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perioperative immunotherapy for pancreatic cancer is on its way

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Hepatobiliary Surgery and Nutrition 2021年第4期10卷 537-540页

作者： Christoph Springfeld peter Bailey Thilo Hackert john p.neoptolemos Department of Medical Oncology National Center for Tumor DiseasesHeidelberg University HospitalHeidelbergGermany Department of Surgery Heidelberg University HospitalHeidelbergGermany Institute of Cancer Sciences University of GlasgowScotlandUK

Interdisciplinary perioperative treatment has greatly improved the outcome of pancreatic cancer *** on randomized,controlled phase III clinical trials,adjuvant chemotherapy with mFOLFIRINOX(pRODIGE-24 study),gemcitabine/capecitabine(ESpAC-4)or 5-fluorouracil/gemcitabine monotherapy(ESpAC-1,CONKO-001,ESpAC-3)is now the clinical standard after curative resection(1).

关键词： chemotherapy curative FOLFIRI

Adjuvant therapy in pancreatic cancer

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World Journal of Gastroenterology 2001年第4期7卷 482-489页

作者： paula Ghaneh john Slavin Robert Sutton Mark Hartley john p.neoptolemos Department of Surgery.University of Liverpool 5~(th)Floor UCD Building.Daulby StreetLiverpool.L69 3GA.UK

The outlook for patients with pancreatic cancer has been grim. There have been major advances in the surgical treatment of pancreatic cancer, leading to a dramatic reduction in post-operative mortality from the development of high volume specialized centres. This stimulated the study of adjuvant and neoadjuvant treatments in pancreatic cancer including chemoradiotherapy and chemotherapy. Initial protocols have been based on the original but rather small GITSG study first reported in 1985. There have been two large European trials totalling over 600 patients (EORTC and ESpAC-1) that do not support the use of chemoradiation as adjuvant therapy. A second major finding from the ESpAC-1 trial (541 patients randomized) was some but not conclusive evidence for a survival benefit associated with chemotherapy. A third major finding from the ESpAC-1 trial was that the quality of life was not affected by the use of adjuvant treatments compared to surgery alone. The ESpAC-3 trial aims to assess the definitive use of adjuvant chemotherapy in a randomized controlled trial of 990 patients.

关键词： pancreatic Neoplasms Antineoplastic Agents Combined Modality Therapy Humans Research Support, Non-U.S. Gov't

pancreatic cancer–Adjuvant therapy

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The Chinese-German Journal of Clinical Oncology 2007年第2期6卷 170-175页

作者： Asma Sultana john neoptolemos paula Ghaneh Division of Surgery and Oncology School of Cancer Studies University of Liverpool Royal Liverpool University Hospital 5th Floor UCD Building Daulby Street Liverpool L69 3GA UK

pancreatic cancer ranks tenth in terms of newly diagnosed cases, but just 10%–15% of these patients can undergo resection. Survival after curative surgery is dismal, as recurrences occur either locally or in the liver. Adjuvant treatment with either chemotherapy or chemoradiation (with or without maintenance chemotherapy) has been employed, to improve the poor prognosis. Justification for the use of chemoradiation, with follow on chemotherapy, is based on the results of an underpowered 1987 GITSG study, which closed prematurely and compared intervention to observation. There has been no survival advantage demonstrated in the one randomized controlled trial that examined chemoradiation compared to chemotherapy. There is a clear cut survival advantage however with chemotherapy compared to observation, based on the results from two large randomized controlled trials, and supported by an individual patient data meta-analysis. The standard of care for adjuvant therapy based on level I evidence (from the ESpAC-1 trial) is post operative chemotherapy using 5-Fluorouracil with folinic acid providing a best estimate of 29% five years survival.

关键词： pancreas cancer chemotherapy chemoradiation adjuvant treatment meta-analysis

Management of necrotizing pancreatitis

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World Journal of Gastroenterology 2001年第4期7卷 476-481页

作者： john Slavin paula Ghaneh Robert Sutton Mark Hartley peter Rowlands Conall Garvey Mark Hughes john neoptolemos Departments of Surgery Royal Liverpool University Hospital Departments of Radiology Royal Liverpool University Hospital

Infection complicating pancreatic necrosis leads to persisting sepsis, multiple organ dysfunction syndrome and accounts for about half the deaths that occur following acute pancreatitis. Severe cases due to gallstones require urgent endoscopic sphincterotomy. patients with pancreatic necrosis should be followed with serial contrast enhanced computed tomography (CE-CT) and if infection is suspected fine needle aspiration of the necrotic area for bacteriology (FNAB) should be undertaken. Treatment of sterile necrosis should initially be non-operative. In the presence of infection necrosectomy is indicated. Although traditionally this has been by open surgery, minimally invasive procedures are a promising new alternative. There are many unresolved issues in the management of pancreatic necrosis. These include, the use of antibiotic prophylaxis, the precise indications for and frequency of repeat CE-CT and FNAB,and the role of enteral feeding.

关键词： Humans pancreatitis, Acute Necrotizing Surgical procedures, Minimally Invasive

Tetracycline-inducible protein expression in pancreatic cancer cells: Effects of CapG overexpression

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World Journal of Gastroenterology 2011年第15期17卷 1947-1960页

作者： Sarah Tonack Sabina patel Mehdi Jalali Taoufik Nedjadi Rosalind E Jenkins Christopher Goldring john neoptolemos Eithne Costello Liverpool CR-UK Centre Department of Molecular and Therapeutic Cancer MedicineUniversity of Liverpool Liverpool L69 3GA United Kingdom MRC Centre forDrug Safety Science Department of Pharmacology and Therapeutics School of Biomedical Sciences University of Liverpool L69 3GA United Kingdom National Institute for Health Research pancreatic Biomedical Research Unit Liverpool L69 3GA United Kingdom

AIM: To establish stable tetracycline-inducible pancreatic cancer cell lines. METHODS: Suit-2, Miapaca-2, and panc-1 cells were transfected with a second generation reverse tetracycline-controlled transactivator protein (rtTA2S-M2), under the control of either a cytomegalovirus (CMV) or a chicken β-actin promoter, and the resulting clones were ***: Use of the chicken (β-actin) promoter proved superior for both the production and maintenance of doxycycline-inducible cell lines. The system proved versatile, enabling transient inducible expression of a variety of genes, including GST-p, CYp2E1, S100A6, and the actin capping protein, CapG. To determine the physiological utility of this system in pancreatic cancer cells, stable inducible CapG expressors were established. Overexpressed CapG was localised to the cytoplasm and the nuclear membrane, but was not observed in the nucleus. High CapG levels were associated with enhanced motility, but not with changes to the cell cycle, or cellular proliferation. In CapG-overexpressing cells, the levels and phosphorylation status of other actin-moduating proteins (Cofilin and Ezrin/Radixin) were not altered. However, preliminary analyses suggest that the levels of other cellular proteins, such as ornithine aminotransferase and enolase, are altered upon CapG induction. CONCLUSION: We have generated pancreatic-cancer derived cell lines in which gene expression is fully controllable.

关键词： pancreatic cancer cells Tetracycline-inducible CapG Suit-2 panc-1 MiapaCa-2

Adjuvant and neoadjuvant chemotherapy in pancreatic ductal adenocarcinoma

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Journal of pancreatology 2020年第1期3卷 1-11页

作者： Leonhardt Carl S. Traub Benno Hackert Thilo Klaiber Ulla Strobel Oliver Büchler Markus W. neoptolemos john p. Department of General Visceral and Transplantation SurgeryUniversity of HeidelbergHeidelbergGermany Department of Surgery Ulm University HospitalUlmGermany

The management of pancreatic cancer has dramatically changed since the first major randomized trial published in 2001 by the European Study Group for pancreatic Cancer(ESpAC)stimulated the development of multimodality oncosurgical ***-1 demonstrated a survival improvement from upfront surgery of only 8%,increasing to 21%5-year survival for 5-fluorouracil/folinic acid but only 10.8%for ***-4 has shown a 5-year survival rate of 30%for all patients without restriction of 30%using a combination of gemcitabine and capecitabine,rising to 40%in those with an R0 resection margin,or nearly 50%in those with N0 lymph node *** selected patients with favorable prognostic features mFOLFIRINOX can produce a 50%5-year survival rate but with added *** a positive resection margin is associated with an increased likelihood of local recurrence,this of itself is not the contributor to reduced survival,but rather reflects the increased probability of systemic ***,strategies aimed at local control,may reduce subsequent local progression,but will not improve overall *** chemotherapy is increasingly utilized in cases of borderline resectable or locally advanced pancreatic cancer,but there is still a lack of proof of concept ***-quality evidence from randomized controlled trials to identify the indications and benefits of neoadjuvant therapy in pancreatic cancer are *** use of patient-derived tumor organoids may predict response to chemotherapy which could open a new opportunity in pancreatic cancer treatment,stratifying patients into treatment groups based on their response to these therapies in the laboratory.

关键词： Adjuvant therapy ESpAC Neoadjuvant therapy pancreatectomy pancreatic cancer Randomized trial