Chemotherapy versus chemoradiotherapy in borderline resectable and locally advanced pancreatic adenocarcinoma.

The role of radiotherapy in borderline resectable (BRPC) and locally advanced pancreatic carcinoma (LAPC) remains controversial. In our study, we retrospectively evaluated 48 patients with BRPC (14; 29.2%) and LAPC (34; 70. 8%) who underwent 6-8 cycles of induction mFOLFIRINOX chemotherapy alone (23; 47.9%) or 4-6 cycles of mFOLFIRINOX followed by hypofractionated radiotherapy (up to the total dose of 39.9 Gy in 15 fractions) (25; 52.1%). Survival parameters were evaluated using the Gehan-Breslow-Wilcoxon Test and compared by using the long-rank test. The addition of radiotherapy was not associated with better survival (16.9 months for chemotherapy only versus 15.9 months for the combined therapy; p=0.486), as well as for both subgroups (13.5 months vs. 18.3 months; p=0.679) and (20.7 months vs. 13.8 months; p=0.425) for BRPC and LAPC, respectively. A higher resection rate was seen in the BRPC group compared to the LAPC group (43% vs. 17.6%, respectively). Our study revealed a significantly higher rate of lung metastases in patients after the combination therapy compared to those treated by chemotherapy only (19% vs. 0%, respectively; p=0.045). Such a borderline result, however, prevents us from drawing clear conclusions about whether this is an artifact caused by the low number of patients or whether radiotherapy leads to a selection of stem cells with a predilection to the generalization to the lungs.

Modern trends in management of complicated gastrointestinal ostomies.

Stoma formation is an important component of many surgical procedures performed for a wide range of disorders of the gastrointestinal tract. Ostomy-related complications remain common and are associated with significant morbidity as well as costs. In 21st century stoma patient care is a dynamically developing field of medicine worldwide. Pouching system production is focused on different physical profiles of population in regards to inequality of the abdominal wall and skin lashes. In many cases it can cause leakage of the pouching system and underflowing of stoma effluent underneath the ostomy device resulting in peristomal skin complications. There is a clear trend of care in patients with inequality of the abdominal wall towards production and distribution of convex ostomy pouching systems. Convex systems of different sizes and depths for patients with ileostomies and colostomies are available on the market. In this way enterostomal therapist has the possibility to use an adequate pouching system (soft, mild and deep convex systems). The authors will review common local complications of stoma creation, detail measures to prevent them and outline recommendations for management including nursing procedures of stoma therapist.

Expression, Epigenetic, and Genetic Changes of HNF1B in Colorectal Lesions: an Analysis of 145 Cases.

Hepatocyte nuclear factor 1 beta (HNF1B) is transcription factor which plays a crucial role in the regulation of the development of several organs, but also seems to be implicated in the development of certain tumours, especially the subset of clear cell carcinomas of the ovary and kidney. Depending on the type of the tumour, HNF1B may act as either a tumour suppressor or an oncogene, although the exact mechanism by which HNF1B participates in the process of cancerogenesis is unknown. Using immunohistochemical approach and methylation and mutation analysis, we have investigated the expression, epigenetic, and genetic changes of HNF1B on 40 cases of colorectal adenomas and 105 cases of colorectal carcinomas. The expression of HNF1B was correlated with the benign or malignant behaviour of the lesion, given that carcinomas showed significantly lower levels of expression compared to adenomas. In carcinomas, lower levels of HNF1B expression were associated with recurrence and shortened disease-free survival. The mutation analysis revealed three somatic mutations (two frameshift and one nonsense) in the carcinoma sample set. Promoter methylation was detected in three carcinomas. These results suggest that in colorectal cancer, HNF1B may play a part in the pathogenesis and act in a tumour suppressive fashion.

Identification of novel HNF1B mRNA splicing variants and their qualitative and semi-quantitative profile in selected healthy and tumour tissues.

Hepatocyte nuclear factor-1-beta (HNF1B) is a transcription factor crucial for the development of several tissues, and a promising biomarker of certain solid tumours. Thus far, two HNF1B alternative splicing variants (ASVs) have been described, however, the complete spectrum, prevalence and role of HNF1B ASVs in tumorigenesis are unclear. Considering the equivocal data about HNF1B ASVs and expression presented in literature, our aim was to characterize the spectrum of HNF1B mRNA splicing variants across different tissues. Here, we characterize HNF1B ASVs with high sensitivity in carcinomas of the uterine corpus, large intestine, kidney, pancreas, and prostate, with selected paired healthy tissues, using the previously described multiplex PCR and NGS approach. We identified 45 ASVs, of which 43 were novel. The spectrum and relative quantity of expressed ASVs mRNA differed among the analysed tissue types. Two known (3p, Δ7_8) and two novel (Δ7, Δ8) ASVs with unknown biological functions were detected in all the analysed tissues in a higher proportion. Our study reveals the wide spectrum of HNF1B ASVs in selected tissues. Characterization of the HNF1B ASVs is an important prerequisite for further expression studies to delineate the HNF1B splicing pattern, potential ASVs functional impact, and eventual refinement of HNF1B's biomarker role.

Novel serum markers HSP60, CHI3L1, and IGFBP-2 in metastatic colorectal cancer.

Colorectal cancer (CRC) is the second leading tumor diagnosis in women and men in the Czech Republic. Patient outcome depends on tumor stage at the time of diagnosis and, in metastatic disease, on the localization and extent of distant metastases. The early detection of metastatic liver disease is an important indication for liver surgery. Therefore, novel biomarkers are urgently required. Serum samples were collected from 97 patients with histologically confirmed metastatic CRC at the time of diagnosis or at the time of progression during palliative treatment, and 79 samples from healthy controls. All patients exhibited adequate liver and renal function and signed informed consent was obtained from all patients included in the current study. The serum levels of Heat shock protein 60 (HSP60), Chitinase-3-like protein 1 (CHI3L1) and Insulin-like growth factor binding protein 2 (IGFBP-2) were measured using immunochemistry. The serum levels of HSP60, CHI3L1 and IGFBP-2 were significantly higher in patients with CRC compared with healthy controls. When compared with carcinoembryonic antigen (CEA), HSP60 exhibited the same sensitivity and specificity, while CHI3L1 and IGFBP-2 exhibited decreased sensitivity. Additionally, the serum levels of HSP60 and IGFBP-2 were indicated to be correlated with the presence of liver metastases, which is in contrast to CEA and Cancer antigen 19-9 (CA19-9). Patients with higher HSP60 and IGFBP-2 levels exhibited a significantly worse survival (P<0.001 and 0.007, respectively). The results of the current study indicate HSP60 to be an effective biomarker in patients with metastatic CRC, with it exhibiting an equal sensitivity to CEA. Additionally, HSP60 and IGFBP-2 levels also strongly correlated with extension of liver metastases and exhibited a prognostic value that contrasted that of CEA.

Serum levels of TIMP-1 and MMP-7 as potential biomarkers in patients with metastatic colorectal cancer.

OBJECTIVE: Tissue inhibitor of metalloproteinases 1 (TIMP-1) and matrix metalloproteinase 7 (MMP-7) were reported to have potent growth promoting activity. Lack of balance between MMPs and TIMPs is an important factor in the development of gastrointestinal malignancies. METHODS: We collected serum samples from 97 patients with metastatic colorectal cancer and 79 samples from healthy controls. Serum levels of TIMP-1 and MMP-7 were measured immunochemically and compared with standard tumor markers carcinoembryonic antigen and CA19-9. RESULTS: Serum levels of TIMP-1 and MMP-7 were significantly higher in patients with colorectal cancer compared to healthy controls (both, P < 0.001). TIMP-1 and MMP-7 correlate with the presence of colon involvement (P = 0.001; P = 0.012) and the presence of liver metastases (P = 0.002; P = 0.037), and negatively correlate with pulmonary metastases (P = 0.014; P = 0.005). MMP-7 had similar sensitivity and the same specificity as carcinoembryonic antigen. TIMP-1 and MMP-7 had better sensitivity than CA19-9. TIMP-1 and MMP-7 level correlate with worse outcome (P = 0.002). CONCLUSION: The results indicate that TIMP-1 and MMP-7 are effective biomarkers in patients with metastatic colorectal cancer with good sensitivity. TIMP-1 and MMP-7 levels strongly correlate with the extent of liver disease and have prognostic value.

Growth/differentiation factor 15 (GDF-15) as new potential serum marker in patients with metastatic colorectal cancer.

BACKGROUND: GDF-15 is a protein belonging to the transforming growth factor beta superfamily that has a role in regulating inflammatory and apoptotic pathways. High level GDF-15 in tumor tissues and plasma correlate with an increased risk of recurrence and reduced overall survival. OBJECTIVE: The aim of this study was to screen GDF-15 capacity to detecting metastatic CRC and compare it with standard tumor markers CEA and CA19-9. METHODS: We collected serum samples from 97 patients with metastatic colorectal cancer and 79 samples from healthy controls. Serum levels of GDF-15, CEA and CA19-9 were measured by immunochemically. A Kaplan-Meier curve was applied for analysis of survival rates, and a log-rank was used for univariate analysis. RESULTS: Serum levels of GDF-15 were significantly higher in patients with colorectal cancer compared to healthy controls (p< 0.001). In addition, serum levels of GDF-15 correlated with extent of liver involvement and patients with higher GDF-15 levels had significantly worse outcome (p< 0.0001). CONCLUSIONS: Our results show GDF-15 as an effective biomarker in patients with metastatic colorectal cancer with the same sensitivity as CEA. In addition, GDF-15 levels strongly correlate with extension of liver involvement in contrast with CEA.

28 day post-operative persisted hypercoagulability after surgery for benign diseases: a prospective cohort study.

BACKGROUND: Surgery for benign disease is associated with a low-risk of developing venous thromboembolism (VTE). Despite a relatively low incidence of postoperative VTE in patients after elective cholecystectomy and abdominal hernia repair there are data proving hypercoagulability in the early postoperative period. We focused on assessment of the systemic inflammatory response and coagulation status in these surgical patients after hospital discharge. METHODS: Prospectively, patients who underwent surgery for benign disease were included. Two hundred sixteen patients were enrolled - 90 patients in laparoscopic cholecystectomy (LC) group and 126 patients in hernia surgery (HS) group. Risk assessment of VTE according to the Caprini risk assessment model was performed in all patients. Prevalence of VTE in postoperative period was observed. Markers of systemic inflammatory response (IL-6, CRP, α-1-acid glycoprotein, transferrin) and coagulation markers (PLT, fibrinogen, prothrombin fragment F1 + 2 and D-dimer) were measured before surgery, on 7-10th postoperative day and on 28-30th postoperative day. RESULTS: Clinically apparent deep vein thrombosis was diagnosed in only one patient - 0.46%. Statistically significant elevation of inflammatory markers IL-6, CRP and α-1-acid glycoprotein (p < 0.001; all) were proved in both groups of patients on 7-10th postoperative day. Statistically significant elevation of coagulation markers PLT, fibrinogen, prothrombin fragment F1 + 2 and D-dimer (p < 0.001; all) were proved in LC and HS groups on 7-10th postoperative day. No statistical difference was observed in IL-6, CRP and α-1-acid glycoprotein levels a month after surgery as compared with preoperative levels within each group. Statistically significant elevation of fibrinogen and prothrombin fragment F1 + 2 levels (p < 0.001; both) persisted on 28-30th postoperative day in both groups. Persisted elevation of D-dimer levels was proved only in HS group (p < 0.001), not in LC group (p = 0.138), a month after surgery. CONCLUSIONS: Activated systemic inflammatory response and hypercoagulable condition were verified in patients after laparoscopic cholecystectomy and hernia surgery after their hospital discharge. Hypercoagulability persisted even a month after surgery. Nevertheless, we observed very low prevalence of clinically apparent VTE in patients with in-hospital postoperative VTE prophylaxis. TRIAL REGISTRATION: Trials of the Czech Ministry of Health No. RVO-VFN64165 and NT 13251-4 .

Premalignant and malignant lesions of the heterotopic pancreas in the esophagus: a case report and review of the literature.

Heterotopic pancreas is a congenital pathology of the gastrointestinal tract, particularly rare in the esophagus. Both symptomatology and findings during preoperative examinations are non-specific and therefore do not often lead to an accurate diagnosis, which is usually revealed only by histopathological assessment of a resected specimen. We report an unusual case of a patient suffering from severe dysphagia caused by heterotopic pancreas in the distal esophagus with chronic inflammation and foci of premalignant changes. This article also reviews 14 adult cases of heterotopic pancreas in the esophagus previously reported in the literature, with the aim of determining the clinical features of this disease and possible complications including rare premalignant lesions and malignant transformation. Especially with regard to those complications, we suggest that both symptomatic and incidentally found asymptomatic lesions should be resected.