췌장암의 절제 가능성에 관한 연구

윤용범(Yong Bum Yoon),최일주(Il Ju Choi),최문석(Moon Suk Choi),김재규(Jae Gyu Kim),김용태(Yong Tae Kim),김정룡(Chung Yong Kim) 대한내과학회 1994 대한내과학회지 Vol.47 No.5

N/A Objectives: The prognosis of pancreatic cancer is very poor. However, considerable progress has been made in the ability to diagnose and manage pancreatic cancer. Accurate preoperative staging has become important Objectives: The prognosis of pancreatic cancer is very poor. However, considerable progress has been made in the ability to diagnose and manage pancreatic cancer. Accurate preoperative staging has become important for proper management of pancreatic cancer patients. The aim of this study was to compare the preoperative and postoperative staging of pancreatic cancers and to find the reason for unresectability according to their size and location. Methods: We reviewed the medical records of 324 patients with pancreatic cancer between 1984 and 1991. We used the AJCC criterion for staging pancreatic cancer. Preoperative staging was made with ultrasonography, CT, ERCP, and angiography. Preoperative and postoperative staging were compared in those who underwent surgery. Results: In total 324 patients with pancreatic cancer, cancers were located at head in 209 cases and at the body and tail in 115 cases. The number of patients with preoperative stage 1 was 67 (21%). One hundred fourteen patients were operated on, and forty-nine patients were of preoperative stage 1. There were 33 cases with head cancers of stage 1 and 16 cases with body and tail cancers of stage 1. However only 10 cases (30%) of head cancer and 3 cases (19%) of body and tail cancer were of stage 1 postoperatively. The major causes of unresectability were vascular invasion (39%), and peripancreatic lymph node metastasis (36%) in head cancer and peripancreatic lymph node metastasis (50%), and peritoneal seeding (41%) in body and tail cancer. If the tumor size was over 4 cm, all body and tail cancers were unresectable and only 1 out of 16 (6%) head cancers was resectable. In head cancer, 3 cases were smaller than 2 cm, but only 1 case was in stage 1, the other two cases were in stages 2 and 4. The size of all cancers located in the body and tail were greater than 2 cm. Conclusion: These results suggest that fewer pancreatic cancers could be resected curatively than thought preoperatively, That was due to the inability to evaluate properly the peripancreatic lymph node metastasis, vascular invasion, peritoneal seeding, and small liver metastasis preoperatively. Hence it is recommended that the stage of pancreatic cancer should be evaluated more accurately before surgery.

Applicative Value of Serum CA19-9, CEA, CA125 and CA242 in Diagnosis and Prognosis for Patients with Pancreatic Cancer Treated by Concurrent Chemoradiotherapy

Gu, Yu-Lei,Lan, Chao,Pei, Hui,Yang, Shuang-Ning,Liu, Yan-Fen,Xiao, Li-Li Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.15

Objective: To evaluate the application value of serum CA19-9, CEA, CA125 and CA242 in diagnosis and prognosis of pancreatic cancer cases treated with concurrent chemotherapy. Materials and Methods: 52 patients with pancreatic cancer, 40 with benign pancreatic diseases and 40 healthy people were selected. The electrochemiluminescence immunoassay method was used for detecting levels of CA19-9, CEA and CA125, and a CanAg CA242 enzyme linked immunoassay kit for assessing the level of CA242. The Kaplan-Meier method was used for analyzing the prognostic factors of patients with pancreatic cancer. The Cox proportional hazard model was applied for analyzing the hazard ratio (HR) and 95% confidential interval (CI) for survival time of patients with pancreatic cancer. Results: The levels of serum CA19-9, CEA, CA125 and CA242 in patients with pancreatic cancer were significantly higher than those in patients with benign pancreatic diseases and healthy people (P<0.001). The sensitivity of CA19-9 was the highest among these, followed by CA242, CA125 and CEA. The specificity of CA242 is the highest, followed by CA125, CEA and CA19-9. The sensitivity and specificity of joint detection of serum CA19-9, CEA, CA125and CA242 were 90.4% and 93.8%, obviously higher than single detection of those markers in diagnosis of pancreatic cancer. The median survival time of 52 patients with pancreatic cancer was 10 months (95% CI7.389~12.611).. Patients with the increasing level of serum CA19-9, CEA, CA125, CA242 had shorter survival times (P=0.047. 0.043, 0.0041, 0.029). COX regression analysis showed that CA19-9 was an independent prognostic factor for patients with pancreatic cancer (P=0.001, 95%CI 2.591~38.243). Conclusions: The detection of serum tumor markers (CA19.9, CEA, CA125 and CA242) is conducive to the early diagnosis of pancreatic cancer and joint detection of tumor markers helps improve the diagnostic efficiency. Moreover, CA19-9 is an independent prognostic factor for patients with pancreatic cancer.

췌장암의 원인 및 발암기전

송시영 대한소화기학회 2008 대한소화기학회지 Vol.51 No.2

Pancreatic cancer is currently the major leading cause of cancer-related deaths in the Western countries with an overall 5-year survival rate of less than 3%. The key aim of investigation is to identify the cellular population in which some of the earliest molecular events occur, presumably the ultimate target for carcinogenic insult. Advances in pathological classification and genetics have improved our descriptive understanding of this disease. However, important aspects of pancreatic cancer biology remain poorly understood. Factors associated with the increased risk of pancreatic cancer include smoking, chronic pancreatitis, diabetes, prior gastric surgery, and exposure to radiation or chemicals. A number of syndromes have been identified with the increased incidence of pancreatic cancer, including familial atypical multiple-mole melanoma syndrome, hereditary nonpolyposis colorectal cancer, and hereditary pancreatitis, etc. Recently, there have been growing evidences that stem cell biology could provide new insights into the understanding of cancer biology. Three postulates regarding the relationship between stem and tumor cells have been proposed. First, the similarities in the mechanims that regulate self-renewal of normal stem cells and cancer cells. Second, the possibility that tumor cells might arise from normal stem cells and third, the notion that tumors might contain ‘cancer stem cells' - rare cells with indefinite proliferative potential which drive the formation and growth of tumors. New insights for the cancer stem cells and their possible markers in pancreatic cancer have been suggested recently. Further observations of molecular and cellular events in the early stage of pancreatic carcinogenesis may have important implications regarding the cellular lineage responsible for pancreatic ductal metaplasia and neoplasia, and provide further support for the presence of stem cell capabilities within mature pancreatic epithelium. (Korean J Gastroenterol 2008;51:71-83)

Dietary Factors and Risk of Pancreatic Cancer: a Multi-Centre Case-Control Study in China

Liu, Shu-Zheng,Chen, Wan-Qing,Wang, Ning,Yin, Meng-Meng,Sun, Xi-Bin,He, Yu-Tong Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.18

Background: Pancreatic cancer is the sixth leading cause of cancer death with an increasing trend in China. Dietary intake is believed to play an important role in pancreatic cancer carcinogenesis. The aim of this paper was to evaluate associations between some dietary factors and risk of pancreatic cancer in a multi-centre case-control study conducted in China. Materials and Methods: Cases (n=323) were ascertained from four provincial cancer hospitals. Controls (n=323) were randomly selected from the family members of patients without pancreatic cancer in the same hospitals, 1:1 matched to cases by gender, age and study center. Data were collected with a questionnaire by personal interview. Odds ratios (OR) and 95% confidence intervals (95%CI) were estimated using conditional logistic regression. Results: Tea intake (OR =0.49; 95%CI: 0.30-0.80) was associated with a half reduction in risk of pancreatic cancer. Reduced vegetable consumption (P trend: 0.04) was significant related to pancreatic cancer. Although no significant association was found for meat and fruit, ORs were all above or below the reference group. A protective effect was found for fruit (OR=1.73 for consumption of 1-2 times/week vs more than 3 times/week; 95%CI: 1.05-2.86). A high intake of meat was associated to a higher risk of pancreatic cancer (OR=0.59 for consumption of 1-2 times/week vs. more than 3 times/week; 95%CI: 0.35-0.97). Conclusions: The present study supports fruit consumption to reduce pancreatic cancer risk and indicates that high consumption of meat is related to an elevated risk. Direct inverse relations with tea and vegetable intake were also confirmed.

Pancreatic Cancer Incidence and Mortality Patterns in China, 2009

Chen, Wan-Qing,Liang, Di,Zhang, Si-Wei,Zheng, Rou-Shou,He, Yu-Tong Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.12

Objective: To estimate the incidence and mortality rates for pancreatic cancer in China. Methods: After checking and reviewing the cancer registry data in 2009 from 72 cancer registry centers, we divided cancer registry areas into urban and rural areas. Incidence/mortality rates, age-specific incidence/mortality rates, age-standardized incidence/mortality rates, proportions, and cumulative incidence/mortality rates for pancreatic cancer were calculated. Results: The total number of newly diagnosed pancreatic cancer cases and deaths in 2009 were 6,220 and 5,650, respectively. The crude incidence rate in all cancer registry areas was 7.28/100,000 (males 8.24, females 6.29). The age-standardized incidence rate by Chinese standard population (ASR) was 3.35/100,000, with ranking at 7th among all cancers. Pancreatic cancer incidence rate was 8.19/100,000 in urban areas whereas it was 5.41/100 000 in rural areas. Cancer mortality rate in all cancer registry areas was 6.61/100,000 (males 7.45; females 5.75), with ranking at 6th among all cancers, and 7.42/100 000 in urban but 4.94/100000 in rural areas. Conclusions: Pancreatic cancer incidence and mortality rates have shown a gradual increase in China. Owing to the difficulty of early diagnosis, identification of high-risk population and modification of risk factors are important to reduce the burden of pancreatic cancer.

기획종설 : 췌장암 ; 췌장암의 원인 및 발암기전

송시영 ( Si Young Song ) 대한소화기학회 2007 대한소화기학회지 Vol.51 No.2

Pancreatic cancer is currently the major leading cause of cancer-related deaths in the Western countries with an overall 5-year survival rate of less than 3%. The key aim of investigation is to identify the cellular population in which some of the earliest molecular events occur, presumably the ultimate target for carcinogenic insult. Advances in pathological classification and genetics have improved our descriptive understanding of this disease. However, important aspects of pancreatic cancer biology remain poorly understood. Factors associated with the increased risk of pancreatic cancer include smoking, chronic pancreatitis, diabetes, prior gastric surgery, and exposure to radiation or chemicals. A number of syndromes have been identified with the increased incidence of pancreatic cancer, including familial atypical multiple-mole melanoma syndrome, hereditary nonpolyposis colorectal cancer, and hereditary pancreatitis, etc. Recently, there have been growing evidences that stem cell biology could provide new insights into the understanding of cancer biology. Three postulates regarding the relationship between stem and tumor cells have been proposed. First, the similarities in the mechanims that regulate self-renewal of normal stem cells and cancer cells. Second, the possibility that tumor cells might arise from normal stem cells and third, the notion that tumors might contain ``cancer stem cells`` - rare cells with indefinite proliferative potential which drive the formation and growth of tumors. New insights for the cancer stem cells and their possible markers in pancreatic cancer have been suggested recently. Further observations of molecular and cellular events in the early stage of pancreatic carcinogenesis may have important implications regarding the cellular lineage responsible for pancreatic ductal metaplasia and neoplasia, and provide further support for the presence of stem cell capabilities within mature pancreatic epithelium. (Korean J Gastroenterol 2008;51:71-83)

Can Serum ICAM 1 Distinguish Pancreatic Cancer from Chronic Pancreatitis?

Mohamed, Amal,Saad, Yasmin,Saleh, Doaa,Elawady, Rehab,Eletreby, Rasha,Kharalla, Ahmed S.,Badr, Eman Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.10

Background and aim: Pancreatic cancer is the fourth leading cause of cancer-related death worldwide, with an overall 5-year survival of <5% mainly due to presence of advanced disease at time of diagnosis. Therefore development of valid biomarkers to diagnose pancreatic cancer in early stages is an urgent need. This study concerned the sensitivity and specificity of serum ICAM 1 versus CA 19-9 in differentiation between pancreatic cancer and healthy subjects and acohort of patients with chronic pancreatitis with a focus on assessing validity in diagnosis of early stages of pancreatic cancer. Methods: A cohort of 50 patients with histologically diagnosed pancreatic tumors, 27 patients with chronic pancreatitis, and 35 healthy controls were enrolled. Serum samples for measurement of CA19-9 and I-CAM 1 were obtained from all groups and analyzed for significance regarding diagnosis and disease stage. Results: At a cut off value of (878.5 u/ml) I-CAM 1 had 82% and 82.26% sensitivity and specificity for differentiation between cancer and non-cancer cases, with higher sensitivity and specificity than CA19-9 at different cut offs (CA19-9 sensitivity and specificity ranged from 64-80% and 56.4 - 61.2% respectively). The AUC was 0.851 for I-CAM and 0.754 for CA19-9. Neither of the markers demonstrated significance for distinguishing between early and late cancer stages. Conclusion: ICAM 1 is a useful marker in differentiation between malignant and benign pancreatic conditions, and superior to CA19-9 in this regard. However, neither of the markers can be recommended for use in differentiation between early and late stage pancreatic cancers.

Non-umbilical Cutaneous Metastasis of Pancreatic Adenocarcinoma

( Hyun Jee Kim ),( Jin Young Choi ),( Soo Young Lee ),( Ji Yoon Choo ),( Jin-wou Kim ),( Young Bok Lee ),( Dong Soo Yu ) 대한피부과학회 2017 大韓皮膚科學會誌 Vol.55 No.1

Pancreatic cancer is known to metastasize rapidly. Because clinical symptoms and signs are usually absent until the late stages of the disease, most cases are diagnosed in the advanced stages^1,2. Pancreatic cancer most commonly metastasizes to the liver and peritoneum, but metastases to the lungs, bones, brain, lymph nodes, adrenal glands, and kidneys have also been reported³. Cutaneous metastases are uncommon, accounting for only 2.0% of all metastases, but those that do occur are generally located in the periumbilical area and are termed Sister Mary Joseph`s nodules<sup>4</sup>. Non-umbilical cutaneous metastases are exceedingly rare, with only a small number of cases reported. Herein, we report the rare case of a 71-year-old woman with advanced pancreatic carcinoma who was found to have a metastatic cutaneous lesion on the scalp. A 71-year-old woman with a known history of pancreatic cancer presented with a solitary nodule on the scalp detected 3 weeks previously. The patient had been diagnosed with pancreatic cancer with multiple liver metastases 1.5 years prior to the current presentation, and had undergone subtotal pancreatectomy along with 3 sessions of chemotherapy. On physical examination, an asymptomatic, solitary, domeshaped, erythematous subcutaneous nodule measuring 0.5 cm in size was observed on the scalp (Fig. 1). For diagnostic clarification of the above-mentioned skin lesion, a biopsy was taken for histopathological analysis. The tissue sample showed an infiltrating tumor mass embedded in a desmoplastic stroma in the dermis and subcutis. The tumor mass was composed of moderately differentiated neoplastic glands lined by anaplastic cells, and invasive strands of pleomorphic cells with hyperchromatic, angulated nuclei were seen (Fig. 2A, B). Immunohistochemically, tumor cells stained positive for CK7 and CK19. Staining for CK20 was negative (Fig. 2C∼E). The histopathological diagnosis was consistent with metastatic carcinoma of pancreatic origin, and radiotherapy was initiated. Despite the therapy, the patient`s condition rapidly deteriorated, and she expired after 1 month of treatment. There have been only a few reported cases of cutaneous metastasis of pancreatic cancer. Recognition of this cancer type is important since the prognosis is very poor when untreated, with survival usually less than 4 months⁴. Chemotherapy or chemoradiotherapy can improve the median overall survival to 6.5 months4. Currently, there are no effective screening modalities for pancreatic cancer, and cutaneous metastases are usually a late finding. If cutaneous lesions are discovered, immunohistochemical staining can be helpful in determining the primary site and predicting the clinical outcome. CK19 shows strong immunoreactivity in pancreatic adenocarcinoma, which makes it a useful diagnostic tool in confirming the pancreatic origin of tumors⁵. Zapata et al. reported that pancreatic adenocarcinoma showed positive staining for SMAD4 in 80%, CK19 in 100%, and CA19-9 in 100% of selected cases and that the expression of CK19 and CA19-9 was variable in non-pancreatic malignancies. These findings suggest that these markers may assist in confirming the diagnosis of pancreatic adenocarcinoma by differentiating it from other metastatic adenocarcinomas5. Pancreatic cancers have also been reported to express CK7, with variable staining for CK20³, and patients who have less intense CK20 staining compared to those with strong CK20 staining have been shown to have better clinical outcomes and increased postoperative survival³. The present case illustrates the importance of considering cutaneous metastasis in any patient with known pancreatic cancer who presents with newly developed skin lesions, even in cases of lesions located in non-umbilical areas. Further investigation including early biopsy is recommended for accurate diagnosis. To the best of our knowledge, this case represents only the second case of cutaneous metastasis of pancreatic cancer in the Korean dermatologic literature.

Special Lecture : Pancreatic Cancer: Japanese Experience

( Masao Tanaka ) 대한소화기학회 2007 SIDDS Vol.9 No.-

Pancreatic cancer is still increasing in Japan. The number of deaths has doubled in these two decades. The Japan Pancreas Society (JPS) is conducting three activities against pancreatic cancer; namely, (1) publication of the guidelines for clinical and histopathological staging, surgical resection, and processing of surgical specimens as the General Rules for the Study of Pancreatic Cancer, (2) publication of the Clinical Guidelines for the Diagnosis and Treatment of Pancreatic Cancer, and (3) the nation-wide Pancreatic Cancer Registry. These three activities are the major subject of this article. Two prominent Japanese contributions to Pancreatology are also described, including the first successful clear visualization of the biliary tract and pancreatic duct by endoscopic retrograde cholangiopancreatography and the first report of "mucin-hypersecreting tumor of the pancreas". The "mucin-hypersecreting tumor" reported in 1982 by Ohhashi and his colleagues are identical to the current concept of malignant main duct intraductal papillary mucinous neoplasms (IPMNs). The Pancreatic Cancer Registry showed the dismal prognosis of pancreatic cancer but slight improvement in survival of patients with unresectable cancer after 2001, when gemcitabine became available in Japan. All these activities would contribute to our better understanding of epidemiology, symptomatology, biology, diagnosis and treatment of pancreatic cancer.

형광 동소 보합법을 이용한 췌장암의 세포유전학적 변화에 대한 분석과 그 임상적 의의

윤유석,이동순,민현정,장진영,이승은,황대욱,한호성,김선회 Korean Association of Hepato-Biliary-Pancreatic Su 2008 Annals of hepato-biliary-pancreatic surgery Vol. No.

Purpose: The purposes of this study are to examine the cytogenetic alterations of pancreatic cancer, by using fluorescent in situ hybridization (FISH), to determine thier correlation with the clinico-pathologic prognostic factors and to identify the cytogenetic factors that can predict the prognosis of pancreatic cancer. Methods: Fresh frozen tissues of pancreatic cancer and normal pancreas that were obtained via pancreatic resection from 20 patients with pancreatic ductal adenocacinoma were analyzed by performing FISH with using locus-specific c-myc, p16, p53 probes and chromosome 18q, 20q probes. We cpmpared the FISH results with the clinico-pathologic prognostic factors. We also examined 16 paraffin-embedded tissues of pancreatic cancer by performing immunohistochemical staining (IHC) with monoclonal antibody to c-myc, p16, p53 and DPC. We then evaluated the correlation between the results of FISH and the results of IHC. Results: At least one alteration of genes or chromosomes was detected in 18 (90.0%) of the 20 pancreatic cancer tissues by FISH, as compared with no alternation in the normal pancreatic tissues: these alteration were an increased copy number of c-myc (66.7%), a decreased copy number of p16 (70.6%), deletion of p53 (100%), loss of chromosome 18q (56.3%) and gain of chromosome 20q (45.0%). IHC demonstrated overexpression of c-myc and p53 in 31.3% and 50.0% of the pancreatic cancer specimens, respectively, and the loss of expressions of p16 and DPC in 25.0% and 93.3% of the pancreatic cancer specimens, respectively. The concordance rate of IHC with FISH was 33.3% to 61.5%. Analysis of the correlation between the cytogenetic changes identified by FISH or IHC and the pathologic prognostic factors showed that only chromosome 20q gain was significantly correlated with the histologic grade (p=0.098) and lymphovascular invasion (p=0.092). However there was no clinical correlation of the cytogenetic changes with respect to recurrence after operation. Conclusion: This study confirms that most pancreatic cancers have cytogenetic alternations, as can be determined by FISH. Especially, the correlation between chromosome 20q gain and the prognostic pathologic factors offers the possibility of a new prognostic biologic marker located in chromosome 20q. However, further studies with more cases are needed to clarify the clinical significance of cytogenetic alternations in pancreatic cancer.