[show abstract][hide abstract] ABSTRACT: Abstract There are controversial views as to whether intratumoral or peritumoral lymphatics play a dominant role in the metastatic process. Most clinical observations originate from studies of colon cancer. Colon contains mucosa and submucosa rich in lymphatics and with high lymph formation rate. This seems to be a prerequisite for easy metastasis of cancer cells to regional lymph nodes. However, there are other tissues as pancreas with a rudimentary lymphatic network where cancer metastasis formation is as intensive as in colon cancer. This contradicts the common notion that intratumor lymphatics play major role in metastases. We visualized interstitial space and lymphatics in the central and peripheral regions of colon and pancreas tumors using the color stereoscopic lymphography and simultaneously immunohistochemical performed stainings specific for lymphatic and blood endothelial cells. The density of open and compressed lymphatic and blood vessels was measured in the tumor core and edge. There were very few lymphatics in the colon and pancreas tumor core but numerous minor fluid "lakes" with no visible connection to the peritumoral lymphatics. Lining of "lakes" did not express molecular markers specific for lymphatic endothelial cells. Dense connective tissue surrounding tumor foci did not contain lymphatics. Peritumoral lymphatics were irregularly distributed in both types of tumor and only sporadically contained cells that might be tumor cells. Similar lymphoscintigraphic and histological pictures were seen in colon and pancreas cancer despite of different structure of both tissues. This suggests a uniform reaction of tissues to the growing cancer irrespective of the affected organ.
Lymphatic Research and Biology 09/2012; 10(3):112-7. · 2.33 Impact Factor
[show abstract][hide abstract] ABSTRACT: Pancreatic adenocarcinoma is the fourth most common cancer occurring in both women and men. In Poland, within the past ten years the number of deaths from pancreatic cancer increased by 29%.The aim of the study was to determine the correlation between the activity of metalloproteinase (MMP) 2 and 9 and progression and aggressiveness of pancreatic cancer.Material and methods. Tissue samples were collected from 36 patients with diagnosed pancreatic adenocarcinoma who underwent Whipple resection. Tumor tissues were analyzed by gel zymography, zymography in situ and immunohistochemistry.Results. The activity of MMPs was found mainly in cancer cells. Active form of MMP2 (62 kDa) was present in 88% of cases and MMP9 (83 kDa) in 38% of cases. By contrast, immunohistochemical staining revealed the presence of metalloproteinase 9 in all studied tissues. MMP activity was assessed against histological grade of the tumor. In the case of group G1 there was no activity of matrix metalloproteinase 9. By comparing the activity we concluded that the activity of MMPs in tumors with the highest degree of differentiation is significantly lower than in G2 and G3. Metalloproteinase 9 expression analysis revealed no significant differences between the groups of various degrees of histological maturity. The level of expression did not differ between the groups N0 and N1.Conclusion. Lack of metalloproteinase 9 activity in group G1 may indicate that MMP9 is activated only in higher tumor grades. We have shown that an active form of MMP2 is found in all histological grades, which supports its involvement in the development of pancreatic cancer. Metalloproteinases are attractive target of anticancer therapy but not only the level of expression of metalloproteinases should be taken into account but also their level of activity and factors associated with their activation.
[show abstract][hide abstract] ABSTRACT: Research over the last twenty years has yielded much insight into pancreatic cancer biology, but it has neither improved diagnostics methods nor the way of treatment. The question remains as to what the critical deciding factor is in making pancreatic cancer such an aggressive disease.
Pancreatic tumor tissue came from 36 patients. To assess lymphatic vessels color lymphangiography and immunohistochemistry were used. Activity of matrix metalloproteinases was studied with gel and in situ zymography. Expression of growth factors and infiltrating immune cells were investigated using immunohistochemistry.
Our study revealed that the structures that correspond to lymphatic vessels were not observed in tumor center but only at the edge of the tumor. All studied growth factors were present in tumor tissue. We found that the difference in expression between G2 and G3 stage was statistically relevant in cases of c-Met receptor. Inflammatory cells were present around neoplastic glands and also strongly around nerves infiltrated by cancer cells. The number of infiltrating macrophages in tumor tissue was significantly higher in group with metastases to lymph nodes.
We showed two factors that influence pancreatic cancer progression and invasion: c-Met receptors and macrophages infiltrating tumor tissue. Based on our analysis, this indicates that epithelial-mesenchymal transition might be crucial in the progression of pancreatic cancer.
[show abstract][hide abstract] ABSTRACT: Introduction. In spite of intensive research during many years, pancreatic adenocarcinoma remains one of the deadliest cancers. The surgical intervention remains main possibility of treatment because chemotherapy and radiotherapy has a minimal impact on long-term survival. We are still looking for the weak points of this devastating disease. Materials and Methods. Pancreatic tumor tissue samples were collected from 36 patients. Immunohistochemistry staining was used to evaluate expression of growth factors and immune infiltrates. Activity of MMP2 and MMP9 was assessed by gelatin zymography on 7.5% SDS-PAGE gel with 0.1% gelatin. Results. All growth factors were strongly expressed in pancreatic tumor tissue. We found that level of expression of c-Met receptor was higher for G3 tumors than for G2 tumors. Also we found that active MMP2 was present at all stages of tumor while active MMP9 just at more advanced tumors. Abundant immune cells infiltration was distinctive for tumor tissue, especially macrophages were infiltrating tumor tissue. We found that amount of macrophages was associated with lymph nodes metastases. Conclusion. In our research we demonstrated that among many factors influencing tumor microenvironment c-Met receptor, infiltrating macrophages and MMP2 have significant influence on development and invasion of pancreatic cancer.
Gastroenterology Research and Practice 01/2012; 2012:585674. · 1.62 Impact Factor
[show abstract][hide abstract] ABSTRACT: The main cause of a negative response to grafting is immune rejection connected with a reaction to the donor's antigens. The process of rejecting transplanted organs is a whole-body process. The reaction of the organism begins when the donor's antigens reach the recipient's lymphatic organs via blood or lymph. The donor's genetic material (DNA) is detected in the recipient's blood and lymphoid tissues even a few months after transplant rejection. Microchimerism occurs when in an individual patient the cells and genetic material from both the donor and recipient are present and the cell count of one of these is overrepresented. Such situations can occur after blood transfusions, grafts or pregnancies. It is suggested that this phenomenon could have an influence on tolerance, prolonged graft survival or the rejection process. The results of many experiments are thus far equivocal; therefore further research is needed elucidate the process and mechanisms of graft rejection and its molecular aspects.
Annals of transplantation: quarterly of the Polish Transplantation Society 12/2011; 16(4):134-7. · 0.82 Impact Factor
[show abstract][hide abstract] ABSTRACT: Simultaneous pancreas-kidney transplantation (SPK) is associated with high risk of infectious complications.
The aim of the study was to evaluate the incidence of bacterial infections within 3 months after SPK transplantation.
17 patients with type 1 diabetes at the age of 32-54 years (mean age 42.5 +/- 7.1) were retrospectively analyzed within 3 months after SPK.
No septic complications were observed in 2 patients (12%). In the remaining 15 patients (88%), at least 1 (from 1 to 5, a total of 30) infection episode was observed during follow-up. The infections were located: only at the surgical site (1 patient--6.7%), only in the urinary tract (6 patients--40%), both at the surgical site and in the urinary tract (7 patients--46.7%), at the surgical site and in blood (1 patient--6.7%). 2 groups of microbes were predominant, namely enterococci represented by 1 species, E. faecium (13 isolates) and the so-called intestinal bacilli, Enterobacteriaceae (19 isolates). No methicillin resistant Staphylococcus aureus strains were isolated. Candida species fungi were isolated only 3 times.
In our study only 2 types of infections were observed (urinary tract and surgical site infections) and each of them comprised nearly half of all the septic episodes recorded. Gram-negative bacilli were collected more often than Gram-positive cocci, both from the surgical site and urinary tract infections. All infections ended with full recovery.
Polskie archiwum medycyny wewnȩtrznej 01/2009; 118(12):700-4. · 1.83 Impact Factor
[show abstract][hide abstract] ABSTRACT: Transplanted vascularized organs shed passenger cells, normal constituents of whole organs, that migrate to recipient lymphoid tissues and produce microchimerism. These cells lyzed by recipient cytotoxic cells release cellular organelles into the recipient circulation. In addition, warm and cold ischemia as well as immune rejection of the transplanted organ or tissue bring about destructive changes in the graft parenchymatous cells. The knowledge of the fate of donor DNA distributed in passenger cells and in fragments of disrupted nuclei as well as the role of recipient cells internalizing donor DNA could give some insight into the mechanism of graft destruction and immunization or tolerance to donor antigens.
In this study we provide evidence that forensic medicine testing of polymorphic genes for phospholipase A2, cytochrome P450 and locus D1S80 may be useful for the detection of donor DNA microchimerism in kidney transplant recipients in sex-matched combinations as well as previous blood transfusion recipients.
Donor DNA was detected in recipient whole blood even 2 years after kidney transplantation.
The biological significance of our findings is not clear. We speculate that donor DNA fragments in recipient immune cells may play a role in the immunization/tolerance process to allogeneic antigens.
Annals of transplantation: quarterly of the Polish Transplantation Society 02/2007; 12(3):12-4. · 0.82 Impact Factor
[show abstract][hide abstract] ABSTRACT: Renal transplantation is associated with frequent gastrointestinal complications. Intestinal metaplasia is a feature of atrophic gastritis whereas the diagnosis of Barrett's esophagus is based on histological demonstration of specialized metaplasia. Both conditions are associated with increased risk of adenocarcinoma. The aim of the present study was to assess whether magnification endoscopy improves the diagnostic accuracy of intestinal metaplasia in stomach and in esophagus.
In this non-randomized, feasibility study thirty one (12 women and 19 men) renal transplant recipients, with a mean age of 44.0 years were evaluated for the presence of intestinal metaplasia. Standard esophagogastroscopy with methylene blue staining was followed by magnification endoscopy. The presence of gastritis and intestinal metaplasia was classified according to modified updated Sydney classification.
Of 31 patients, 16 patients had endoscopic and histopathological evidence of gastric intestinal metaplasia, and standard endoscopy with methylene blue staining was sufficient for diagnosis (15 from 16). Magnification endoscopy allowed identification of 6 patients with specialized intestinal metaplasia in Barrett's esophagus, which would be otherwise missed.
In this study diagnostic accuracy of standard endoscopy for identification of intestinal metaplasia in the stomach was not improved by the use of magnification endoscopy, but the latter was an accurate method of predicting specialized intestinal metaplasia in Barrett's esophagus. The use of magnification endoscopy in the clinical setting of renal transplantation needs further studies.
Advances in Medical Sciences 02/2006; 51:115-8. · 0.80 Impact Factor
[show abstract][hide abstract] ABSTRACT: Pancreatic transplantation is a generally accepted treatment modality for patients with type I diabetes mellitus to control metabolism of glucose and prevent complications of diabetes. Graft thrombosis, chronic rejection, surgical complications are the leading cause of pancreatic graft loss among diabetic patients who undergo pancreas transplantation. Pancreas retransplantation is an important option for patients, who lost their primary pancreatic grafts. The 1-year graft survival rates for pancreas retransplantations are comparable to a primary pancreas transplantation. We report a case of pancreas retransplantation in 51-year-old male with a history of type I diabetes mellitus of a 40-year duration, after SKP 20 month before and graft pancreatectomy because of thrombosis 2 weeks after SKP. Pancreatic graft was placed on the right side of the pelvis and enteric drainage was used. Immunosuppressive regimen included daclizumab and thymoglobulin for induction, and mycophenolate mofetil, tacrolimus and short-term steroids for the maintenance of treatment. Four reexplorations were performed due to donor duodenum perforation caused by the stricture of the intestine situated in the area of previous anastomosis or/and after the transplant pancreatectomy. Enteroplasty was performed. Three months after surgery the patient remains normoglycemic, insulin-independent with good kidney function.
Annals of transplantation: quarterly of the Polish Transplantation Society 02/2006; 11(4):12-4. · 0.82 Impact Factor
[show abstract][hide abstract] ABSTRACT: Transplantation of pancreas is a generally accepted treatment option for patients with type 1 diabetes mellitus. This procedure restores physiological insulin secretion, resulting in long-term normoglycemia and preventing complications of diabetes. One of the therapeutic possibilities is pancreas after kidney transplantation (PAK) for patients with previous successful kidney transplantation. There is evidence that patient and kidney graft survival is higher in PAK compared with diabetic recipients of kidney or pancreas alone (PTA). We report a case of pancreas after kidney transplantation in a 38 year-old male with type 1 diabetes mellitus of 21 year duration. One year before PAK he received cadaveric kidney transplant. Pancreatic graft was placed on the left side of the pelvis and enteric drainage was used. Immunosuppression consisted of antithymocyte globulin (ATG), daclizumab, tacrolimus, mycophenolate mofetil, and steroids. Ten months after surgery the patient stays normoglycemic, insulin-independent with good kidney function (Cr-1,5 mg/dl).
Annals of transplantation: quarterly of the Polish Transplantation Society 02/2005; 10(4):59-62. · 0.82 Impact Factor
[show abstract][hide abstract] ABSTRACT: Isolated syngeneic and allogeneic hepatocytes transplanted to spleen parenchyma are rapidly disintegrated. Host scavenger monocytes and macrophages are responsible for this reaction. We designed a method overcoming early disintegration of the intra-splenic grafted hepatocytes. It consisted of administration of anti-asialoGM I antiserum eliminating NK cells, sublethal whole body irradiation for depletion of scavenging cells and reconstitution with syngeneic bone marrow cells, ligation of host bile duct, intrasplenic hepatocyte transplantation and 3 consecutive partial hepatectomies. Six months after transplantation a glycogen-rich, trabeculae-forming, dividing hepatocytes, situated along strands of newly-formed fibrous tissue and numerous dilated blind bile canaliculae were observed. There was evidently more bile canaliculae in hosts with ligated bile duct than non-ligated controls. This is the first study showing fibrous tissue formed at the site of hepatocyte implantation and stellate cells are presumably responsible for this process.
Annals of transplantation: quarterly of the Polish Transplantation Society 02/2004; 9(4):40-2. · 0.82 Impact Factor
[show abstract][hide abstract] ABSTRACT: Transplantation of a vascularized limb should be considered as a double graft: composite parenchymatous non-lymphoid tissue (skin, subcutaneous tissue, muscles, nerves and bones in a block) and bone marrow (BM) tissue. Ready-to-function BM releases mature and precursor cells migrating to the recipient tissues immediately after transplantation. Donor BM-derived cells home to recipient BM cavities and lymphoid organs (LO) and to lesser extent to the non-lymphoid tissues. Interestingly, no acute and subacute graft-versus-host reaction develops. Cellular microchimerism is detected with the presence of donor cells in recipient tissues, at least as long as the transplanted limb is not rejected. Free donor DNA appears in high concentrations in recipient tissues at the time of rejection. The biological significance of the cellular and DNA microchimerism is not clear. Slight prolongation of limb and free-flap skin grafts survival time may be attributed to microchimerism. The beneficial and unwanted effects of transplanted BM tissue should be taken into consideration in the clinical limb transplantation programme. Long-term experimental and clinical observations will allow to draw more clinically applicable conclusions. Abbreviations used in this review: BM: bone marrow, BMC: bone marrow cells, BMTx: bone marrow transplantation, il-BMTx: in limb-bone marrow transplantation, iv-BMCTx: intravenous isolated bone marrow cell transplantation, MLN: mesenteric lymph node, SPL: spleen, LO: lymphoid organs, PHA: phytohemagglutinin, ConA: concavalin A, PWM: pokeweed mitogen, CsA: cyclosporin A, TBI: total body irradiation.
Annals of transplantation: quarterly of the Polish Transplantation Society 02/2004; 9(4):26-31. · 0.82 Impact Factor
[show abstract][hide abstract] ABSTRACT: The transplanted limb contains bone marrow tissue. The hematopoietic cells contained in the bone of the graft normally differentiate after transplantation and can be released to the recipient. The cells migrate to the recipient bone marrow cavities and lymphoid organs. This causes the immune reaction between the donor and the recipient, which develops not only in the graft itself but also in the recipient immune organs where donor bone marrow cells home. The purpose of this study was to investigate the process of migration of the hematopoietic cells from the donor limb to the recipient bone marrow cavities and lymphoid tissues. The questions the authors asked were: what is the rate of release of bone marrow cells from the transplanted bone, where do the released bone marrow cells home in the recipient, how fast are donor bone marrow cells rejected by the recipient, and can some bone marrow cells homing in the recipient tissues survive and create a state of microchimerism. Experiments were performed on Brown Norway and Lewis inbred rat strains (n = 30). Limb donors received intravenous chromium-51-labeled bone marrow cells. Twenty-four hours later, the limb with homing labeled bone marrow cells was transplanted to an allogeneic or syngeneic recipient. The rate of radioactivity of bone marrow cells released from the graft and homing in recipient tissues was measured after another 24 hours. To eliminate factors adversely affecting homing such as the "crowding effect" and allogeneic elimination of bone marrow cells by natural killer cells, total body irradiation and antiasialo-GM1 antiserum were applied to recipients before limb transplantation. In rats surviving with the limb grafts for 7 and 30 days, homing of donor bone marrow cells was studied by specific labeling of donor cells and flow cytometry as well as by detecting donor male Y chromosome. The authors found that transplantation of the limb with bone marrow in its natural spatial relationship with stromal cells and blood perfusion brings about immediate but low-rate release of bone marrow cells and their migration to recipient bone marrow and lymphoid tissues. Large portions of allogeneic bone marrow cells are rapidly destroyed in the mechanism of allogeneic elimination by radioresistant but antiasialo-GM1-sensitive natural killer cells. Some transplanted bone marrow cells remain in the recipient's tissues and create a state of cellular and DNA microchimerism. A low number of physiologically released donor bone marrow cells do not seem to adversely affect the clinical outcome of limb grafting. Quite the opposite, a slight prolongation of the graft survival time was observed.
Plastic & Reconstructive Surgery 12/2003; 112(6):1628-35. · 3.54 Impact Factor
[show abstract][hide abstract] ABSTRACT: The specificity of a limb transplant lies in its anatomy. It is a graft of an organ, in analogy to the kidney or heart transplant,
but in addition, it is a graft of bone marrow (BM) whose cells (BMC) do not only proliferate and mature in the graft but also
migrate to the recipient bone marrow cavities and lymphoid organs (LO). Thus, the immune contact between the donor and recipient
takes place not only in the graft itself but also in the recipient's immune organs, where the released BMC home. The BMC released
from the graft may also home in other tissues, especially those with direct contact with environment as skin, gut, and lungs.
Interestingly, there have been reports that the donor bone marrow cells may survive in the allogeneic recipient and create
a state of cellular microchimerism. Microchimerisms are, according to some researchers, linked with the development of partial
tolerance to donor alloantigens. This is a controversial issue with a number of observations supporting and negating the concept
of microchimerism as a causative factor in prolongation of survival of organ allograft transplanted concomitantly with bone
marrow. Another problem is the graft-versus-host reaction developing after bone marrow transplantation. There are reports
providing evidence for lack of the graft-versus-host reaction after limb transplantation.
[show abstract][hide abstract] ABSTRACT: Hyperhomocysteinemia occurs in approximately 60-70% of renal transplant recipients and is associated with increased risk of cardiovascular events, mortality and kidney allograft loss. In normal subjects N-acetylcysteine (NAC) given either orally or intravenously markedly reduces plasma total homocysteine (tHcy) level. In cardiac transplant recipients it was reported, that oral treatment with NAC does not affect Hcy levels. We have therefore, investigated the effect of intravenous NAC on plasma tHcy levels in renal transplant recipients.
Eleven renal transplant recipients who had normal plasma levels of vitamin B12 and folic acid, were treated with intravenous NAC or placebo in a crossover manner.
Intravenous administration of NAC significantly reduced plasma tHcy (p=0.0008). Decrease in tHcy was related to its initial concentration.
Intravenous NAC profoundly reduces tHcy level in renal transplant recipients. Further research is needed to establish the effect of orally administered NAC on plasma homocysteine concentration in this clinical condition.
Annals of transplantation: quarterly of the Polish Transplantation Society 14(4):5-9. · 0.82 Impact Factor