Carcinoma of the Pancreas and Papilla of Vater: Presenting Symptoms, Signs, and Diagnosis Related to Stage and Tumour Site a Prospective Multicentre Trial in 472 Patients

K, Bakkevold; Arnesjö, B; Kambestad, Brit

doi:10.3109/00365529209000081

Cited by 111 publications

(53 citation statements)

References 48 publications

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“…Pain occurs in 80% of patients with locally advanced or metastatic disease, and it can be felt in the upper abdomen, radiating to the back [42,43] . Weight loss can be significant and is associated with anorexia, steatorrhea, diarrhea and early satiety which are other symptoms related to cancer of the pancreas [42,43] . Jaundice with pain is present in 50% of patients with advanced disease, while painless jaundice affects approximately one-half of patients with a potentially resectable and curable lesion [42] .…”

Section: Clinical Manifestationmentioning

confidence: 99%

Medical Management of Pancreatic Adenocarcinoma

et al. 2009

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Section: Clinical Manifestationmentioning

confidence: 99%

Medical Management of Pancreatic Adenocarcinoma

et al. 2009

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“…At the time of diagnosis, over 80% of the patients have advanced regional disease or distant metastasis. 20 Therefore, curative resections cannot be considered for the majority of patients with pancreatic cancer. Despite multiple clinical trials using a large panel of chemotherapeutic regimens, the prognosis of advanced pancreatic cancer has not significantly improved in recent decades.…”

mentioning

confidence: 99%

Ligands for peroxisome proliferator-activated receptor ? inhibit growth of pancreatic cancers bothin vitro andin vivo

et al. 2001

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Peroxisome proliferator-activated receptor ␥ (PPAR␥) is expressed largely in adipose tissues and plays an important role in adipocyte differentiation. Several studies have recently shown that ligands of PPAR␥ could lead to growth inhibition in some malignancies. In our study, we focused on pancreatic cancers, because the prognosis of advanced pancreatic cancer has not significantly improved due to its resistance to various chemotherapeutic regimens, so that a novel strategy should be required. We show here that PPAR␥ is expressed in 5 pancreatic cancer cell lines detected in both mRNA and protein level as well as in human primary and metastatic pancreatic carcinomas examined by immunohistochemical studies. A specific ligand of PPAR␥, troglitazone, led to G1 accumulation with the increase in p27(Kip1), but not p21(Waf1/Cip1) and inhibited cellular proliferation in a pancreatic cancer cell line, Panc-1. Peroxisome proliferator-activated receptor gamma (PPAR␥) is one of the members of the nuclear hormone receptor superfamily like receptors for steroids, thyroid hormone, vitamin D and retinoic acid. 1 Like other members of this superfamily, PPAR␥ binds to DNA response element and regulates the expression of specific target genes. 2,3 15-Deoxy⌬ 12,14 prostaglandin J 2 and various polyunsaturated fatty acids have been identified as natural receptor ligands for PPAR␥ 4 -6 and the anti-diabetic thiazolidinedione (TZD) drugs as synthetic ligands. 4,7 TZDs are a new class of oral anti-diabetic agents.PPAR␥ is predominantly expressed in adipose tissue and functions as a central regulator of adipocyte differentiation. 8 The receptor is induced very early in this process and, in the presence of ligand, causes morphological changes, lipid accumulation and the activation of fat-specific genes in adipocytes. 9 PPAR␥ gene gives rise to 2 isoforms. Forced expression of PPAR␥2 activates expression of a number of typical differentiation-linked adipocyte genes, including adipocyte P2 (aP2), adipsin, lipoprotein lipase in cultured fibroblasts. 10 The common process of cell differentiation involves the slowing or complete cessation of cell growth and is referred to as terminal differentiation. On the basis of its effects on differentiation and cell-cycle regulation, induction of terminal differentiation represents an alternative convention therapy for human malignancies that may have reduced toxicity. The most successful clinical application of differentiation therapy has been the use of all-trans retinoic acid, a ligand for the retinoic acid receptor ␣ (RAR␣) in the standard treatments for acute promyelocytic leukemia. 11 Other nuclear receptors also may become the promising targets for novel therapeutic strategies in some malignancies. It has been investigated whether PPAR␥ might be a useful target for the treatment of tumors. Several studies have shown that TZDs can lead to growth inhibition in liposarcoma, 12 breast cancer, 13,14 colon cancer, [15][16][17] prostatic cancer 18 and gastric cancer. 19 In the present study, we observe...

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“…Yet the presenting symptoms are nonspecific such as weight loss and abdominal pain [Bakkevold et al 1992]. This population of patients (and their general practitioners) is accustomed to aches and pains, and so in most cases, the earliest signs of malignancy go unnoticed; a high level of perception is required to avoid delays in diagnostic workup.…”

Section: Patient Population and Diagnosismentioning

confidence: 99%

Pancreatic cancer: why is it so hard to treat?

Oberstein

Olive

2013

Therap Adv Gastroenterol

273

201

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Abstract:No common malignancy is as rapidly and inevitably fatal as pancreatic ductal adenocarcinoma (PDA). This grim fact has driven substantial research efforts into this disease in recent decades. Unfortunately, the investment has yet to result in a meaningful increase in 5-year survival. This has prompted many pancreatic cancer researchers and advocates to redouble their efforts, but also requires one to step back and ask why the previous efforts were lacking and to consider why pancreatic cancer is so difficult to treat. The difficulties are legion. PDA is characterized by an insidious clinical syndrome, but is rarely diagnosed at a time when surgical resection is feasible. We lack markers of early detection and screening programs remain unproven even in high risk populations. The location of the tumor in the retroperitoneum, the advanced age of patients, and the systemic effects of disease limit the options for local therapy. Chemotherapy may provide a small benefit, but most efforts to improve on the current regimens consistently and stubbornly fail in advanced clinical trials. The molecular and cellular features of ductal pancreatic tumors are aggressive and underlay multiple levels of therapeutic resistance. Non-cell-autonomous features including stromal proliferation, reduced vascular density and immune suppression also contribute to therapeutic resistance. Growing awareness of these the fundamental features of PDA has begun to guide ongoing research efforts. Clinical trials are now specifically targeting these tumor properties and actively focusing on the therapeutic implications of tumor stroma. As reviewed here, reflecting on the fundamental question of why pancreatic cancer is so difficult to treat is a necessary and informative exercise that will aid our efforts to improve patient outcomes. These efforts will lead to improvements in clinical trial design, expand our focus to include the molecular and histologic implications of novel treatment paradigms, and ultimately change the lives of our patients.

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Carcinoma of the Pancreas and Papilla of Vater: Presenting Symptoms, Signs, and Diagnosis Related to Stage and Tumour Site a Prospective Multicentre Trial in 472 Patients

Cited by 111 publications

References 48 publications

Medical Management of Pancreatic Adenocarcinoma

Medical Management of Pancreatic Adenocarcinoma

Ligands for peroxisome proliferator-activated receptor ? inhibit growth of pancreatic cancers bothin vitro andin vivo

Pancreatic cancer: why is it so hard to treat?

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