Tumor grade as significant prognostic factor in pancreatic cancer: validation of a novel TNMG staging system.

Aim of the study was to asses the tumor grade prognostic value in the Czech pancreatic cancer patients and to evaluate the accuracy of TNMG prognostic model. Retrospective analysis of 431 pancreatic cancer patients undergoing pancreatic resection in seven Czech oncological centers between 2003 and 2013 was performed. The impact of tumor grade and the accuracy of TNMG prognostic model were evaluated. Lymph node status, tumor size, tumor stage and grade were proved as statistically significant survival predictors. The lower tumor differentiation (grade 3 and 4) was associated with poorer prognosis in all stages (stage I: HR 2.23 [1.14; 4.36, CI 95%] p=0.019, stage II: HR 3.09 [2.01; 4.77, CI 95%] p=0.001, stage III and IV: HR 3.52 [1.73; 7.18, CI 95%] p=0.001). Kaplan-Meier analysis verified statistically significant impact of new TNMG stages on survival after resection for pancreatic cancer (p=0.001). In conclusion, we can state that the tumor grade was confirmed as statistically significant prognostic factor in pancreatic cancer. Its incorporation into the current TNM classification enables more accurate prognosis prediction within particular clinical stages. That is why an inclusion of the grade to the standard TNM classification should be discussed.

[Current status regarding surgical treatment of pancreatic cancer in the Czech Republic]. / Aktuální stav chirurgické lécby karcinomu pankreatu v Ceské republice.

INTRODUCTION: The aim is to map the current situation in the surgical treatment of pancreatic cancer in the Czech Republic. This information has been obtained from surgical treatment providers using a simple questionnaire and by identifying the so called high volume centres. The information has been collected in the interest of organizing and planning research projects in the field of pancreatic cancer treatment. METHOD: We addressed centres known to provide surgical treatment of pancreatic cancer. A simple questionnaire formulated one question about the total number of pancreatic resections, also separately for the diagnoses PDAC - C25, in the last two years (2014 and 2015). Other questions focused on the use of diagnostic methods, neoadjuvant therapy, preoperative assessment of risks, the possibility of rapid intraoperative histopathology examination, Leeds protocol, monitoring of morbidity and mortality including long-term results, and the method of postoperative follow-up and treatment. ÚZIS (Institute of Health Information and Statistics of the Czech Republic) was addressed with a request to analyze the frequency of reported total numbers for DPE, LPE, TPE and to do the same with respect to diagnosis C 25 for the last two years, available for the entire Czech Republic (2013, 2014). RESULTS: Altogether 19 institutions were identified by the preceding audit, which reported more than 10 pancreatic resections annually; these institutions were addressed with the questionnaire. Sixteen institutions responded to the questions, 13 of them completely. CONCLUSION: The majority of potentially radical surgeries for PDAC in the Czech Republic are carried out at 6 institutions. All of the institutions that participated in the survey collect data about morbidity and mortality and monitor their results. KEY WORDS: pancreas cancer outcomes surgery.

The association between glutathione S-transferase gene polymorphisms and pancreatic cancer in a central European Slavonic population.

In the first case-control study on pancreatic cancer conducted on 253 cases and 403 controls in the Czech Republic we observed that the GSTP1-codon 105 Val variant allele and the GSTT1-null genotype were associated with an elevated risk for pancreatic cancer (OR = 1.38; 95%CI = 0.96-1.97 and OR = 1.56; 95%CI = 0.93-2.61, respectively). Combination of GSTT1-null and GSTP1-codon 105 Val variants further increased the risk for pancreatic cancer (OR = 2.50; 95%CI = 1.20-5.20). In conclusion, this study suggests population-specific associations of polymorphisms in key biotransformation genes with elevated risk for pancreatic cancer.

[Radical resection in patients with pancreatic head carcinomas. A retrospective survival analysis in a group of 307 subjects]. / Radikální resekce u nemocných s karcinomem hlavy pankreatu. Retrospektivní analýza prezívání u souboru 307 nemocných.

INTRODUCTION: The Czech Republic has the world's highest rates of pancreatic carcinomas. The pancreatic carcinoma is the fourth commonest cause of deaths due to malignancies, in our republic. Resection procedure is currently the only current treatment method, which has a curative potential and significantly prolongs a patient's life. AIM: To assess morbidity, mortality and survival of patients following radical and paliative procedures in the pancreatic head carcinoma patients. METHODS AND PATIENT GROUP: Only patients, who, based on the preoperative staging, were expected to require the following procedures, were indicated for surgery: I radical resection, i.e. stage I, II patients, 2 - palliative resection - i.e. stage III or IV patients, where no angioinvasion was detected preoperatively. Patients with peroperative detection of angioinvasion into the portomesenteric venous drainage area who required partial vein resection, were also included in the above subgroup. 3 - palliative bypass, where longer survival was expected. Radical resection included proximal pancreatoduodenectomy (PDE) with preservation of the pylorus according to Traverso-Longmire, with N1-2 lymphadenectomy and with reconstruction to an excluded jejunal loop. The same procedure was followed in cases of palliative resections. The collected data were statistically assessed using the Logrank test. From 05/1998 to 12/2006, a total of 307 patients with carcinomas of the pancreas and the Vater papila were treated. In 242 patients, the carcinoma was located within the pancreatic head, in 65 subjects, the pancreatic body and cauda were affected. Resection for the pancreatic head carcinoma was performed in 78 patients: 46 males, 32 females, the mean age was 63.5 y.o.a, with the median of 64 years. Bypass procedures were performed in 109 subjects and explorations in 55 subjects. RESULTS: Surgical procedures, with exception of 55 subjects who underwent exploration only, were performed in 187 subjects. Out of the total 78 PDEs, resections in stage I and II were performed in 22 subjects, in stage III in 41 subjects. In the group of 63 radical resection subjects, 2 subjects exited: the first one due to multiorgan failure, the second one for necrotizing postoperative pancreatitis. In the group of 15 palliative resections, 3 subjects exited. 10 patients died during the early postoperative period after palliative bypass procedures. A total of 15 subjects, i.e. 8%, exited during the early postoperative period. 5 subjects exited after resection procedures, i.e. 6.4%, 3% after radical resections. 3 subjects exited after palliative resections. Early complications were recorded in 44 subjects: pancreato-jejuno anastomosis insufficiency in 6 patients, insufficiency of hepaticojejunoanastomosis in 5 subjects, postoperative pancreatitis in 5 subjects, intraabdominal absces in 10 subjects, wounds infections with secondary healing in 19 subjects and cardiopulmonary complications in 33 subjects. In 19 subjects (43% of all complications), surgical revision was performed. Three-year survival rates were recorded in 60, resp. 29.5 and 39.5% of the patients in stage I, resp. II and III, while they were recorded in 15.6.% of the stage IVa subjects and only in 10.5% of the stage IVb subjects. There is a significant difference between survival rates of the stage I, II and III patients, compared to the stage IV patients (p < 0.005). There is no significant difference in the over- 3-years survival rates between the patients undergoing radical or palliative resections, however, the radical resection patients have significantly higher survival rates 3 months to 2 years postoperatively (p < 0.05). The radical resection subjects have significantly higher survival rates during the first 36 postoperative months, compared to the palliative resection and BDA subjects (p < 0.05). Comparison of sur vival rates in patients with radical or palliative resections is affected by a small number of the palliative resection subjects (n = 15), where no differences in survival rates were detected from the end of 9th postoperative month to the end of 3rd postoperative year. There is a significant difference in the survival rates between the resection and exploration subjects (p < 0.05). The survival rates differences between the subjects with palliative resections and BDAs cannot be evaluated in our study, due to nonhomogenity of the subjects. CONCLUSION: Radical PDEs for the pancreatic head carcinoma results in significantly longer survival of the subjects, compared to palliative bypasses. Stage I, II or III patients survive significantly longer, compared to those operated in stage IV.

Evaluation of clinical relevance of examining K-ras, p16 and p53 mutations along with allelic losses at 9p and 18q in EUS-guided fine needle aspiration samples of patients with chronic pancreatitis and pancreatic cancer.

AIM: To establish an optimum combination of molecular markers resulting in best overall diagnostic sensitivity and specificity for evaluation of suspicious pancreatic mass. METHODS: Endoscopic ultrasound (EUS)-guided fine needle aspiration cytology (FNA) was performed on 101 consecutive patients (63 males, 38 females, 60 +/- 12 years; 81 with subsequently diagnosed pancreatic cancer, 20 with chronic pancreatitis) with focal pancreatic mass. Samples were evaluated on-site by an experienced cytopathologist. DNA was extracted from Giemsa stained cells selected by laser microdissection and the presence of K-ras, p53 and p16 somatic mutations was tested by cycling-gradient capillary electrophoresis (CGCE) and single-strand conformation polymorphism (SSCP) techniques. In addition, allelic losses of tumor suppressor genes p16 (INK4, CDKN2A) and DPC4 (MADH4, SMAD4) were detected by monitoring the loss of heterozygosity (LOH) at 9p and 18q, respectively. RESULTS: Sensitivity and specificity of EUS-guided FNA were 75% and 85%, positive and negative predictive value reached 100%. The remaining 26% samples were assigned as inconclusive. Testing of molecular markers revealed sensitivity and specificity of 70% and 100% for K-ras mutations (P < 0.001), 24% and 90% for p53 mutations (NS), 13% and 100% for p16 mutations (NS), 85% and 64% for allelic losses at 9p (P < 0.001) and 78% and 57% for allelic losses at 18q (P < 0.05). When tests for different molecular markers were combined, the best results were obtained with K-ras + LOH at 9p (92% and 64%, P < 0.001), K-ras + LOH at 18q (92% and 57%, P < 0.001), and K-ras + LOH 9q + LOH 18q (96% and 43%, P < 0.001). When the molecular markers were used as complements to FNA cytology to evaluate inconclusive samples only, the overall sensitivity of cancer detection was 100% in all patients enrolled in the study. CONCLUSION: EUS-guided FNA cytology combined with screening of K-ras mutations and allelic losses of tumor suppressors p16 and DPC4 represents a very sensitive approach in screening for pancreatic malignancy. Molecular markers may find its use particularly in cases where FNA cytology has been inconclusive.

[Prediction of treatment outcome after adjuvant loco-regional chemotherapy following liver resection for colorectal metastases--preliminary results]. / Predikce lécebné odpovedi na adjuvantní lokoregionální chemoterapii po resekci jater pro metastázy kolorektálního karcinomu--predbezné vysledky.

INTRODUCTION AND AIM OF STUDY: Czech Republic leads the worldwide league in colorectal cancer's occurrence. Colorectal liver metastases are detected in about a half of patients with colorectal cancer. Liver resection of colorectal metastases is currently the only potentially curative treatment with a chance for a long-term survival rate. Until now there has remained a question of whether adjuvant HAIC can improve the treatment results of radical resection. The aim of our study is to verify predictive efficiency of thymidylátsyntasis (TS), dihydropyrimidindehydrogenasis (DPD) and thymidinfosforylasis (TP) in patients undergoing adjuvant hepatic artery infusion chemotherapy (HAIC) following radical liver resection for colorectal metastases. METHODS: From 1990 to 2005 80 patients underwent 84 liver resections for colorectal metastases. R0 resection was achieved in 60 events. Ten patients who underwent R0 resection both for primary cancer and for colorectal liver metastases and who were given portcatheter for HAIC were included in this study. Adjuvant chemotherapy contained 5-fluorourycil (1200 mg/m2) combined with oxyliplatinum and leukovorin. Whole dose was administered via hepatic artery. The samples were procured both from healthy liver tissue and from metastases for imunohistochemical and molecular biological analysis. RESULTS: The recurrence of disease was verified in 2 of 10 included patients (20%). We detected neither occurrence of death nor serious complication in early postoperative course in none of ten patients. Low expression of TS was found in both events and very high expression of DPD in one event was detected. DISCUSSION: High expression of DPD in one of these patients could contribute to lower outcome of adjuvant chemotherapy. Low expression of TS in both patients responds to the written statement regarding contribution of adjuvant chemotherapy only in patients with high TS level. CONCLUSION: The expression of TS and DPD responds to expected outcome of HAIC. Low number of patient does not permit statistic evaluation.

[Sonography and angiography in the investigation of space-occupying lesions of the kidney (author's transl)]. / Sonographie und Angiographie bei der Suche nach raumfordernden Prozessen der Nieren.

The results of angiography and sonography in 132 patients suspected of having a space-occuping lesion in a kidney were compared; they were examined by excretion urography, ultrasound and renal angiography. All lesions demonstrated angiographically had already been seen by ultrasound. Difficulties were experienced with cysts of less than 3 cm. Diameter situated in the region of the hilum, which did not always produce echo-free images. Infected renal cysts appeared as avascular space-occupying lesions on angiography, but showed echoes on sonography.

[The effect of contrast volume on the radiographic demonstration of the gall bladder and bile duct (author's transl)]. / Einfluss der Kontrastmittelmenge auf die Darstellungsqualität der Gallenblase und des Choledochus im Röntgenbild.

No differences could be detected subjectively in the quality of cholangiograms after the use of varying amounts of contrast medium (20 and 30 ml iodoxaminic acid). Pharmacolinetic data which would indicate the use of either quantity are not available. Densitometric measurements carried out by us showed no significant statistical difference between the results of using 20 or 30 ml iodoxaminic acid.

[Broncho-vascular branching in the sub-segment (author's transl)]. / Uber bronchovaskuläre Verästelungen im Subsegmentbereich

The three pulmonary branching systems in the sub-segment have been studied by making casts. A comparison between them shows considerable differences between the vascular systems and the air passages. The bronchi show two types of branching: we can distinguish between irregular, dichotomous acute angled branching and predominantly regular dichotomous, wide-angled branching. The second type is often found in the bifurcations of large vessels and bronchi in the lung centre, where the lung parenchyma is made to fit into a confined space. Branching of the bronchi is very different from that of the vessels. The characteristic features of the latter are that the lateral branches are more numerous but smaller than the corresponding bronchi and show less contact with the lung periphery.

[Serial observations of a pulmonary echinococcus, with rupture into the bronchial system (author's transl)]. / Verlaufsbeobachtungen eines Lungenechinokokkus mit Einbruch in das Bronchialsystem

The radiological course of an echinococcus cyst of the lung before and after rupture is described, together with the cytological and histological findings. The resultant tissue changes and appropriate treatment (lobectomy) are discussed. In the presence of the appropriate radiological changes, eosinophil granulocytes in the sputum suggest cyst rupture, even in the absence of echinococcus tissue. However, bronchial asthma or Löffler's infiltrates should be excluded clinically. They delayed appearance of peripheral blood eosinophilia after cyst rupture and the development of an eosinophilic broncho-pneumonia is noteworthy.