Differentiation of Solid Pancreatic Tumors by Using Dynamic Contrast-Enhanced MRI

최승준,김형식,박현진 한국물리학회 2014 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.64 No.2

Distinguishing among different solid pancreatic tumor types, pancreatic ductal adenocarcinomas,neuroendocrine tumors (NETs), and solid pseudopapillary tumors (SPTs) is important, as the treatmentoptions are vastly different. This study compared characteristics of solid pancreatic tumorsby using dynamic contrast enhanced magnetic resonance imaging (MRI). Fifty patients underwentMR imaging of pancreatic masses with a histopathology that was later confirmed as an adenocarcinoma(n = 27), a NET (n = 16), and a SPT (n = 7). For qualitative analysis, two reviewersevaluated the morphologic features of the tumors: locations, margins, shapes, contained products,pancreatic ductal dilatation, and grade of signal intensity (SI). For the quantitative analysis, allphases of the MR images were co-registered using proprietary image registration software; thus, aregion of interest (ROI) defined on one phase could be re-applied in other phases. The followingfour ratios were considered: tumor-to-uninvolved pancreas SI ratio, percent SI change, tumor-touninvolvedpancreas enhancement index, and arterial-to-delayed washout rate. The areas under thereceiver operating characteristic (ROC) curves were assessed for the four ratios. Adenocarcinomashad ill-defined margins, irregular shapes, and ductal dilatation compared with NETs and SPTs (P< 0.001). The tumor-to-uninvolved pancreas ratio on all dynamic phases was significantly higherfor NETs than for both adenocarcinomas and SPTs (P < 0.05). Percentage SI changes of pancreatictumors on the pancreatic and the portal venous phases were significantly higher for NETsthan for both adenocarcinomas and SPTs (P < 0.05). A significant difference between NETs andadenocarcinomas was also found with respect to the tumor-to-uninvolved pancreas enhancementindex and arterial-to-delayed washout rate. The percentage SI changes in the pancreatic phase andthe arterial-to-delayed washout rate best distinguished between adenocarcinomas and NETs withthe area under the ROC curve being 0.87. The percentage SI changes in the pancreatic and theportal venous phases best distinguished between NETs and SPTs with area under the ROC curve0.87. In summary, contrast-enhanced MRI can be useful in differentiating solid pancreatic tumorsin qualitative and quantitative analyses

췌장신경내분비종양의 내과적 치료

성민제 ( Min Je Sung ),정문재 ( Moon Jae Chung ) 대한췌장담도학회 2021 대한췌담도학회지 Vol.26 No.1

췌장신경내분비종양은 랑게르한스 소도에서 기원한 종양을 의미하며, 호르몬 분비에 의한 증상 발현 유무, Ki-67 분열 지수 및 세포분화도를 기준으로 한 분류 외에도, Tumor-Node-Metastasis (TNM) 병기 분류를 통한 병의 진행 정도에 따라 다양한 예후를 보인다. 췌장신경내분비종양의 내과적 치료목표는 증상을 조절하거나, 종양의 성장을 억제하는 것이다. 내과적 치료 약제 중 하나인 소마토스타틴 유사체는 호르몬 분비와 연관된 증상 조절 목적뿐만 아니라 항암 효과를 위해서도 사용되고 있으며, Ki-67 분열 지수가 20% 미만인 WHO 분류기준 Grade 1/Grade 2 (G1/G2) 종양의 진행을 억제하는 데에 효과적인 약물로 받아들여지고 있다. 분자표적치료제 중 everolimus와 sunitinib은 소마토스타틴 유사체 치료 후 진행된 WHO G1/G2 췌장신경내분비종양 환자에서 고려될 수 있다. 항암화학요법은 주로 Ki-67 분열지수가 높거나 급속히 진행하는 종양 또는 타 장기로 전이가 동반된 경우, 다른 치료에 실패하였거나 소마토스타틴 수용체 음성인 신경내분비 암종에 우선적으로 사용이 고려되며, 주로 etoposide/cisplatin 병합 요법이 표준 치료제로 받아들여지고 있다. 하지만 Grade 3 췌장신경내분비종양(well differentiated, high grade) 환자군에 대해서는 아직까지 표준 치료에 대한 가이드라인이 확립되어 있지 않으며, 기존의 전신 항암제에 치료 반응률이 상대적으로 저조한 것으로 보고되고 있어, G1/G2 종양에서 사용되는 소마토스타틴 유사체나 분자표적치료제 등의 치료 반응률을 평가할 연구가 필요한 상황이다. 췌장신경내분비종양은 다양한 임상 경과를 보이는 만큼 다양한 치료의 선택이 필요하며, 내과적 치료뿐만 아니라 원발 부위 및 전이성 병소에 대한 근치적 절제술, 간동맥 색전술과 고주파 소작술 등의 국소 치료, 방사선 동위 원소를 이용한 방사선표적치료(PRRT) 등 모든 가능한 치료 방법을 고려하는 다학제적 접근이 중요하다고 하겠다. Pancreatic neuroendocrine tumor (PNET) refer to tumors originating from the islet of Langerhans and shows various prognosis based on the presence or absence of symptoms due to hormone secretion, the Ki-67 cell proliferation index, and the histologic grade, and according to the degree of disease progression defined by the tumor-node-metastasis (TNM) stage classification. The purpose of medical treatment for PNET is to control symptoms or inhibit tumor growth. Somatostatin analogues can be administered for the purpose of controlling symptoms caused by the secretion of specific hormones, and are accepted as effective drugs for inhibiting the progression of G1/G2 tumors based on World Health Organization (WHO) classification with a Ki- 67 cell proliferation index less than 20%. Among the molecularly targeted agents, everolimus and sunitinib can be considered in patients with WHO G1/G2 PNET showing progression after somatostatin analog therapy. Cytotoxic chemotherapy is generally administered to patients with large tumor volume and rapidly progressing metastatic NET, and etoposide/cisplatin combination therapy has been considered as a standard treatment. For the patient group of Grade 3 PNET (well differentiated) newly classified by the WHO 2017 classification, guidelines for standard treatment have not yet been established. As it has been reported, studies are needed to evaluate the treatment response rate of somatostatin analogues or molecularly targeted therapies for the patient with Grade 3 PNET. It is important to consider a multidisciplinary approach with all possible treatment options including medical treatment, radical resection of primary or metastatic lesions, liver-directed therapies, and peptide receptor radionuclide therapy for the patients with PNET. Korean J Pancreas Biliary Tract 2021;26(1):24-32

Non-Functioning, Malignant Pancreatic Neuroendocrine Tumor in a 16-Year-old Boy: A Case Report

임세웅,이영환,최시성,조현선 대한자기공명의과학회 2010 Investigative Magnetic Resonance Imaging Vol.14 No.2

We report the case of a 16-year-old boy with a solid pancreatic mass which proved to be a nonfunctioning, malignant pancreatic neuroendocrine tumor (PNET). In pediatric patients, malignant pancreatic tumors are rare, especially malignant PNET. When dynamic contrast enhanced MRI showed a well enhancing solid pancreatic tumor on arterial and delayed phases and combined with malignant features, such as vascular invasion, invasion of adjascent organs, and lymphadenopathy, we should include malignant pancreatic neuroendocrine tumor in the differential diagnosis of childhood pancreatic tumors.

Prognostic Factors and Characteristics of Pancreatic Neuroendocrine Tumors: Single Center Experience

오탁근,송시영,정문재,박정엽,방승민,박승우,정재복 연세대학교의과대학 2012 Yonsei medical journal Vol.53 No.5

Purpose: Pancreatic neuroendocrine tumors (PNET) are a rare subgroup of tumors. For PNETs, the predictive factors for survival and prognosis are not well known. The purpose of our study was to evaluate the predictive factors for survival and disease progression in PNETs. Materials and Methods: We retrospectively analyzed 37 patients who were diagnosed with PNET at Severance Hospital between November 2005 and March 2010. Prognostic factors for survival and disease progression were evaluated using the Kaplan-Meier method. Results: The mean age of the patients was 50.0±15.0 years. Eight cases (21.6%) were described as functioning tumors and 29 cases (78.4%) as non-functioning tumors. In univariate analysis of clinical factors, patients with liver metastasis (p=0.002), without resection of primary tumors (p=0.002), or American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) stage III/IV (p=0.002) were more likely to demonstrate shorter overall survival (OS). Patients with bile duct or pancreatic duct invasion (p=0.031), sized-lesions larger than 20 mm (p=0.036), liver metastasis (p=0.020), distant metastasis (p=0.005), lymph node metastasis (p=0.009) or without resection of primary tumors (p=0.020) were more likely to demonstrate shorter progression-free survival (PFS). In multivariate analysis of clinical factors, bile duct or pancreatic duct invasion [p=0.010, hazard ratio (HR)=95.046] and tumor location (non-head of pancreas) (p=0.036, HR=7.381) were confirmed as independent factors for predicting shorter PFS. Conclusion: Patients with liver metastasis or without resection of primary tumors were more likely to demonstrate shorter OS. Patients with bile duct or pancreatic duct invasion or tumors located at body or tail of pancreas were more likely to demonstrate shorter PFS.

Utility of fistula risk score in assessing the risk of postoperative pancreatic fistula occurrence and other significant complications after different types of pancreatic neuroendocrine tumor resections

Bartosz Molasy,Patryk Zemła,Sławomir Mrowiec,Katarzyna Kusnierz 대한외과학회 2022 Annals of Surgical Treatment and Research(ASRT) Vol.103 No.6

Purpose: This study was performed to evaluate the utility of the fistula risk score (FRS) and its components in predicting the occurrence of postoperative pancreatic fistula and other significant postoperative complications after resections of pancreatic neuroendocrine tumors. Methods: Retrospective analysis of 131 patients operated on for pancreatic neuroendocrine tumors between 2015 and 2021 was performed. The correlation of the FRS scale with the occurrence of postoperative pancreatic fistulas and postoperative complications according to the Clavien-Dindo classification was analyzed; only in 109 cases of distal resections and pancreatoduodenectomies (PD). Results: Soft pancreatic texture and intraoperative blood loss of >700 mL are risk factors for clinically significant pancreatic fistula (P = 0.001 and P = 0.001, respectively) and significant postoperative complications (P = 0.016 and P = 0.001, respectively). Wirsung duct diameter (WDD) was associated only with the occurrence of postoperative pancreatic fistula (P = 0.013). FRS scale is associated with the occurrence of pancreatic fistulas and clinically significant postoperative complications in cases of distal resections and PDs (P < 0.001 and P = 0.005, respectively). Postoperative complications are correlated with the occurrence of fistula type B or C (P < 0.001). Conclusion: Soft pancreatic texture, intraoperative blood loss of >700 mL, and a WDD of ≤3 mm are risk factors for clinically significant postoperative pancreatic fistula. FRS may be applied not only in PDs but also in distal pancreatectomies. Unfortunately, it is not used in total pancreatic resections and enucleations since FRS takes into account the WDD.

Advances in the Management of Unresectable or Metastatic Pancreatic Neuroendocrine Tumors: Chemotherapy, Targeted Therapy, Hormonal Treatment, and Future Directions

Bilici, Ahmet Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.6

Pancreatic neuroendocrine tumors (pNETs) are rare and heterogenous tumors and surgery to remove the primary tumor is the mainstay of treatment for resectable disease. However, curative surgery is often not feasible, because half of patients with pNET have metastases at the time of diagnosis. Palliative dubulking surgery and liver-directed therapies are appropriate options for these patients. Streptozocin-based regimens are standard, although temozolamide-based treatments are rapidly gaining wide clinical application. Somatostatin analogs are mainly indicated in hormonally active tumors to ameliorate symptoms. In addition, anti-tumoral activity has been proven in well-differentiated NETs. Recently, there has been tremendous progress in the molecular biology of pNETs; thereby, the efficacy of sunitinib and everolimus in the treatment of patients with metastatic pNETs has been proven by large placebo-controlled phase III trials. Currently, there are no definitively proven predictive biomarkers to evaluate response to medical therapies in patients with pNET. Therefore, further studies are needed to individualize and optimize their management. This article reviews systemic chemotherapy, targeted therapies, and anti-secretory treatments for the management of patients with unresectable or metastatic pNETs, summarized in the light of recent advances.

Current Status of the Diagnosis and Management of Pancreatic Neuroendocrine Tumors in Japan

Tetsuhide Ito,Masami Miki,Keijiro Ueda,Lingaku Lee,Ken Kawabe,Hisato Igarashi,Nao Fujimori,Kazuhiko Nakamura,Kohei Yasunaga,Robert T. Jensen,Takao Ohtsuka,Yoshihiro Ogawa Korean Society of Gastrointestinal Cancer 2016 Journal of digestive cancer reports Vol.4 No.2

The epidemiology of pancreatic neuroendocrine neoplasms (PNENs) in Asia has been clarified through epidemiological studies, including one conducted in Japan, and subsequently another in South Korea. As endoscopic ultrasonography (EUS) has become more widely accessible, endoscopic ultrasound-fine needle aspiration (EUS-FNA) has been performed in pancreatic tumors for which the clinical course was only monitored previously. This has enabled accurate diagnosis of pancreatic tumors based on the 2010 WHO classification; as a result, the number of patients with an accurate diagnosis has increased. Although surgery has been the standard therapy for PNENs, new treatment options have become available in Japan for the treatment of advanced or inoperable PNENs; of particular note is the recent introduction of molecular target drugs (such as everolimus and sunitinib) and streptozocin. Treatment for progressive PNENs needs to be selected for each patient with consideration of the performance status, degree of tumor differentiation, tumor mass, and proliferation rate. Somatostatin receptor (SSTR)-2 is expressed in many patients with neuroendocrine tumor. Somatostatin receptor scintigraphy (SRS), which can visualize SSTR-2 expression, has been approved in Japan. The SRS will be a useful diagnostic tool for locating neuroendocrine neoplasms, detecting distant metastasis, and evaluating therapy outcomes. In this manuscript, we review the latest diagnostic methods and treatments for PNENs.

Diagnosis of Pancreatic Neuroendocrine Tumors

이동욱,Michelle Kang Kim,김호각 대한소화기내시경학회 2017 Clinical Endoscopy Vol.50 No.6

Pancreatic neuroendocrine tumors (PNETs) are relatively rare; however, the incidence has increased over the last few decades. They are classified as functional or non-functional tumors according to the presence of associated clinical symptoms. The majority are non-functional tumors. For classification and staging, the World Health Organization 2010 classification system is the most commonly accepted. Chromogranin A is the most sensitive marker but has insufficient specificity. In general, PNETs are hypervascular tumors, and multiphasic contrast-enhanced computed tomography is considered the first choice for imaging study. Multiphasic magnetic resonance imaging can detect PNETs smaller than 2 cm and small liver metastasis compared with other modalities. Somatostatin receptor scintigraphy is often used in cases where functional PNETs are suspected. Positron emission tomography (PET) scan with 18F-fluorodeoxyglucose cannot visualize PNETs, but PET with 68-Ga DOTATATE can. Endoscopic ultrasonography can characterize smaller PNETs using contrast and confirm histology through fine needle aspiration or biopsy. In this article, we review the characteristics of grading systems and diagnostic modalities commonly used for PNETs.

Prognostic Value of Volume-Based Metabolic Parameters Measured by 18F-FDG PET/CT of Pancreatic Neuroendocrine Tumors

김호성,김병태,최준영,최동욱,임호영,이주희,홍선표,조영석,이경한 대한핵의학회 2014 핵의학 분자영상 Vol.48 No.3

Purpose To date, the prognostic value of 18F-FDG PET/CTfor patients with pancreatic neuroendocrine tumors (PNETs)has not been well characterized.We investigated the prognosticvalue of volumetric parameters using 18F-FDG PET/CT inthis patient population. Methods We retrospectively reviewed 20 cases of pathologicallyproven PNET in patients who had undergone pretherapeutic18F-FDG PET/CT. PET parameters includingmaximum and average standardized uptake values (SUVmax,SUVave), metabolic tumor volume (MTV), and total lesionglycolysis (TLG) of the primary tumor were measured using athreshold SUV to determine the boundaries of the tumors. Univariate and multivariate survival analyses were performedwith adjustments for PET parameters and other clinicalvalues. Results The median clinical follow-up was 22.3 (range, 1.2–95.4) months. Cancer-related death occurred in 5 of 20patients (25 %). Patients had clinical or pathological stagesof I in seven patients, II in six patients, III in three patient, andIV in four patients. According to the WHO histological classificationof subtypes, 3 patients exhibited well-differentiatedPNETs, 13 patients had well-differentiated endocrine carcinomas,and 4 had poorly differentiatedendocrine carcinomas. Univariate analysis showed that tumor size (p=0.028), AJCCstage (p=0.009), T stage (p=0.028), M stage (p=0.029),treatment modality (p=0.045), MTV (p=0.003) and TLG(p=0.027) were significant predictors of overall survival. Onmultivariate analysis, MTV (HR=10.859, p=0.031) was asignificant independent predictor of overall survival alongwith the AJCC stage (HR=11.556, p=0.027). Conclusion In patients with PNETs, the MTVof the primarytumor asmeasured by 18F-FDG PET/CTalong with the AJCCstage may be a significant independent prognostic factor foroverall survival.

Review : The Current Strategy for Managing Pancreatic Neuroendocrine Tumors in Multiple Endocrine Neoplasia Type 1

( Yusuke Niina ),( Nao Fujimori ),( Taichi Nakamura ),( Hisato Igarashi ),( Takamasa Oono ),( Kazuhiko Nakamura ),( Masaki Kato ),( Robert T. Jensen ),( Tetsuhide Ito ),( Ryoichi Takayanagi ) The Editorial Office of Gut and Liver 2012 Gut and Liver Vol.6 No.3

Multiple endocrine neoplasia type 1 (MEN1) is an inherited autosomal dominant disease presenting with pancreatic neuroendocrine tumors (pNETs), parathyroid tumors, or pitu-itary tumors. Using the PubMed database, we reviewed the literature on information regarding the proper diagnosis and treatment of MEN1-associated pNET. Many cases of MEN1-associated pNET are functioning pNETs. Gastrinomas and insulinomas tend to occur frequently in the duodenum and pancreas, respectively. In addition to diagnostic imaging, the selective arterial secretagogue injection test (SASI test) is useful for localizing functioning pNET. The standard treat-ment is surgical resection. However, in the case of a func-tioning pNET, the tumor should first be accurately located using the SASI test before an appropriate surgical method is selected. In cases of a MEN1-associated non-functioning pNET that exceeds 2 cm in diameter, the incidence of distant metastasis is significantly increased, and surgery is recom-mended. In cases of unresectable pNET, a somatostatin analog has been shown to demonstrate antitumor effects and is considered to be a promising treatment. In addition, molecular-targeted drugs have recently been found to be ef-fective in phase III clinical trials. (Gut Liver 2012;6:287-294)