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Pancreatic Neoplasms: HELP
Articles from Czech Republic
Based on 146 articles published since 2008
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These are the 146 published articles about Pancreatic Neoplasms that originated from Czech Republic during 2008-2019.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4 · 5 · 6
1 Review The Use of Biomarkers in Early Diagnostics of Pancreatic Cancer. 2018

Kunovsky, Lumir / Tesarikova, Pavla / Kala, Zdenek / Kroupa, Radek / Kysela, Petr / Dolina, Jiri / Trna, Jan. ·Department of Gastroenterology, University Hospital Brno Bohunice, Faculty of Medicine, Masaryk University, Czech Republic. · Department of Surgery, University Hospital Brno Bohunice, Faculty of Medicine, Masaryk University, Czech Republic. · Department of Internal Medicine, Hospital Boskovice, Czech Republic. ·Can J Gastroenterol Hepatol · Pubmed #30186820.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal solid malignancies with increasing incidence. The poor prognosis is due to the aggressive nature of the tumor, late detection, and the resistance to chemotherapy and radiotherapy. A radical surgery procedure is the only treatment that has been shown to improve the 5-year survival rate to 20-25%. However, the majority of patients (80-85%) are diagnosed with locally advanced or metastatic disease and just 15-20% patients are diagnosed in an early stage allowing them to undergo the potentially curative surgical resection. The early detection of PDAC without the use of invasive methods is challenging and discovery of a cost-effective biomarker with high specificity and sensitivity could significantly improve the treatment and survival in these patients. In this review, we summarize current and newly examined biomarkers in early PDAC detection.

2 Review Different clinical presentations of metachronous pulmonary metastases after resection of pancreatic ductal adenocarcinoma: Retrospective study and review of the literature. 2017

Lovecek, Martin / Skalicky, Pavel / Chudacek, Josef / Szkorupa, Marek / Svebisova, Hana / Lemstrova, Radmila / Ehrmann, Jiri / Melichar, Bohuslav / Yogeswara, Tharani / Klos, Dusan / Vrba, Radek / Havlik, Roman / Mohelnikova-Duchonova, Beatrice. ·Department of Surgery I, University Hospital Olomouc and Faculty of Medicine and Dentistry, Palacky University, 77520 Olomouc, Czech Republic. · Department of Oncology, University Hospital Olomouc and Faculty of Medicine and Dentistry, Palacky University, 77520 Olomouc, Czech Republic. · Department of Molecular Pathology, Faculty of Medicine and Dentistry, Palacky University Olomouc, University Hospital Olomouc, 77520 Olomouc, Czech Republic. · Department of Oncology, Faculty of Medicine and Dentistry, Palacky University Olomouc, University Hospital Olomouc, 77520 Olomouc, Czech Republic. · Department of Surgery I, Faculty of Medicine and Dentistry, Palacky University, 775220 Olomouc, Czech Republic. ·World J Gastroenterol · Pubmed #29085191.

ABSTRACT: AIM: To analyze pancreatic cancer patients who developed metachronous pulmonary metastases (MPM) as a first site of recurrence after the curative-intent surgery. METHODS: One-hundred-fifty-nine consecutive pancreatic ductal adenocarcinoma (PDAC) patients who underwent radical pancreatic surgery between 2006 and 2013 were included in this retrospective analysis. The clinical data including age, sex, grade, primary tumor location, pTNM stage, lymph node infiltration, microangioinvasion, perineural invasion, lymphovascular invasion, the therapy administered, and follow-up were all obtained from medical records. Further analysis covered only patients with metachronous metastases. Clinical and histopathological data (age, sex, grade, primary tumor location, pTNM stage, lymph node infiltration, microangioinvasion, perineural invasion, lymphovascular invasion, the therapy administered and follow-up) of patients with metachronous non-pulmonary metastases and patients with metachronous pulmonary metastases were statistically assessed. Disease-free survival (DFS) from pancreas resection until metastases onset and overall survival (OS) were calculated. Wilcoxon test, χ RESULTS: Metachronous pulmonary metastases were observed in 20 (16.9%) and were operable in 3 (2.5%) of PDAC patients after a prior curative-intent surgery. Patients with isolated pulmonary metastases (oligometastases and multiple metastases) had estimated prior DFS and OS of 35.4 and 81.4 mo, respectively, and those with metachronous pulmonary metastases accompanied by other metastases had prior DFS and OS of 17.3 and 23.4 mo, respectively. Patients with non-pulmonary metastases had prior DFS and OS of 9.4 and 15.8 mo, respectively. Different clinical scenarios according to the presentation of MPM were observed and patients could be divided to three subgroups with different prognosis which could be used for the selection of treatment strategy: isolated pulmonary oligometastases, isolated multiple pulmonary metastases and pulmonary metastases accompanied by other metastases. CONCLUSION: Surgery should be considered for all patients with isolated pulmonary oligometastases, but the risk of intervention has to be individually weighted for each patient.

3 Review Current challenges in optimizing systemic therapy for patients with pancreatic cancer: expert perspectives from the Australasian Gastrointestinal Trials Group (AGITG) with invited international faculty. 2017

Segelov, Eva / Lordick, Florian / Goldstein, David / Chantrill, Lorraine A / Croagh, Daniel / Lawrence, Ben / Arnold, Dirk / Chau, Ian / Obermannova, Radka / Price, Timothy Jay. ·a Department of Oncology , Monash Medical Centre and Monash University , Melbourne , Australia. · b Department of Oncology, University Cancer Center Leipzig , University Medicine Leipzig , Leipzig , Germany. · c Department of Oncology, Nelune Cancer Centre , Prince of Wales Hospital and University of New South Wales , Sydney , Australia. · d Department of Oncology , The Kinghorn Cancer Centre and University of Western Sydney , Sydney , Australia. · e Department of Oncology , University of Auckland , Auckland , New Zealand. · f Department of Oncology , Instituto CUF de Oncologia , Lisbon , Portugal. · g Department of Oncology , Royal Marsden Hospital , London & Surrey , UK. · h Department of Comprehensive Cancer Care , Masaryk Memorial Cancer Institute , Brno , Czech Republic. · i Queen Elizabeth Hospital and Lyell McEwin Hospital , Adelaide , Australia. ·Expert Rev Anticancer Ther · Pubmed #28817982.

ABSTRACT: INTRODUCTION: Despite recent progress, the outlook for most patients with pancreatic cancer remains poor. There is variation in how patients are managed globally due to differing interpretations of the evidence, partly because studies in this disease are challenging to undertake. This article collates the evidence upon which current best practice is based and offers an expert opinion from an international faculty on how latest developments should influence current treatment paradigms. Areas covered: Optimal chemotherapy for first and subsequent lines of therapy; optimal management of locally advanced, non-metastatic cancer including the role of neoadjuvant chemo(radio)therapy, current evidence for adjuvant chemotherapy, major advances in pancreatic cancer genomics and challenges in supportive care particularly relevant to patients with pancreatic cancer. For each section, literature was reviewed by comprehensive search techniques, including clinical trial websites and abstracts from international cancer meetings. Expert commentary: For each section, a commentary is provided. Overall the challenges identified were: difficulties in diagnosing pancreatic cancer early, challenges for performing randomised clinical trials in all stages of the disease, some progress in systemic therapy with new agents and in identifying molecular subtypes that may be clinically relevant and move towards personalized therapy, but still, pancreatic cancer remains a very poor prognosis cancer with significant palliative care needs.

4 Review Early detection of sporadic pancreatic cancer: time for change. 2017

Frič, Přemysl / Šedo, Aleksi / Škrha, Jan / Bušek, Petr / Laclav, Martin / Škrha, Pavel / Zavoral, Miroslav. ·aDepartment of Medicine/Gastroenterology, Military University Hospital bInstitute of Biochemistry and Experimental Oncology cLaboratory of Endocrinology and Metabolism, General University Hospital, First Faculty of Medicine dSecond Department of Medicine, University Hospital, Third Faculty of Medicine, Charles University, Prague, Czech Republic. ·Eur J Gastroenterol Hepatol · Pubmed #28471824.

ABSTRACT: Sporadic pancreatic cancer amounts to ∼90% of all pancreatic cancers. It is a gloomy depressive disease and the most recalcitrant malignancy, with a very low 5-year survival (3-6%). At present, diagnostic methods are commonly applied, as used half a century ago, after the appearance of local and systemic symptoms (abdominal and back pain, cholestasis, painless jaundice, fatigue, anorexia, weight loss, anemia, peripheral phlebitis, and cachexia). Unfortunately, these symptoms are harbingers of an advanced disease. The subsequent imaging methods may offer additional information on the location, size, and morphology of the lesion, but they do not influence the prognosis. Radical surgery may be offered to 15-20% of patients. The relapses after surgery are frequent and chemotherapy may be palliative. Preventive programs represent the only possibility of improvement. We propose the first multistep and multidisciplinary preventive program for early detection of sporadic pancreatic cancer for the differential identification of average-risk patients who probably have the disease from those who do not.

5 Review Precursors of pancreatic cancer. 2017

Frič, Přemysl / Škrha, Jan / Šedo, Aleksi / Bušek, Petr / Laclav, Martin / Bunganič, Bohuš / Zavoral, Miroslav. ·aGastroenterology Unit, Department of Medicine, Military University Hospital bLaboratory of Endocrinology and Metabolism cInstitute of Biochemistry and Experimental Oncology, First Faculty of Medicine, General University Hospital, and Charles University, Prague, Czech Republic. ·Eur J Gastroenterol Hepatol · Pubmed #28009716.

ABSTRACT: Pancreatic cancer (PC) behaves very differently in comparison with other malignancies. Its incidence has been increasing continuously; mortality has not decreased, the diagnosis is frequently late, radical surgery is performed only in 15-20% of patients, and chemotherapy is only palliative. PC occurs in three different forms. Sporadic PC accounts for 90% of all PCs. Its most frequent form is the pancreatic ductal adenocarcinoma. The remaining 10% constitute two minority groups: familial PC (7%) and PC as a manifestation of a genetic cancer syndrome (3%). PCs are preceded by a precancerous lesion (precursor). At present, six different precursors are known. They have different histomorphological characteristics and malignant potential. The recognition and correct interpretation of individual precursors influences adequate clinical decision-making. The publication surveys the present knowledge of individual precursors and their role in the early pancreatic carcinogenesis.

6 Review Early detection of pancreatic cancer: impact of high-resolution imaging methods and biomarkers. 2016

Frič, Přemysl / Škrha, Jan / Šedo, Aleksi / Zima, Tomaš / Bušek, Petr / Kmochová, Klára / Laclav, Martin / Bunganič, Bohuš / Solař, Svatopluk / Hrabal, Petr / Bělina, František / Záruba, Pavel / Škrha, Pavel / Zavoral, Miroslav. ·Departments of aMedicine/GastroenterologybPathologycSurgery, Military University HospitaldLaboratory of Endocrinology and MetabolismeInstitute of Biochemistry and Experimental OncologyfInstitute of Clinical Biochemistry and Laboratory Diagnostics, General University Hospital, 1st and 2nd Faculty of MedicinegDepartment of Medicine, 3rd Faculty of Medicine, Charles University, Prague, Czech Republic. ·Eur J Gastroenterol Hepatol · Pubmed #27769077.

ABSTRACT: High-resolution imaging methods (HRIMs) and biomarkers present the second step of pancreatic cancer (PC) diagnostics in at-risk individuals. These include patients with positive risk factors, early symptoms, nonresponders to the initial antidiabetic therapy, patients older than 50 years of age with new-onset unstable diabetes requiring insulin as well as patients with long-term insulin-non-dependent diabetes and recent (up to 6 months) failure of antidiabetic therapy. The procedures should be started without delay and the co-operation between the primary and tertiary medical centers is highly desirable. An early indication of HRIMs and biomarkers is a prerequisite for the diagnosis of a resectable PC. This publication reviews the recent contribution of HRIMs and biomarkers toward an early diagnosis of PC.

7 Review Therapeutic potential of taxanes in the treatment of metastatic pancreatic cancer. 2016

Lemstrova, Radmila / Melichar, Bohuslav / Mohelnikova-Duchonova, Beatrice. ·Department of Oncology, Palacky University Medical School and Teaching Hospital, IP Pavlova 6, 775 20, Olomouc, Czech Republic. · Department of Oncology, Palacky University Medical School and Teaching Hospital, IP Pavlova 6, 775 20, Olomouc, Czech Republic. mohelnikova@szu.cz. · Department of Toxicogenomics, National Institute of Public Health, Prague, Czech Republic. mohelnikova@szu.cz. ·Cancer Chemother Pharmacol · Pubmed #27250969.

ABSTRACT: Most patients with pancreatic ductal adenocarcinoma (PDAC) present with unresectable or metastatic disease with very poor prognosis. Chemotherapy is the primary treatment modality for patients with locally advanced and metastatic PDAC, but the efficacy of currently available regimens is limited. Taxanes are widely used in many primary cancers including breast, ovarian and lung cancers. The activity of combined regimen of taxanes plus nucleoside analogue or platinum derivate in terms of response rate ranges between 20 and 57 % in PDAC and may prolong overall survival. Since 2013 nab-paclitaxel (paclitaxel-albumin-bound particles) became a new treatment option for patients with metastatic pancreatic cancer based on the results of MPACT trial. Moreover, encouraging activity in PDAC of the combination regimen of paclitaxel and carboplatin that is being widely used in other solid tumors has been reported recently. Biomarkers, including biomarkers predictive of taxane resistance, could allow individualized tailored therapy. BRCA mutation status could serve as predictor of better chemotherapy treatment outcome in PDAC. The present review summarizes the principal clinical trials evaluating the efficacy of taxanes both as monotherapy and in combination in view of the potential use in the treatment of PDAC.

8 Review Early pancreatic carcinogenesis - risk factors, early symptoms, and the impact of antidiabetic drugs. 2016

Frič, Přemysl / Škrha, Jan / Šedo, Aleksi / Bušek, Petr / Kmochová, Klára / Laclav, Martin / Solař, Svatopluk / Bunganič, Bohuš / Zavoral, Miroslav. ·aDepartment of Medicine and Gastroenterology, Military University Hospital bLaboratory of Endocrinology and Metabolism cInstitute of Biochemistry and Experimental Oncology, General University Hospital, 1st Faculty of Medicine, Charles University, Prague, Czech Republic. ·Eur J Gastroenterol Hepatol · Pubmed #27120389.

ABSTRACT: Risk factors (long-term diabetes, obesity) and early symptoms (new-onset diabetes, loss of weight, or persistent low body mass) are the initial symptoms of pancreatic carcinogenesis. They may be influenced by antidiabetic drugs and their correct evaluation is a prerequisite for early diagnosis of pancreatic cancer (PC). We review the risk factors, early symptoms, and the impact of antidiabetic drugs on early pancreatic carcinogenesis. The main source of data was the database Medline/PubMed and abstracts of international congresses (DDW, UEGW). The risk factors and early symptoms are integral components of the familial PC surveillance and sporadic PC screening. Preventive programs should always be include multistep and multidisciplinary procedures. The correct evaluation of antidiabetic drugs and their interactions with other components of pancreatic carcinogenesis may influence the early diagnosis of PC.

9 Review Pancreatic Cancer Diagnostics and Treatment--Current State. 2015

Krška, Zdeněk / Šváb, Jan / Hoskovec, David / Ulrych, Jan. ·1st Department of Surgery - Department of Abdominal, Thoracic Surgery and Traumatology, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic. krskaz@vfn.cz. · 1st Department of Surgery - Department of Abdominal, Thoracic Surgery and Traumatology, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic. ·Prague Med Rep · Pubmed #26654799.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) represents permanent and ever rising issue worldwide. Five-year survival does not exceed 3 to 6%, i.e. the worst result among solid tumours. The article evaluates the current state of PDAC diagnostics and treatment specifying also development and trends. Percentage of non-resectable tumours due to locally advanced or metastatic condition varies 60-80%, mostly over 80%. Survival with non-resectable PDAC is 4 to 8 months (median 3.5). In contrast R0 resection shows the survival 18-27 months. Laboratory and imaging screening methods are not indicated on large scale. Risk factors are smoking, alcohol abuse, chronic pancreatitis, diabetes mellitus. Genetic background in most PDAC has not been detected yet. Some genes connected with high risk of PDAC (e.g. BRCA2, PALB2) have been identified as significant and highly penetrative, but link between PDAC and these genes can be seen only in 10-20%. This article surveys perspective oncogenes, tumour suppressor genes, microRNA. Albeit CT is still favoured over other imaging methods, involvement of NMR rises. Surgery prefers the "vessel first" approach, which proves to be justified especially in R0 resection. According to EBM immunotherapy same as radiotherapy are not significant in PDAC treatment. Chemotherapy shows limited importance in conversion treatment of locally advanced or borderline tumours or in case of metastatic spread. Unified procedures cannot be defined due to inhomogenous arrays. Surgical resection is the only chance for curative treatment of PDAC and depends mainly on timely indication for surgery and quality of multidisciplinary team in a high-volume centre.

10 Review Premalignant and malignant lesions of the heterotopic pancreas in the esophagus: a case report and review of the literature. 2015

Ulrych, Jan / Fryba, Vladimir / Skalova, Helena / Krska, Zdenek / Krechler, Tomas / Zogala, David. ·1st Department of Surgery - Department of Abdominal, Thoracic Surgery and Traumatology; First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Czech Republic. Jan.Ulrych@vfn.cz. · 1st Department of Surgery - Department of Abdominal, Thoracic Surgery and Traumatology; First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Czech Republic. · Institute of Pathology; First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Czech Republic. · 4th Department of Medicine - Department of Gastroenterology and Hepatology; First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Czech Republic. · Institute of Nuclear Medicine; First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Czech Republic. ·J Gastrointestin Liver Dis · Pubmed #26114184.

ABSTRACT: 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.

11 Review Role of solute carrier transporters in pancreatic cancer: a review. 2014

Lemstrová, Radmila / Souček, Pavel / Melichar, Bohuslav / Mohelnikova-Duchonova, Beatrice. ·Department of Oncology, Palacky University Medical School & Teaching Hospital, Olomouc, Czech Republic. ·Pharmacogenomics · Pubmed #25084206.

ABSTRACT: Nucleoside analogs such as gemcitabine and 5-fluorouracil are currently the cornerstone of chemotherapy in patients with pancreatic ductal adenocarcinoma (PDAC). Decreased drug transport into tumor cells that may be caused by low expression of membrane proteins, such as solute carrier transporters, represents one of the principal mechanisms of chemotherapy resistance. Individual diversity of multidrug resistance is the major challenge limiting the success of anticancer treatment. Novel biomarkers and pharmacogenomic approaches could further optimize treatment algorithms leading to better survival and lower treatment toxicity in PDAC patients. In this review, the most promising predictive biomarkers from the solute carrier transporter family of membrane transporters and the potential applications for PDAC therapy with nucleoside analogues are summarized.

12 Review [Surgical treatment of pancreatic carcinoma]. 2012

Záruba, P / Ryska, M. ·Chirurgická klinika 2. LF UK a ÚVN Praha. pavel.zaruba@uvn.cz ·Rozhl Chir · Pubmed #23448711.

ABSTRACT: -- No abstract --

13 Review [GIST: current knowledge and treatment modalities]. 2012

Páral, J / Lochman, P / Kalábová, H / Hadzi-Nikolov, D. ·Katedra válecné chirurgie, Fakulta vojenského zdravotnictví Hradec Králové, Univerzita obrany Brno. paral@pmfhk.cz ·Rozhl Chir · Pubmed #22880266.

ABSTRACT: GISTs represent a specific group of mesenchymal tumors with unpredictable biological features. Approximately 30% of newly diagnosed GIST tumors are malignant or have a high potential for malignancy. Currently, GISTs are routinely identified using histological, immunohistochemical, and molecular genetic assays. However, clinical diagnosis, particularly of small or intramural GISTs, might be difficult. Endoscopic examinations and fused PET/CT imaging are the most useful techniques for imaging and monitoring the disease progression. Surgical treatment is the first-line treatment and the only method that might lead to full remission in patients with primary GISTs. At the present time, there is no consensus on the issues whether to perform resections in patients with positive margins and resections of metastases. Biological therapy with imatinib mesylate is recommended in patients with newly diagnosed, locally advanced, inoperable, or metastasizing gastrointestinal GISTs that express the c-KIT protein. Treatment may reduce a primary tumor to a size small enough for surgical excision. Current research is focused on the development of new therapies for the treatment of advanced disease and/or disease prophylaxis.

14 Review Early diagnosis of pancreatic adenocarcinoma: role of stroma, surface proteases, and glucose-homeostatic agents. 2012

Fric, Premysl / Zavoral, Miroslav. ·Department of Medicine, First Faculty of Medicine and Central Military Hospital, Charles University, Prague, Czech Republic. premysl.fric@uvn.cz ·Pancreas · Pubmed #22695086.

ABSTRACT: OBJECTIVES: New-onset diabetes in pancreatic adenocarcinoma is due to a combination of insulin resistance and decreased β-cell function. Its differentiation from the common type 2 diabetes is the prerequisite for early diagnosis of pancreatic adenocarcinoma. Little attention has been paid to pancreatic stroma and surface proteases. METHODS: The activated fibroblasts selectively express fibroblast activation protein α, a structural homolog of the ubiquitously expressed dipeptidyl peptidase 4. Their role in pancreatic carcinogenesis is reviewed. RESULTS: Homodimers and heterodimers of both enzymes display high specificity for peptides and proteins with penultimate proline or alanine. Most glucose-homeostatic agents are candidate substrates of these enzymes. The biological activity of truncated substrates is decreased or absent. CONCLUSIONS: The interactions of surface proteases with glucose-homeostatic agents may adequately explain the evolution of diabetes associated with pancreatic adenocarcinoma and differentiate it from the common type 2 diabetes.

15 Review [Current status of pancreatic cancer diagnosis]. 2011

Krechler, Tomás / Horejs, Josef / Ulrych, Jan / Zeman, Miroslav / Macásek, Jaroslav / Dusková, Jaroslava / Zák, Ales. ·Univerzita Karlova v Praze, 1. lékarská fakulta, IV. interní klinika VFN. tomas.krechler@vfn.cz ·Cas Lek Cesk · Pubmed #22292339.

ABSTRACT: Pancreatic cancer still remains one of the tumors with the worst prognosis. The five-year survival rate ranges between 0.4 to 2 per cent. In most cases the tumor is diagnosed at an advanced stage, which does not allow a radical surgical treatment. Currently, the diagnosis of pancreatic cancer is based on dynamically developing imaging methods that allow detecting even small lesions. The basic testing method is the contrast computed tomography which is, in most cases, linked up to the endoscopic ultrasonography. In most patients results of the cytopathological and histological examinations are obtained before surgical or oncological therapy. The decisive factor for further therapeutic approach is the tumor staging. Despite the apparent progress in diagnostic techniques, the early diagnosis of pancreatic cancer remains unsatisfactory.

16 Review Molecular biology of pancreatic cancer. 2011

Zavoral, Miroslav / Minarikova, Petra / Zavada, Filip / Salek, Cyril / Minarik, Marek. ·Charles University, 1st Medical Faculty, Internal Clinic, 128 00 Prague 2, Czech Republic. ·World J Gastroenterol · Pubmed #21734801.

ABSTRACT: In spite of continuous research efforts directed at early detection and treatment of pancreatic cancer, the outlook for patients affected by the disease remains dismal. With most cases still being diagnosed at advanced stages, no improvement in survival prognosis is achieved with current diagnostic imaging approaches. In the absence of a dominant precancerous condition, several risk factors have been identified including family history, chronic pancreatitis, smoking, diabetes mellitus, as well as certain genetic disorders such as hereditary pancreatitis, cystic fibrosis, familial atypical multiple mole melanoma, and Peutz-Jeghers and Lynch syndromes. Most pancreatic carcinomas, however, remain sporadic. Current progress in experimental molecular techniques has enabled detailed understanding of the molecular processes of pancreatic cancer development. According to the latest information, malignant pancreatic transformation involves multiple oncogenes and tumor-suppressor genes that are involved in a variety of signaling pathways. The most characteristic aberrations (somatic point mutations and allelic losses) affect oncogenes and tumor-suppressor genes within RAS, AKT and Wnt signaling, and have a key role in transcription and proliferation, as well as systems that regulate the cell cycle (SMAD/DPC, CDKN2A/p16) and apoptosis (TP53). Understanding of the underlying molecular mechanisms should promote development of new methodology for early diagnosis and facilitate improvement in current approaches for pancreatic cancer treatment.

17 Review [The role of membrane transporters in cellular resistance of pancreatic carcinoma to gemcitabine]. 2010

Mohelníková-Duchonová, B / Soucek, P. ·Laboratore toxikogenomiky, Státní zdravotní ustav, Praha. mohelnikova@szu.cz ·Klin Onkol · Pubmed #21061681.

ABSTRACT: BACKGROUNDS: Pancreatic carcinoma is one of the most serious forms of cancer, with a very high mortality rate, and is the fourth leading cause of cancer-related death in the Czech Republic. The etiology and molecular pathogenesis of the disease is still poorly understood. Gemcitabine is a cytotoxic nucleoside analog, which is widely used in the treatment of malignancies, and in particular in pancreatic carcinoma. Interindividual differences in gemcitabine pharmacokinetics and pharmacodynamics have been demonstrated, which can significantly influence the outcome of the therapy in thus treated patients. Resistance developed to nucleoside analogs limits their clinical use, just like in the case of any other cytostatics. AIM: This review summarizes available data concerning the membrane proteins involved in the transport mechanism of gemcitabine through cellular membrane, and their role in the cellular resistance of pancreatic carcinoma to gemcitabine.

18 Review [Clinical perspective of precancerotic states in gastroenterology and their molecular genetics]. 2010

Mináriková, P / Zavoral, M. ·Interní klinika 1. lékarské fakulty UK a UVN Praha. petra.minarikova@uvn.cz ·Vnitr Lek · Pubmed #20184111.

ABSTRACT: Gastrointestinal tract tumours represent an important cause of death in the Czech Republic. Diagnosis of the disease at its advanced stage with progression precluding radical surgical solution is a frequent common denominator. Detection of precancerous states, including congenital genetic defects or premalignant syndromes and malignant lesions may serve as a useful tool for early detection of disease risk or disease onset. Considering the incidence of individual types of tumours, this paper Focuses mainly on precancerotic states leading to malignant alterations of oesophagus, colorectum and pancreas. Apart from a concise morphological description of each premalignancy and its malignant transformation, a description of traditional molecular models of development and progression is also provided. Furthermore, we include a brief list of the most important genes contributing to the mechanism of malignant transformation in these three most important tumour diseases.

19 Clinical Trial Phase 2 placebo-controlled, double-blind trial of dasatinib added to gemcitabine for patients with locally-advanced pancreatic cancer. 2017

Evans, T R J / Van Cutsem, E / Moore, M J / Bazin, I S / Rosemurgy, A / Bodoky, G / Deplanque, G / Harrison, M / Melichar, B / Pezet, D / Elekes, A / Rock, E / Lin, C / Strauss, L / O'Dwyer, P J. ·Beatson West of Scotland Cancer Centre, University of Glasgow, Glasgow, UK. · Department of Oncology, University Hospitals Leuven and KU Leuven, Leuven, Belgium. · Princess Margaret Cancer, Toronto, Canada. · Federal State Budgetary Institution, Dubna, Russia. · Surgery, Florida Hospital, Tampa, Tampa, USA. · Oncology, St.László Teaching Hospital, Budapest, Hungary. · Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland. · East and North Hertfordshire NHS Trust, Northwood, Middlesex, UK. · Department of Oncology, Lekarska Fakulta Univerzity Palackeho a Fakultni Nemocnice, Olomouc, Czech Republic. · CHU Estaing, Clermont-Ferrand, France. · Otsuka Pharmaceutical Development and Commercialization, Princeton. · Bristol-Myers Squibb Company, Princeton. · Abramson Cancer Center, University of Pennsylvania, Philadelphia, USA. ·Ann Oncol · Pubmed #27998964.

ABSTRACT: Background: Pancreatic ductal adenocarcinoma (PDAC) has a high mortality rate with limited treatment options. Gemcitabine provides a marginal survival benefit for patients with advanced PDAC. Dasatinib is a competitive inhibitor of Src kinase, which is overexpressed in PDAC tumors. Dasatinib and gemcitabine were combined in a phase 1 clinical trial where stable disease was achieved in two of eight patients with gemcitabine-refractory PDAC. Patients and methods: This placebo-controlled, randomized, double-blind, phase II study compared the combination of gemcitabine plus dasatinib to gemcitabine plus placebo in patients with locally advanced, non-metastatic PDAC. Patients received gemcitabine 1000 mg/m2 (30-min IV infusion) on days 1, 8, 15 of a 28-day cycle combined with either 100 mg oral dasatinib or placebo tablets daily. The primary objective was overall survival (OS), with safety and progression-free survival (PFS) as secondary objectives. Exploratory endpoints included overall response rate, freedom from distant metastasis, pain and fatigue progression and response rate, and CA19-9 response rate. Results: There was no statistically significant difference in OS between the two treatment groups (HR = 1.16; 95% confidence interval [CI]: 0.81-1.65; P = 0.5656). Secondary and exploratory endpoint analyses also showed no statistically significant differences. The burden of toxicity was higher in the dasatinib arm. Conclusions: Dasatinib failed to show increased OS or PFS in patients with locally advanced PDAC. Alternative combinations or trial designs may show a role for src inhibition in PDAC treatment.

20 Clinical Trial Phase I/II Study of Refametinib (BAY 86-9766) in Combination with Gemcitabine in Advanced Pancreatic cancer. 2017

Van Laethem, Jean-Luc / Riess, Hanno / Jassem, Jacek / Haas, Michael / Martens, Uwe M / Weekes, Colin / Peeters, Marc / Ross, Paul / Bridgewater, John / Melichar, Bohuslav / Cascinu, Stefano / Saramak, Piotr / Michl, Patrick / Van Brummelen, David / Zaniboni, Alberto / Schmiegel, Wollf / Dueland, Svein / Giurescu, Marius / Garosi, Vittorio L / Roth, Katrin / Schulz, Anke / Seidel, Henrik / Rajagopalan, Prabhu / Teufel, Michael / Childs, Barrett H. ·Department of Gastroenterology, Erasme University Hospital, CP 572/10, route de Lennik 808, 1070, Brussels, Belgium. JL.VanLaethem@erasme.ulb.ac.be. · Medical Department, Division of Hematology, Oncology and Tumor Immunology, Charity Hospital, Virchow-Klinikum Campus, Augustenburger Platz 1, 13353, Berlin, Germany. · Department of Oncology and Radiotherapy, Medical University of Gdansk, M. Skłodowskiej-Curie 3a Street, Gdansk, 80-210, Poland. · Department of Hematology and Oncology, University of Munich Medical Center, Marchioninistraße 15, 81366, Munich, Germany. · Department of Hematology and Oncology, Cancer Center Heilbronn-Franken, Am Gesundbrunnen 20-26, 74078, Heilbronn, Germany. · Division of Medical Oncology, University of Colorado Cancer Center, 1665 Aurora Ct, Aurora, CO, 80045, USA. · Department of Oncology, Antwerp University Hospital, Wilrijkstraat 10, 2650, Edegem, Belgium. · Department of Medical Oncology, Guy's & St Thomas' Hospital, Westminster Bridge Road, London, SE1 7EH, UK. · Department of Oncology, UCL Cancer Institute, 72 Huntley Street, London, WC1E 6DD, UK. · Department of Oncology, Palacky University Medical School and University Hospital Olomouc, Křížkovského 8, 771 47, Olomouc, Czech Republic. · Department of Medical Oncology, A.O.U. United Hospitals, Polytechnic University of Marche, Piazza Roma, 22, Ancona, Italy. · Department of Oncological Gastroenterology, Maria Skłodowska-Curie Memorial Cancer Center, ul. W.K. Roentgena 5, 02-781, Warsaw, Poland. · Department of Gastroenterology, Endocrinology, Metabolism and Infectiology, University Hospital of Giessen and Marburg, Baldingerstraße, 35043, Marburg, Germany. · Universitätsklinikum Halle - University Hospital Halle (Saale), Ernst-Grube-Straße 40, 06120, Halle (Saale), Germany. · Department of Radiotherapy, UZ Brussels, Avenue du Laerbeek 101, 1090, Brussels, Belgium. · Department of Medical Oncology, Poliambulanza Foundation Hospital Institute, Via Bissolati, 57, Brescia, Italy. · Department of Gastroenterology and Hepatology, Medical University Hospital Bochum, Alexandrinenstraße 1, Bochum, 44791, Germany. · Department of Oncology, Oslo University Radium Hospital, Trondheimsveien 235, Bjerke, 0514, Oslo, Norway. · Bayer Pharma AG, Müllerstraße 178, 13353, Berlin, Germany. · Bayer S.p.A., Viale Certosa 126-130, 20156, Milan, Italy. · Bayer HealthCare Pharmaceuticals, Inc., 100 Bayer Blvd, Whippany, NJ, 07981, USA. ·Target Oncol · Pubmed #27975152.

ABSTRACT: BACKGROUND: Activating KRAS mutations are reported in up to 90% of pancreatic cancers. Refametinib potently inhibits MEK1/2, part of the MAPK signaling pathway. This phase I/II study evaluated the safety and efficacy of refametinib plus gemcitabine in patients with advanced pancreatic cancer. METHODS: Phase I comprised dose escalation, followed by phase II expansion. Refametinib and gemcitabine plasma levels were analyzed for pharmacokinetics. KRAS mutational status was determined from circulating tumor DNA. RESULTS: Ninety patients overall received treatment. The maximum tolerated dose was refametinib 50 mg twice daily plus standard gemcitabine (1000 mg/m CONCLUSION: Refametinib plus gemcitabine was well tolerated, with a promising objective response rate, and had an acceptable safety profile and no pharmacokinetic interaction. There was a trend towards improved outcomes in patients without detectable KRAS mutations that deserves future investigation.

21 Clinical Trial Anti-tumour effects of lanreotide for pancreatic and intestinal neuroendocrine tumours: the CLARINET open-label extension study. 2016

Caplin, Martyn E / Pavel, Marianne / Ćwikła, Jarosław B / Phan, Alexandria T / Raderer, Markus / Sedláčková, Eva / Cadiot, Guillaume / Wolin, Edward M / Capdevila, Jaume / Wall, Lucy / Rindi, Guido / Langley, Alison / Martinez, Séverine / Gomez-Panzani, Edda / Ruszniewski, Philippe / Anonymous721030. ·Royal Free HospitalLondon, UKCharité University Medicine BerlinBerlin, GermanyUniversity of Warmia and MazuryOlsztyn, PolandUniversity of Texas MD Anderson Cancer CenterHouston, Texas, USAUniversity HospitalVienna, AustriaDepartment of Oncology of the First Faculty of Medicine and General Teaching HospitalPrague, Czech RepublicRobert-Debré HospitalReims, FranceMarkey Cancer CenterUniversity of Kentucky, Lexington, Kentucky, USAVall d'Hebron University HospitalBarcelona, SpainWestern General HospitalEdinburgh, UKUniversità Cattolica del Sacro CuoreRome, ItalyIpsenLes Ulis, FranceIpsenBasking Ridge, New Jersey, USABeaujon HospitalClichy, FranceParis Diderot UniversityParis, France m.caplin@ucl.ac.uk. · Royal Free HospitalLondon, UKCharité University Medicine BerlinBerlin, GermanyUniversity of Warmia and MazuryOlsztyn, PolandUniversity of Texas MD Anderson Cancer CenterHouston, Texas, USAUniversity HospitalVienna, AustriaDepartment of Oncology of the First Faculty of Medicine and General Teaching HospitalPrague, Czech RepublicRobert-Debré HospitalReims, FranceMarkey Cancer CenterUniversity of Kentucky, Lexington, Kentucky, USAVall d'Hebron University HospitalBarcelona, SpainWestern General HospitalEdinburgh, UKUniversità Cattolica del Sacro CuoreRome, ItalyIpsenLes Ulis, FranceIpsenBasking Ridge, New Jersey, USABeaujon HospitalClichy, FranceParis Diderot UniversityParis, France. · Royal Free HospitalLondon, UKCharité University Medicine BerlinBerlin, GermanyUniversity of Warmia and MazuryOlsztyn, PolandUniversity of Texas MD Anderson Cancer CenterHouston, Texas, USAUniversity HospitalVienna, AustriaDepartment of Oncology of the First Faculty of Medicine and General Teaching HospitalPrague, Czech RepublicRobert-Debré HospitalReims, FranceMarkey Cancer CenterUniversity of Kentucky, Lexington, Kentucky, USAVall d'Hebron University HospitalBarcelona, SpainWestern General HospitalEdinburgh, UKUniversità Cattolica del Sacro CuoreRome, ItalyIpsenLes Ulis, FranceIpsenBasking Ridge, New Jersey, USABeaujon HospitalClichy, FranceParis Diderot UniversityParis, France Royal Free HospitalLondon, UKCharité University Medicine BerlinBerlin, GermanyUniversity of Warmia and MazuryOlsztyn, PolandUniversity of Texas MD Anderson Cancer CenterHouston, Texas, USAUniversity HospitalVienna, AustriaDepartment of Oncology of the First Faculty of Medicine and General Teaching HospitalPrague, Czech RepublicRobert-Debré HospitalReims, FranceMarkey Cancer CenterUniversity of Kentucky, Lexington, Kentucky, USAVall d'Hebron University HospitalBarcelona, SpainWestern General HospitalEdinburgh, UKUniversità Cattolica del Sacro CuoreRome, ItalyIpsenLes Ulis, FranceIpsenBasking Ridge, New Jersey, USABeaujon HospitalClichy, FranceParis Diderot UniversityParis, France. ·Endocr Relat Cancer · Pubmed #26743120.

ABSTRACT: In the CLARINET study, lanreotide Autogel (depot in USA) significantly prolonged progression-free survival (PFS) in patients with metastatic pancreatic/intestinal neuroendocrine tumours (NETs). We report long-term safety and additional efficacy data from the open-label extension (OLE). Patients with metastatic grade 1/2 (Ki-67 ≤ 10%) non-functioning NET and documented baseline tumour-progression status received lanreotide Autogel 120 mg (n = 101) or placebo (n = 103) for 96 weeks or until death/progressive disease (PD) in CLARINET study. Patients with stable disease (SD) at core study end (lanreotide/placebo) or PD (placebo only) continued or switched to lanreotide in the OLE. In total, 88 patients (previously: lanreotide, n = 41; placebo, n = 47) participated: 38% had pancreatic, 39% midgut and 23% other/unknown primary tumours. Patients continuing lanreotide reported fewer adverse events (AEs) (all and treatment-related) during OLE than core study. Placebo-to-lanreotide switch patients reported similar AE rates in OLE and core studies, except more diarrhoea was considered treatment-related in OLE (overall diarrhoea unchanged). Median lanreotide PFS (core study randomisation to PD in core/OLE; n=101) was 32.8 months (95% CI: 30.9, 68.0). A sensitivity analysis, addressing potential selection bias by assuming that patients with SD on lanreotide in the core study and not entering the OLE (n=13) had PD 24 weeks after last core assessment, found median PFS remaining consistent: 30.8 months (95% CI: 30.0, 31.3). Median time to further PD after placebo-to-lanreotide switch (n=32) was 14.0 months (10.1; not reached). This OLE study suggests long-term treatment with lanreotide Autogel 120 mg maintained favourable safety/tolerability. CLARINET OLE data also provide new evidence of lanreotide anti-tumour benefits in indolent and progressive pancreatic/intestinal NETs.

22 Clinical Trial A randomized, placebo-controlled phase III trial of masitinib plus gemcitabine in the treatment of advanced pancreatic cancer. 2015

Deplanque, G / Demarchi, M / Hebbar, M / Flynn, P / Melichar, B / Atkins, J / Nowara, E / Moyé, L / Piquemal, D / Ritter, D / Dubreuil, P / Mansfield, C D / Acin, Y / Moussy, A / Hermine, O / Hammel, P. ·Department of Medical Oncology, Saint Joseph Hospital, Paris gdeplanque@hpsj.fr. · Department of Medical Oncology, University Hospital of Besançon, Besançon. · Department of Medical Oncology, University Hospital, Lille, France. · Metro-Minnesota Community Clinical Oncology Program, Park Nicollet Institute, Minneapolis, USA. · Department of Oncology, Palacký University Medical School & Teaching Hospital, Olomouc, Czech Republic. · Southeastern Medical Oncology Center, Goldsboro, USA. · Department of Clinical and Experimental Oncology, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice, Poland. · Department of Biostatistics, University of Texas School of Public Health, Houston, USA. · Clinical Development, Acobiom, Montpellier. · Signaling, Hematopoiesis and Mechanism of Oncogenesis, Inserm U1068, CRCM, Marseille Institut Paoli-Calmettes, Marseille Aix-Marseille University, UM 105, Marseille CNRS, UMR7258, CRCM, Marseille Clinical Development, AB Science, Paris. · Clinical Development, AB Science, Paris. · Clinical Development, AB Science, Paris Department of Clinical Hematology, Necker Hospital, Paris INSERM UMR 1163, Laboratory of Cellular and Molecular Mechanisms of Hematological Disorders and Therapeutic Implications, Paris Paris Descartes - Sorbonne Paris Cité University, Imagine Institute, Paris CNRS ERL 8254, Paris Laboratory of Excellence GR-Ex, Paris National Reference Center on Mastocytosis (CEREMAST), Paris. · Department of Gastroenterology, Hôpital Beaujon, Clichy, France. ·Ann Oncol · Pubmed #25858497.

ABSTRACT: BACKGROUND: Masitinib is a selective oral tyrosine-kinase inhibitor. The efficacy and safety of masitinib combined with gemcitabine was compared against single-agent gemcitabine in patients with advanced pancreatic ductal adenocarcinoma (PDAC). PATIENTS AND METHODS: Patients with inoperable, chemotherapy-naïve, PDAC were randomized (1 : 1) to receive gemcitabine (1000 mg/m(2)) in combination with either masitinib (9 mg/kg/day) or a placebo. The primary endpoint was overall survival (OS) in the modified intent-to-treat population. Secondary OS analyses aimed to characterize subgroups with poor survival while receiving single-agent gemcitabine with subsequent evaluation of masitinib therapeutic benefit. These prospectively declared subgroups were based on pharmacogenomic data or a baseline characteristic. RESULTS: Three hundred and fifty-three patients were randomly assigned to receive either masitinib plus gemcitabine (N = 175) or placebo plus gemcitabine (N = 178). Median OS was similar between treatment-arms for the overall population, at respectively, 7.7 and 7.1 months, with a hazard ratio (HR) of 0.89 (95% CI [0.70; 1.13]. Secondary analyses identified two subgroups having a significantly poor survival rate when receiving single-agent gemcitabine; one defined by an overexpression of acyl-CoA oxidase-1 (ACOX1) in blood, and another via a baseline pain intensity threshold (VAS > 20 mm). These subgroups represent a critical unmet medical need as evidenced from median OS of 5.5 months in patients receiving single-agent gemcitabine, and comprise an estimated 63% of patients. A significant treatment effect was observed in these subgroups for masitinib with median OS of 11.7 months in the 'ACOX1' subgroup [HR = 0.23 (0.10; 0.51), P = 0.001], and 8.0 months in the 'pain' subgroup [HR = 0.62 (0.43; 0.89), P = 0.012]. Despite an increased toxicity of the combination as compared with single-agent gemcitabine, side-effects remained manageable. CONCLUSIONS: The present data warrant initiation of a confirmatory study that may support the use of masitinib plus gemcitabine for treatment of PDAC patients with overexpression of ACOX1 or baseline pain (VAS > 20mm). Masitinib's effect in these subgroups is also supported by biological plausibility and evidence of internal clinical validation. TRIAL REGISTRATION: ClinicalTrials.gov:NCT00789633.

23 Clinical Trial A phase 3 randomized, double-blind, placebo-controlled trial of ganitumab or placebo in combination with gemcitabine as first-line therapy for metastatic adenocarcinoma of the pancreas: the GAMMA trial. 2015

Fuchs, C S / Azevedo, S / Okusaka, T / Van Laethem, J-L / Lipton, L R / Riess, H / Szczylik, C / Moore, M J / Peeters, M / Bodoky, G / Ikeda, M / Melichar, B / Nemecek, R / Ohkawa, S / Świeboda-Sadlej, A / Tjulandin, S A / Van Cutsem, E / Loberg, R / Haddad, V / Gansert, J L / Bach, B A / Carrato, A. ·Department of Medical Oncology/Solid Tumor Oncology, Dana-Farber Cancer Institute, Boston, USA charles_fuchs@dfci.harvard.edu. · Oncology Service, Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil. · Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan. · Department of Gastroenterology, Erasme University Hospital, Brussels, Belgium. · Medical Oncology, Royal Melbourne Hospital, Parkville, VIC, Australia. · Department of Hematology, Oncology, and Tumor Immunology, Charité University, Berlin, Germany. · Department of Oncology, Military Institute of Health Services, Warsaw, Poland. · Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada. · Department of Oncology, Antwerp University Hospital, Edegum, Belgium. · Department of Oncology, St László Hospital, Budapest, Hungary. · Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa, Japan. · Department of Oncology, Palacký University Medical School and Teaching Hospital, Olomouc. · Department of Oncology, Masaryk University Medical School and Masaryk Memorial Cancer Institute, Brno, Czech Republic. · Department of Gastroenterology, Kanagawa Cancer Center, Yokohama, Japan. · Department of Haematology, Oncology and Internal Medicine, Medical University of Warsaw, Warsaw, Poland. · Department of Clinical Pharmacology and Chemotherapy, Russian Cancer Research Center, Moscow, Russia. · Digestive Oncology, University Hospitals Gasthuisberg/Leuven and KU Leuven, Leuven, Belgium. · Medical Sciences, Amgen Inc., Thousand Oaks, USA. · Global Biostatistical Science, Amgen Ltd, Cambridge, UK. · Global Development, Thousand Oaks. · Development Oncology Therapeutics, Amgen Inc., Thousand Oaks, USA. · Medical Oncology Department, University Hospital Ramon y Cajal, Madrid, Spain. ·Ann Oncol · Pubmed #25609246.

ABSTRACT: BACKGROUND: This double-blind, phase 3 study assessed the efficacy and safety of ganitumab combined with gemcitabine as first-line treatment of metastatic pancreatic cancer. PATIENTS AND METHODS: Patients with previously untreated metastatic pancreatic adenocarcinoma were randomly assigned 2 : 2 : 1 to receive intravenous gemcitabine 1000 mg/m(2) (days 1, 8, and 15 of each 28-day cycle) plus placebo, ganitumab 12 mg/kg, or ganitumab 20 mg/kg (days 1 and 15 of each cycle). The primary end point was overall survival (OS). Secondary end points included progression-free survival (PFS), safety, and efficacy by levels of circulating biomarkers. RESULTS: Overall, 322 patients were randomly assigned to placebo, 318 to ganitumab 12 mg/kg, and 160 to ganitumab 20 mg/kg. The study was stopped based on results from a preplanned futility analysis; the final results are reported. Median OS was 7.2 months [95% confidence interval (CI), 6.3-8.2] in the placebo arm, 7.0 months (95% CI, 6.2-8.5) in the ganitumab 12-mg/kg arm [hazard ratio (HR), 1.00; 95% CI, 0.82-1.21; P = 0.494], and 7.1 months (95% CI, 6.4-8.5) in the ganitumab 20-mg/kg arm (HR, 0.97; 95% CI, 0.76-1.23; P = 0.397). Median PFS was 3.7, 3.6 (HR, 1.00; 95% CI, 0.84-1.20; P = 0.520), and 3.7 months (HR, 0.97; 95% CI, 0.77-1.22; P = 0.403), respectively. No unexpected toxicity was observed with ganitumab plus gemcitabine. The circulating biomarkers assessed [insulin-like growth factor-1 (IGF-1), IGF-binding protein-2, and -3] were not associated with a treatment effect on OS or PFS by ganitumab. CONCLUSION: Ganitumab combined with gemcitabine had manageable toxicity but did not improve OS, compared with gemcitabine alone in unselected patients with metastatic pancreatic cancer. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT01231347.

24 Clinical Trial Lanreotide in metastatic enteropancreatic neuroendocrine tumors. 2014

Caplin, Martyn E / Pavel, Marianne / Ćwikła, Jarosław B / Phan, Alexandria T / Raderer, Markus / Sedláčková, Eva / Cadiot, Guillaume / Wolin, Edward M / Capdevila, Jaume / Wall, Lucy / Rindi, Guido / Langley, Alison / Martinez, Séverine / Blumberg, Joëlle / Ruszniewski, Philippe / Anonymous1220800. ·From Royal Free Hospital, London (M.E.C.) · Charité University Medicine Berlin, Berlin (M.P.) · University of Warmia and Mazury, Olsztyn, Poland (J.B.Ć.) · University of Texas M.D. Anderson Cancer Center, Houston (A.T.P.) · University Hospital, Vienna (M.R.) · Department of Oncology of the First Faculty of Medicine and General Teaching Hospital, Prague, Czech Republic (E.S.) · Robert-Debré Hospital, Reims (G.C.), Ipsen, Les Ulis, (A.L., S.M., J.B.), Beaujon Hospital, Clichy (P.R.), and Paris Diderot University, Paris (P.R.) - all in France · Samuel Oschin Cancer Center, Cedars-Sinai Medical Center, Los Angeles (E.M.W.) · Vall d'Hebron University Hospital, Barcelona (J.C.) · Western General Hospital, Edinburgh (L.W.) · and Università Cattolica del Sacro Cuore, Rome (G.R.). ·N Engl J Med · Pubmed #25014687.

ABSTRACT: BACKGROUND: Somatostatin analogues are commonly used to treat symptoms associated with hormone hypersecretion in neuroendocrine tumors; however, data on their antitumor effects are limited. METHODS: We conducted a randomized, double-blind, placebo-controlled, multinational study of the somatostatin analogue lanreotide in patients with advanced, well-differentiated or moderately differentiated, nonfunctioning, somatostatin receptor-positive neuroendocrine tumors of grade 1 or 2 (a tumor proliferation index [on staining for the Ki-67 antigen] of <10%) and documented disease-progression status. The tumors originated in the pancreas, midgut, or hindgut or were of unknown origin. Patients were randomly assigned to receive an extended-release aqueous-gel formulation of lanreotide (Autogel [known in the United States as Depot], Ipsen) at a dose of 120 mg (101 patients) or placebo (103 patients) once every 28 days for 96 weeks. The primary end point was progression-free survival, defined as the time to disease progression (according to the Response Evaluation Criteria in Solid Tumors, version 1.0) or death. Secondary end points included overall survival, quality of life (assessed with the European Organization for Research and Treatment of Cancer questionnaires QLQ-C30 and QLQ-GI.NET21), and safety. RESULTS: Most patients (96%) had no tumor progression in the 3 to 6 months before randomization, and 33% had hepatic tumor volumes greater than 25%. Lanreotide, as compared with placebo, was associated with significantly prolonged progression-free survival (median not reached vs. median of 18.0 months, P<0.001 by the stratified log-rank test; hazard ratio for progression or death, 0.47; 95% confidence interval [CI], 0.30 to 0.73). The estimated rates of progression-free survival at 24 months were 65.1% (95% CI, 54.0 to 74.1) in the lanreotide group and 33.0% (95% CI, 23.0 to 43.3) in the placebo group. The therapeutic effect in predefined subgroups was generally consistent with that in the overall population, with the exception of small subgroups in which confidence intervals were wide. There were no significant between-group differences in quality of life or overall survival. The most common treatment-related adverse event was diarrhea (in 26% of the patients in the lanreotide group and 9% of those in the placebo group). CONCLUSIONS: Lanreotide was associated with significantly prolonged progression-free survival among patients with metastatic enteropancreatic neuroendocrine tumors of grade 1 or 2 (Ki-67 <10%). (Funded by Ipsen; CLARINET ClinicalTrials.gov number, NCT00353496; EudraCT 2005-004904-35.).

25 Article Indications and outcomes of duodenum-preserving resection of the pancreatic head in children. 2019

Snajdauf, Jiri / Rygl, Michal / Petru, Ondrej / Nahlovsky, Jiri / Frybova, Barbora / Durilova, Marianna / Mixa, Vladimir / Keil, Radan / Kyncl, Martin / Kodet, Roman / Whitley, Adam. ·Department of Pediatric Surgery, Institute of Postgraduate Medicine, 2nd Faculty of Medicine, Charles University, Prague, Czech Republic. · Department of Pediatric Surgery, 2nd Faculty of Medicine, Charles University in Prague and Motol University Hospital, Prague, Czech Republic. · Department of Pediatric Surgery, 2nd Faculty of Medicine, Charles University in Prague and Motol University Hospital, Prague, Czech Republic. jiri.nahlovsky@gmail.com. · Department of Anesthesiology and Intensive Care Medicine, 2nd Faculty of Medicine, Charles University in Prague and Motol University Hospital, Prague, Czech Republic. · Department of Internal Medicine, 2nd Faculty of Medicine, Charles University in Prague and Motol University Hospital, Prague, Czech Republic. · Department of Radiology, 2nd Faculty of Medicine, Charles University in Prague and Motol University Hospital, Prague, Czech Republic. · Department of Pathology and Molecular Medicine, 2nd Faculty of Medicine, Charles University in Prague and Motol University Hospital, Prague, Czech Republic. · Department of Surgery, University Hospital Kralovske Vinohrady, Prague, Czech Republic. · Department of Anatomy, 2nd Faculty of Medicine, Charles University, Prague, Czech Republic. ·Pediatr Surg Int · Pubmed #30386905.

ABSTRACT: AIM OF STUDY: Duodenum-preserving resection of the pancreatic head (DPRPH) with Roux-en-Y pancreatojejunostomy is a procedure used to remove focal pathological lesions of the pancreatic head. Although predominantly used in adult patients, it is both safe and effective in children. The aim of this study was to review our experience with this procedure, with focus on its indications, complications and long-term outcomes. METHODS: A retrospective analysis of pediatric patients who underwent DPRPH between 1994 and 2015 was performed. Patient files were reviewed for demographic, diagnostic, operative and histological details, postoperative complications. Patients were contacted telephonically and sent questionnaires to determine long-term outcomes. RESULTS: The study cohort consists of 21 patients, 14 girls and 7 boys, with an average age of 11.72 years (range 3 months to 18.6 years), who underwent DPRPH with end-to-end anastomosis of the jejunum to the pancreatic body (Roux-en-Y anastomosis). In four cases the head and also part of the body of the pancreas was resected. In the remaining 17 cases, only the head of the pancreas was resected. Indications for DPRPH were solid pseudopapillary tumor of the pancreas (n = 10), trauma (n = 8), pancreas divisum (n = 1), focal congenital hyperinsulinism (n = 1) and pancreatic cyst (n = 1). The length of follow-up ranged from 1 to 22 years (average 9.66). One patient developed a biliary fistula, which closed spontaneously within 2 weeks after stent insertion. A recurrence of abdominal pain was reported in two patients, occurring at 7 months after the operation in one patient and at 1 year in the other. Pancreatic endocrine insufficiency did not occur in any of the 21 patients. Seven patients currently require a low fat diet, five of which need pancreatic enzyme supplementation. An additional two patients need enzyme supplementation without dietary restriction. CONCLUSION: DPRPH is a safe and effective procedure for the treatment of large focal pathological lesions of the pancreatic head in children. As a less invasive procedure than pancreatoduodenectomy, it is more appropriate for the developing child.

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