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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pancreatic cancer is the fourth leading cause of cancer death in our society, with a mortality that virtually parallels its incidence, a median survival of <12 months even with maximal therapy, and a 5-year survival rate of <5 %. The diversity of clinical outcomes and the molecular heterogeneity of histopathologically similar cancer types, incomplete knowledge of the genomic aberrations that drive carcinogenesis and the lack of therapeutics that specifically target most known genomic aberrations necessitates large-scale detailed analysis of cancer genomes to identify novel potential therapeutic strategies. As part of the International Cancer Genome Consortium (ICGC), the Australian Pancreatic Cancer Genome Initiative (APGI) used exomic sequencing and copy number analysis to define genomic aberrations that characterize a large, clinically focused, prospectively accrued cohort of patients with pancreatic cancer. The cohort consisted of early (clinical stages I and II) non-pre-treated patients with pancreatic ductal adenocarcinoma who underwent operative resection with curative intent. We devised approaches to adjust for low epithelial content in primary tumours and to define the genomic landscape of pancreatic cancer to identify novel candidate driver genes and mechanisms. We aim to develop stratified, molecular phenotype-guided therapeutic strategies using existing therapeutics that are either rescued, repurposed, in development, or are known to be effective in an undefined subgroup of PC patients. These are then tested in primary patient-derived xenografts and cell lines from the above deeply characterized cohort. In addition, we return information to treating clinicians that influences patient care and are launching a clinical trial called IMPaCT (Individualized Molecular Pancreatic Cancer Therapy). This umbrella design trial randomizes patients with metastatic disease to either standard first-line therapy with gemcitabine, or a molecular phenotype-guided approach using next-generation sequencing strategies to screen for actionable mutations defined through the ICGC effort.
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PMID:Understanding pancreatic cancer genomes. 2366 Sep 61

Undifferentiated carcinoma of the pancreas with osteoclast-like giant cells (OGCs) is very rare, less than 1% of all pancreatic malignancies, and shows worse prognosis than that of invasive ductal adenocarcinoma of the pancreas. We present a case of en bloc resection for a huge undifferentiated carcinoma with OGCs that invaded the stomach and transverse mesocolon. A 67-year female was admitted for left upper quadrant pain and computed tomography demonstrated a mass occupying the lesser sac and abutting the stomach and pancreas. There were no distant metastases and the patient underwent subtotal pancreatectomy with splenectomy, total gastrectomy, and segmental resection of the transverse colon. Histopathological examination confirmed an 11 cm-sized undifferentiated carcinoma of the pancreas with OGCs. Immunohistochemical staining revealed reactivity with pan-cytokeratin in adenocarcinoma component, with vimentin in neoplastic multi-nucleated cells, with CD45/CD68 in OGCs, and with p53 in tumor cells, respectively. The patient had suffered from multiple bone metastases and survived 9 mo after surgery. This case supports the ductal epithelial origin of undifferentiated carcinoma with OGCs and early diagnosis could result in favorable surgical outcomes. Investigations on the surgical role and prognostic factors need to be warranted in this tumor.
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PMID:Huge undifferentiated carcinoma of the pancreas with osteoclast-like giant cells. 2462 10

Patients with metastasized carcinoma of the pancreas have a very poor prognosis, and long-term survival cannot be expected. This case report describes two patients with an initial diagnosis of metastatic pancreatic cancer, both with hepatic metastases and one with an additional peritoneal carcinomatosis. Initially, both patients were treated intravenously with the FOLFIRINOX chemotherapy regimen, consisting of 5-FU, folinic acid, irinotecan and oxaliplatin. Surprisingly, the FOLFIRINOX treatment resulted in complete resolution of the hepatic metastases in both patients, with no lesions detectable by computed tomography scan. Furthermore, treatment response included decreased diameter of the primary tumor in the tail of the pancreas and disappearance of the additional peritoneal carcinomatosis. Both patients were discussed by our multidisciplinary tumor board, which recommended surgical resections of the carcinoma. The R0 resection of the primary tumor was successful in both cases and, interestingly, the resected tissues showed no evidence of the hepatic metastases intraoperatively. In the first case, the patient received a postoperative 6-mo course of adjuvant chemotherapy with gemcitabine. In the second case, the patient continued to receive the FOLFIRINOX regimen for an additional 6 mo postoperatively. At 12 mo after the operation, a nonresectable retroperitoneal lymph node metastasis was detected in the first patient, whereas the second patient remained in complete remission at the time of this report (5 mo after the adjuvant therapy was discontinued). This case report is the first of its kind to describe two cases of hepatic metastatic pancreatic carcinoma that were resectable following treatment with FOLFIRINOX. Further studies are required to examine the role of FOLFIRINOX as a neoadjuvant treatment option in subgroups of patients with initially metastasized pancreatic carcinoma.
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PMID:Metastasized pancreatic carcinoma with neoadjuvant FOLFIRINOX therapy and R0 resection. 2603 75

Understanding and formulating an appropriate strategy for the para-aortic lymph nodes (LN16) during curative surgery for pancreatic head cancer have been controversial for some time. This study intended to provide a recommendation for surgeons to perform an optimal curative surgery on pancreatic cancer patients with or without LN16 involvement. Based on an updated literature search and review, the members of the Chinese Study Group for Pancreatic Cancer (CSPAC) from high-volume centers reached a consensus on the issue of LN16 in pancreatic head cancer. Metastasis to LN16 is quite common in pancreatic head cancer cases. Depending on the location of the tumor, including the ventral and dorsal pancreas, there could be various lymph node drainage pathways whereby LN16 does not necessarily belong to the Group 3 lymph node stations for all cases of pancreatic head cancer. Although LN16 involvement generally indicates a poor prognosis, some cohorts of LN16-involved cases have benefited from a curative surgery, and there is still a lack of level I evidence to convince surgeons to abandon all resectable cases with LN16 positivity. Resection of LN16 combined with a standard lymphadenectomy during pancreatoduodenectomy is recommended by CSPAC, except in patients with both positive LN16 and criteria based on: i) the resectability status of primary tumor; ii) the extent of involved para-aortic lymph nodes; and iii) the serum tumor burden assessed preoperatively.
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PMID:Should a standard lymphadenectomy during pancreatoduodenectomy exclude para-aortic lymph nodes for all cases of resectable pancreatic head cancer? A consensus statement by the Chinese Study Group for Pancreatic Cancer (CSPAC). 2631 52

Pancreatic cancer is predicted by the Pancreatic Cancer Action Network to soon become the 2nd leading cause of cancer related deaths in this country. This cannot be attributed to a lack of resources focused on interrogating the genomic landscape of pancreatic cancer genomes. Additionally, a large number of researchers and federal dollars have been directed towards inhibiting the most frequent genetic lesion in pancreatic cancer, Kras. Even with these advances, cytotoxic chemotherapy is currently the best option for patients with metastatic disease. Besides developing better early detection strategies, translating our knowledge of the molecular aspects of pancreatic cancer to the clinic via a targeted, personalized medicine approach may be the best way to dramatically improve patient outcomes. Herein, we briefly describe the scope of the problem in targeting pancreatic cancer on both the cellular and molecular levels. We also outline some promising, ongoing efforts to develop better therapeutic interventions for this deadly disease. For instance, we discuss novel strategies to target molecules and pathways that go beyond targeting genetic mutations and the level of transcriptional gene regulation. Finally, we summarize a clinical trial that is designed to answer the question whether with the available arsenal of drugs and molecular targets, can we now "personalize" therapy for pancreatic cancer patients?
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PMID:Personalized therapy for pancreatic cancer: Do we need better targets, arrows, or both? 2701 Oct 47

Pancreatic carcinoma ranks among the most lethal of human cancers. Besides late detection, other factors contribute to its lethality, including a high degree of chemoresistance, invasion, and distant metastases. Currently, the mainstay of therapy involves resection of local disease in a minority of patients (Whipple procedure) and systemic gemcitabine. While systemic chemotherapy has some benefit, even with optimal treatment, the five year survival after diagnosis is dismal. Thus, treatment of pancreatic carcinoma remains a tremendous unmet need.The organometallic compound tris DBA palladium is a potent inhibitor of N-myristoyltransferase 1 (NMT1), an enzyme that catalyzes the transfer of myristate to protein substrates. This compound is highly effective in vivo against murine models of melanoma with both mutant and wild type b-RAF genotypes. Based upon the signaling similarities between melanoma and pancreatic carcinoma, we evaluated the efficacy of tris DBA palladium in vitro and in vivo against pancreatic carcinoma. We found that tris DBA palladium decreased proliferation and colony formation of pancreatic cancer cells in vitro. In an orthotopic mouse model, tris DBA palladium was highly active in inhibiting growth, ascites production, and distant metastases in vivo. Furthermore, tris DBA palladium impaired chemotaxis and inhibited cilia formation in Pan02 cells in a NMT1-dependent manner. We propose that NMT1 is a novel regulator of cilia formation and tris DBA palladium a novel inhibitor of cilia formation and metastasis in pancreatic cancer. Thus, further evaluation of tris DBA palladium for the treatment of pancreatic cancer is warranted.
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PMID:Tris DBA palladium is highly effective against growth and metastasis of pancreatic cancer in an orthotopic model. 2743 40

The author reports a typical but rare case of non-functioning well differentiated endocrine carcinoma of the pancreas. A 67-year-old man was admitted to our hospital because of abdominal pain. No hormone-related symptoms were recognized. He has no familiar history of pancreatic neoplasms. Various imaging modalities including US, CT and MRI revealed a tumor of the pancreatic body. Distal pancreatectomy and splenectomy were performed. A solid well demarcated tumor was present in the pancreatic body. Peripancreatic lymph nodes showed marked swelling suggestive of metastases. Immunohistyochemically, tumor cells were positive for cytokeratin, synaptophysin, neuron-specific enolase, and CD56; they were negative for chromogranin, gastrin, glucagon, somatostatin, pancreatic polypeptide, and vasoactive intestinal polypeptide. The pathological diagnosis was non-functioning well differentiated endocrine carcinoma of the pancreas.
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PMID:Non-functioning Well Differentiated Endocrine Carcinoma of the Pancreas. 2799 Feb 10

We discuss the prognosis of cases of Stage IV pancreatic carcinoma with distant metastases(7th Edition of General Rules for the Study of Pancreatic Cancer, Japan Pancreas Society)for which any treatment was performed at our hospital. Fiftythree patients were radiographically or pathologically diagnosed as having Stage IV pancreatic carcinoma with definite prognosis, and received treatments, includingsurg ery or chemotherapy, at our department. Twenty-two cases showed more metastases, and celiac artery or superior mesenteric artery invasion was suspected in 28 cases. The 5-year survival rate of all 53 cases was 3.8%, and the median survival time(MST)was 6.2 months. The MST in the palliative surgery cases was 6.7 months, and that in the cases given best supportive care(BSC)was only 1.9 months. There were no 2-year survivors in the group given chemotherapy without any other treatments and in the group given BSC alone, while the longest survival time and MST were 66.9 and 31.3 months(p<0.001), respectively, in the 10 patients treated by primary tumor resection. There was only 1 patient who showed relapse-free survival. Primary site resection and chemotherapy over 4 cycles was revealed as an independent prognostic factor by multivariable analysis. Patients with Stage IV pancreatic carcinoma have a poor prognosis. However, the possibility of achievingimproved prognosis was noted with combined-modality therapy, including aggressive resection in limited cases showinga good response to chemotherapy or cases in whom preoperative metastasis assessment was difficult.
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PMID:[Long-Term Survivors after Resection for Primary Pancreatic Carcinoma Stage IV]. 2939 38

We report 2 cases of prolonged survival achieved with surgical resection and multidisciplinary therapy for acinar cell carcinoma of the pancreas with liver metastases.Case 1: The patient was a 55-year-old woman.She presented with upper right abdominal pain and anemia.We diagnosed a tumor originating from the pancreas and multiple liver metastases.To avoid death caused by bleeding from the tumor, we performed pancreaticoduodenectomy and right-hemi hepatectomy, and a rapid diagnosis of acinar cell carcinoma of the pancreas was confirmed intraoperatively.After the hospital discharge, we administered hepatic intra-arterial chemotherapy and performed microwave ablation for the remnant liver metastases.Additionally, systemic chemotherapy with gemcitabine was administered; however, multiple metastases of the lung and liver became uncontrollable and she died 2 and half years postoperatively.Case 2: The patient was a 42-year-old woman.Through a medical checkup, gastric varix and elevated tumor markers were detected.The examination revealed a tumor at the tail of the pancreas and liver metastasis.We performed distal pancreatomy and partial liver resection.The pathological diagnosis was acinar cell carcinoma and liver metastasis.We administered adjuvant chemotherapy by using gemcitabine and achieved 5 years of relapse-free survival.The prognosis of ACC is better than that for PDAC.However, prognosis of unresectable cases is still unfavorable.Therapeutic strategies including aggressive surgical resection for metastatic ACC are worthy of consideration.
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PMID:[Prolonged Survival Achieved with Surgical Resection and Multidisciplinary Therapy for Acinar Cell Carcinoma of the Pancreas with Liver Metastases]. 2948 31

Pancreatic carcinoma is a highly malignant disease associated with an extremely poor prognosis, which is caused by late presentation, aggressive invasion and metastases, as well as the detection of pancreatic carcinoma in its advanced stages. Thus, better understanding of the tumour biology of this malignancy is sorely needed to improve the clinical outcome. A great challenge for the medical practice is finding a new biomarker of pancreatic carcinoma that will be helpful in diagnosis, in prognosis and in making clinical decisions, including the assessment of patients' response to therapy. It is suggested that selected chemokines and their specific receptors play an important role in tumour progression, such as tumour growth, angiogenesis, proliferation and development of metastasis. In the present review, general characteristics of chemokines and their specific receptors as well as the significance of these molecules in tumour development are described. The crucial issue of this review is to summarise the importance of various chemokines and their specific receptors in pancreatic carcinoma. Understanding the role of chemokines in the pathogenesis of pancreatic carcinoma is extremely important since these proteins may be used as a potential tool in the diagnosis and prognosis of pancreatic carcinoma patients.
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PMID:The role of selected chemokines and their specific receptors in pancreatic cancer. 2979 54


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