The Behavior of MMP-2, MMP-7, MMP-9, and Their Inhibitors TIMP-1 and TIMP-2 in Adenoma-Colorectal Cancer Sequence.

BACKGROUND: We and others have previously shown that matrix metalloproteinases (MMPs) play a role in colorectal cancer (CRC) invasion and metastasis. However, the serum changes of various MMPs and their inhibitors (TIMPs) have scarcely been concomitantly investigated in identical blood samples in the normal colon-adenoma-CRC sequence. METHODS: The MMP-2, MMP-7, MMP-9, TIMP-1, and TIMP-2 serum antigen concentrations were determined concomitantly in 19 tumor-free control patients, 19 patients with high-risk colorectal adenoma, and 47 patients with CRC by ELISA technique. The analyzed parameters were also investigated in correlation with CRC stages. Statistical analysis with one-way ANOVA and Student's t test was performed. p values <0.05 were considered significant. RESULTS: Serum antigen levels of MMPs and TIMPs were significantly increased in patients with CRC and adenomas compared to controls (mean values, ng/mL) (MMP-7: 5.88, 4.44, and 2.89, respectively, p = 0.001; MMP-9: 1,075.81, 999.22, and 845.97, respectively, p = 0.01; TIMP-1: 241.80, 205.98, and 166.53, respectively, p = 0.001; TIMP-2: 83.40, 80.30, and 69.62, respectively, p = 0.01). The elevated serum MMP-7, MMP-9, TIMP-1, and TIMP-2 levels significantly correlated with advanced tumor stages (p < 0.05). No statistically significant differences were observed in MMP-2 levels. CONCLUSIONS: We demonstrate that serum antigen concentrations of MMP-7, MMP-9, TIMP-1, and TIMP-2 were significantly increased in patients with CRC and adenomas compared to controls. These results suggest that MMPs and their inhibitors TIMP-1 and TIMP-2 play an important role in CRC invasion; however, they are also activated in premalignant adenomas. Furthermore, MMP-7, MMP-9, TIMP-1, and TIMP-2 may have a potential prognostic impact in CRC.

Pharmacological Approach to Gastric Acid Suppression: Past, Present, and Future.

Less than 2 centuries have elapsed since the identification of hydrochloric acid in the stomach. The clarification of the molecular mechanisms allowed the effective therapeutic suppression of gastric acid secretion. The spectacular advances in the treatment of acid-related disorders represent a synthesis of the contributions of several brilliant pharmacologists, basic scientists, and clinical physicians. Effective gastric acid suppressive therapy has dramatically improved the therapy and outcome of acid-related disorders. The introduction of proton pump inhibitors (PPIs) in clinical practice has significantly changed the medical management of upper gastrointestinal disorders. PPIs represent the "gold-standard" therapy in acid-related disorders. However, some challenges persist in the therapy of acid related diseases, including management of patients who respond inadequately to PPI therapy, more effective gastroprotection, or more powerful antisecretory treatment for the eradication of Helicobacter pylori infection. New antisecretory drugs are currently being developed and investigated to further provide a more effective and profound gastric acid secretion inhibition. The major advance has been the development of acid pump -antagonists, the potassium channel acid blocking drugs (-P-CABs). Long-term studies comparing P-CABs with PPIs will help to define the exact place and safety profile of this class of drug in the management of acid-related disorders.

High serum Hsp70 level predicts poor survival in colorectal cancer: Results obtained in an independent validation cohort.

BACKGROUND: Hsp70 plays important role in the development and progression of cancer. Previously we described the association between serum Hsp70 levels and mortality of colorectal cancer. OBJECTIVE: In this new prospective study we aimed to confirm and extend our previous findings in a larger cohort of patients, based on a longer follow-up period. METHODS: Two hundred and thirty-two patients diagnosed with colorectal cancer were enrolled in the study. Baseline serum Hsp70 level and classical biomarker levels were measured. Patients were treated according to stage of the tumor and follow-up lasted for a median 46.4 months. RESULTS: We found that serum Hsp70 concentrations increase significantly with stage of the disease (1.79; 2.23 and 3.21 ng/ml in stage I+II, III and IV respectively, p= 0.012 and 0.002, Mann-Whitney test) and with other known biomarkers of the disease. We managed to confirm our previous findings that high baseline serum Hsp70 level (> 1.64 ng/ml) predicted poor 5-year survival (risk of death HR: 1.94 CI: 1.294-2.909; univariate; HR: 2.418 CI: 1.373-4.258; multivariate Cox regression analysis) in the whole patient population and also in subgroups of stage IV and stage III disease. The strongest association was observed in women under age of 70 (HR: 8.12, CI: 2.02-35.84; p= 0.004; multivariate Cox regression). The power of this colorectal cancer prognostic model could be amplified by combining Hsp70 levels and inflammatory markers. Patients with high Hsp70, CRP and high baseline WBC or platelet count had 5-times higher risk of death (HR: 5.07 CI: 2.74-9.39, p< 0.0001; and HR: 4.98 CI: 3.08-8.06, p< 0.0001 respectively). CONCLUSIONS: These results confirm and validate our previous findings that serum Hsp70 is a useful biomarker of colorectal cancer.

Platelet Count, ADAMTS13 Activity, von Willebrand Factor Level and Survival in Patients with Colorectal Cancer: 5-Year Follow-up Study.

Distant metastasis is a major cause of colorectal cancer-related death, but the mechanism of tumour progression is not fully understood. There is growing evidence of an interaction between tumour cells and platelets which may influence tumour progression and metastasis formation. Quality and quantity of von Willebrand factor may regulate the interaction between tumour cells and platelets. Our aim was to measure the platelet count, von Willebrand factor antigen (VWF:Ag) levels and ADAMTS13 activity in a large (n = 232) cohort of colorectal cancer patients and to examine their relationships with the stage of the disease and 5-year survival without thrombotic complications using multivariable models. Significantly higher platelet counts (p = 0.005), VWF:Ag levels (p = 0.008) and decreased ADAMTS13 activity (p = 0.006) were observed in patients with metastatic disease. Results of the Kaplan-Meier analysis showed that lower platelet counts (p < 0.0001), lower VWF:Ag (p = 0.0008) levels and higher ADAMTS13 activity (p < 0.0001) were associated with better event-free survival. Finally, to investigate the association between overall event-free survival and the three study variables, multivariate Cox proportional hazard models were generated. All models were adjusted for age, gender and disease stage. Platelet count, ADAMTS13 activity or VWF:Ag level were incorporated and all of these variables turned out to be age-, gender- and stage-independent predictors of mortality (all hazard ratio >1.7, p < 0.05). In summary, this is the first observational study reporting association between higher mortality or thrombotic complications and increased platelet count, increased VWF:Ag levels and decreased ADAMTS13 activity in colorectal cancer.

Circulating mitochondrial stress 70 protein/mortalin and cytosolic Hsp70 in blood: Risk indicators in colorectal cancer.

Mitochondrial mortalin and cytosolic Hsp70 are essential chaperones overexpressed in cancer cells. Our goals were to reproduce our earlier findings of elevated circulating levels of mortalin and Hsp70 in colorectal cancer (CRC) patients with a larger patient cohort, to compare death risk assessment of mortalin, Hsp70, CEA and C19-9 and to assess their prognostic value in various CRC stages. Mortalin, Hsp70, CEA and CA19-9 levels were determined in sera of 235 CRC patients enrolled in the study and followed up 5 years after surgery. Association between their concentrations and patients' survival was analyzed by Kaplan-Meier estimator and subjected to Cox Proportional hazards analysis. Serum level of mortalin was independent of that of Hsp70, CEA and CA19-9, whereas Hsp70 level weakly correlated with CEA and CA19-9 levels. Improved short-term survival was found in early or advanced disease stages associated with lower mortalin and Hsp70 levels. Cox regression analysis showed a high mortality hazard (HR = 3.7, p < 0.001) in patients with both high mortalin and Hsp70 circulating levels. Multivariate analysis showed that high mortalin and Hsp70 significantly enhances risk score over a baseline model of age, number of affected lymph nodes, CEA, CA19-9, disease stage and perioperative therapy. Analysis of mortalin and Hsp70 in CRC patients' sera adds a high prognostic value to TNM stage and to CEA and CA19-9 and identifies patients with lower or higher survival probability in all CRC stages. Determination of mortalin and Hsp70 in blood could be a useful additive prognostic tool in guiding clinical management of patients.

[Colon reconstruction after the Hartmann procedure. Laparoscopy or laparotomy?] / Colonrekonstrukció Hartmann-mutét után. Laparoszkópia vagy laparotomia?

The Hartmann procedure - primarily - was introduced for the treatment of cancerous diseases of sigmoid colon and rectum. In the last few years it was performed in cases with complicated inflammation of the left colon, colon cancers with bowel obstruction or perforation, or in the case of insufficiency of the anastomoses, or in urgent operations after traumatics bowel injuries, when making the anastomosis is at very high risk. Later on the restoration of the continuity of the GI tract can be done traditionally (by laparotomy) or laparoscopically. We present our experiences with the above technique, and also compare our results with traditional open surgeries in our patients.

[Reconstruction of the inguinal ligament with fascia lata sling. First reported case in Hungary]. / Poupart-szalag rekonstrukciója autológ fascia lata lebennyel. Az elso ismertetett hazai eset.

INTRODUCTION: A technique of reconstructing the inguinal ligament using pedicled fascia lata flap is described. PRESENTATION OF CASE: A 66-year-old woman was referred with massive incarcerated left inguinal hernia, following acute surgery on a femoral vein leasion and numerous attempts at repair and subsequent recurrences. There was complete absence of the left inguinal ligament. The inguinal ligament was reconstructed using a strip of fascia lata, pedicled on the anterior superior iliac spine. This was transposed to cover the external iliac vessels, and sutured to the pubic tubercle. The musculoaponeurotic abdominal wall was reconstructed with 15×13 cm sheet of polypropylene mesh, placed preperitoneal and sutured to the remaining abdominal wall muscles and to the neo-Pouoart ligament. DISCUSSION: Complete destruction of the inguinal ligament is rare but can occur following multiple operative procedures or trauma. Published reports of inguinal ligament reconstruction have been performed using synthetic mesh. The use of autologous tissue should reduce the risk of erosion into the neurovascular bundle, seroma formation, and enhance integration into surrounding tissues. CONCLUSION: This new technique for autologous reconstruction of the inguinal ligament provides a safe alternative to the use of synthetic mesh in the operative armamentarium of plastic and general surgeons. This is the first reported case in Hungary.

Colorectal cancer in patients with inflammatory bowel disease: the true impact of the risk.

Patients with long-standing inflammatory bowel disease (IBD) have an increased risk of colorectal cancer (CRC). The association between IBD and CRC is well supported, but reported risk estimates vary widely. Although recent evidence from population-based studies reports a decline in risk, CRC accounts for 10-15% of all deaths in IBD. The potential causes of recent epidemiological trends and the real magnitude of risk of CRC in IBD are subjects of debate. The molecular pathway leading to CRC differs from the classic adenoma-to-CRC sequence. Chronic inflammation contributes to the development of low- and high-grade dysplasia which may further convert into CRC. Patients with a young age at onset, long-standing and extensive colitis with severe inflammatory burden, a family history of sporadic CRC, and concomitant primary sclerosing cholangitis are at greatest risk. The CRC risk in patients with colonic Crohn's disease is similar to that of ulcerative colitis. IBD-associated CRC can frequently be detected at late stages and at a younger age. The long-term prognosis of CRC may be poorer in patients with IBD than in those with sporadic CRC. Regular surveillance colonoscopies may permit earlier detection of CRC, with a corresponding improved prognosis. The interval between surveillance colonoscopies is dependent on each patient's personal risk profile.

Impact of proteolytic enzymes in colorectal cancer development and progression.

Tumor invasion and metastasis is a highly complicated, multi-step phenomenon. In the complex event of tumor progression, tumor cells interact with basement membrane and extracellular matrix components. Proteolytic enzymes (proteinases) are involved in the degradation of extracellular matrix, but also in cancer invasion and metastasis. The four categories of proteinases (cysteine-, serine-, aspartic-, and metalloproteinases) are named and classified according to the essential catalytic component in their active site. We and others have shown that proteolytic enzymes play a major role not only in colorectal cancer (CRC) invasion and metastasis, but also in malignant transformation of precancerous lesions into cancer. Tissue and serum-plasma antigen concentrations of proteinases might be of great value in identifying patients with poor prognosis in CRC. Our results, in concordance with others indicate the potential tumor marker impact of proteinases for the early diagnosis of CRC. In addition, proteinases may also serve as potential target molecules for therapeutic agents.

[Retroareolar breast cancer: oncoplastic resection technique with central quadrantectomy and reconstruction with Grisotti's inferior dermo-glandular flap]. / Retroareolarisan elhelyezkedo emlotumorok onkoplasztikai mutéte: centrális quadrantectomia és Grisotti-féle inferior dermoglandularis lebennyel való rekonstrukció

Centrally located breast cancers account for 5-20% of all breast cancer cases. Historically, patients with central breast cancers were not offered breast conservation surgery but conventional mastectomy only. The relatively frequent nipple-areola-complex involvement and consequent nipple-areolar resections with an adequate safety margin around the tumor usually result in an unacceptable cosmetic result. However, breast conservation surgery can be offered to these patients applyingoncoplastic surgical techniques. In this study, central quadrantectomy and breast reconstruction with Grisotti's dermo-glandular flap is evaluated.

[Definitive treatment of multiple recurrences of sacral dermoid cysts using an inferior gluteal artery perforator fasciocutaneous flap]. / Többszörösen kiújult sacralis dermoid definitív megoldása az arteria glutealis inferior direct fasciocutan ágára nyelezett transzpozíciós lebeny alkalmazásával.

AIM: Treatment of sacral dermoid cysts (SDC) is a surgical challenge. Etiology and adequate operative technique of that are debated widely up to now, and recurrence rates remained high despite various surgical techniques applied. In cases of unsuccessfully operated and repeatedly recurrent SDC a fascio-cutaneous flap on the first perforating branch of the inferior gluteal artery (IGA) is a definitive procedure. MATERIAL AND METHOD: Following preparation and dissection of sidebranches of IGA in cadavers, a repeatedly recurrent SDC was operated. CONCLUSION: a flap harvested and transferred on the first superficial perforating branch(es) of the inferior gluteal artery offers a definitive and recurrence-free surgical solution for SDC.

[Analysis of two different operative techniques for laparoscopic splenectomy]. / Két mutéti technika elemzése laparoscopos splenectomiák kapcsán.

INTRODUCTION: Laparosocopic splenectomy gradually became the gold standard procedure in the surgical treatment of certain haematological disorders. Operative experience in laparoscopic procedures facilitates the comparison of various techniques. AIM: Two variants in laparoscopic spelenectomy are analysed and presented. MATERIAL AND METHOD: Sixteen patients underwent laparoscopic spelenectomy. Anterior- and postero-anterior laparoscopic approaches are compared with respect to clinicopathologic features. CONCLUSIONS: Using the postero-anterior technique dissection of splenic hilum is more straightforward, recognition of accessory spleen is easier and the likelihood of intraoperative complications is less. In selected cases of splenomegaly the anterior technique is recommended though.

[Successfully operated cases of mediastinal and retroperitoneal bronchial cysts]. / Mediastinalis és retroperitonealis bronchogen cysták sikeresen operált esetei és tanulságaik.

CASE REPORT: Two young men were operated in our department for bronchiogen cysts with unusual locations. In the first case a mediastinal cyst caused severe swallowing problems, while in the second a retroperitoneal cyst resembled to an adrenal adenoma. It was only the postoperative histology, which clarified the exact diagnosis of the removed cysts. DISCUSSION: Only a few percent of mediastinal tumours are bronchial cysts that develop due to developmental disorders. Symptomatic ones are more easily detectable. Bronchial cysts localized in the abdominal cavity or retroperitoneum are especially rare. In most of the cases the final diagnosis is made only after excision with histological examination of the cyst.

[Pectoral major muscle-sling flap for treatment of recurrent subareolar abscess: a new surgical technique]. / Pectoralis major izomlebeny a recurráló subareolaris abscessus kezelésében: egy új mutéti módszer.

Recurrent subareolar abscess is an uncommon benign disease of the breast, which is caused by peri-ductal mastitis with various etiology. Radical surgical procedure is necessary for cure instead of inadequate courses of antibiotics or incisions. In some cases the use of the pectoral muscle sling flap can be an alternative technique for the treatment of recurrent subareolar abscess after repeated standard surgical treatment. A 36 year old woman, who successfully underwent this procedure, is presented here.

[Large bowel obstruction due to colonic and omental metastasis as the first clinical sign of metastatic ductal carcinoma of the breast]. / Colon- és csepleszmetastasis okozta ileus mint a ductalis emlorák elso klinikai jele.

Distant spread from breast cancer is commonly found in bones, lungs, liver and central nervous system. Metastatic involvement of peritoneum, omentum or/and gastro-intestinal tract is unusual and unexpected. We present the case of a 48 year-old woman who presented with gastro-intestinal symptoms as signs of omental and colonic metastasis of an invasive ductal breast cancer, which was not diagnosed before her admission. Ileus was diagnosed and urgent surgery was performed. Histology revealed metastatic ductal breast carcinoma. Mastectomy and axillary lymphadenectomy were performed therefore. Reviewing the literature--to the best of our knowledge--such a case has never been published before.

[Precursors of Pancreatic cancer: Intraepithelial Neoplasia (PanIN) and Intraductal Papillary Mucinous Neoplasms (IPMN)]. / A pancreas praecancerosisai: intraepithelialis neoplasia (PanIN) és intraductalis papillaris mucinosus neoplasia (IPMN).

Pancreatic Intraepithelial Neoplasia (PanIN1-3) and Intraductal Papillary Mucinous Neoplasms (IPMN) putative precursors of and associated to pancreatic cancer represent a distinct, however pathologically heterogenous entity. Recently a new classification and nomenclature was established. We review the clinicopathologic and cytogenetic characteristics of PanIN and IPMN highlighting the nonaggressive biological behavior of intraepithelial and intraductal neoplasms which, in part explain their favorable prognosis.

[An uncommon malignancy of the breast: dermatofibrosarcoma protuberans with fibrosarcomatous transformation (DFSP-FS)]. / Az emlo ritka malignomája: dermatofibrosarcoma protuberans fibrosarcomás átalakulással (DFSP-FS).

Dermatofibrosarcoma protuberans (DFSP) is a morphologically distinct dermal/subcutaneous fibrohystiocytic neoplasm seen mainly on the trunk and the proximal extremities, which generally is regarded as a low-grade or "borderline" neoplasm. Dermatofibrosarcoma protuberans is characterized clinically by locally aggressive growth and a high rate of local recurrence, but distant metastases and tumor-related deaths are very rare. DFSP in the breast is extremely uncommon. Immunohistochemically, DFSP is characterized by positive staining for vimentin and CD34. We present a case of a 65 years old female patient with a giant DFSP developed in the sight of several excised fibroadenoma and neurofibroma treated by radical mastectomy and axillary block-dissection. Perioperative hystological and immunohistochemical images demonstrate the characteristics of the giant nonphylloid sarcoma.

[Recurrent retroperitoneal liposarcoma presenting as an incarcerated femoral hernia]. / Kizárt combsérv klinikai képét mutató recidív retroperitonealis liposarcoma.

56-year-old man was admitted to our hospital 18 month after extirpation of retroperitoneal liposarcoma. We diagnosed recurrent tumor in the inguinal fossa. The tumor situated along the femoral artery and propagated to the thigh among the muscles, mimicking incarcerated femoral hernia. We performed resection with synchronous abdominal and femoral exploration. By our knowledge this is the first case report about recurrent retroperitoneal liposarcoma presenting as an incarcerated femoral hernia.

[Laparoscopic knot tying]. / Laparoscopos csomózás.

Wound closure with sutures has been routinely used as a result of the technical and surgical development since the 20th Century. Knot tying in open surgery can be easily learned and performed; however, knot tying becomes challenging and frustrating when performed laparoscopically. Laparoscopic vessel ligation, suturing and performing anastomosis opened up a new horizon for laparoscopy. Laparoscopic knots can be performed extracorporally or intraabdominally. The most common intracorporal knots are the tumble square, Dundee, Aberdeen, midship and blood knots. Inherent disadvantages of intracorporal laparoscopic knot tying are decreased sensation of the tension applied to the tissues and the knot; and difficulty in knotting because of technical requirements and limited space. The most common extracorporal knots: Duncan, Roeder, modified 4-S Roeder, Tayside, Yanni and GEA knots. Extracorporally tied knots are obviously much easier to tie than intracorporal one;, but they can cause tissue trauma from pulling long lengths of suture through the needle tract, excessive tension on the tissue while pushing the knot into position, and loss of focus on the operative field during knotting. One kind of knot-pusher would not fit for all and we suggest to use different knot-pushers for different suture materials. In robotic assisted suturing the operative time decreased, the stability has increased and the skills can be developed in simulation labs.