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Agarwal S, Gunjan D, Gopi S, Saraya A. Combination of Serum CA 19-9 and Endoscopic Ultrasound Findings Can Predict Malignancy Risk in Patients With Chronic Pancreatitis Presenting With Pancreatic Head Mass: A Proof-of-Concept Study. Pancreas 2024; 53:e168-e175. [PMID: 38019612 DOI: 10.1097/mpa.0000000000002279] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/01/2023]
Abstract
BACKGROUND AND AIMS Inflammatory head mass of pancreas (IMP) developing in background of chronic pancreatitis (CP) is difficult to distinguish from carcinoma pancreas. We aimed to delineate natural course of IMP and predict their malignancy risk, avoiding unnecessary biopsies. MATERIALS AND METHODS In this retrospective single-center study, clinical records of patients with CP with diagnosed pancreatic head mass were reviewed. Clinical, laboratory, imaging, endoscopic findings, and follow-up details were retrieved from prospectively maintained database. A diagnostic nomogram was developed combining serum cancer antigen 19-9 and endoscopic ultrasound (EUS) findings to predict the risk of malignancy. RESULTS We identified 107 patients with pancreatic head mass with CP of whom 87 (81.3%) were IMP and 20 (18.7%) were malignant. Patients with IMP were more frequently young males with alcohol-related CP and low CA 19-9 in comparison with those with malignancy (age IMP: 41.3 ± 11.3 vs carcinoma: 49.3 ± 14.5 years [ P = 0.009]; males 89.7% vs 65% [ P = 0.011]; alcoholic etiology: 71.3% vs 20% [ P < 0.001]; median CA 19-9: 25.78 [interquartile range, 7.20-120.60] vs 1034.50 [106.65-7808.25] [ P < 0.001]). A diagnostic nomogram combining CA 19-9 and EUS findings could identify malignancy with an optimism-corrected c-statistic of 0.905, which was better than both CA 19-9 (0.80) and EUS alone (0.826). Patients with IMP had relatively benign disease course with 40.2% biliary obstruction, 20.7% portal venous thrombosis, 14.9% gastric outlet obstruction, and 1-, 3-, and 5-year survival being 97.3%, 92.7%, and 92.0%, respectively. Surgery was required in only 12 patients (13.8%) with IMP. CONCLUSIONS Combination of CA 19-9 and EUS best identifies malignancy risk in patients with IMP, who have otherwise benign course.
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Affiliation(s)
- Samagra Agarwal
- From the Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, India
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Zhao B, Zhao B, Chen F. Diagnostic value of serum carbohydrate antigen 19-9 in pancreatic cancer: a systematic review and meta-analysis. Eur J Gastroenterol Hepatol 2022; 34:891-904. [PMID: 35913776 DOI: 10.1097/meg.0000000000002415] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
Carbohydrate antigen 19-9 (CA19-9) is the most widely used serum biomarker for detecting pancreatic cancer (PC). Since early diagnosis is important for improving PC prognosis, a comprehensive understanding of the diagnostic performance of CA19-9 is critical. This study focused on comprehensive evaluation of the efficacy of CA19-9 in PC diagnosis. Literature research was based on the seven databases. Studies released from January 2002 to January 2022 focused on the efficacy of CA19-9 in the detection of PC were included. Summarized sensitivity, specificity, and sROC/accuracy of discrimination (AUC) were estimated. Potential publication bias was measured with Funnel plot and Egger's test. Meta-regression was performed to detect possible causes of heterogeneity. Subgroup analysis was used to assess the diagnostic efficacy of CA19-9 under different conditions. The study is registered on PROSPERO (CRD42021253861). Seventy-nine studies containing 20 991 participants who met the criteria were included. The pooled sensitivity, specificity, and AUC of CA19-9 in diagnose PC were 72% (95% CI, 71-73%), 86% (95% CI, 85-86%), and 0.8474 (95% CI, 0.8272-0.8676). Subgroup analysis suggested that the diagnostic efficiency of CA19-9 in studies with healthy controls was the highest, followed by intraductal papillary mucinous neoplasm, in pancreatitis and diabetes were consistent with the overall result. Our analysis showed that serum CA19-9 had high and stable diagnostic efficacy for PC (not affected by diabetes). Subgroup analysis showed that serum CA19-9 yielded highest effectiveness in the diagnosis of pancreatic precancerous lesions, which indicated an irreplaceable clinical value in the early detection and warning value for PC.
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Affiliation(s)
- Boqiang Zhao
- Xi'an Jiaotong University Health Science Center, Xi'an, China
- The First School of Clinical Medicine, Xi'an, China
| | - Boyue Zhao
- Xi'an Jiaotong University Health Science Center, Xi'an, China
- Department of Epidemiology and Biostatistics, School of Public Health, Xi'an, China
| | - Fangyao Chen
- Xi'an Jiaotong University Health Science Center, Xi'an, China
- Department of Epidemiology and Biostatistics, School of Public Health, Xi'an, China
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Circulating Nucleic Acids as Novel Biomarkers for Pancreatic Ductal Adenocarcinoma. Cancers (Basel) 2022; 14:cancers14082027. [PMID: 35454933 PMCID: PMC9031361 DOI: 10.3390/cancers14082027] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2022] [Revised: 04/12/2022] [Accepted: 04/15/2022] [Indexed: 02/01/2023] Open
Abstract
Despite considerable advancements in the clinical management of PDAC it remains a significant cause of mortality. PDAC is often diagnosed at advanced stages due to vague symptoms associated with early-stage disease and a lack of reliable diagnostic biomarkers. Late diagnosis results in a high proportion of cases being ineligible for surgical resection, the only potentially curative therapy for PDAC. Furthermore, a lack of prognostic biomarkers impedes clinician's ability to properly assess the efficacy of therapeutic interventions. Advances in our ability to detect circulating nucleic acids allows for the advent of novel biomarkers for PDAC. Tumor derived circulating and exosomal nucleic acids allow for the detection of PDAC-specific mutations through a non-invasive blood sample. Such biomarkers could expand upon the currently limited repertoire of tests available. This review outlines recent developments in the use of molecular techniques for the detection of these nucleic acids and their potential roles, alongside current techniques, in the diagnosis, prognosis and therapeutic governance of PDAC.
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Arivazhagan S, Kantamani D, Tanner NE, Kundranda MN, Stagg MP. Infection Masquerading as Recurrence of Pancreatic Ductal Adenocarcinoma: A Cautionary Tale. Cureus 2021; 13:e17010. [PMID: 34540411 PMCID: PMC8424059 DOI: 10.7759/cureus.17010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/08/2021] [Indexed: 11/05/2022] Open
Abstract
We present a case of a 59-year-old male undergoing adjuvant chemotherapy for his pancreatic adenocarcinoma post-surgical resection. He had an acute rise in carbohydrate antigen (CA) 19-9 level, which raised suspicion of metastatic disease. Instead, the patient was diagnosed to have a liver abscess, the treatment of which brought the CA 19-9 level back to normal. Unfortunately, although CA 19-9 is Food and Drug Administration (FDA)-approved tumor marker for pancreatic cancer, it is also elevated in several benign conditions, causing fear of cancer and unnecessary diagnostic workup. Hence, caution is necessary for interpreting the significance of its elevation.
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Affiliation(s)
| | - Deepti Kantamani
- Internal Medicine, Baton Rouge General Medical Center, Baton Rouge, USA
| | | | | | - M Patrick Stagg
- Internal Medicine Residency Program, Baton Rouge General Medical Center, Baton Rouge, USA
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Xia J, Zhang H, Guan Q, Wang S, Li Y, Xie J, Li M, Huang H, Yan H, Chen T. Qualitative diagnostic signature for pancreatic ductal adenocarcinoma based on the within-sample relative expression orderings. J Gastroenterol Hepatol 2021; 36:1714-1720. [PMID: 33150986 DOI: 10.1111/jgh.15326] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2020] [Revised: 10/18/2020] [Accepted: 10/24/2020] [Indexed: 12/13/2022]
Abstract
BACKGROUND Pancreatic ductal adenocarcinoma (PDAC) accounts for about 90% of pancreatic cancer, which is one of the most aggressive malignant neoplasms with a 9.3% five-year survival rate. The pathological biopsy is the current golden standard for confirming suspicious lesions of PDAC, but it is not entirely reliable because of the insufficient sampling amount and inaccurate sampling location. Therefore, developing a robust signature to aid the accurate diagnosis of PDAC is critical. METHODS Based on the within-sample relative expression orderings of gene pairs, we identified a qualitative signature to discriminate both PDAC and adjacent samples from both chronic pancreatitis and normal samples in the training datasets and validated it in other independent datasets produced by different laboratories with different measuring platforms. RESULTS A six-gene-pair signature was identified in the training data and validated in eight independent datasets. For surgical samples, 96.63% of 356 PDAC tissues, 100% of 11 pancreatitis tissues of non-cancer patients, and 23 of 24 normal pancreatic tissues were correctly classified. Especially, 59 of 60 cancer-adjacent normal tissues of PDAC patients were correctly identified as PDAC. For biopsy samples, all of 11 PDAC biopsy tissues were correctly classified as PDAC. CONCLUSION The signature can distinguish both PDAC and PDAC-adjacent normal tissues from both chronic pancreatitis and normal tissues of non-cancer patients even when the sampling locations are inaccurate, which can aid the diagnosis of PDAC.
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Affiliation(s)
- Jie Xia
- Department of Bioinformatics, Fujian Key Laboratory of Medical Bioinformatics, Key Laboratory of Ministry of Education for Gastrointestinal Cancer, The School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China
| | - Huarong Zhang
- Department of Bioinformatics, Fujian Key Laboratory of Medical Bioinformatics, Key Laboratory of Ministry of Education for Gastrointestinal Cancer, The School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China
| | - Qingzhou Guan
- Department of Bioinformatics, Fujian Key Laboratory of Medical Bioinformatics, Key Laboratory of Ministry of Education for Gastrointestinal Cancer, The School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China
| | - Shanshan Wang
- Department of Bioinformatics, Fujian Key Laboratory of Medical Bioinformatics, Key Laboratory of Ministry of Education for Gastrointestinal Cancer, The School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China
| | - Yawei Li
- Department of Bioinformatics, Fujian Key Laboratory of Medical Bioinformatics, Key Laboratory of Ministry of Education for Gastrointestinal Cancer, The School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China
| | - Jiajing Xie
- Department of Bioinformatics, Fujian Key Laboratory of Medical Bioinformatics, Key Laboratory of Ministry of Education for Gastrointestinal Cancer, The School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China
| | - Meifeng Li
- Department of Bioinformatics, Fujian Key Laboratory of Medical Bioinformatics, Key Laboratory of Ministry of Education for Gastrointestinal Cancer, The School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China
| | - Haiyan Huang
- Department of Bioinformatics, Fujian Key Laboratory of Medical Bioinformatics, Key Laboratory of Ministry of Education for Gastrointestinal Cancer, The School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China
| | - Haidan Yan
- Department of Bioinformatics, Fujian Key Laboratory of Medical Bioinformatics, Key Laboratory of Ministry of Education for Gastrointestinal Cancer, The School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China
| | - Ting Chen
- Department of Bioinformatics, Fujian Key Laboratory of Medical Bioinformatics, Key Laboratory of Ministry of Education for Gastrointestinal Cancer, The School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China
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Pancreatoduodenectomy for Periampullary Tumors Presenting with Acute Pancreatitis. Gastroenterol Res Pract 2020; 2020:7246895. [PMID: 32190043 PMCID: PMC7064839 DOI: 10.1155/2020/7246895] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2019] [Accepted: 02/12/2020] [Indexed: 12/30/2022] Open
Abstract
Background Periampullary tumors (PT) may rarely present as acute pancreatitis (AP) or acute recurrent pancreatitis (ARP). Unlike other cases of AP and ARP, these conditions necessitate pancreaticoduodenectomy (PD), and timely diagnosis is crucial. Materials and Methods. A retrospective review of clinical, radiological, surgical, and pathological data was conducted for patients admitted to the Binzhou Medical University Hospital during the period from January 2010 to December 2017, for AP or ARP caused by PT. All patients included in the study group had undergone PD. The perioperative data for these patients was compared with data for patients with PT but without AP or ARP who underwent PD during the same period (control group). Results During the study period, 412 patients with AP or ARP were treated; among this group, 15 patients had PT. Compared with controls, patients in the study group were younger in age and had a longer course of disease, more frequent hospitalizations, and more severe derangements in laboratory data (P < 0.05). Operative time and intraoperative blood loss were significantly higher in the study group, but the incidence of postoperative outcomes such as pancreatic/biliary fistula, abdominal infection, postoperative hospital stay, and mortality were similar between groups (P < 0.05). Operative time and intraoperative blood loss were significantly higher in the study group, but the incidence of postoperative outcomes such as pancreatic/biliary fistula, abdominal infection, postoperative hospital stay, and mortality were similar between groups ( Conclusions Neither AP nor ARP has any adverse impact on the outcomes of PD. However, in the treatment of younger patients suffering from AP or ARP, unexplained pancreatic duct dilation and weight loss should raise the suspicion of PT. EUS and EUS-FNA may be helpful in making the diagnosis.
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Sabetkish N, Sabetkish S, Mohseni MJ, Kajbafzadeh AM. Prevention of Renal Scarring in Acute Pyelonephritis by Probiotic Therapy: an Experimental Study. Probiotics Antimicrob Proteins 2019; 11:158-164. [PMID: 29204797 DOI: 10.1007/s12602-017-9363-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
We evaluated the protective effects of probiotic administration as a prophylaxis treatment and immediately after fever onset in increasing the immune response and decreasing the renal scarring in a rat model of acute pyelonephritis. Twenty-four rats were apportioned to three groups. In GI (n = 8), the rats were injected with direct inoculation of Escherichia coli into the right kidney. In GII (n = 8), the rats received a probiotic regimen 1 month before E. coli injection and the probiotic regimen was continued for the next 2 months. In GIII (n = 8), the probiotic regimen was started just after E. coli injection and was continued for 2 months. Technetium-99m-DMSA renal scan, histopathological evaluations, concentrations of CA19-9, IgA, blood urea nitrogen (BUN), and creatinine were assessed 1 and 2 months post-injection. It took an average of 4.2 ± 1.1 h between the injection and onset of fever in GI and GII. In GIII, this period was longer (7.5 ± 1.4). Probiotic administration resulted in reduction of interstitial fibrosis and tubular and glomerular atrophy in GII in all follow-ups. Technetium-99m-DMSA renal scan showed that the right kidney reached near the normal cortical integrity (47%) in GII compared to GI (32%) after 2 months of injection. However, the renal integrity did not improve significantly in GIII (41%). In GII, CA19-9 was lower (p < 0.05), while the levels of serum and fecal IgA were higher (p < 0.05). Administration of the probiotic regimen in the rat model may decrease renal damage in pyelonephritis. In spite of better results in the prophylactic group compared to the treatment group, no strong evidence was found to prove the advantage of its prophylactic application over the treatment administration.
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Affiliation(s)
- Nastaran Sabetkish
- Pediatric Urology and Regenerative Medicine Research Center, Section of Tissue Engineering and Stem Cells Therapy, Children's Hospital Medical Center, Tehran University of Medical Sciences, No. 62, Dr. Qarib's Street, Keshavarz Boulevard, Tehran, 1419433151, Iran
| | - Shabnam Sabetkish
- Pediatric Urology and Regenerative Medicine Research Center, Section of Tissue Engineering and Stem Cells Therapy, Children's Hospital Medical Center, Tehran University of Medical Sciences, No. 62, Dr. Qarib's Street, Keshavarz Boulevard, Tehran, 1419433151, Iran
| | - Mohammad Javad Mohseni
- Pediatric Urology and Regenerative Medicine Research Center, Section of Tissue Engineering and Stem Cells Therapy, Children's Hospital Medical Center, Tehran University of Medical Sciences, No. 62, Dr. Qarib's Street, Keshavarz Boulevard, Tehran, 1419433151, Iran
| | - Abdol-Mohammad Kajbafzadeh
- Pediatric Urology and Regenerative Medicine Research Center, Section of Tissue Engineering and Stem Cells Therapy, Children's Hospital Medical Center, Tehran University of Medical Sciences, No. 62, Dr. Qarib's Street, Keshavarz Boulevard, Tehran, 1419433151, Iran.
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Igbinigie E, Guo F, Jiang SW, Kelley C, Li J. Dkk1 involvement and its potential as a biomarker in pancreatic ductal adenocarcinoma. Clin Chim Acta 2019; 488:226-234. [PMID: 30452897 DOI: 10.1016/j.cca.2018.11.023] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2018] [Revised: 11/12/2018] [Accepted: 11/14/2018] [Indexed: 02/05/2023]
Abstract
Dickkopf-1 (Dkk1)'s dysregulation has been implicated in the pathogenesis of a variety of cancers. It is part of the Dkk family of proteins that includes Dkk2, Dkk3 and Dkk4. This family of secreted proteins shares similar conserved cysteine domains and inhibits the Wnt/b-catenin pathway by causing proteasomal B-catenin degradation, inducing apoptosis, and preventing cell proliferation. Pancreatic ductal adenocarcinoma (PDAC) is the 4th leading cause of cancer mortality in the United States due to the late stage of diagnosis and the limited effectiveness of current therapy. Dkk1 is found increased in PADC patients' specimens and serum. Dkk1 can be a promising biomarker specific to PDAC, which has the potential to increase PDAC survival rates through improving early stage detection and monitoring progression compared to current biomarker gold standards. In addition, recent studies suggest that Dkk1 could be an excellent target for cancer immunotherapy. Interestingly, Dkk1-CKAP4-PI3K/AKT signal pathway also plays role in pancreatic cancer cell proliferation. In this review, we present the multiple mechanisms of Dkk1 in PDAC studied thus far and explore its function, regulation, and clinical applications in gynecological cancers including pancreatic ductal adenocarcinoma (PDAC), breast, ovarian, cervical, and endometrial cancer. Further research into Dkk1's mechanism and use as a diagnostic tool, alone or in combination with other biomarkers, could prove clinically useful for better understanding the pathology of PDAC and improving its early detection and treatment.
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Affiliation(s)
- Eseosaserea Igbinigie
- Department of Biomedical Sciences, Mercer University School of Medicine, Savannah, GA 31404, USA.
| | - Fengbiao Guo
- Department of Biomedical Sciences, Mercer University School of Medicine, Savannah, GA 31404, USA; Department of Histology and Embryology, Shantou University Medical College, Shantou 515000, China.
| | - Shi-Wen Jiang
- Department of Biomedical Sciences, Mercer University School of Medicine, Savannah, GA 31404, USA.
| | - Cullen Kelley
- Department of Biomedical Sciences, Mercer University School of Medicine, Savannah, GA 31404, USA.
| | - Jinping Li
- Department of Biomedical Sciences, Mercer University School of Medicine, Savannah, GA 31404, USA; Department of Biochemistry and Molecular Biology, Mayo Clinic, Florida Campus, Jacksonville, FL 32224, USA.
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Kakkat S, Rajan R, Sindhu RS, Natesh B, Raviram S. Comparison of platelet-lymphocyte ratio and CA 19-9 in differentiating benign from malignant head masses in patients with chronic pancreatitis. Indian J Gastroenterol 2017; 36:263-267. [PMID: 28916969 DOI: 10.1007/s12664-017-0768-y] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2016] [Accepted: 07/01/2017] [Indexed: 02/04/2023]
Abstract
INTRODUCTION Pancreatic head ductal adenocarcinoma (PDAC) and inflammatory head masses (IHM) related to chronic pancreatitis are often difficult to differentiate. PDAC produces significant inflammatory response with resultant lymphopenia and thrombocytosis. The prognostic role of platelet-lymphocyte ratio (PLR) as a tumor marker has been defined. We aimed to find the role of PLR as a diagnostic marker for PDAC in differentiating benign head mass comparing with carbohydrate antigen 19-9 (CA 19-9). METHODS A prospective study of patients with biopsy-proven PDAC and benign IHM with underlying chronic pancreatitis from 1st November 2014 to 30th June 2016 was performed. Total blood count including platelet count and CA 19-9 were recorded and statistically analyzed. RESULTS There was no significant difference in total leukocyte counts (7789±2027 vs. 7568±1289 cells/mm3) between PDAC (n = 34) and IHM (n = 27). However, the mean lymphocyte (2235±837 vs. 2701±631 cells/mm3) and platelet counts in mm3 (3.36±0.789) × 105 vs. (2.45±0.598) × 105 showed difference. The median PLR was 161.9 (IQR = 117.5-205.6) in PDAC and 91 (IQR = 77.2-106.6) in IHM. The median CA 19-9 (U/mL) in PDAC and IHM was 69.3 (IQR = 22.7-427.7) and 13.9 (IQR = 7.2-23.6), respectively. On plotting the receiver operator characteristic curve (ROC curve), area under the curve was maximum for PLR (88.7%) compared to CA 19-9 (77.8%) in diagnosing PDAC (p<0.0001). Using coordinates of ROC, PLR cutoff value was 113.5 (sensitivity-79.4%, specificity-92.6%, positive predictive value (PPV)-91.5%, negative predictive value (NPV)-99.7%) while CA 19-9 cutoff value was 25.3 U/mL (sensitivity-73.5%, specificity-77.8%, PPV-78.5%, NPV-74.6%). CONCLUSION PLR may be useful to differentiate PDAC from benign IHM in patients with chronic pancreatitis.
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Affiliation(s)
- Shanavas Kakkat
- Department of Surgical Gastroenterology, Government Medical College, Trivandrum, 695 011, India
| | - Ramesh Rajan
- Department of Surgical Gastroenterology, Government Medical College, Trivandrum, 695 011, India.
| | - R S Sindhu
- Department of Surgical Gastroenterology, Government Medical College, Trivandrum, 695 011, India
| | - Bonny Natesh
- Department of Surgical Gastroenterology, Government Medical College, Trivandrum, 695 011, India
| | - S Raviram
- Department of Surgical Gastroenterology, Government Medical College, Trivandrum, 695 011, India
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Saraswat M, Joenväärä S, Seppänen H, Mustonen H, Haglund C, Renkonen R. Comparative proteomic profiling of the serum differentiates pancreatic cancer from chronic pancreatitis. Cancer Med 2017; 6:1738-1751. [PMID: 28573829 PMCID: PMC5504330 DOI: 10.1002/cam4.1107] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2017] [Revised: 03/23/2017] [Accepted: 04/24/2017] [Indexed: 02/06/2023] Open
Abstract
Finland ranks sixth among the countries having highest incidence rate of pancreatic cancer with mortality roughly equaling incidence. The average age of diagnosis for pancreatic cancer is 69 years in Nordic males, whereas the average age of diagnosis of chronic pancreatitis is 40–50 years, however, many cases overlap in age. By radiology, the evaluation of a pancreatic mass, that is, the differential diagnosis between chronic pancreatitis and pancreatic cancer is often difficult. Preoperative needle biopsies are difficult to obtain and are demanding to interpret. New blood based biomarkers are needed. The accuracy of the only established biomarker for pancreatic cancer, CA 19‐9 is rather poor in differentiating between benign and malignant mass of the pancreas. In this study, we have performed mass spectrometry analysis (High Definition MSE) of serum samples from patients with chronic pancreatitis (13) and pancreatic cancer (22). We have quantified 291 proteins and performed detailed statistical analysis such as principal component analysis, orthogonal partial least square discriminant analysis and receiver operating curve analysis. The proteomic signature of chronic pancreatitis versus pancreatic cancer samples was able to separate the two groups by multiple statistical techniques. Some of the enriched pathways in the proteomic dataset were LXR/RXR activation, complement and coagulation systems and inflammatory response. We propose that multiple high‐confidence biomarker candidates in our pilot study including Inter‐alpha‐trypsin inhibitor heavy chain H2 (Area under the curve, AUC: 0.947), protein AMBP (AUC: 0.951) and prothrombin (AUC: 0.917), which should be further evaluated in larger patient series as potential new biomarkers for differential diagnosis.
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Affiliation(s)
- Mayank Saraswat
- Transplantation LaboratoryHaartman InstituteUniversity of HelsinkiHelsinkiFinland
- HUSLABHelsinki University HospitalHelsinkiFinland
| | - Sakari Joenväärä
- Transplantation LaboratoryHaartman InstituteUniversity of HelsinkiHelsinkiFinland
- HUSLABHelsinki University HospitalHelsinkiFinland
| | - Hanna Seppänen
- Department of SurgeryUniversity of Helsinki and Helsinki University HospitalHelsinkiFinland
| | - Harri Mustonen
- Department of SurgeryUniversity of Helsinki and Helsinki University HospitalHelsinkiFinland
| | - Caj Haglund
- Department of SurgeryUniversity of Helsinki and Helsinki University HospitalHelsinkiFinland
- Translational Cancer Biology ProgramResearch Programs UnitUniversity of HelsinkiHelsinkiFinland
| | - Risto Renkonen
- Transplantation LaboratoryHaartman InstituteUniversity of HelsinkiHelsinkiFinland
- HUSLABHelsinki University HospitalHelsinkiFinland
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Khalifa MO, Ahmed OA, Fouad MH, Abo Deif MAEK, Mansour MA. Value of serum CA 19-9 in obstructive jaundice. EGYPTIAN LIVER JOURNAL 2016; 6:54-60. [DOI: 10.1097/01.elx.0000515715.11964.86] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
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Pandiaraja J, Viswanathan S, Antomy TB, Thirumuruganand S, Kumaresan DS. The Role of CA19-9 in Predicting Tumour Resectability in Carcinoma Head of Pancreas. J Clin Diagn Res 2016; 10:PC06-9. [PMID: 27134925 DOI: 10.7860/jcdr/2016/17106.7398] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2015] [Accepted: 01/18/2016] [Indexed: 12/11/2022]
Abstract
INTRODUCTION Carbohydrate antigen 19-9 (CA 19-9) is a tumour associated antigen. Blood levels may be elevated in benign as well as malignant conditions. Its sensitivity (70-90%) and specificity (68-91%) are inadequate for accurate diagnosis. It can be used to predict the extent of disease and outcome after resection. AIM The aim of the present study was to assess the role of CA 19-9 in predicting the resectability of the tumour in the head of pancreas. MATERIALS AND METHODS This was a prospective study which included 30 patients and study period was from May 2012 to October 2014. Data collected from all patients with carcinoma of the head of pancreas on the basis of contrast enhanced computed tomography/Magnetic resonance cholangiopancreaticography. CA 19-9 levels were measured and recorded. Patients who were medically unfit for surgery or those who didn't warrant palliative surgery were excluded from the study. During surgery the operative findings on operability were documented and tabulated against corresponding CA 19-9 levels. RESULTS Of the 30 patients who were operated, 13(43.3%) patients had operable tumours and underwent Whipple's procedure and 17(56.7%) underwent palliative bypass procedure. Of the 30, CA 19-9 levels were elevated in 9(30.0%) and were normal in 21(70.0%). Among 13(43.3%) who had operable tumours, CA 19-9 was elevated in 4(13.3) and was normal in 9(30.0%). Of the 17(56.7%) who had inoperable tumours CA 19-9 was elevated in 5(16.7%) and was normal in 12(40.0%). Among the 17 who had inoperable tumours, 8(47.1%) were diagnosed preoperatively and of them CA 19-9 levels were raised in 2(11.8%) and normal in 6(35.3%). In the group of 9(52.9%) who had inoperable tumours diagnosed intraoperatively, CA 19-9 was raised in 3(17.6%) of them and was normal in the remaining 6(35.3%) of them. CONCLUSION Based on the study findings, it can be stated that there is no significant correlation with resectability of pancreatic adenocarcinoma and CA 19-9 and it doesn't predict vascular involvement and liver metastasis.
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Affiliation(s)
- Jayabal Pandiaraja
- Assistant Professor, Department of General Surgery, Srm Medical College and Hospital , Chennai, Tamilnadu, India
| | - Subramanian Viswanathan
- Professor, Department of General Surgery, Govt. Stanley Medical College and Hospital , Chennai, Tamilnadu, India
| | - Thomas Babu Antomy
- Assistant Professor, Department of General Surgery, Govt. Stanley Medical College and Hospital , Chennai, Tamilnadu, India
| | - Sathyamoorthy Thirumuruganand
- Assistant Professor, Department of General Surgery, Govt. Stanley Medical College and Hospital , Chennai, Tamilnadu, India
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Camara SN, Ramdany S, Zhao G, Gou SM, Xiong JX, Yang ZY, Yin T, Yang M, Balde OT, Barry AB, Adji S, Li X, Jin Y, Wu HS, Wang CY. Etiology, pathology, management and prognosis of chronic pancreatitis in Chinese population: A retrospective study. ACTA ACUST UNITED AC 2015; 35:384-389. [PMID: 26072078 DOI: 10.1007/s11596-015-1442-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2014] [Revised: 05/01/2015] [Indexed: 01/30/2023]
Abstract
The purpose of this study was to investigate the etiology, pathological characteristics, management and prognosis of chronic pancreatitis in the Chinese population. The clinical data of 142 patients with chronic pancreatitis were retrospectively studied. All patients were of Chinese nationality and hospitalized from January 2008 to December 2011. Their ages ranged from 14 to 76 years, with a mean of 43 years. Of 142 patients, there were 72 cases of obstructive chronic pancreatitis (50.70%), 19 cases of alcoholic chronic pancreatitis (13.38%), 14 cases of autoimmune pancreatitis (9.86%) and 37 cases of undetermined etiology (26.06%). Pathologically, the average inflammatory mass diameter was 3.8 ± 3.3 cm, biliary obstruction occurred in 36 cases, gall stones in 70 cases, calcification in 88 cases, ductal dilatation in 61 cases, side branch dilatation in 32 cases, ductal irregularity in 10 cases, lymphocytic inflammation in 23 cases, obliterative phlebitis in 14 cases, extra pancreatic lesion in 19 cases and fibrosis in 142 cases. Location of pancreatic lesion in the region of head (n=97), neck (n=16), body (n=12), tail (n=15) and whole pancreas (n=2) influenced the choice of surgical procedures. Ninety-four patients (66.20%) received surgical treatment and 33.80% received other treatments. After operation, 80.85% of 94 patients experienced decreased pain, and 8.51% of 94 showed recovery of endocrine function but with a complication rate of 12.77%. All the operations were performed successfully. According to the pain scale of European Organization for Research and Treatment of Cancer (QLQ-C30) a decrease from 76 ± 22 to 14 ± 18 was observed. Etiology, pathological characteristics, management and prognosis of chronic pancreatitis in the Chinese population vary from others.
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Affiliation(s)
- Soriba Naby Camara
- Department of General Surgery, Pancreatic Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Sonam Ramdany
- Department of General Surgery, Pancreatic Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Gang Zhao
- Department of General Surgery, Pancreatic Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Shan-Miao Gou
- Department of General Surgery, Pancreatic Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Jiong-Xin Xiong
- Department of General Surgery, Pancreatic Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Zhi-Yong Yang
- Department of General Surgery, Pancreatic Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Tao Yin
- Department of General Surgery, Pancreatic Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Ming Yang
- Department of General Surgery, Pancreatic Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | | | | | - Seid Adji
- Department of Gastroenterology, Pancreatic Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Xiang Li
- Department of General Surgery, Pancreatic Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Yan Jin
- Department of General Surgery, Pancreatic Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - He-Shui Wu
- Department of General Surgery, Pancreatic Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Chun-You Wang
- Department of General Surgery, Pancreatic Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
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Rammohan A, Cherukuri SD, Palaniappan R, Perumal SK, Sathyanesan J, Govindan M. Preoperative Platelet–Lymphocyte Ratio Augments CA 19-9 as a Predictor of Malignancy in Chronic Calcific Pancreatitis. World J Surg 2015; 39:2323-8. [DOI: 10.1007/s00268-015-3087-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
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Su SB, Qin SY, Chen W, Luo W, Jiang HX. Carbohydrate antigen 19-9 for differential diagnosis of pancreatic carcinoma and chronic pancreatitis. World J Gastroenterol 2015; 21:4323-4333. [PMID: 25892884 PMCID: PMC4394095 DOI: 10.3748/wjg.v21.i14.4323] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2014] [Revised: 10/30/2014] [Accepted: 01/08/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate the utility of carbohydrate antigen 19-9 (CA19-9) for differential diagnosis of pancreatic carcinoma and chronic pancreatitis.
METHODS: We searched the literature for studies reporting the sensitivity, specificity, and other accuracy measures of serum CA19-9 levels for differentiating pancreatic carcinoma and chronic pancreatitis. Pooled analysis was performed using random-effects models, and receiver operating characteristic (ROC) curves were generated. Study quality was assessed using Standards for Reporting Diagnostic Accuracy and Quality Assessment for Studies of Diagnostic Accuracy tools.
RESULTS: A total of 34 studies involving 3125 patients with pancreatic carcinoma and 2061 patients with chronic pancreatitis were included. Pooled analysis of the ability of CA19-9 level to differentiate pancreatic carcinoma and chronic pancreatitis showed the following effect estimates: sensitivity, 0.81 (95%CI: 0.80-0.83); specificity, 0.81 (95%CI: 0.79-0.82); positive likelihood ratio, 4.08 (95%CI: 3.39-4.91); negative likelihood ratio, 0.24 (95%CI: 0.21-0.28); and diagnostic odds ratio, 19.31 (95%CI: 14.40-25.90). The area under the ROC curve was 0.88. No significant publication bias was detected.
CONCLUSION: Elevated CA19-9 by itself is insufficient for differentiating pancreatic carcinoma and chronic pancreatitis, however, it increases suspicion of pancreatic carcinoma and may complement other clinical findings to improve diagnostic accuracy.
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16
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Pancreatic cancer in chronic pancreatitis. Indian J Surg Oncol 2015; 6:57-62. [PMID: 25937765 DOI: 10.1007/s13193-014-0373-9] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2014] [Accepted: 12/17/2014] [Indexed: 02/08/2023] Open
Abstract
Data exists to indicate a definite association between chronic pancreatitis and pancreatic cancer. The strength of this association varies between various causes of pancreatitis, with hereditary and tropical pancreatitis more likely to result in malignancy. Pathogenesis may involve genetic factors, diabetes, smoking and alcohol consumption. Clinically a significant overlap exists between the two conditions, with histology difficult to obtain and interpret in this setting. Biomarkers like CA19-9 and others may be useful, as is a variety of newer imaging modalities. Treatment needs to be individualised as surgery offers the only chance of cure, albeit in but a few.
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17
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van Heerde MJ, Buijs J, Hansen BE, de Waart M, van Eijck CHJ, Kazemier G, Pek CJ, Poley JW, Bruno MJ, Kuipers EJ, van Buuren HR. Serum level of Ca 19-9 increases ability of IgG4 test to distinguish patients with autoimmune pancreatitis from those with pancreatic carcinoma. Dig Dis Sci 2014; 59:1322-9. [PMID: 24385012 DOI: 10.1007/s10620-013-3004-3] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2013] [Accepted: 12/17/2013] [Indexed: 12/11/2022]
Abstract
BACKGROUND Autoimmune pancreatitis (AIP) is often difficult to distinguish from pancreatic carcinoma or other pancreatobiliary diseases. High serum levels of carbohydrate antigen 19-9 (Ca 19-9) are indicative of malignancies, whereas high levels of immunoglobulin (Ig)G4 (>1.4 g/l) are characteristic of AIP. We investigated whether serum levels of these proteins can differentiate between these diseases. METHODS We measured levels of Ca 19-9 and IgG4 in serum samples from 33 patients with AIP, 53 with pancreatic carcinoma, and 145 with other pancreatobiliary disorders. We determined cut-off levels for each assay. Logistic regression analysis was used to evaluate combined data on Ca 19-9, IgG4, and bilirubin levels. RESULTS Low levels of Ca 19-9 were independently associated with AIP, compared with pancreatic adenocarcinoma [odds ratio (OR) 0.28; 95% confidence interval (CI) 0.13-0.59; p = 0.0001]. Using an upper level of 74 U/ml, the assay for Ca 19-9 identified patients with AIP with 73% sensitivity and 74% specificity. Using a lower level of 2.6 g/l, the assay for IgG4 identified these patients with 70% sensitivity and 100% specificity. Combining data, levels of Ca 19-9 < 74 U/ml and IgG4 > 1.0 g/l identified patients with AIP with 94% sensitivity and 100 % specificity. CONCLUSIONS Patients with AIP have lower levels of Ca 19-9 than those patients with pancreatic carcinoma. Measurement of either the Ca 19-9 or the IgG4 level alone are not accurate enough for diagnosis. However, the combination of Ca 19-9 < 74 U/ml and IgG4 > 1.0 g/l distinguishes patients with AIP from those patients with pancreatic carcinoma with 94% sensitivity and 100% specificity.
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Affiliation(s)
- Marianne J van Heerde
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands,
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Farina A. Proximal fluid proteomics for the discovery of digestive cancer biomarkers. BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS 2014; 1844:988-1002. [DOI: 10.1016/j.bbapap.2013.10.011] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/11/2013] [Revised: 09/15/2013] [Accepted: 10/22/2013] [Indexed: 12/13/2022]
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Jazieh KA, Foote MB, Diaz LA. The clinical utility of biomarkers in the management of pancreatic adenocarcinoma. Semin Radiat Oncol 2014; 24:67-76. [PMID: 24635863 DOI: 10.1016/j.semradonc.2013.11.007] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Pancreatic cancer is the fourth leading cause of cancer-related deaths in the United States and survival rates have seen minimal improvement over the past few decades. Although results are poor, surgical resection is considered the only curative therapeutic intervention for pancreatic cancer, thereby emphasizing the significance of effective diagnostic and prognostic tools to improve outcomes. As such, biomarkers play a promising role in the development of personalized treatments for patients with pancreatic cancer. Prognostic biomarkers, such as serum carbohydrate antigen 19-9 in particular, as well as cancer stem cell markers, provide valuable insight into the biological processes of an individual and their likely course of disease. This, consequently, allows for the assessment of optimal therapeutic intervention. Furthermore, current efforts target putative predictive biomarkers such as BRCA2, PALB2, and SPARC so as to determine their influence on tumor response on targeted therapies. As research progresses, more evidence will provide clinicians with guidelines on the utilization of biomarkers to accurately stage and tailor personalized treatment to the needs of specific patients with pancreatic cancer.
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Affiliation(s)
- Khalid A Jazieh
- The Swim Across America Laboratory, The Ludwig Center for Cancer Genetics and Therapeutics, Baltimore, MD; The Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD
| | - Michael B Foote
- The Swim Across America Laboratory, The Ludwig Center for Cancer Genetics and Therapeutics, Baltimore, MD; The Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD
| | - Luis A Diaz
- The Swim Across America Laboratory, The Ludwig Center for Cancer Genetics and Therapeutics, Baltimore, MD; The Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD.
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20
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Parikh DA, Durbin-Johnson B, Urayama S. Utility of serum CA19-9 levels in the diagnosis of pancreatic ductal adenocarcinoma in an endoscopic ultrasound referral population. J Gastrointest Cancer 2014; 45:74-9. [PMID: 24272911 PMCID: PMC4559348 DOI: 10.1007/s12029-013-9563-x] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
PURPOSE Recent data suggest the use of carbohydrate antigen (CA) 19-9 as a potential marker in the early detection of pancreatic ductal adenocarcinoma (PDAC) when used in the appropriate clinical setting. Here, we assess the utility of CA19-9 in PDAC detection in a select population of pancreatic endoscopic ultrasound (EUS) referrals. METHODS Retrospective review of an institutional EUS Pancreas Registry containing cases referred from November 2002 to November 2011 was completed for categorical analyses with CA19-9 level. A separate case-control study for the subset of non-elevated CA19-9 PDAC population was also performed to characterize the clinical features in this unique group of patients. RESULTS Two hundred eighty-three patients had available CA19-9 data in the registry and were included in the study. Compared to the typical PDAC distribution, the proportion of patients with stage I disease was significantly higher in our registry population (P < 0.0001). Elevated CA19-9 levels most often reflected a diagnosis of PDAC relative to other pancreaticobiliary diagnoses. However, we observed that 15 % of patients with PDAC had normal CA19-9 levels. Clinical characteristics for this false-negative PDAC group compared to the true-positive group demonstrated a predilection for detection of cancer in the body/tail of the pancreas (P = 0.03), increased likelihood of lymph node metastases (P = 0.03), and initial presentation with vague abdominal pain or pancreatic mass as an incidental finding on imaging studies (P = 0.01). CONCLUSIONS Elevated CA19-9 demonstrated a greater likelihood of PDAC diagnosis relative to benign pancreatic pathology, and higher levels of CA19-9 were in line with worse PDAC stage. Patients with normal CA19-9 PDAC may represent a unique subclass of patients, presenting with atypical clinical features, and possibly more advanced stage disease at the time of diagnosis. These patients may benefit from more diligent EUS examination or perhaps closer follow-up management.
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Affiliation(s)
- Dhavan A. Parikh
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of California, Davis Medical Center, 4150 V St. PSSB 3500, Sacramento, CA 95817-1460, USA
| | - Blythe Durbin-Johnson
- Department of Public Health Sciences, School of Medicine, University of California, Davis Medical Center, Sacramento, CA, USA
| | - Shiro Urayama
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of California, Davis Medical Center, 4150 V St. PSSB 3500, Sacramento, CA 95817-1460, USA
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21
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Hinton J, Callan R, Bodine C, Glasgow W, Brower S, Jiang SW, Li J. Potential epigenetic biomarkers for the diagnosis and prognosis of pancreatic ductal adenocarcinomas. Expert Rev Mol Diagn 2014; 13:431-43. [DOI: 10.1586/erm.13.38] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
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22
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Perumal S, Palaniappan R, Pillai SA, Velayutham V, Sathyanesan J. Predictors of malignancy in chronic calcific pancreatitis with head mass. World J Gastrointest Surg 2013; 5:97-103. [PMID: 23717745 PMCID: PMC3664296 DOI: 10.4240/wjgs.v5.i4.97] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2012] [Revised: 12/28/2012] [Accepted: 02/06/2013] [Indexed: 02/06/2023] Open
Abstract
AIM: To prospectively analyse the clinical, biochemical and radiological characteristics of the mass lesions arising in a background of chronic calcific pancreatitis (CCP).
METHODS: Eighty three patients, who presented with chronic pancreatitis (CP) and a mass lesion in the head of pancreas between February 2005 and December 2011, were included in the study. Patients who were identified to have malignancy underwent Whipple’s procedure and patients whose investigations were suggestive of a benign lesion underwent Frey’s procedure. Student t-test was used to compare the mean values of imaging findings [common bile duct (CBD), main pancreatic duct (MPD) size] and laboratory data [Serum bilirubin, carbohydrate antigen 19-9 (CA 19-9)] between the groups. Receiver operating characteristic curve (ROC curve) analysis was done to calculate the cutoff valves of serum bilirubin, CA 19-9, MPD and CBD size. The sensitivity, specificity, positive predictive valve (PPV) and negative predictive value (NPV) were calculated using these cut off points. Multivariate analysis was performed using logistic regression model.
RESULTS: The study included 56 men (67.5%) and 27 women (32.5%). Sixty (72.3%) patients had tropical calcific pancreatitis and 23 (27.7%) had alcohol related CCP. Histologically, it was confirmed that 55 (66.3%) of the 83 patients had an inflammatory head mass and 28 (33.7%) had a malignant head mass. The mean age of individuals with benign inflammatory mass and those with malignant mass was 38.4 years and 45 years respectively. Significant clinical features that predicted a malignant head mass in CP were presence of a head mass in CCP of tropics, old age, jaundice, sudden worsening abdominal pain, gastric outlet obstruction and significant weight loss (P≤ 0.05). The ROC curve analysis showed a cut off value of 5.8 mg/dL for serum bilirubin, 127 U/mL for CA 19-9, 11.5 mm for MPD size and 14.5 mm for CBD size.
CONCLUSION: Elevated Serum bilirubin and CA 19-9, and dilated MPD and CBD were useful in predicting malignancy in patients with CCP and head mass.
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23
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Nieß H, Albertsmeier M, Thomas M, Kleespies A, Angele M, Bruns CJ. [Chronic pancreatitis or pancreatic malignancy: clinical and radiological differential diagnosis of pancreas head space-occupying mass]. Chirurg 2013; 84:106-11. [PMID: 23400785 DOI: 10.1007/s00104-012-2374-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Chronic pancreatitis can be complicated both by an inflammatory benign mass and by the development of pancreatic cancer. The distinction of these complications is not only difficult but also crucial as patients suffering from either of the two have significantly different prognoses. This article describes typical clinical and radiological findings, which may help the physician in differentiating these two maladies. Furthermore, we conducted a retrospective study where we evaluated the clinical patterns in patients with chronic pancreatitis who underwent resection for a pancreatic mass. Although certain findings may be indicative for benign tumors, none of the diagnostic tools available offers a sufficient degree of certainty. In cases of tumors secondary to autoimmune pancreatitis the diagnostic error is exceptionally high. Because of the poor prognosis related to untreated pancreatic cancer, the general recommendation is to perform resection of the tumor when technically possible and when carcinoma cannot be ruled out completely.
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Affiliation(s)
- H Nieß
- Klinik für Allgemeine, Visceral-, Transplantations-, Gefäß- und Thoraxchirurgie, LMU München, Campus Großhadern, Marchioninistr. 15, 81377, München, Deutschland.
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24
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Kaur S, Chakraborty S, Baine MJ, Mallya K, Smith LM, Sasson A, Brand R, Guha S, Jain M, Wittel U, Singh SK, Batra SK. Potentials of plasma NGAL and MIC-1 as biomarker(s) in the diagnosis of lethal pancreatic cancer. PLoS One 2013; 8:e55171. [PMID: 23383312 PMCID: PMC3562325 DOI: 10.1371/journal.pone.0055171] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2012] [Accepted: 12/19/2012] [Indexed: 12/17/2022] Open
Abstract
Pancreatic cancer (PC) is lethal malignancy with very high mortality rate. Absence of sensitive and specific marker(s) is one of the major factors for poor prognosis of PC patients. In pilot studies using small set of patients, secreted acute phase proteins neutrophil gelatinase associated lipocalin (NGAL) and TGF-β family member macrophage inhibitory cytokine-1 (MIC-1) are proposed as most potential biomarkers specifically elevated in the blood of PC patients. However, their performance as diagnostic markers for PC, particularly in pre-treatment patients, remains unknown. In order to evaluate the diagnostic efficacy of NGAL and MIC-1, their levels were measured in plasma samples from patients with pre-treatment PC patients (n = 91) and compared it with those in healthy control (HC) individuals (n = 24) and patients with chronic pancreatitis (CP, n = 23). The diagnostic performance of these two proteins was further compared with that of CA19-9, a tumor marker commonly used to follow PC progression. The levels of all three biomarkers were significantly higher in PC compared to HCs. The mean (± standard deviation, SD) plasma NGAL, CA19-9 and MIC-1 levels in PC patients was 111.1 ng/mL (2.2), 219.2 U/mL (7.8) and 4.5 ng/mL (4.1), respectively. In comparing resectable PC to healthy patients, all three biomarkers were found to have comparable sensitivities (between 64%-81%) but CA19-9 and NGAL had a higher specificity (92% and 88%, respectively). For distinguishing resectable PC from CP patients, CA19-9 and MIC-1 were most specific (74% and 78% respectively). CA19-9 at an optimal cut-off of 54.1 U/ml is highly specific in differentiating resectable (stage 1/2) pancreatic cancer patients from controls in comparison to its clinical cut-off (37.1 U/ml). Notably, the addition of MIC-1 to CA19-9 significantly improved the ability to distinguish resectable PC cases from CP (p = 0.029). Overall, MIC-1 in combination with CA19-9 improved the diagnostic accuracy of differentiating PC from CP and HCs.
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Affiliation(s)
- Sukhwinder Kaur
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska, United States of America
| | - Subhankar Chakraborty
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska, United States of America
| | - Michael J. Baine
- Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, Nebraska, United States of America
| | - Kavita Mallya
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska, United States of America
| | - Lynette M. Smith
- Department of Biostatistics, University of Nebraska Medical Center, Omaha, Nebraska, United States of America
| | - Aaron Sasson
- Department of Surgery, University of Nebraska Medical Center, Omaha, Nebraska, United States of America
| | - Randall Brand
- Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America
| | - Sushovan Guha
- Departments of Gastroenterology, Hepatology, and Nutrition, UT MD Anderson Cancer Center, Houston, Texas, United States of America
| | - Maneesh Jain
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska, United States of America
| | - Uwe Wittel
- Department of General and Visceral Surgery, Universitätsklinik Freiburg, Freiburg, Germany
| | - Shailender K. Singh
- Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska, United States of America
| | - Surinder K. Batra
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska, United States of America
- Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, Nebraska, United States of America
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25
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Vijayakumar A, Vijayakumar A. Imaging of focal autoimmune pancreatitis and differentiating it from pancreatic cancer. ISRN RADIOLOGY 2013; 2013:569489. [PMID: 24967284 PMCID: PMC4045528 DOI: 10.5402/2013/569489] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 11/19/2012] [Accepted: 12/24/2012] [Indexed: 12/13/2022]
Abstract
Autoimmune pancreatitis (AIP) is an inflammatory disorder of pancreas. Two types have been identified: the diffuse and the focal or mass forming. Clinical presentation of AIP overlaps that of pancreatic cancer (PC). Sometimes serum IgG4 and CA 19-9 levels are unable to differentiate AIP from PC. Various series have shown that 5%–21% of resected pancreatic masses for suspected malignancy turned out to be AIP. Accurate diagnosis of focal AIP can avoid unnecessary surgeries. This paper elaborates the various imaging modalities useful in differentiating focal AIP from PC.
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Affiliation(s)
- Abhishek Vijayakumar
- Department of General Surgery, Victoria Hospital, Bangalore Medical College and Research Institute, 128 Vijay Doctors Colony, Konanakunte, Bangalore, Karnataka 560062, India
| | - Avinash Vijayakumar
- Department of Radiology, Banaras Hindu University, Varanasi, Uttar Pradesh 221005, India
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26
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Ballehaninna UK, Chamberlain RS. The clinical utility of serum CA 19-9 in the diagnosis, prognosis and management of pancreatic adenocarcinoma: An evidence based appraisal. J Gastrointest Oncol 2012. [PMID: 22811878 DOI: 10.3978/j.ssn.2078-6891.2011.021] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Serum carbohydrate antigen (CA 19-9) is the most common tumor marker assessed in pancreatic cancer patients; nevertheless few articles have comprehensively evaluated the evidence for its utility in pancreatic cancer management. METHODS Literature search was performed using Medline with keywords "pancreatic cancer", "tumor markers", "CA 19-9", "diagnosis", "screening", "prognosis", "resectability" and "recurrence". All English language articles pertaining to the role of CA 19-9 in pancreatic cancer were critically analyzed to determine its utility as a biomarker for pancreatic cancer. RESULTS Serum CA 19-9 is the most extensively validated pancreatic cancer biomarker with multiple clinical applications. CA 19-9 serum levels have a sensitivity and specificity of 79-81% and 82-90% respectively for the diagnosis of pancreatic cancer in symptomatic patients; but are not useful as a screening marker because of low positive predictive value (0.5-0.9%). Pre-operative CA 19-9 serum levels provide useful prognostic information as patients with normal levels (<37 U/mL) have a prolonged median survival (32-36 months) compared to patients with elevated levels (>37 U/mL) (12-15 months). A CA 19-9 serum level of <100 U/mL implies likely resectable disease whereas levels >100 U/mL suggest unresectablity or metastatic disease. Normalization or a decrease in post-operative CA 19-9 serum levels by ≥20-50% from baseline following surgical resection or chemotherapy is associated with prolonged survival compared to failure of CA 19-9 serum levels to normalize or an increase. Important limitations to CA 19-9 serum level evaluation in pancreatic cancer include poor sensitivity, false negative results in Lewis negative phenotype (5-10%) and increased false positivity in the presence of obstructive jaundice (10-60%). CONCLUSIONS CA 19-9 is the most extensively studied and validated serum biomarker for the diagnosis of pancreatic cancer in symptomatic patients. CA 19-9 serum levels can provide important information with regards to prognosis, overall survival, and response to chemotherapy as well as predict post-operative recurrence. However, non-specific expression in several benign and malignant diseases, false negative results in Lewis negative genotype and an increased false positive results in the presence of obstructive jaundice severely limit the universal applicability of serum CA 19-9 levels in pancreatic cancer management.
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Haus-Cohen M, Assaraf YG, Binyamin L, Benhar I, Reiter Y. The clinical utility of serum CA 19-9 in the diagnosis, prognosis and management of pancreatic adenocarcinoma: An evidence based appraisal. J Gastrointest Oncol 2012; 109:750-8. [PMID: 14999785 DOI: 10.1002/ijc.20037] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Serum carbohydrate antigen (CA 19-9) is the most common tumor marker assessed in pancreatic cancer patients; nevertheless few articles have comprehensively evaluated the evidence for its utility in pancreatic cancer management. METHODS Literature search was performed using Medline with keywords "pancreatic cancer", "tumor markers", "CA 19-9", "diagnosis", "screening", "prognosis", "resectability" and "recurrence". All English language articles pertaining to the role of CA 19-9 in pancreatic cancer were critically analyzed to determine its utility as a biomarker for pancreatic cancer. RESULTS Serum CA 19-9 is the most extensively validated pancreatic cancer biomarker with multiple clinical applications. CA 19-9 serum levels have a sensitivity and specificity of 79-81% and 82-90% respectively for the diagnosis of pancreatic cancer in symptomatic patients; but are not useful as a screening marker because of low positive predictive value (0.5-0.9%). Pre-operative CA 19-9 serum levels provide useful prognostic information as patients with normal levels (<37 U/mL) have a prolonged median survival (32-36 months) compared to patients with elevated levels (>37 U/mL) (12-15 months). A CA 19-9 serum level of <100 U/mL implies likely resectable disease whereas levels >100 U/mL suggest unresectablity or metastatic disease. Normalization or a decrease in post-operative CA 19-9 serum levels by ≥20-50% from baseline following surgical resection or chemotherapy is associated with prolonged survival compared to failure of CA 19-9 serum levels to normalize or an increase. Important limitations to CA 19-9 serum level evaluation in pancreatic cancer include poor sensitivity, false negative results in Lewis negative phenotype (5-10%) and increased false positivity in the presence of obstructive jaundice (10-60%). CONCLUSIONS CA 19-9 is the most extensively studied and validated serum biomarker for the diagnosis of pancreatic cancer in symptomatic patients. CA 19-9 serum levels can provide important information with regards to prognosis, overall survival, and response to chemotherapy as well as predict post-operative recurrence. However, non-specific expression in several benign and malignant diseases, false negative results in Lewis negative genotype and an increased false positive results in the presence of obstructive jaundice severely limit the universal applicability of serum CA 19-9 levels in pancreatic cancer management.
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Affiliation(s)
- Maya Haus-Cohen
- Department of Biology, Technion-Israel Institute of Technology, Technion City, Haifa 32000, Israel
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Ballehaninna UK, Chamberlain RS. The clinical utility of serum CA 19-9 in the diagnosis, prognosis and management of pancreatic adenocarcinoma: An evidence based appraisal. J Gastrointest Oncol 2012; 3:105-19. [PMID: 22811878 DOI: 10.3978/j.issn.2078-6891.2011.021] [Citation(s) in RCA: 341] [Impact Index Per Article: 26.2] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2011] [Accepted: 04/27/2011] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Serum carbohydrate antigen (CA 19-9) is the most common tumor marker assessed in pancreatic cancer patients; nevertheless few articles have comprehensively evaluated the evidence for its utility in pancreatic cancer management. METHODS Literature search was performed using Medline with keywords "pancreatic cancer", "tumor markers", "CA 19-9", "diagnosis", "screening", "prognosis", "resectability" and "recurrence". All English language articles pertaining to the role of CA 19-9 in pancreatic cancer were critically analyzed to determine its utility as a biomarker for pancreatic cancer. RESULTS Serum CA 19-9 is the most extensively validated pancreatic cancer biomarker with multiple clinical applications. CA 19-9 serum levels have a sensitivity and specificity of 79-81% and 82-90% respectively for the diagnosis of pancreatic cancer in symptomatic patients; but are not useful as a screening marker because of low positive predictive value (0.5-0.9%). Pre-operative CA 19-9 serum levels provide useful prognostic information as patients with normal levels (<37 U/mL) have a prolonged median survival (32-36 months) compared to patients with elevated levels (>37 U/mL) (12-15 months). A CA 19-9 serum level of <100 U/mL implies likely resectable disease whereas levels >100 U/mL suggest unresectablity or metastatic disease. Normalization or a decrease in post-operative CA 19-9 serum levels by ≥20-50% from baseline following surgical resection or chemotherapy is associated with prolonged survival compared to failure of CA 19-9 serum levels to normalize or an increase. Important limitations to CA 19-9 serum level evaluation in pancreatic cancer include poor sensitivity, false negative results in Lewis negative phenotype (5-10%) and increased false positivity in the presence of obstructive jaundice (10-60%). CONCLUSIONS CA 19-9 is the most extensively studied and validated serum biomarker for the diagnosis of pancreatic cancer in symptomatic patients. CA 19-9 serum levels can provide important information with regards to prognosis, overall survival, and response to chemotherapy as well as predict post-operative recurrence. However, non-specific expression in several benign and malignant diseases, false negative results in Lewis negative genotype and an increased false positive results in the presence of obstructive jaundice severely limit the universal applicability of serum CA 19-9 levels in pancreatic cancer management.
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Brauner E, Lachter J, Ben-Ishay O, Vlodavsky E, Kluger Y. Autoimmune pancreatitis misdiagnosed as a tumor of the head of the pancreas. World J Gastrointest Surg 2012; 4:185-9. [PMID: 22905288 PMCID: PMC3420987 DOI: 10.4240/wjgs.v4.i7.185] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2011] [Revised: 01/05/2012] [Accepted: 02/23/2012] [Indexed: 02/06/2023] Open
Abstract
Autoimmune pancreatitis can mimic pancreatic cancer in its clinical presentation, imaging features and laboratory parameters. Differentiating between those two entities requires implementation of clinical judgment and experience along with objective parameters that may suggest either condition. Few strategies have been proposed for the surgeon to implement when facing borderline cases. The following case is an example of a clinical scenario compatible with an accepted algorithm for diagnosis of pancreatic cancer, which eventually proved wrong. We present a 75-year-old patient who was admitted for obstructive jaundice. Imaging features were highly suggestive for pancreatic cancer as was the carbohydrate antigen 19-9 (CA 19-9) level, leading to a decision for surgery. Pathological examination revealed autoimmune pancreatitis. Though no frank carcinoma was found, premalignant ductal changes of pancreatic intraepithelial neoplasia (PanIN) I and PanIN II were discovered throughout the pancreatic duct. Caution is advised when relying on the combination of highly suggestive radiology features and elevated levels of CA 19-9 in the diagnosis of pancreatic cancer. When the tissue diagnosis is not conclusive, obtaining IgG4 and antinuclear Ab levels is advised, to rule out the rare possibility of autoimmune pancreatitis. Patients with autoimmune pancreatitis should be followed carefully as precancerous lesions may accompany the benign disease and the correlation of these two entities has not been ruled out.
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Affiliation(s)
- Eran Brauner
- Eran Brauner, Offir Ben-Ishay, Yoram Kluger, Department of General Surgery B, Rambam Health Care Campus, 31096 Haifa, Israel
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Winter JM, Yeo CJ, Brody JR. Diagnostic, prognostic, and predictive biomarkers in pancreatic cancer. J Surg Oncol 2012; 107:15-22. [PMID: 22729569 DOI: 10.1002/jso.23192] [Citation(s) in RCA: 175] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2012] [Accepted: 05/18/2012] [Indexed: 12/13/2022]
Abstract
Serum CA 19-9 is the only FDA approved biomarker recommended for use in the routine management of pancreatic ductal adenocarcinoma (PDA). Over 2,000 biomarker studies related to pancreatic cancer appear in the literature, highlighting the need to discover and develop improved tests. Diagnostic biomarkers have implications for early detection of PDA, prognostic markers predict patient survival and recurrence patterns, and predictive markers can help personalize treatment regimens.
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Affiliation(s)
- Jordan M Winter
- Department of Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
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Miglani RK, Bhateja N, Bhat RS, Kumar KVA. Diagnostic Role of Platelet Lymphocyte Ratio(PLR) in Pancreatic Head Masses. Indian J Surg 2012; 75:4-9. [PMID: 24426375 DOI: 10.1007/s12262-012-0443-6] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2011] [Accepted: 03/04/2012] [Indexed: 11/29/2022] Open
Abstract
Masses in and around pancreas constitute an important clinical entity in gastrointestinal surgical practice. Most common being adenocarcinoma of head of pancreas followed by inflammatory masses due to chronic pancreatitis. Accurate diagnosis is of central importance as therapeutic strategies range from observation to complete surgical removal including total pancreatectomy.Several tumor markers are available which could help in prognostication and diagnosis of carcinoma pancreas. Carbohydrate antigen 19-9(CA 19-9) is traditionally accepted best marker available. The role of new tumor marker platelet lymphocyte ratio (PLR) has been defined recently in prognostication of carcinoma pancreas. Role of PLR in diagnosing and its efficacy after combining it with CA 19-9 is not known. The aim of study was to assess the demographics of histologically proven neoplastic and inflammatory pancreatic head masses in our department. To assess the role of CA19-9 and platelet lymphocyte ratio(PLR) in determining nature of pancreatic head mass. Data consisted of histologically proven 45 patients .23 having head mass due to chronic pancreatitis and 22 because of neoplastic lesions. Demographics in terms of age, sex, previous pain episodes, presence of jaundice, history of alcohol intake were compared in both groups. Also tumor markers CA 19-9 and PLR individually and in combination were compared in both groups. Cancer pancreas significantly (p < 0.001) occurred in older age group, was significantly associated with jaundice (p = 0.005) and weight loss (p < 0.001). Accuracy in diagnosis of cancer pancreas was similar with CA 19-9 and PLR (68.89 %), where as combining CA 19-9 with PLR showed increased sensitivity(81.82 %) and accuracy(71.11 %) in diagnosing cancer pancreas. Other combinations showed no advantage. PLR is at least as good as CA 19-9 as diagnostic marker to differentiate between malignant and inflammatory head mass of pancreas.
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Affiliation(s)
- Ripan K Miglani
- Department of Surgical Gastroenterology Bangalore Medical College and Research Institute, 67 B Tagore Nagar, Ludhiana, Punjab 141001 India
| | - Neeraj Bhateja
- Department of Surgical Gastroenterology Bangalore Medical, Civil Lines, Ludhiana, Punjab 141001 India
| | - Ravi Shanker Bhat
- Department of Surgical Gastroenterology Bangalore Medical, Civil Lines, Ludhiana, Punjab 141001 India
| | - K V Ashok Kumar
- Department of Surgical Gastroenterology Bangalore Medical, Civil Lines, Ludhiana, Punjab 141001 India
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Is intraoperative confirmation of malignancy during pancreaticoduodenectomy mandatory? J Gastrointest Surg 2012; 16:370-5. [PMID: 22033700 DOI: 10.1007/s11605-011-1728-y] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2011] [Accepted: 10/05/2011] [Indexed: 01/31/2023]
Abstract
INTRODUCTION Differentiating between chronic pancreatitis and pancreatic adenocarcinoma can be difficult due to considerable overlap in disease presentation and radiological signs and the frequent co-existence of the two conditions. In this situation, surgeons may have to proceed to "blind" pancreaticoduodenectomy or attempt to confirm malignancy intraoperatively with frozen section (FS) histology. METHODS This study attempted to ascertain the false-negative and false-positive rates of undertaking pancreaticoduodenectomies (PD) based on clinical suspicion (CS) or after intraoperative confirmation of malignancy using FS histology. RESULTS Of patients, 13.6% (nine out of 66) underwent a benign PD in the CS group; 6.7% of patients had a missed malignancy in the FS group (n = 62), but intraoperative histology prevented PD in 35% of patients with benign disease in the FS group. Specificity and sensitivity of intraoperative FS in detecting malignancy was 100% and 89.7%, respectively. Sensitivity of clinical assessment in detecting malignancy was 86.4%. CONCLUSIONS In experienced hands, intraoperative confirmation of malignancy is effective and will avoid resection in patients with benign disease. However, for many surgeons the chance of missing a small tumour with a false-negative biopsy will be unacceptable and they would prefer to undertake a "blind" resection and accept the mortality risk of pancreaticoduodenectomy for benign disease.
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Prevalence of autoimmune pancreatitis and other benign disorders in pancreatoduodenectomy for presumed malignancy of the pancreatic head. Dig Dis Sci 2012; 57:2458-65. [PMID: 22588243 PMCID: PMC3428528 DOI: 10.1007/s10620-012-2191-7] [Citation(s) in RCA: 61] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2011] [Accepted: 04/14/2012] [Indexed: 12/18/2022]
Abstract
BACKGROUND Occasionally patients undergoing resection for presumed malignancy of the pancreatic head are diagnosed postoperatively with benign disease. Autoimmune pancreatitis (AIP) is a rare disease that mimics pancreatic cancer. We aimed to determine the prevalence of benign disease and AIP in patients who underwent pancreatoduodenectomy (PD) over a 9-year period, and to explore if and how surgery could have been avoided. METHODS All patients undergoing PD between 2000 and 2009 in a tertiary referral centre were analyzed retrospectively. In cancer-negative cases, postoperative diagnosis was reassessed. Preoperative index of suspicion of malignancy was scored as non-specific, suggestive, or high. In AIP patients, diagnostic criteria systems were checked. RESULTS A total of 274 PDs were performed for presumed malignancy. The prevalence of benign disease was 8.4 %, overall prevalence of AIP was 2.6 %. Based on preoperative index of suspicion of malignancy, surgery could have been avoided in 3 non-AIP patients. All AIP patients had sufficient index to justify surgery. If diagnostic criteria would have been checked; however, surgery could have been avoided in one to five AIP patients. CONCLUSIONS The prevalence of benign disease in patients who underwent PD for presumed malignancy was 8.4 %, nearly one-third attributable to AIP. Although misdiagnosis of AIP as carcinoma is a problem of limited quantitative importance, every effort to establish the correct diagnosis should be undertaken considering the major therapeutic consequences. IgG4 measurement and systematic use of diagnostic criteria systems are recommended for every candidate patient for PD when there is no histological proof of malignancy.
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Brody JR, Witkiewicz AK, Yeo CJ. The past, present, and future of biomarkers: a need for molecular beacons for the clinical management of pancreatic cancer. Adv Surg 2011; 45:301-21. [PMID: 21954696 DOI: 10.1016/j.yasu.2011.04.002] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/09/2023]
Affiliation(s)
- Jonathan R Brody
- Department of Surgery, Jefferson Pancreas Biliary and Related Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA
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Sivaraman A, Sivarman A, Muthukrishnan A, Boopathy Senguttvan N, Anil Suchak S, Kannan U. Predictors of malignancy in pancreatic head mass: a prospective study. Pan Afr Med J 2011; 9:30. [PMID: 22145063 PMCID: PMC3215552 DOI: 10.4314/pamj.v9i1.71206] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2011] [Accepted: 07/19/2011] [Indexed: 01/28/2023] Open
Abstract
Introduction The objective of the study was to identify the predictive factors for malignancy in pancreatic head mass as a primary outcome and assess the value of CA 19-9 as a diagnostic tool for malignancy as a secondary outcome. Methods A prospective study of patients presented with pancreatic head mass was conducted in a tertiary care referral hospital, Manipal, India from May 2006 to November 2008. The study population was divided into malignant and benign groups based on the final histopathology report. A univariate and multivariate analysis of potential predictive factors for malignancy were conducted. Results A total of 102 patients with pancreatic head mass were included in the study after fulfilling the inclusion/exclusion criteria. 78 were malignant and 24 were benign. There was significant weight loss (p<0.001) and high mean bilirubin levels (p=0.002) in the malignant group. Mean CA 19-9 was significantly higher in the malignant group (290.7 vs. 30.3 U/ml; p<0.001). Sensitivity and specificity of CA 19-9 for detecting malignancy in pancreatic head mass at a cut off of 35U/ml was 86% and 79% respectively. CA 19-9 positivity rate was higher with increasing cut off values of 100, 200 and 300U/ml but such high levels occurred in fewer patients. All the non-jaundiced patients (100%) with raised CA 19-9 levels were found to be malignant compared to 86% malignancy in jaundiced patients. In multivariate analysis, a combination of weight loss>10% of body weight and bilirubin>3 mg/dl and CA 19-9>35U/ml had specificity and positive predictive value of 100% for predicting malignancy in pancreatic head mass. Conclusion The presence of weight loss and jaundice and raised CA 19-9 levels together in a patient with pancreatic head mass can be predictive of malignancy. A very high CA 19-9 level can be an indicator of malignancy in a pancreatic head mass. A raised CA 19-9 level may be more predictive of malignancy in non-jaundiced patients than in jaundiced patients.
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Affiliation(s)
| | - Arjun Sivarman
- Department of Surgery , Kasturba Medical College, Manipal, Karnataka, India
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Ballehaninna UK, Chamberlain RS. Serum CA 19-9 as a Biomarker for Pancreatic Cancer-A Comprehensive Review. Indian J Surg Oncol 2011; 2:88-100. [PMID: 22693400 DOI: 10.1007/s13193-011-0042-1] [Citation(s) in RCA: 169] [Impact Index Per Article: 12.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2010] [Accepted: 01/13/2011] [Indexed: 02/07/2023] Open
Abstract
Pancreatic cancer is an aggressive tumor with a dismal prognosis, biomarkers that can detect tumor in its early stages when it may be amenable to curative resection may improve prognosis. At present, serum CA 19-9 is the only validated tumor marker in widespread clinical use, but precise knowledge of its role in pancreatic cancer diagnosis, staging, determining resectability, response to chemotherapy and prognosis remains limited. A comprehensive search was performed using PubMed with keywords "pancreatic cancer" "tumor markers" "CA 19-9" "diagnosis" "screening" "prognosis" "resectability" and "recurrence". All English language articles pertaining to the role of CA 19-9 in pancreatic cancer were critically analyzed to determine its utility as a biomarker for pancreatic cancer. Serum CA 19-9 is the most extensively studied and clinically useful biomarker for pancreatic cancer. Unfortunately, CA 19-9 serum level evaluation in pancreatic cancer patients is limited by poor sensitivity, false negative results in Lewis negative phenotype (5-10%) and increased false positivity in the presence of obstructive jaundice (10-60%). Serum CA 19-9 level has no role in screening asymptomatic populations, and has a sensitivity and specificity of 79-81% and 82-90% respectively for the diagnosis of pancreatic cancer in symptomatic patients. Pre-operative CA 19-9 serum level provide useful prognostic information as patients with normal CA 19-9 serum levels (<37 U/ml) have a prolonged median survival (32-36 months) compared to patients with elevated CA 19-9 serum levels (>37 U/ml) (12-15 months). A CA 19-9 serum level of <100 U/ml implies likely resectable disease whereas levels >100 U/ml may suggest unresectablity or metastatic disease. Normalization or a decrease in post-operative CA 19-9 serum levels by ≥20-50% from baseline following surgical resection or chemotherapy is associated with prolonged survival compared to failure of CA 19-9 serum levels to normalize or an increase. Carbohydrate antigen (CA 19-9) is the most extensively studied and validated serum biomarker for the diagnosis of pancreatic cancer in symptomatic patients. The CA 19-9 serum level can provide important information with regards to prognosis, overall survival, and response to chemotherapy as well as predict post-operative recurrence. Non-specific expression in several benign and malignant diseases, false negative results in Lewis negative genotype and an increased false positive results in the presence of obstructive jaundice severely limit the universal applicability of serum CA 19-9 levels in pancreatic cancer management.
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Talar-Wojnarowska R, Gasiorowska A, Olakowski M, Lekstan A, Lampe P, Malecka-Panas E. Clinical value of serum neopterin, tissue polypeptide-specific antigen and CA19-9 levels in differential diagnosis between pancreatic cancer and chronic pancreatitis. Pancreatology 2011; 10:689-94. [PMID: 21242708 DOI: 10.1159/000320693] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2010] [Accepted: 08/20/2010] [Indexed: 12/11/2022]
Abstract
BACKGROUND Neopterin and tissue polypeptide-specific antigen (TPS) have been suggested to be useful in differential diagnosis between pancreatic adenocarcinoma (PA) and chronic pancreatitis (CP). The aim of our study was to compare the clinical usefulness of CA19-9, neopterin and TPS serum levels in patients with PA and CP. METHODS The study included 85 patients with PA, 72 with CP and 50 healthy controls. The serum concentrations of neopterin, TPS and CA19-9 were measured (DRG International, USA). The associations of the analyzed markers and clinical data at diagnosis have been evaluated. RESULTS Serum levels of neopterin, TPS and CA19-9 were higher in PA patients compared to CP (p < 0.001). TPS and CA19-9 levels were also elevated in patients with CP compared to the control group (p < 0.001). In contrast, there was no difference between neopterin serum levels in CP patients and the control group (p > 0.05). Neopterin showed the best sensitivity and specificity (91.8 and 87.5%) in PA diagnosis compared to CA19-9 (respectively 83.5 and 75%) and TPS (75.3 and 65.3%). CONCLUSION Our results indicate that neopterin may be potentially useful in differential diagnosis between PA and CP. Assessment of TPS probably adds no significant information to that obtained with CA19-9 and neopterin. and IAP.
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Botsis T, Anagnostou VK, Hartvigsen G, Hripcsak G, Weng C. Modeling prognostic factors in resectable pancreatic adenocarcinomas. Cancer Inform 2010; 7:281-91. [PMID: 20508721 PMCID: PMC2865167 DOI: 10.4137/cin.s3835] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Background: The accurate prognosis for patients with resectable pancreatic adenocarcinomas requires the incorporation of more factors than those included in AJCC TNM system. Methods: We identified 218 patients diagnosed with stage I and II pancreatic adenocarcinoma at NewYork-Presbyterian Hospital/Columbia University Medical Center (1999 to 2009). Tumor and clinical characteristics were retrieved and associations with survival were assessed by univariate Cox analysis. A multivariable model was constructed and a prognostic score was calculated; the prognostic strength of our model was assessed with the concordance index. Results: Our cohort had a median age of 67 years and consisted of 49% men; the median follow-up time was 14.3 months and the 5-year survival 3.6%. Age, tumor differentiation and size, alkaline phosphatase, albumin and CA 19-9 were the independent factors of the final multivariable model; patients were thus classified into low (n = 14, median survival = 53.7 months), intermediate (n = 124, median survival = 19.7 months) and high risk groups (n = 80, median survival = 12.3 months). The prognostic classification of our model remained significant after adjusting for adjuvant chemotherapy and the concordance index was 0.73 compared to 0.59 of the TNM system. Conclusion: Our prognostic model was accurate in stratifying patients by risk and could be incorporated into clinical decisions.
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Affiliation(s)
- Taxiarchis Botsis
- Department of Biomedical Informatics, Columbia University, 10032 New York, USA
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