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Diffuse Pancreatic Carcinoma with Hepatic Metastases

Diffuse Pancreatic Carcinoma with Hepatic Metastases Hindawi Case Reports in Oncological Medicine Volume 2020, Article ID 8815745, 5 pages https://doi.org/10.1155/2020/8815745 Case Report 1 2 3 Hoang Quan Nguyen , Ngoc Trinh Thi Pham , Van Trung Hoang , 3 4 5 Hoang Anh Thi Van , Chinh Huynh, and Duc Thanh Hoang Department of Radiology, Da Nang Oncology Hospital, Da Nang, Vietnam School of Medicine and Pharmacy, The University of Danang, Da Nang, Vietnam Department of Radiology, Thien Hanh Hospital, Buon Ma Thuot, Vietnam Department of Radiology, Tu Du Hospital, Ho Chi Minh, Vietnam Division of Endocrinology, Department of Medicine, Walter Reed National Military Medical Center, Bethesda, USA Correspondence should be addressed to Van Trung Hoang; dr.hoangvantrungradiology@gmail.com Received 2 May 2020; Revised 15 October 2020; Accepted 16 October 2020; Published 31 October 2020 Academic Editor: Mauro Cives Copyright © 2020 Hoang Quan Nguyen et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Pancreatic cancer is one of the seven leading causes of cancer death worldwide. Diffuse pancreatic carcinoma is very rare and underreported in the literature. Many advances have been made in the diagnosis and management of pancreatic cancer. However, most pancreatic cancer cases are detected at the terminal or metastatic stages. Therefore, timely diagnosis and therapeutic management are desirable goals for this disease. Although the proliferation of pancreatic cancer has been reduced by intervention, more work is needed to treat and prevent the disease. The purpose of this article is to present a case of a 54-year-old male with pancreatic cancer and to review the epidemiology, diagnosis, management, and prevention of pancreatic tumors in general as well as pancreatic carcinoma in particular. chemotherapy and radiation is poor. Surgery is the only 1. Introduction treatment that has the potential to prolong survival but is Pancreatic cancer can derive from epithelial and nonepithe- usually performed late at the time of discovery [4]. Diffuse lial tumors such as pancreatic metastases, connective cancer, pancreatic carcinoma is usually rare compared to focal pan- and lymphoma. Epithelial tumors include nonendocrine and creatic cancer. In a major study of general pathology, the location of pancreatic carcinoma at the head of the pancreas endocrine tumors such as pancreatic ductal adenocarcinoma, serous cystadenocarcinoma, and mucinous cystadenocarci- was 60%, the pancreatic body 13%, pancreatic tail 5%, and noma [1]. Among all cancers, pancreatic cancer is one of the remaining 22% diffuse pancreatic carcinoma [2, 5, 6]. the worst; despite improvements in both diagnostic and sur- Biochemical testing and diagnostic imaging are the main gical techniques, survival has not improved substantially for diagnostic methods [4]. Differential diagnosis includes dif- more than 50 years. The 5-year survival rate still remains at fuse pancreatitis, autoimmune pancreatitis, multiple pancre- 9% only. Pancreatic carcinoma can occur at any age but is atic cancer, and diffuse pancreatic metastases. Distinguishing more common in the elderly. Pancreatic cancer is the 11th between pancreatic tumors and pancreatitis is crucial because most common cancer in the world, accounting for 2.5% of the clinical course, treatment, and prognosis of these two dis- all cancers and causing 4.5% of all cancer deaths [2]. Due to eases are quite different [5, 7]. Metastatic pancreatic carci- the increasing incidences, late diagnosis, and limited treat- noma mainly affects the liver, peritoneum, lung, and bone, ment options, its mortality rate is estimated to increase grad- although bone metastases usually occur late [5, 8, 9]. In this ually over the next decade [3]. The tumor’s response to case report, we describe a rare case of a 54-year-old male with 2 Case Reports in Oncological Medicine of 68-91%. Its main value is to assess the response to the diffuse pancreatic carcinoma with hepatic metastases diag- nosed by ultrasound, computed tomography (CT), and mag- treatment and monitor follow-up recurrence of the disease netic resonance imaging (MRI). [4, 5, 9]. A novel array set of biomarkers for diagnostic, pre- dictive, and prognostic potential for pancreatic cancer is cur- rently being used and studied with the hope of finding 2. Case Presentation effective management methods for this challenging disease A 54-year-old man was hospitalized with diffuse abdominal (Table 1) [10]. Further studies of novel biomarkers for pan- pain and abdominal distention. The pain occurred 4 days creatic cancer subtyping, diagnosis, and treatment response prior to admission and was gradually increasing. At first, prediction are underway [11]. the pain was localized in the epigastric region, then radiating In patients presenting with pancreatic malignancy, abdominal ultrasound is often used as an initial diagnostic throughout the abdomen. The patient reported nausea but no vomiting nor jaundice. He was normotensive with a blood modality [12, 13]. CT scan is used in evaluating the stage of pressure of 120/60 mmHg, pulse rate 75 bpm, respiratory pancreatic cancer with a sensitivity of 89-97% and specificity rate 21 per minute, and temperature 37.7 C. He noticed of 95%. CT findings indicate the presence of the tumor, recent weight loss of 4 kg over 3 months. He reported rare involvement of vessels (the celiac axis and hepatic or superior alcohol consumption, no smoking, and noncontributing mesenteric artery) and organs, enlarged lymph nodes, ascites, family history. Examination showed no symptoms of biliary and distant metastases. In our case, the peripheral capsule- obstruction but diffuse abdominal tenderness on palpation. like structure was a characteristic CT finding of diffuse pan- Serum amylase, lipase, and IgG4 were within normal ranges, creatic cancer that was rarely seen in focal pancreatic cancer and CA19-9 and CA242 were 69.6 U/mL (normal value ≤ and other pancreatic lesions [5, 8, 12]. MRI is another appro- 37 U/mL) and 82.1 U/mL (normal value ≤ 20 U/mL), respec- priate option for patients who have contraindications to CT tively. Bilirubin, alpha-fetoprotein, and HBsAg were normal. or where CT images are unclear [5, 13]. High resolution of Abdominal ultrasound revealed a diffusely enlarged and MRI can better detect pancreatic lesions, small liver metasta- heterogeneous hypoechoic pancreas. Slightly infiltrated fat ses, lymph nodes, and peritoneal metastases. The recogniza- layer was found around the pancreas without associated tion of the liver and peritoneal metastases is critical for fluid. Simultaneously, the liver also showed multiple solid accurately staging pancreatic carcinoma because the cancer hypoechoic or hyperechoic masses. CT scan confirmed is unresectable if metastases are present [4, 14]. Multislice enlargement of the pancreas with relatively homogenous CT can also detect small liver lesions; however, if the lesions enhancement remarkably in the arterial phase and washout are less than 10 mm, it is often difficult to characterize. MRI in the delayed phase (Figure 1). Multiple liver lesions showed may be more clearly delineate lesions like hemangiomas, early arterial enhancement with washout in the delayed cysts, or metastases [3]. According to Danet et al. [15], liver phase suggesting hypervascular metastases (Figure 2). The metastases have usually signals from isointensity to slightly pancreatic duct and biliary tract did not dilate; there was no high intensity on T2-weighted images, with a slightly lower presence of pathological lymph nodes. The patient subse- signal on T1-weighted images. Positron emission tomogra- quently underwent MRI that showed characteristics similar phy (PET) is becoming more widely available and may help to ultrasound and CT with a diffusely enlarged pancreas with distinguish chronic pancreatitis from pancreatic cancer. It low signal intensity on T1-weighted, high signal intensity het- may help detect regional lymph nodes or distant metastases erogeneous on T2-weighted, restricted diffusion on diffusion- from pancreatic cancer [4, 8]. Endoscopic ultrasound (EUS) weighted imaging, and relatively homogenous enhancement can be used to detect small pancreatic masses that could be on postcontrast T1-weighted images (Figure 3). missed by CT scan and is commonly used to perform According to the clinical presentation, laboratory results, biopsy [6, 9]. and radiological findings, we had a provisional diagnosis of The malignancy of the pancreas is classified into resect- diffuse pancreatic carcinoma with liver metastasis. We per- able, borderline resectable, and advanced disease (either locally advanced or metastatic) [16]. Multidisciplinary treat- formed pancreatic FNA under ultrasound guidance; cytology revealed suspected carcinoma. The patient then underwent ment of pancreatic carcinoma needs to combine surgery, ultrasound-guided biopsy of liver lesions; histopathological radiotherapy, chemotherapy, and supportive care. Some cur- findings confirmed metastases from carcinoma. He received rent methods include personalized medicine, immunother- conservative treatment, and after 2 weeks, the symptoms apy, innovative targets, therapeutic vaccines, stemness inhibitors, adoptive T-cell transfer, and stem-cell therapy were much improved. We offered chemoradiotherapy and palliative care, but he refused and requested to be discharged [3, 5, 9]. The stratification of pancreatic cancer patients 1 week later. We contacted the patient after 2 months, but according to the tumor transcriptome is a major approach family members said his conditions were getting worse. to predict treatment response. Other strategies concentrate on genomic or chromosome alterations and the determina- tion of targeted therapies [11, 17]. 3. Discussion Comprehensive analyses from genomes of primary and metastatic pancreatic tumors indicate that there are two pro- Pancreatic cancer poses a significant diagnostic challenge, and the majority of cases present late with either locally gressive processes in pancreatic cancer: (1) the early cancer- advanced or metastatic disease. Serum marker CA19-9 has initiating phase in which most mutations would establish a preneoplastic tumor and (2) the rapid cancer-transforming been evaluated with a sensitivity of 70-90% and specificity Case Reports in Oncological Medicine 3 (a) (b) Figure 1: Contrast-enhanced CT images in the arterial (a) phase and delayed (b) phase. CT shows a sausage-shape enlargement of the pancreas (arrows), with relatively homogenously remarkable enhancement in the arterial phase and washout in the delayed phase with the capsule-like rim at the surface (arrowheads). The pancreatic duct did not dilate. (a) (b) (c) (d) Figure 2: CT images before (a) and in the late arterial (b), portal venous (c), and delayed (d) phases after contrast administration. The metastases hyper enhance dramatically in the arterial phase and subsequently fade toward mild hypoattenuation relative to the liver in the delayed phase (arrows). Some portions of the lesions do not enhance, suggesting necrosis. Many similar lesions are scattered throughout the liver parenchyma (not shown). phase that generates invasive clones and colonization of where pancreatic cancer would be optimally treated depend- distant sites. Moreover, the gradual increasing mutational ing on its molecular subtype. Besides, the characterization of burden of CDKN2A, KRAS, SMAD4, and TP53 genes pro- cell signaling pathways and the diverse tumor cell types would be useful in the approach to novel therapy [11, 18]. motes the early accelerated progression and metastasis of pancreatic cancer. When the biological and molecular land- Recent combination therapies are based on mechanisms scape of pancreatic carcinoma is unraveling, there would be of resistance to immune checkpoint inhibitors, which a shift of clinical practice to utilize molecular taxonomy, improve condition in patients with unresectable pancreatic 4 Case Reports in Oncological Medicine T1 noncontrast T2W (a) (b) T1 postcontrast arterial phase T1 postcontrast delayed phase (c) (d) Figure 3: MRI on T1-weighted image (a), T2-weighted image (b), and arterial phase (c) and delayed phase (d) in T1-weighted image with fat- sat after contrast administration. MRI shows a diffusely enlarged pancreas with low intensity on T1-weighted imaging and heterogeneous high intensity on T2-weighted imaging, particularly in the body and tail region of the pancreas. The pancreas also shows remarkable enhancement in the arterial phase and washout in the delayed phase. Table 1: Pancreatic cancer biomarkers. stroma may sequester albumin-bound paclitaxel, enhancing the distribution of paclitaxel into the tumor microenviron- Carbohydrate antigens, microRNAs, ment. Additionally, some preclinical studies showed an anti- Diagnostic macrophage inhibitory cytokine 1, PAM4 markers antibodies, glypican, KRAS mutation, tumor activity novel agent against PDAC cells. Furthermore, osteopontin, epigenetic markers Wnt inhibitors and other novel immunomodulators have been reported to stimulate lymphocytes and innate immu- Gemcitabine markers, FOLFIRINOX markers, Predictive nab-paclitaxel markers, stromal markers, nity antitumor response through γδ-type T-cell receptors biomarkers BRCA mutated tumors, microsatellite and impact the median time to the first metastasis-related instability, PD-1/PD-L1 event and overall survival, in which restoring dendritic cells CA19-9, SMAD4, angiogenesis markers, also mediates immunity. Remarkably, innate immunity also Prognostic inflammatory markers, immune markers, seems to be related to zoledronic acid efficacy via tumor- markers microRNAs, SPARC associated macrophages [11, 20]. Challenges in targeted cancer therapy comprising var- ied resistance mechanisms emerged. They can be caused cancer. According to Porcelli et al. [19], cancer-associated by the cancer mutational landscape, microenvironment, fibroblasts and mast cells reduced the effectiveness of gemci- and inflammation perspectives. Drug resistance could preex- tabine/nab-paclitaxel on inhibition of tumor cells’ regrowth. ist or be acquired during the course of treatment. Alterations Knowledge of the molecular characteristics of an individual in the concentration of chemokines, cytokines, and growth can allow treatment modifications and monitoring of the factors have presented as a mechanism of conferring resis- response to gemcitabine/nab-paclitaxel [19]. tance to chemotherapeutic therapies. Anti-inflammatory Because the pancreatic tumor microenvironment has an agents, beyond their ability to decrease or prevent chemo- important role in the disease progression; therefore, it is a toxicity, can also act synergistically when combined with che- novel area related to targeted therapy that is under active motherapy agents. They may cause sensitization of cancer research. More recent therapies including SPARC-targeting cells to treatment with conventional anticancer agents. Sev- are discussed. Studies suggested that SPARC in the tumor eral studies suggest that anti-inflammatory agents will be Case Reports in Oncological Medicine 5 of clinical diagnosis, epidemiology, treatment and outcomes,” most effective in combination with cytotoxic, antiangiogenic, World Journal of Gastroenterology, vol. 24, no. 43, pp. 4846– and cytostatic agents. Furthermore, clinical managers would 4861, 2018. need to identify carefully for each drug the appropriate [10] S. Hasan, R. Jacob, U. Manne, and R. Paluri, “Advances in pan- molecular target, disease stage, cancer type, and treatment creatic cancer biomarkers,” Oncology Reviews, vol. 13, no. 1, duration [18–21]. pp. 410–410, 2019. [11] I. Regel, J. Mayerle, and M. Ujjwal Mukund, “Current strate- 4. Conclusion gies and future perspectives for precision medicine in pancre- atic cancer,” Cancers, vol. 12, no. 4, p. 1024, 2020. Diffuse pancreatic carcinoma is rare and difficult to manage because there are not many samples to study. It is often [12] Y. J. Choi, J. H. Byun, J. Y. Kim et al., “Diffuse pancreatic ductal adenocarcinoma: characteristic imaging features,” European reported sporadically as our case, with the weakness of no Journal of Radiology, vol. 67, no. 2, pp. 321–328, 2008. thorough treatment for our patient. This is a challenge that needs more precise approaches and well-designed clinical tri- [13] R. Ashida, S. Tanaka, H. Yamanaka et al., “The role of transab- dominal ultrasound in the diagnosis of early stage pancreatic als. Researchers need to further investigate other modalities cancer: review and single-center experience,” Diagnostics, to assess survival and tumor regression. It is necessary to vol. 9, no. 1, p. 2, 2019. increase the ability to diagnose and detect pancreatic cancer [14] F. H. Miller, N. J. Rini, and A. L. Keppke, “MRI of adenocarci- early by various laboratory methods such as serological noma of the pancreas,” American Journal of Roentgenology, markers, biomarkers, and cytological markers and radiologi- vol. 187, no. 4, pp. W365–W374, 2006. cal modalities such as ultrasound, CT, and MRI. A clinical [15] I.-M. Danet, R. C. Semelka, L. L. Nagase, J. T. Woosely, stratification and screening system combined with preven- P. Leonardou, and D. Armao, “Liver metastases from pancre- tion techniques and new technologies are needed in both atic adenocarcinoma: MR imaging characteristics,” Journal of diagnosis and treatment. Magnetic Resonance Imaging, vol. 18, no. 2, pp. 181–188, 2003. [16] M. A. Tempero, J. P. Arnoletti, S. W. Behrman et al., “Pancre- Data Availability atic Adenocarcinoma, version 2.2012,” Journal of the National Comprehensive Cancer Network, vol. 10, no. 6, pp. 703–713, No data were used for this case report. [17] W. Yao, A. Maitra, and H. Ying, “Recent insights into the biol- Conflicts of Interest ogy of pancreatic cancer,” eBioMedicine, vol. 53, p. 102655, All authors declare no conflict of interest. [18] E. Pelosi, G. Castelli, and U. Testa, “Pancreatic cancer: molec- ular characterization, clonal evolution and cancer stem cells,” References Biomedicine, vol. 5, no. 4, p. 65, 2017. [19] L. Porcelli, R. Iacobazzi, R. di Fonte et al., “CAFs and TGF-β [1] M. E. Mostafa, I. Erbarut-Seven, B. Pehlivanoglu, and signaling activation by mast cells contribute to resistance to V. Adsay, “Pathologic classification of "pancreatic cancers": gemcitabine/nabpaclitaxel in pancreatic cancer,” Cancers, current concepts and challenges,” Chinese Clinical Oncology, vol. 11, no. 3, p. 330, 2019. vol. 6, no. 6, p. 59, 2017. [20] J. Vaz, D. Ansari, A. Sasor, and R. Andersson, “SPARC: a [2] P. Rawla, T. Sunkara, and V. Gaduputi, “Epidemiology of pan- potential prognostic and therapeutic target in pancreatic can- creatic cancer: global trends, etiology and risk factors,” World cer,” Pancreas, vol. 44, no. 7, pp. 1024–1035, 2015. Journal of Oncology, vol. 10, no. 1, pp. 10–27, 2019. [21] E. A. Comen, R. L. Bowman, and M. Kleppe, “Underlying [3] A. Lambert, L. Schwarz, I. Borbath et al., “An update on treat- causes and therapeutic targeting of the inflammatory tumor ment options for pancreatic adenocarcinoma,” Therapeutic microenvironment,” Frontiers in Cell and Development Biol- Advances in Medical Oncology, vol. 11, 2019. ogy, vol. 6, p. 56, 2018. [4] Z. S. Kanji and S. Gallinger, “Diagnosis and management of pancreatic cancer,” Canadian Medical Association Journal, vol. 185, no. 14, pp. 1219–1226, 2013. [5] P. Tummala, O. Junaidi, and B. Agarwal, “Imaging of pancre- atic cancer: an overview,” Journal of Gastrointestinal Oncology, vol. 2, no. 3, pp. 168–174, 2011. [6] C. S. Yabar and J. M. Winter, “Pancreatic Cancer,” Gastroen- terology Clinics of North America, vol. 45, no. 3, pp. 429–445, [7] H. Miyoshi, M. Kano, S. Kobayashi et al., “Diffuse pancreatic cancer mimicking autoimmune pancreatitis,” Internal Medi- cine, vol. 58, no. 17, pp. 2523–2527, 2019. [8] E. Lee and J. Lee, “Imaging diagnosis of pancreatic cancer: a state-of-the-art review,” World Journal of Gastroenterology, vol. 20, no. 24, pp. 7864–7877, 2014. [9] A. McGuigan, P. Kelly, R. C. Turkington, C. Jones, H. G. Coleman, and R. S. McCain, “Pancreatic cancer: a review http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Case Reports in Oncological Medicine Hindawi Publishing Corporation

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Abstract

Hindawi Case Reports in Oncological Medicine Volume 2020, Article ID 8815745, 5 pages https://doi.org/10.1155/2020/8815745 Case Report 1 2 3 Hoang Quan Nguyen , Ngoc Trinh Thi Pham , Van Trung Hoang , 3 4 5 Hoang Anh Thi Van , Chinh Huynh, and Duc Thanh Hoang Department of Radiology, Da Nang Oncology Hospital, Da Nang, Vietnam School of Medicine and Pharmacy, The University of Danang, Da Nang, Vietnam Department of Radiology, Thien Hanh Hospital, Buon Ma Thuot, Vietnam Department of Radiology, Tu Du Hospital, Ho Chi Minh, Vietnam Division of Endocrinology, Department of Medicine, Walter Reed National Military Medical Center, Bethesda, USA Correspondence should be addressed to Van Trung Hoang; dr.hoangvantrungradiology@gmail.com Received 2 May 2020; Revised 15 October 2020; Accepted 16 October 2020; Published 31 October 2020 Academic Editor: Mauro Cives Copyright © 2020 Hoang Quan Nguyen et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Pancreatic cancer is one of the seven leading causes of cancer death worldwide. Diffuse pancreatic carcinoma is very rare and underreported in the literature. Many advances have been made in the diagnosis and management of pancreatic cancer. However, most pancreatic cancer cases are detected at the terminal or metastatic stages. Therefore, timely diagnosis and therapeutic management are desirable goals for this disease. Although the proliferation of pancreatic cancer has been reduced by intervention, more work is needed to treat and prevent the disease. The purpose of this article is to present a case of a 54-year-old male with pancreatic cancer and to review the epidemiology, diagnosis, management, and prevention of pancreatic tumors in general as well as pancreatic carcinoma in particular. chemotherapy and radiation is poor. Surgery is the only 1. Introduction treatment that has the potential to prolong survival but is Pancreatic cancer can derive from epithelial and nonepithe- usually performed late at the time of discovery [4]. Diffuse lial tumors such as pancreatic metastases, connective cancer, pancreatic carcinoma is usually rare compared to focal pan- and lymphoma. Epithelial tumors include nonendocrine and creatic cancer. In a major study of general pathology, the location of pancreatic carcinoma at the head of the pancreas endocrine tumors such as pancreatic ductal adenocarcinoma, serous cystadenocarcinoma, and mucinous cystadenocarci- was 60%, the pancreatic body 13%, pancreatic tail 5%, and noma [1]. Among all cancers, pancreatic cancer is one of the remaining 22% diffuse pancreatic carcinoma [2, 5, 6]. the worst; despite improvements in both diagnostic and sur- Biochemical testing and diagnostic imaging are the main gical techniques, survival has not improved substantially for diagnostic methods [4]. Differential diagnosis includes dif- more than 50 years. The 5-year survival rate still remains at fuse pancreatitis, autoimmune pancreatitis, multiple pancre- 9% only. Pancreatic carcinoma can occur at any age but is atic cancer, and diffuse pancreatic metastases. Distinguishing more common in the elderly. Pancreatic cancer is the 11th between pancreatic tumors and pancreatitis is crucial because most common cancer in the world, accounting for 2.5% of the clinical course, treatment, and prognosis of these two dis- all cancers and causing 4.5% of all cancer deaths [2]. Due to eases are quite different [5, 7]. Metastatic pancreatic carci- the increasing incidences, late diagnosis, and limited treat- noma mainly affects the liver, peritoneum, lung, and bone, ment options, its mortality rate is estimated to increase grad- although bone metastases usually occur late [5, 8, 9]. In this ually over the next decade [3]. The tumor’s response to case report, we describe a rare case of a 54-year-old male with 2 Case Reports in Oncological Medicine of 68-91%. Its main value is to assess the response to the diffuse pancreatic carcinoma with hepatic metastases diag- nosed by ultrasound, computed tomography (CT), and mag- treatment and monitor follow-up recurrence of the disease netic resonance imaging (MRI). [4, 5, 9]. A novel array set of biomarkers for diagnostic, pre- dictive, and prognostic potential for pancreatic cancer is cur- rently being used and studied with the hope of finding 2. Case Presentation effective management methods for this challenging disease A 54-year-old man was hospitalized with diffuse abdominal (Table 1) [10]. Further studies of novel biomarkers for pan- pain and abdominal distention. The pain occurred 4 days creatic cancer subtyping, diagnosis, and treatment response prior to admission and was gradually increasing. At first, prediction are underway [11]. the pain was localized in the epigastric region, then radiating In patients presenting with pancreatic malignancy, abdominal ultrasound is often used as an initial diagnostic throughout the abdomen. The patient reported nausea but no vomiting nor jaundice. He was normotensive with a blood modality [12, 13]. CT scan is used in evaluating the stage of pressure of 120/60 mmHg, pulse rate 75 bpm, respiratory pancreatic cancer with a sensitivity of 89-97% and specificity rate 21 per minute, and temperature 37.7 C. He noticed of 95%. CT findings indicate the presence of the tumor, recent weight loss of 4 kg over 3 months. He reported rare involvement of vessels (the celiac axis and hepatic or superior alcohol consumption, no smoking, and noncontributing mesenteric artery) and organs, enlarged lymph nodes, ascites, family history. Examination showed no symptoms of biliary and distant metastases. In our case, the peripheral capsule- obstruction but diffuse abdominal tenderness on palpation. like structure was a characteristic CT finding of diffuse pan- Serum amylase, lipase, and IgG4 were within normal ranges, creatic cancer that was rarely seen in focal pancreatic cancer and CA19-9 and CA242 were 69.6 U/mL (normal value ≤ and other pancreatic lesions [5, 8, 12]. MRI is another appro- 37 U/mL) and 82.1 U/mL (normal value ≤ 20 U/mL), respec- priate option for patients who have contraindications to CT tively. Bilirubin, alpha-fetoprotein, and HBsAg were normal. or where CT images are unclear [5, 13]. High resolution of Abdominal ultrasound revealed a diffusely enlarged and MRI can better detect pancreatic lesions, small liver metasta- heterogeneous hypoechoic pancreas. Slightly infiltrated fat ses, lymph nodes, and peritoneal metastases. The recogniza- layer was found around the pancreas without associated tion of the liver and peritoneal metastases is critical for fluid. Simultaneously, the liver also showed multiple solid accurately staging pancreatic carcinoma because the cancer hypoechoic or hyperechoic masses. CT scan confirmed is unresectable if metastases are present [4, 14]. Multislice enlargement of the pancreas with relatively homogenous CT can also detect small liver lesions; however, if the lesions enhancement remarkably in the arterial phase and washout are less than 10 mm, it is often difficult to characterize. MRI in the delayed phase (Figure 1). Multiple liver lesions showed may be more clearly delineate lesions like hemangiomas, early arterial enhancement with washout in the delayed cysts, or metastases [3]. According to Danet et al. [15], liver phase suggesting hypervascular metastases (Figure 2). The metastases have usually signals from isointensity to slightly pancreatic duct and biliary tract did not dilate; there was no high intensity on T2-weighted images, with a slightly lower presence of pathological lymph nodes. The patient subse- signal on T1-weighted images. Positron emission tomogra- quently underwent MRI that showed characteristics similar phy (PET) is becoming more widely available and may help to ultrasound and CT with a diffusely enlarged pancreas with distinguish chronic pancreatitis from pancreatic cancer. It low signal intensity on T1-weighted, high signal intensity het- may help detect regional lymph nodes or distant metastases erogeneous on T2-weighted, restricted diffusion on diffusion- from pancreatic cancer [4, 8]. Endoscopic ultrasound (EUS) weighted imaging, and relatively homogenous enhancement can be used to detect small pancreatic masses that could be on postcontrast T1-weighted images (Figure 3). missed by CT scan and is commonly used to perform According to the clinical presentation, laboratory results, biopsy [6, 9]. and radiological findings, we had a provisional diagnosis of The malignancy of the pancreas is classified into resect- diffuse pancreatic carcinoma with liver metastasis. We per- able, borderline resectable, and advanced disease (either locally advanced or metastatic) [16]. Multidisciplinary treat- formed pancreatic FNA under ultrasound guidance; cytology revealed suspected carcinoma. The patient then underwent ment of pancreatic carcinoma needs to combine surgery, ultrasound-guided biopsy of liver lesions; histopathological radiotherapy, chemotherapy, and supportive care. Some cur- findings confirmed metastases from carcinoma. He received rent methods include personalized medicine, immunother- conservative treatment, and after 2 weeks, the symptoms apy, innovative targets, therapeutic vaccines, stemness inhibitors, adoptive T-cell transfer, and stem-cell therapy were much improved. We offered chemoradiotherapy and palliative care, but he refused and requested to be discharged [3, 5, 9]. The stratification of pancreatic cancer patients 1 week later. We contacted the patient after 2 months, but according to the tumor transcriptome is a major approach family members said his conditions were getting worse. to predict treatment response. Other strategies concentrate on genomic or chromosome alterations and the determina- tion of targeted therapies [11, 17]. 3. Discussion Comprehensive analyses from genomes of primary and metastatic pancreatic tumors indicate that there are two pro- Pancreatic cancer poses a significant diagnostic challenge, and the majority of cases present late with either locally gressive processes in pancreatic cancer: (1) the early cancer- advanced or metastatic disease. Serum marker CA19-9 has initiating phase in which most mutations would establish a preneoplastic tumor and (2) the rapid cancer-transforming been evaluated with a sensitivity of 70-90% and specificity Case Reports in Oncological Medicine 3 (a) (b) Figure 1: Contrast-enhanced CT images in the arterial (a) phase and delayed (b) phase. CT shows a sausage-shape enlargement of the pancreas (arrows), with relatively homogenously remarkable enhancement in the arterial phase and washout in the delayed phase with the capsule-like rim at the surface (arrowheads). The pancreatic duct did not dilate. (a) (b) (c) (d) Figure 2: CT images before (a) and in the late arterial (b), portal venous (c), and delayed (d) phases after contrast administration. The metastases hyper enhance dramatically in the arterial phase and subsequently fade toward mild hypoattenuation relative to the liver in the delayed phase (arrows). Some portions of the lesions do not enhance, suggesting necrosis. Many similar lesions are scattered throughout the liver parenchyma (not shown). phase that generates invasive clones and colonization of where pancreatic cancer would be optimally treated depend- distant sites. Moreover, the gradual increasing mutational ing on its molecular subtype. Besides, the characterization of burden of CDKN2A, KRAS, SMAD4, and TP53 genes pro- cell signaling pathways and the diverse tumor cell types would be useful in the approach to novel therapy [11, 18]. motes the early accelerated progression and metastasis of pancreatic cancer. When the biological and molecular land- Recent combination therapies are based on mechanisms scape of pancreatic carcinoma is unraveling, there would be of resistance to immune checkpoint inhibitors, which a shift of clinical practice to utilize molecular taxonomy, improve condition in patients with unresectable pancreatic 4 Case Reports in Oncological Medicine T1 noncontrast T2W (a) (b) T1 postcontrast arterial phase T1 postcontrast delayed phase (c) (d) Figure 3: MRI on T1-weighted image (a), T2-weighted image (b), and arterial phase (c) and delayed phase (d) in T1-weighted image with fat- sat after contrast administration. MRI shows a diffusely enlarged pancreas with low intensity on T1-weighted imaging and heterogeneous high intensity on T2-weighted imaging, particularly in the body and tail region of the pancreas. The pancreas also shows remarkable enhancement in the arterial phase and washout in the delayed phase. Table 1: Pancreatic cancer biomarkers. stroma may sequester albumin-bound paclitaxel, enhancing the distribution of paclitaxel into the tumor microenviron- Carbohydrate antigens, microRNAs, ment. Additionally, some preclinical studies showed an anti- Diagnostic macrophage inhibitory cytokine 1, PAM4 markers antibodies, glypican, KRAS mutation, tumor activity novel agent against PDAC cells. Furthermore, osteopontin, epigenetic markers Wnt inhibitors and other novel immunomodulators have been reported to stimulate lymphocytes and innate immu- Gemcitabine markers, FOLFIRINOX markers, Predictive nab-paclitaxel markers, stromal markers, nity antitumor response through γδ-type T-cell receptors biomarkers BRCA mutated tumors, microsatellite and impact the median time to the first metastasis-related instability, PD-1/PD-L1 event and overall survival, in which restoring dendritic cells CA19-9, SMAD4, angiogenesis markers, also mediates immunity. Remarkably, innate immunity also Prognostic inflammatory markers, immune markers, seems to be related to zoledronic acid efficacy via tumor- markers microRNAs, SPARC associated macrophages [11, 20]. Challenges in targeted cancer therapy comprising var- ied resistance mechanisms emerged. They can be caused cancer. According to Porcelli et al. [19], cancer-associated by the cancer mutational landscape, microenvironment, fibroblasts and mast cells reduced the effectiveness of gemci- and inflammation perspectives. Drug resistance could preex- tabine/nab-paclitaxel on inhibition of tumor cells’ regrowth. ist or be acquired during the course of treatment. Alterations Knowledge of the molecular characteristics of an individual in the concentration of chemokines, cytokines, and growth can allow treatment modifications and monitoring of the factors have presented as a mechanism of conferring resis- response to gemcitabine/nab-paclitaxel [19]. tance to chemotherapeutic therapies. Anti-inflammatory Because the pancreatic tumor microenvironment has an agents, beyond their ability to decrease or prevent chemo- important role in the disease progression; therefore, it is a toxicity, can also act synergistically when combined with che- novel area related to targeted therapy that is under active motherapy agents. They may cause sensitization of cancer research. More recent therapies including SPARC-targeting cells to treatment with conventional anticancer agents. Sev- are discussed. Studies suggested that SPARC in the tumor eral studies suggest that anti-inflammatory agents will be Case Reports in Oncological Medicine 5 of clinical diagnosis, epidemiology, treatment and outcomes,” most effective in combination with cytotoxic, antiangiogenic, World Journal of Gastroenterology, vol. 24, no. 43, pp. 4846– and cytostatic agents. Furthermore, clinical managers would 4861, 2018. need to identify carefully for each drug the appropriate [10] S. Hasan, R. Jacob, U. 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Case Reports in Oncological MedicineHindawi Publishing Corporation

Published: Oct 31, 2020

References