Minimally-invasive pancreatic surgery in high volume centers in the Czech Republic - current status and possible implementations.

INTRODUCTION: Minimally-invasive surgical methods have been becoming ever more common also in the segment of pancreatic surgery. The aim of this paper was to analyze the current state of minimally-invasive surgery in the Czech Republic and the justification and potential of implementing such procedures. METHODS: Analysis of high volume centers using healthcare providers´ and payers´ data. RESULTS: Thirteen pancreatic surgical centers meet the proposed criteria for being called a high volume center - a center of highly specialized care in pancreatic surgery based on the annual number of at least 17 major resections of the pancreas. According to data from healthcare payers, laparoscopy was used in 0.6%-65.7% of procedures in individual centers. However, these are not resection procedures. The centers themselves report a significantly smaller number of minimally-invasive pancreatic resection procedures. The actual numbers of minimally-invasive resection procedures in the current system are practically impossible to verify. The potential for implementing minimally-invasive pancreatic surgery in the Czech Republic can be estimated based on the identification of candidate patients. CONCLUSION: Due to the fragmentation of this operative segment, its costs and small numbers of patients suitable for minimally-invasive pancreatic surgery even among high volume centers, the implementation rate of these methods is very slow. The need to centralize this segment of care appears to be very urgent from all points of view.

Correlation of survival length after pancreaticoduodenectomy for pancreatic head adenocarcinoma depending on tumor characteristics detected by means of computed tomography and resection margins status.

Pancreatic carcinoma is an aggressive tumor with a grim prognosis. Accurate staging is essential for indicating surgery in patients with borderline resectable tumors. This paper examines the correlation between pre-operation characteristics of tumors found on CT, infiltration of individual resection margins as confirmed by a pathologist, and the survival of patients with resectable pancreatic head ductal adenocarcinoma. This prospective cohort study involved patients operated on for pancreatic head adenocarcinoma, which was clearly resectable based on the staging CT and intraoperative observation between 2011-2014. Only patients without postoperative complications who underwent adjuvant chemotherapy were analyzed. Seventy-nine patients were assessed, of which 16 (20.3%) had R0 resection and 63 (79.7%) had R1 resection. Patients with R1 results had up to 2.7 times higher risk of death than patients with R0 resection. We found a trend towards shorter survival associated with a closer relationship of the tumor to the superior mesenteric vein/portal vein (SMV/PV) wall in the pre-operation CT examination. Patients with a tumor interface between the vein wall of up to 180 ° circumference had up to 1.97 times higher risk of death than patients without (p=0.131). The results of our work confirmed that in our center, even surgically treated, clearly resectable pancreatic head tumors still have a high occurrence of positive surgical margins (R1 resection) and that tumors with R1 resection had statistically significantly reduced survival compared to R0 resection. A trend for shorter overall survival was found after tumor resection depending on the increasing interface between the tumor and the SMV/PV wall, but this result was not statistically significant.

Radiofrequency ablation in pancreatic cancer.

INTRODUCTION: Clinical study evaluating the impact of intraoperative radiofrequency ablation in pancreatic cancer. METHODS: Patients with histologically proved pancreatic cancer were included. Two groups were defined. In the RFA group (n=24) intraoperative RFA of the pancreatic tumour was performed. In the control group (n=24) only the bypass procedure was indicated (gastroenteric and hepaticojejunal anastomosis). No patient received neoadjuvant chemotherapy. Three-month morbidity and mortality, overall survival, quality of life, pain relief and radiological response were studied. RESULTS: Overall three-month morbidity and mortality were 41.7% and 8.3%, respectively. RFA related morbidity and mortality reached 16.6% and 8.3%, respectively. The overall median survival time was 9.9 and 8.3 months in the RFA group and in the control group, respectively. The survival difference was not of statistical significance (p=0.758). QoL improvement after RFA was not proved. There was no statistically significant analgesic effect of RFA. Postoperative CT scan assessed as per RECIST criteria displayed progressive disease, stable disease, partial response and complete response in 41.6%, 45.8%, 8.3% and 0% cases, respectively. CONCLUSION: Intraoperative RFA of locally advanced and metastatic pancreatic cancer is a feasible palliative method. A survival benefit of this method remains doubtful, even though some positive results have been achieved in patients with localized, well-differentiated tumours. Although RFA was not associated with any impairment of the quality of life, no convincing evidence of a positive impact thereof on QoL was shown, either, during the three-month postoperative period. Pain relief was not achieved during the first 3 months after RFA.

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.

Hedgehog pathway overexpression in pancreatic cancer is abrogated by new-generation taxoid SB-T-1216.

The Hedgehog pathway is one of the major driver pathways in pancreatic ductal adenocarcinoma. This study investigated prognostic importance of Hedgehog signaling pathway in pancreatic cancer patients who underwent a radical resection. Tumors and adjacent non-neoplastic pancreatic tissues were obtained from 45 patients with histologically verified pancreatic cancer. The effect of experimental taxane chemotherapy on the expression of Hedgehog pathway was evaluated in vivo using a mouse xenograft model prepared using pancreatic cancer cell line Paca-44. Mice were treated by experimental Stony Brook Taxane SB-T-1216. The transcript profile of 34 Hedgehog pathway genes in patients and xenografts was assessed using quantitative PCR. The Hedgehog pathway was strongly overexpressed in pancreatic tumors and upregulation of SHH, IHH, HHAT and PTCH1 was associated with a trend toward decreased patient survival. No association of Hedgehog pathway expression with KRAS mutation status was found in tumors. Sonic hedgehog ligand was overexpressed, but all other downstream genes were downregulated by SB-T-1216 treatment in vivo. Suppression of HH pathway expression in vivo by taxane-based chemotherapy suggests a new mechanism of action for treatment of this aggressive tumor.

[Confocal Laser Endomicroscopy in the Diagnostics of Malignancy of the Gastrointestinal Tract]. / Konfokální laserová mikroskopie v diagnostice onkologických onemocnení gastrointestinálního traktu.

In confocal laser endomicroscopy (CLE), a type of optical microscope that uses a laser beam as its light source and processes the acquired image by processor unit is used. Although the principle behind the device has been known since 1957, its use in clinical practice has only recently been enabled by technical developments, and it is therefore a relatively new modality in differential diagnosis. CLE enables real-time microscopic imaging of the tissue under investigation and in fact non-invasive in vivo biopsy. First experiences with CLE have primarily been obtained in the field of endoscopy, in particular in the pathology of the esophagus, stomach, bile duct, pancreas, and colon. Further to its use in endoscopy, CLE was recently developed for perioperative use, with the most experience gained in neurological, breast, and prostate surgery. Numerous prospective randomized trials have confirmed the benefits of CLE in tumor screening, differential diagnosis of tumors or inflammatory diseases, earlier diagnostics of diseases, and reducing the number of required endoscopic examinations. In addition, CLE is associated with minimal side effects. A known possible side effect is allergy to the fluorescein used to stain tissues during the examination. Extending of endoscopic examination or surgery is minimal in the hands of trained personnel. Current limiting factors of CLE include insufficient clinical experience, the price of the CLE device and probes, and the subjectivity inherent in the evaluation of microscopic images by the endoscopist or surgeon. This article summarizes published studies of CLE in the diagnostics of oncological diseases of the gastrointestinal tract.Key words: confocal microscopy - gastrointestinal tract - neoplasms The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 9. 2. 2017Accepted: 26. 2. 2017.

[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.

[Standardization of pancreatic cancer specimen pathological examination]. / Standardizace patologického vysetrení resekátu pankreatu.

INTRODUCTION: The frequency of R1 resections for pancreatic cancer in studies where a non-standardized protocol of pathological evaluation of the specimen is used varies from 17 to 30%. The aim of our study is to apply the standardized (so-called Leeds) protocol of resected pancreatic specimen pathological examination, and to evaluate the frequency of R1 resections for pancreatic cancer using this new protocol. MATERIAL AND METHODS: Ninety-one patients who underwent pancreatoduodenectomy for pancreatic cancer were included in the study. This group was divided into two subgroups: patients examined by the Leeds protocol (n=20) and those examined by a non-standardized pathological protocol (n=71). The R1 resection rate was evaluated separately in each group. The positivity rate of every individual resection margin was specified in the Leeds protocol group. The correlation of R1 resection rate and "tumour - resection margin distance" parameter was evaluated. The tumour infiltration of peripancreatic adipose tissue was assessed in the non-standardized group. RESULTS: In the Leeds protocol subgroup, R1 and R0 resection rate was 60% (12/20) and 40% (8/20), respectively. Resection line positivity rates were as follows: dorsal 45% (9/20), ventral 35% (7/20), VMS 20% (4/20), cervical 20% (4/20), AMS 15% (3/20). The correlation between the tumour - resection line distance and R1 resection frequency was the following: direct infiltration 30% R1, tumour-resection margin border 0.5 mm 50% R1, 1mm 60%, 1.5 mm 75% R1, 2 mm 80% R1, >2 mm 80% R1. If the criterion of resection line positivity ( 1mm) was set, the R1 resection rate difference between the two groups was of statistical significance. In the subgroup where the non-standardized protocol was used (n=71), R1 resection was recorded in 25 (35.2%) patients. The main cancer-positive areas were peripancreatic adipose tissue in 26.8% (19/71) of cases, and VMS, AMS or retroperitoneal line in 8.5% (6/71), respectively. R0 resection was achieved in 46 (64.8%) patients. The statistically significant (p=0.046) difference in R0 and R1 resection rates was detected (Leeds protocol and non-standardized one: R0 40.0% vs. 64.8% and R1 60.0% vs. 35.2%, respectively) in the studied groups. CONCLUSION: The rate of R1 resections for pancreatic cancer increased in all studies, including ours, where the standardized (Leeds) protocol of pancreatic specimen pathological examination was used. The higher R1 resection rate when using the Leeds protocol is approaching to the local recurrence rate of pancreatic cancer. Therefore, the Leeds protocol can provide more realistic evaluation of local radicality of pancreatoduodenectomy and can also offer more accurate evaluation of the surgical and adjuvant therapy of pancreatic cancer.

[Radiofrequency ablation of pancreatic neuroendocrine tumor]. / Radiofrekvencní ablace neuroendokrinního nádoru pankreatu.

BACKGROUNDS: Pancreatic neuroendocrine tumors (PNETs) include a broad range of neoplasms spanning from relatively benign to malignant. Radical resection has been advocated as the only curative method. Debulking (R2) resection can be indicated for locally unresectable PNETs. Debulking surgery improves the quality of life and prolongs overall survival. The disadvantages of this approach include bleeding, pancreatic fistula and tumor spread. No alternative method that would eliminate these complications has been published yet. Considering the encouraging results of the studies describing radiofrequency ablation (RFA) of locally advanced pancreatic cancer, a question arises, whether it might be possible to use RFA as a R2 resection alternative in PNETs. CASE: A 73-year-old gentleman had been admitted due to abdominal pain and hyperglycaemic syndrome. Contrast-enhanced CT showed a tumor of pancreatic head invading portal vein (PV) and superior mesenteric vein (VMS). A surgery was indicated on the basis of EUS-guided FNAB that verified a PNET of uncertain biological behaviour. The surgery confirmed a locally advanced tumor of pancreatic head invading the PV and SMV. Due to the polymorbidity, radical pancreatoduodenectomy with SMV resection was not indicated. Because of the presence of symptoms, RFA of the PNET using ValleyLab generator with cooltip cluster electrode, was performed. Postoperative course was uneventful. Final immunohistochemical examination verified a well-differentiated grade 1 PNET. The patient was regularly monitored during a three-year follow-up. The quality of life was evaluated using standardized EORT QLQ-30 questionnaire. Pain was assessed by a ten-point visual analogue scale (VAS). Ablated area was evaluated annually by contrast-enhanced CT. Postoperatively, abdominal pain ceased (pain decrease from 2 to 0 on VAS). Insulin dose was reduced from 46 IU (international units) to 20 IU of Humulin-R per day. CT verified tumor regression according to RECIST (response evaluation criteria in solid tumors). During the three-year follow-up, no local progression or tumor dissemination was observed. CONCLUSION: We present the first case report of a patient with locally advanced symptomatic pancreatic neuroendocrine tumor successfully treated by intraoperative radiofrequency ablation. More clinical studies are needed to evaluate the clinical relevance of this cytoreductive method in the PNET indication.

Ampullary tumours (ampullomas) in the elderly--an interdisciplinary problem.

BACKGROUND & OBJECTIVES: Ampullary cancer is one of the periampullary tumours with better prognosis, but relapses occur early in some patients. This study was carried out to assess whether pancreatoduodenectomy (PDE, Whipple operation) could be a safe therapeutic procedure for elderly patients with periampullary tumours. METHODS: Between 2005 and 2007, 19 patients (12 male, 7 female) aged over 65 yr (range 66 and 83 yr) with diagnosis of ampulloma were operated. RESULTS: Of the 19 patients, 6 underwent local surgical ampullectomy with reinsertion of ductus choledochus and Wirsungi's duct for benign or early cancer lesion and 13 underwent PDE (Whipple operation). Of these 13, only one was in T1 stage, one was in T4 stage, two patients were T3 and the rest in T2 stage. Lesion of lymphatic system had 40 per cent of patients in T2 stage and all in T3 and T4 stages. One patient died of pulmonary embolism several days after operation. Post-operative complications occurred in 3 cases: 1 patient with partial dehiscence of gastroenteroanastomosis - treated by conservative approach, 2 patients with dehiscence of pancreatojejunoanastomosis. INTERPRETATION & CONCLUSIONS: Diagnosis and therapy of ampullary tumours is multimodal. With careful patient selection, PDE can be performed in elderly people (>65 yr) safely. The post-operative morbidity in this group is essentially influenced by their multi-morbidity.

Analysis of Blood Plasma MicroRNAs to Enable Identification of Patients with Pancreatic Ductal Adenocarcinoma Who Will Benefit from Surgical Resection

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is the most common malignancy of pancreas, characterized by extremely poor prognosis largely due to problem with early diagnosis and lack of progress in personalization of therapy. Of all available treatment strategies, radical surgical resection of the tumour in its early stage remains the only possibility how to reach long-term survival. However, even a technically perfect surgical resection may still not provide a survival benefit for all PDAC patients. Appropriate selection of patients for surgical resection is one the important medical needs in management of PDAC patients. MATERIAL AND METHODS: To this study we enrolled 24 PDAC patients who underwent surgical resection and preoperatively collected their blood plasma specimends. Patients were divided into to two prognostic groups according to their overall survival - 12 patients with poor prognosis (median overall survival 10 months) and 12 patients with good prognosis (median overall survival 25 months). Small RNA sequencing technology was applied to screen for microRNAs (miRNA) with differential levels between both PDAC patients group. cDNA libraries were prepared using QIAseq miRNA Library Kit (Qiaqen) and sequencing by NextSeq500 instrument (Illumina). RESULTS: When miRNA expression profiles of the PDAC patients from good and poor prognostic groups were compared, 61 miRNAs were identified to have significantly different plasma levels between the two groups (p < 0.05). A total of 21 miRNAs showed increased expression and 40 miRNAs showed decreased expression in a group of patients with poor prognosis compared to patients with good prognosis. CONCLUSION: This study demonstrated differences in miRNA expression profiles in preoperative plasma specimens of PDAC patients with short and long overall survival. Our observations indicate that after independent validations plasma miRNAs might become useful biomarkers for identification of PDAC patients having clinical benefit from surgical resection of the tumour. This work was supported by Czech Ministry of Health, grant No. 16-31314A. All rights reserved. The authors declare they have no potential confl icts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. Submitted: 8. 3. 2019 Accepted: 9. 3. 2019.

[Outcomes of pancreatic resections in the elderly and geriatric patients]. / Výsledky resekcní lécby pankreatu u starsích a geriatrických pacientu.

As a result of the population aging, we are confronted with the problematics of geriatric patients more and more frequently. The aim of this retrospective study was to compare outcomes of pancreatic resections in patients of three different age groups. During 2000-2007, 150 pancreatic resections were performed in our clinic, including 34 (22.7%) patients aged 65 and over at the time of the procedure and 5 (3.3%) patients over 75 y.o.a. The procedures were heterogenous, including indications for oncologic diagnoses, as well as for chronic pancreatitis. Our assessment demonstrated no significant differences in the 30-day postoperative mortality between the group of subjects over 65 y.o.a, geriatric group (i.e. over 75 y.o.a) and the group of subjects below 54 y.o.a. (8.8% vs. 0% vs. 5.2%). Furthermore, the postoperative morbidity showed no statistically significant differences between the all three groups (30.2% vs. 29.4% vs. 20%). The commonest postoperative complications included secondary healing of the surgical wound (7.8%) and pancreatic fistules (6.9%) in the group of subjects below 65 y.o.a., and insufficiency of the pancreatic-jejunal anastomosis (5.8%) and hepatic- jejunal anastomosis (5.88%) in the group aged 65 and over. Pancreatic-jejunal anastomosis insufficiency, complicated by consecutive bleeding, contributed to postoperative mortality most significantly. Significant increase in postoperative complication rates connected to proximal pancreatoduodenectomies and total pancreatoduodenectomies, was recorded in patients over 65, compared to those in the young patient group (p = 0.014). No statistically significant relation was found between a particular comorbidity and onset of postoperative complications or deaths in patients over 65 or geriatric patients. Based on the results, the authors do not consider the patient's age a contraindication for pancreatic resection procedures. Radical resections can be performed with acceptable mortality and morbidity rates in geriatric patients.

[Radiofrequency ablation (RFA) of pancreatic tumors]. / Radiofrekvencní ablace tumoru pankreatu.

UNLABELLED: The authors refer about their first experience with radiofrequency ablation of locally advanced pancreatic tumors. They put forward the prospective study of five patients (four with ductal adenocarcinoma of the head and one with malignant neuroendocrine tumor of pancreatic body), who either because of local advanced disease or performance status, were not able to undergo radical curative surgery. All patients underwent peroperative radiofrequency ablation of pancreatic tumors. In the case of pancreatic head localization, posterior retrocolic gastro-enterostomy and hepatico-jejunostomy to Y Roux jejunal loop were performed. There was no perioperative mortality. In one case duodenal leak apeared in the fourth postoperative day. This was healed conservatively by drainage. At one patient the subfascial absces developed. This was solved by drainage reoperation at the fourteenth postoperative day. After consolidation, all patients were released to home care. CONCLUSION: According to our early experience, radiofrequency ablation of inoperable pancreatic tumors is relatively save cytoreductive procedure.