoms of unclear etiology were included to the study. Patients with diagnosed CRC, clinical symptoms suggesting CRC or those with family history of CRC were excluded from the study. All subjects had FOB testing done. All were subjected to sigmoidoscopy, no matter what the result of the screening test was. The sensitivity and specificity of the screening test for CRC was evaluated.

Results: The total of 342 subjects aged 29-68 years (median 59 yrs), including 189 (58%) females and 153 (42%) males, were eventually qualified for the study. Colorectal pathology was found in 117 subjects (34.6%). Out of 62 patients with positive tests, 55 (89%) had a colorectal disorder diagnosed during sigmoidoscopy. The results were false positive in 7 cases. Colorectal neoplasia was recognized in 33 cases. These were neoplastic polyps (23) and adenocarcinoma (10). The great majority of neoplastic conditions were found in FOB positive subjects. The sensitivity of the test was 90%, while its specificity reached 84%. Diagnostic accuracy was 84%. Positive and negative predictive values were 15% and 99% respectively.

Conclusions: FOB testing appears highly sensitive and specific for colorectal cancer in patients with unclear abdominal symptoms.
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December 2004