Pancreatic cyst aspiration analysis for cystic neoplasms: Mucin or carcinoembryonic antigen-Which is better?
Pancreatic cyst aspiration analysis for cystic neoplasms: Mucin or carcinoembryonic antigen-Which is better?
Surgery. 2010 Aug 24;
Authors: Morris-Stiff G, Lentz G, Chalikonda S, Johnson M, Biscotti C, Stevens T, Matthew Walsh R
BACKGROUND: Differentiation between the various pathologies presenting as a cystic pancreatic lesion is clinically important but often challenging. We have previously advocated the performance of endoscopic ultrasound (EUS) with aspiration and determination of mucin and carcinoembryonic antigen (CEA) content. We sought to report the results of this ongoing protocol and determine the relative importance of cyst fluid mucin and CEA for the diagnostic process. METHODS: The institutions prospectively maintained pancreatic cyst database was accessed to identify patients who had undergone pancreatic EUS and cyst aspiration as part of their evaluation. Only those patients who had subsequently undergone resection were selected, with histopathology being the gold standard for comparison. RESULTS: From January 2000 to July 2009, 174 patients with pancreatic cystic disease underwent surgery, 121 of whom had an EUS with aspiration attempted at our institution with specimens sent for mucin and CEA. Based on histopathology, 86 mucinous lesions were identified, including 44 cystadenomas, 34 intraductal papillary mucinous neoplasms, 7 mucinous adenocarcinomas, and 1 intraductal oncocytic papillary neoplasm; 42 were nonmucinous lesions. The median cyst CEA levels were significantly higher in the mucinous lesions group at 850 versus 2 ng/mL (P = .001). The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive diagnostic likelihood ratio, and negative diagnostic likelihood ratio (NDLR) were calculated respectively for mucin alone (0.80, 0.40, 0.61, 0.63, 1.33, 0.68); CEA alone (0.93, 0.43, 0.51, 0.91, 1.63, 0.16); cytology alone (0.38, 0.9, 0.92, 0.31, 3.67, 0.69); mucin or CEA (0.83, 0.65, 0.87, 0.57, 2.51, 0.26); mucin or CEA or cytology (0.92, 0.52, 0.86, 0.68, 1.91, 0.15); mucin plus CEA (0.96, 0.34, 0.25, 0.97, 1.45, 0.12); mucin plus cytology (0.25, 0.97, 0.96, 0.29,7.25, 0.78); CEA plus cytology (0.12, 1.00, 1.00, 0.26, infinity, 0.88); and mucin plus CEA plus cytology (0.08, 1.00, 1.00, 0.25, infinity, 0.92). CONCLUSION: Assessment of cyst mucin and CEA are complementary, with the best profile obtained when both markers are determined along with cytology. This combination provides a good sensitivity, PPV, and NDLR, as well as reasonable PPV and PDNR.
PMID: 20797749 [PubMed - as supplied by publisher]
Malignant potential of intraductal papillary mucinous neoplasms of the pancreas.
Malignant potential of intraductal papillary mucinous neoplasms of the pancreas.
Surg Today. 2010 Sep;40(9):816-24
Authors: Nakajima Y, Yamada T, Sho M
An intraductal papillary mucinous neoplasm (IPMN) is now a well-recognized disease entity. In general, the prognosis of IPMN is much more favorable than that of pancreatic ductal adenocarcinoma (PDAC). However, IPMN has a broad biological spectrum and it sometimes progresses, slowly showing neoplastic transformations. International consensus guidelines have been recently proposed for the management of IPMN. While they significantly contribute to appropriate management of IPMN, various issues including the natural history and malignant potential of IPMN are not fully elucidated. This review focuses on the malignant potential, including the postoperative recurrence of IPMN, coincidence of IPMN with PDAC, and extrapancreatic malignancy that may affect the long-term survival of the patients rather than IPMN itself.
PMID: 20740343 [PubMed - in process]
[Consensus guidelines for diagnosis, treatment and follow-up of patients with pancreatic neuroendocrine tumors]
[Consensus guidelines for diagnosis, treatment and follow-up of patients with pancreatic neuroendocrine tumors]
Lijec Vjesn. 2010 May-Jun;132(5-6):127-33
Authors: RustemoviÄ N, BerkoviÄ MC, ZjaciÄ-RotkviÄ V, OstojiÄ R, Hrabar D, SertiÄ J, JakiÄ-RazumoviÄ J, Kruslin B, Stern-Padovan R, Tezak S, KovaciÄ K, Vrbanec D, Belev B, Skegro M
Pancreatic neuroendocrine tumors (PETs) are increasingly recognized. In order to assure an optimal treatment of patients and to propose an efficient diagnostic algorithm we were prompted to organize meetings, with participating experts, specialists in different fields of expertise. The idea for the meetings was to try to give a standardized approach, which would in future help in stratification of PET patients. Results of meetings are given in a form of Consensus guidelines for diagnosis, treatment and follow-up of patients with pancreatic neuroendocrine tumors.
PMID: 20677617 [PubMed - indexed for MEDLINE]
[Our experience with pancreatic cancer and its relation to diabetes mellitus]
[Our experience with pancreatic cancer and its relation to diabetes mellitus]
Cas Lek Cesk. 2010;149(6):291-6
Authors: Krechler T, Zeman M, Vecka M, Jáchymová M, Horejs J, Krska Z, Ulrych J, Dusková J, Zák A
BACKGROUND: Despite the introduction of new imaging methods, the prognosis of pancreatic carcinoma (PC) remains hopeless. Therefore, there has been exerted much effort to elucidate the risk factor enabling the diagnosis of PC in the "preclinical state". At the time of PC diagnosis, more than 30% of patients suffer from diabetes mellitus, much more often than in the rest of the population. It is not clear whether DM is a risk factor for PC onset or DM appears secondary to the destruction of the gland by the tumor progression or by the effect of unknown factors produced by the cancer cells. METHODS AND RESULTS: We enrolled 204 individuals into the study, 69 of them were controls, 70 patients had type 2 diabetes mellitus and 65 cases had newly diagnosed PC. The patients with PC had in 68% of cases disturbed glucose homeostasis and significantly higher values of insulin resistance index (HOMA-IR) in comparison with the control group. The presence of glucose homeostasis disturbances does not influence tumor staging and localization. CONCLUSIONS: Results of our pilot study confirmed the so far unsatisfactory state of PC diagnostics (majority of cases fall to stages III and IV) and corroborated the close relation to DM. The early markers for the risk of pancreatic carcinoma development should be searched among the factors participating in the regulation of the glucose homeostasis and insulin sensitivity.
PMID: 20662478 [PubMed - indexed for MEDLINE]
Safety, efficacy and pharmacokinetics of nimotuzumab, a humanized monoclonal anti-epidermal growth factor receptor (EGFR) antibody, in patients with locally advanced or metastatic pancreatic cancer.
Safety, efficacy and pharmacokinetics of nimotuzumab, a humanized monoclonal anti-epidermal growth factor receptor (EGFR) antibody, in patients with locally advanced or metastatic pancreatic cancer.
Int J Clin Pharmacol Ther. 2010 Jul;48(7):473-5
Authors: Strumberg D, Schultheis B, Scheulen ME, Hilger RA, Krauss J, Marschner N, Lordick F, Bach F, Reuter D, Edler L, Mross K
PMID: 20557849 [PubMed - indexed for MEDLINE]
First-line treatment of patients with metastatic pancreatic cancer: results of a Phase II trial with S-1 (CESAR-Study group).
First-line treatment of patients with metastatic pancreatic cancer: results of a Phase II trial with S-1 (CESAR-Study group).
Int J Clin Pharmacol Ther. 2010 Jul;48(7):470-2
Authors: Strumberg D, Bergmann L, Graeven U, Hanauske A, Lipp R, Schuette J, Schultheis B, Scigalla P, Urrea P, Scheulen ME
PMID: 20557848 [PubMed - indexed for MEDLINE]
ARQ-197, an oral small-molecule inhibitor of c-Met for the treatment of solid tumors.
ARQ-197, an oral small-molecule inhibitor of c-Met for the treatment of solid tumors.
IDrugs. 2010 Jun;13(6):404-14
Authors: Bagai R, Fan W, Ma PC
ARQ-197 is an oral, selective c-Met inhibitor under development by ArQule Inc, in partnership with Daiichi Sankyo Co Ltd and Asian licensee Kyowa Hakko Kirin Co Ltd, for the potential treatment of solid tumors, including NSCLC, hepatocellular carcinoma and pancreatic cancer, as well as microphthalmia transcription factor-driven tumors. c-Met, a key cell surface receptor tyrosine kinase involved in diverse regulatory functions, is often aberrantly activated in human cancers. While the precise mechanism of action of ARQ-197 remains undefined, data from preclinical studies have demonstrated that ARQ-197 inhibits c-Met activation in numerous human tumor cell lines and specifically targets c-Met in various cancer types; uniquely, ARQ-197 inhibits c-Met in a non-ATP-competitive manner. Phase I/II clinical trials demonstrated promise in terms of both tolerability and tumor response. Intriguingly, dose-limiting adverse effects were hematological in nature. Combinational trials are also ongoing to take advantage of the signaling crosstalk between c-Met and other oncogenic signaling systems. Prioritization of the clinical development of c-Met inhibitors, such as ARQ-197, among different tumor disease types is a key challenge at present; an improved understanding of the prediction of molecular determinants in tumors with respect to c-Met kinase as the driver oncogenic receptor, and of the prediction of tumor response, is still urgently needed.
PMID: 20506063 [PubMed - indexed for MEDLINE]
Functionalized near-infrared quantum dots for in vivo tumor vasculature imaging.
Functionalized near-infrared quantum dots for in vivo tumor vasculature imaging.
Nanotechnology. 2010 Apr 9;21(14):145105
Authors: Hu R, Yong KT, Roy I, Ding H, Law WC, Cai H, Zhang X, Vathy LA, Bergey EJ, Prasad PN
In this paper, we report the use of near-infrared (NIR)-emitting alloyed quantum dots (QDs) as efficient optical probes for high contrast in vivo imaging of tumors. Alloyed CdTe(1 - x)Se(x)/CdS QDs were prepared in the non-aqueous phase using the hot colloidal synthesis approach. Water dispersion of the QDs were accomplished by their encapsulation within polyethyleneglycol (PEG)-grafted phospholipid micelles. For tumor-specific delivery in vivo, the micelle-encapsulated QDs were conjugated with the cyclic arginine-glycine-aspartic acid (cRGD) peptide, which targets the alpha(v)beta(3) integrins overexpressed in the angiogenic tumor vasculatures. Using in vivo NIR optical imaging of mice bearing pancreatic cancer xenografts, implanted both subcutaneously and orthotopically, we have demonstrated that systemically delivered cRGD-conjugated QDs, but not the unconjugated ones, can efficiently target and label the tumors with high signal-to-noise ratio. Histopathological analysis of major organs of the treated mice showed no evidence of systemic toxicity associated with these QDs. These experiments suggest that cRGD-conjugated NIR QDs can serve as safe and efficient probes for optical bioimaging of tumors in vivo. Furthermore, by co-encapsulating these QDs and anticancer drugs within these micelles, we have demonstrated a promising theranostic, nanosized platform for both cancer imaging and therapy.
PMID: 20234074 [PubMed - indexed for MEDLINE]
Proportional hazards models and age-period-cohort analysis of cancer rates.
Proportional hazards models and age-period-cohort analysis of cancer rates.
Stat Med. 2010 May 20;29(11):1228-38
Authors: Rosenberg PS, Anderson WF
Age-period-cohort (APC) analysis is widely used in cancer epidemiology to model trends in cancer rates. We develop methods for comparative APC analysis of two independent cause-specific hazard rates assuming that an APC model holds for each one. We construct linear hypothesis tests to determine whether the two hazards are absolutely proportional or proportional after stratification by cohort, period, or age. When a given proportional hazards model appears adequate, we derive simple expressions for the relative hazards using identifiable APC parameters. To demonstrate the utility of these new methods, we analyze cancer incidence rates in the United States in blacks versus whites for selected cancers, using data from the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. The examples illustrate that each type of proportionality may be encountered in practice.
PMID: 20209480 [PubMed - indexed for MEDLINE]
[Liver metastases of pancreatic endocrine carcinoma]
[Liver metastases of pancreatic endocrine carcinoma]
Med Clin (Barc). 2010 Apr 17;134(11):519
Authors: Antón MartÃnez J, Alvarez GarcÃa JF, Ruiz-Ayucar Imbert JM
PMID: 19767030 [PubMed - indexed for MEDLINE]
Postoperative external beam radiotherapy for resected pancreatic adenocarcinoma: impact of chemotherapy on local control and survival.
Postoperative external beam radiotherapy for resected pancreatic adenocarcinoma: impact of chemotherapy on local control and survival.
Anticancer Res. 2010 Jul;30(7):2959-67
Authors: Ogawa K, Shibuya H, Uchida N, Onishi H, Okuno Y, Myojin M, Kobayashi M, Ogawa Y, Kanesaka N, Shibuya K, Tokumaru S, Sasamoto R, Karasawa K, Nemoto K, Nishimura Y,
AIM: To analyze retrospectively the results of postoperative external beam radiotherapy (EBRT) for resected pancreatic adenocarcinoma. PATIENTS AND METHODS: The records of 47 patients treated with gross complete resection (R0: 24 patients, R1: 23 patients) and post-operative EBRT were reviewed. The median dose of EBRT was 50 Gy (range, 12-60 Gy), and chemotherapy was used in 37 patients (78.7%). The median follow-up period for all 47 patients was 14.4 months (range, 0.9-67.9 months). RESULTS: At the time of this analysis, 24 patients (51.1%) had disease recurrence. Local failure was observed in 10 patients (21.3%), and the 2-year local control (LC) rate in all patients was 68.7%. Patients treated with EBRT and chemotherapy had a significantly more favorable LC (2-year LC rate: 76.0%) than those treated with EBRT alone (2-year LC rate: 40%, p=0.0472). The median survival time and the 2-year actuarial overall survival (OS) in all 47 patients were 30.0 months and 54.5%, respectively. Patients treated with EBRT and chemotherapy had a significantly more favorable OS (2-year OS rate: 61.6%) than those treated with EBRT alone (2-year OS: 25.0%, p=0.0454). On univariate analysis, chemotherapy use alone had a significant impact on OS, and on multivariate analysis, chemotherapy use also was a significant prognostic factor. There were no late morbidities of NCI-CTC Grade 3 or greater. CONCLUSION: Post-operative EBRT with chemotherapy yields a favorable LC rate for resected pancreatic adenocarcionoma, and EBRT combined with chemotherapy confers a survival benefit compared to EBRT alone.
PMID: 20683039 [PubMed - indexed for MEDLINE]
Gemcitabine alone or in combination with cisplatin in patients with biliary tract cancer: a comparative multicentre study in Japan.
Gemcitabine alone or in combination with cisplatin in patients with biliary tract cancer: a comparative multicentre study in Japan.
Br J Cancer. 2010 Aug 10;103(4):469-74
Authors: Okusaka T, Nakachi K, Fukutomi A, Mizuno N, Ohkawa S, Funakoshi A, Nagino M, Kondo S, Nagaoka S, Funai J, Koshiji M, Nambu Y, Furuse J, Miyazaki M, Nimura Y
BACKGROUND: A British randomised study of gemcitabine plus cisplatin (GC) combination showed promising results in biliary tract cancer (BTC) patients. In our study, we evaluated the efficacy and safety of this combination compared with gemcitabine alone (G) in Japanese BTC patients. METHODS: Overall, 84 advanced BTC patients were randomised to either cisplatin 25 mg m(-2) plus gemcitabine 1000 mg m(-2) on days 1, 8 of a 21-day cycle (GC-arm), or single-agent gemcitabine 1000 mg m(-2) on days 1, 8 and 15 of a 28-day cycle (G-arm). Treatments were repeated for at least 12 weeks until disease progression or unacceptable toxicity occurred, up to a maximum of 48 weeks. RESULTS: A total of 83 patients were included in the analysis. For the GC and G-arms, respectively, the 1-year survival rate was 39.0 vs 31.0%, median survival time 11.2 vs 7.7 months, median progression-free survival time 5.8 vs 3.7 months and overall response rate 19.5 vs 11.9%. The most common grade 3 or 4 toxicities (GC-arm/G-arm) were neutropenia (56.1%/38.1%), thrombocytopenia (39.0%/7.1%), leukopenia (29.3%/19.0%), haemoglobin decrease (36.6%/16.7%) and gamma-GTP increase (29.3%/35.7%). CONCLUSIONS: Gemcitabine plus cisplatin combination therapy was found to be effective and well tolerated, suggesting that it could also be a standard regimen for Japanese patients.
PMID: 20628385 [PubMed - indexed for MEDLINE]
Safety, efficacy and pharmacokinetics of nimotuzumab, a humanized monoclonal anti-epidermal growth factor receptor (EGFR) antibody, in patients with locally advanced or metastatic pancreatic cancer.
Safety, efficacy and pharmacokinetics of nimotuzumab, a humanized monoclonal anti-epidermal growth factor receptor (EGFR) antibody, in patients with locally advanced or metastatic pancreatic cancer.
Int J Clin Pharmacol Ther. 2010 Jul;48(7):473-5
Authors: Strumberg D, Schultheis B, Scheulen ME, Hilger RA, Krauss J, Marschner N, Lordick F, Bach F, Reuter D, Edler L, Mross K
PMID: 20557849 [PubMed - indexed for MEDLINE]
First-line treatment of patients with metastatic pancreatic cancer: results of a Phase II trial with S-1 (CESAR-Study group).
First-line treatment of patients with metastatic pancreatic cancer: results of a Phase II trial with S-1 (CESAR-Study group).
Int J Clin Pharmacol Ther. 2010 Jul;48(7):470-2
Authors: Strumberg D, Bergmann L, Graeven U, Hanauske A, Lipp R, Schuette J, Schultheis B, Scigalla P, Urrea P, Scheulen ME
PMID: 20557848 [PubMed - indexed for MEDLINE]
Phase I study of the botanical formulation PHY906 with capecitabine in advanced pancreatic and other gastrointestinal malignancies.
Phase I study of the botanical formulation PHY906 with capecitabine in advanced pancreatic and other gastrointestinal malignancies.
Phytomedicine. 2010 Mar;17(3-4):161-9
Authors: Saif MW, Lansigan F, Ruta S, Lamb L, Mezes M, Elligers K, Grant N, Jiang ZL, Liu SH, Cheng YC
PURPOSE: The botanical formulation, PHY906, has been used widely in Eastern countries to treat gastrointestinal symptoms including diarrhea, nausea and vomiting. PHY906 may also have anti-tumor properties and may potentiate the action of several chemotherapeutic agents based on pre-clinical studies. We conducted a Phase I study using PHY906 in combination with capecitabine in patients with advanced pancreatic and gastrointestinal malignancies to determine the maximum tolerated dose (MTD) of capecitabine in combination with PHY906. PATIENTS AND METHODS: This study was a single institution, open-label, Phase I study of PHY906 800mg BID on days 1-4 in combination with escalating doses of capecitabine (1000, 1250, 1500, and 1750mg/m(2)) orally twice daily on days 1-7 of a 14-day cycle (7/7 schedule). Capecitabine was increased until the appearance of dose limiting toxicities (DLTs). Measurements of efficacy included tumor response by Response Evaluation Criteria in Solid Tumors (RECIST). RESULTS: Twenty-four patients with a median age of 67 years (range 40-84) with pancreatic cancer (15), colon cancer (6), cholangiocarcinoma (1), esophageal cancer (1) and unknown primary (1) received a total of 116 cycles (median 5 cycles; range 1-17 cycles) over 4 dose levels of capecitabine. One DLT (Grade 4 AST/ALT, Grade 3 hyponatremia) was observed in the 1000mg/m(2) cohort of patients. No further DLT was observed in the subsequent cohorts and doses of capecitabine were escalated to 1750mg/m(2) BID. There were no DLTs at the maximum dose level of 1750mg/m(2), however, the delivered dose-intensity of capecitabine was similar at the 1750mg/m(2) dose level as the 1500mg/m(2) dose level. Therefore, the MTD was defined at 1500mg/m(2) of capecitabine in this dosing schedule with PHY906. One patient achieved a partial response, and 13 patients had stable disease that lasted more than six weeks. CONCLUSION: The MTD of capecitabine was determined to be 1500mg/m(2) BID administered in a 7/7 schedule, in combination with PHY906 800mg BID on days 1-4. This combination was well tolerated and warrants further study.
PMID: 20092990 [PubMed - indexed for MEDLINE]
Well-differentiated neuroendocrine carcinoma (malignant carcinoid) of the extrahepatic biliary tract: report of two cases and literature review.
Well-differentiated neuroendocrine carcinoma (malignant carcinoid) of the extrahepatic biliary tract: report of two cases and literature review.
APMIS. 2010 Aug;118(8):543-56
Authors: Squillaci S, Marchione R, Piccolomini M, Colombo F, Bucci F, Bruno M, Bisceglia M
The objectives of this study were to evaluate the frequency of carcinoid tumors of the extrahepatic biliary ducts (EHBDs) and the pathologic progression and the role of surgery in the management of this disease. We describe two cases of malignant carcinoids of the EHBDs, which presented as common bile duct tumors in two adult male patients, aged 52 and 70 years, who were diagnosed histologically on surgical resection specimens. A comprehensive review of the literature has also been performed with a focus on survival data. Microscopically, the tumors presented herein were composed of relatively small rounded cells with a trabecular or nesting pattern. Both cases were diffusely immunopositive for chromogranin and synaptophysin, and one of them was also focally reactive with somatostatin and pancreatic polypeptide. There was no expression in any of these tumors of thyroid transcription factor-1 (TTF-1), gastrin, insulin, glucagon, vasoactive intestinal peptide (VIP) and prolactin. The tumor showed transmural invasion in both cases, with lymph node metastasis and subcapsular liver tissue infiltration in one. Both patients are alive with no evidence of disease 41 months and 59 months, respectively, after surgery. Despite being extremely uncommon, with only 70 cases reported to date, carcinoids should be included in the differential diagnosis of EHBD tumors. This study emphasizes the necessity of complete surgical resection as the gold standard treatment for these lesions, and the importance of a correct pathologic diagnosis for prognostic implications.
PMID: 20666735 [PubMed - indexed for MEDLINE]
Well-differentiated neuroendocrine carcinoma (malignant carcinoid) of the extrahepatic biliary tract: report of two cases and literature review.
Well-differentiated neuroendocrine carcinoma (malignant carcinoid) of the extrahepatic biliary tract: report of two cases and literature review.
APMIS. 2010 Aug;118(8):543-56
Authors: Squillaci S, Marchione R, Piccolomini M, Colombo F, Bucci F, Bruno M, Bisceglia M
The objectives of this study were to evaluate the frequency of carcinoid tumors of the extrahepatic biliary ducts (EHBDs) and the pathologic progression and the role of surgery in the management of this disease. We describe two cases of malignant carcinoids of the EHBDs, which presented as common bile duct tumors in two adult male patients, aged 52 and 70 years, who were diagnosed histologically on surgical resection specimens. A comprehensive review of the literature has also been performed with a focus on survival data. Microscopically, the tumors presented herein were composed of relatively small rounded cells with a trabecular or nesting pattern. Both cases were diffusely immunopositive for chromogranin and synaptophysin, and one of them was also focally reactive with somatostatin and pancreatic polypeptide. There was no expression in any of these tumors of thyroid transcription factor-1 (TTF-1), gastrin, insulin, glucagon, vasoactive intestinal peptide (VIP) and prolactin. The tumor showed transmural invasion in both cases, with lymph node metastasis and subcapsular liver tissue infiltration in one. Both patients are alive with no evidence of disease 41 months and 59 months, respectively, after surgery. Despite being extremely uncommon, with only 70 cases reported to date, carcinoids should be included in the differential diagnosis of EHBD tumors. This study emphasizes the necessity of complete surgical resection as the gold standard treatment for these lesions, and the importance of a correct pathologic diagnosis for prognostic implications.
PMID: 20666735 [PubMed - indexed for MEDLINE]