Pancreatographic investigation of pancreatic duct system and pancreaticobiliary malformation

To clarify the anatomy of the pancreatic duct system and to investigate its embryology, we reviewed 256 pancreatograms with normal pancreatic head, 81 with pancreas divisum and 74 with pancreaticobiliary maljunction. Accessory pancreatograms were divided into two patterns. The long-type accessory pancreatic duct forms a straight line and joins the main pancreatic duct at the neck portion of the pancreas. The short-type accessory pancreatic duct joins the main pancreatic duct near its first inferior branch. The short-type accessory pancreatic duct is less likely to have a long inferior branch arising from the accessory pancreatic duct. The length of the accessory pancreatic duct from the orifice to the first long inferior branch was similar in the short- and long-type accessory pancreatic ducts. The first long inferior branch from the long-type accessory pancreatic duct passes though the main pancreatic duct near the origin of the inferior branch from the main pancreatic duct. Immunohistochemically, in the short-type accessory pancreatic duct, the main pancreatic duct between the junction with the short-type accessory pancreatic duct and the neck portion was located in the ventral pancreas. The long-type accessory pancreatic duct represents a continuation of the main duct of the dorsal pancreatic bud. The short-type accessory pancreatic duct is probably formed by the proximal main duct of the dorsal pancreatic bud and its long inferior branch.     

Pancreatographic investigation of the pancreatic duct system

Background Embryologically, the pancreatic duct system develops by the fusion between the dorsal and ventral pancreatic bud ducts. It has been suggested that the proximal part of the main dorsal pancreatic duct partially regresses to form the accessory pancreatic duct (APD). Aim of this study was to clarify the anatomy of the pancreatic duct system of the head of the pancreas and investigate the embryology of the normal pancreatic duct system. Methods We reviewed endoscopic retrograde pancreatography of normal pancreatic heads (n = 256) and pancreas divisum (n = 36), focusing on long inferior branches arising from the APD and the main pancreatic duct (MPD). The accessory pancreatograms were divided into two patterns of course and shape, the long type (171 cases) and the short type (85 cases) according to the length of the MPD from the orifice to the junction with the APD. The long-type APD formed a straight line and joined the MPD at the neck portion of the pancreas. The short-type APD joined the MPD near its first inferior branch. Results The shape of the long-type APD was quite similar to that of the dorsal pancreatic duct of pancreas divisum. The short-type APD was less likely to have a long inferior branch arising from the APD. The length of the APD from the orifice to the first long inferior branch was similar in the long-type APD (19.4 ± 4.0 mm) and in the short-type APD (18.8 ± 4.2 mm). The first long inferior branch from the long-type APD passed though the MPD near the origin of the inferior branch from the MPD, whereas the short-type APD joined the MPD near its inferior branch. Conclusions There are two types of APD. The long-type APD was quite similar to the shape of the dorsal pancreatic duct of pancreas divisum, and seems to represent a continuation of the main duct of the dorsal pancreatic bud. The short-type APD was less likely to have a long inferior branch, and seems to be formed by the most proximal part of the main duct of the dorsal pancreatic bud and its long inferior branch.     

Bile duct carcinoma involving the common channel associated with pancreaticobiliary maljunction shows an extension pattern similar to ductal carcinoma of the pancreas

Biliary tract cancer occurs frequently in patients with pancreaticobiliary maljunction (PBM), although no details of its clinicopathological characteristics have been reported. Here we describe a case of bile duct (BD) cancer that developed in association with PBM. This BD cancer involved the common channel, extended to the main pancreatic duct (MPD) via the common channel, and invaded the pancreatic parenchyma, where its growth and spread, and features of its recurrence, were similar to those of ductal carcinoma of the pancreas. We assumed that MPD extension of BD cancer via the common channel was the reason for its deep spread to the pancreas, since BD cancer usually spreads along the BD and rarely reaches the common channel of the ampulla of Vater. During the follow‐up of patients with PBM, attention should be paid to involvement of the common channel by BD cancer and also to cancer developing silently in the pancreas after extrahepatic BD resection.     

Combining fine needle aspiration with brushing cytology has improved yields in diagnosing pancreatic ductal adenocarcinoma

The aim of this retrospective study is to evaluate the diagnostic yields of combining fine needle aspiration (FNA) with brushing cytology (BC) in clinical work‐up of pancreatic ductal adenocarcinoma. The study included a total of 97 patients who underwent both FNA and BC along with histologic/clinical follow‐up (F/U). Cytologic diagnoses were categorized as negative for neoplasm (NEG), atypical/favor neoplasm (AN), and suspicious or positive for neoplasm (POS). Based on the cytologic diagnoses, the cohort was divided as follows: 23 had concordant FNA and BC diagnoses of POS/AN, all were neoplasms on F/U; 34 had disconcordant (POS/AN vs. NEG) FNA and BC diagnoses, all but 2 were neoplasms on F/U; The remaining 40 were NEG on both FNA and BC, F/U revealed that 10 were neoplasms and 30 were chronic pancreatitis. Overall, FNA rendered more true positive diagnoses than BC. However, BC but not FNA detected neoplasms in 10 patients. Most of the neoplasms identified on F/U were ductal adenocarcinoma (59 of 65). Diagnostic sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 69.2, 93.8, 95.7, 60, and 77.3% for FNA alone, 50.8, 100, 100, 50.0, and 67.0% for BC alone, and 84.6, 100, 100, 76.2, and 89.7% for combining FNA with BC. In conclusion, both EUS‐guided FNA and BC are valuable modalities in the preoperative diagnosis of pancreatic ductal adenocarcinoma. When used in combination, the two modalities complement each other and achieve better diagnostic yield in pancreatic ductal adenocarcinoma than either FNA or BC alone. Diagn. Cytopathol. 2009. © 2009 Wiley‐Liss, Inc.     

胰腺导管腺癌中胰腺星形细胞的研究进展

胰腺星形细胞(pancreatic stellate cells,PSC)是胰腺导管腺癌(pancreatic ductal adenocarcinoma,PDAC)肿瘤微环境中最重要的成分,在PDAC发生发展中具有非常关键的作用.目前大量研究关注于PSC与胰腺癌细胞(pancreatic cancer cells,PCC)之间的相互作用及PSC在PDAC微环境中发挥的作用.PSC在许多情况下发生活化,如乙醇、氧化应激和高血糖等.PDAC早期即可出现PSC的活化,PCC可以诱导刺激PSC发生活化,活化的PSC可以产生大量胶原纤维,形成适宜PCC生长的间质微环境,促进PCC的增殖,减少化疗药物对肿瘤细胞的杀伤作用.另外,PSC还可以与间质中各种细胞成分如内皮细胞和各种免疫细胞相互作用,在血管生成、免疫逃逸和神经侵犯等方面协助肿瘤进展.因此,阐明PSC与肿瘤细胞以及其他间质成分之间复杂的相互作用至关重要.     

Molecular diagnostic testing as an adjunct to morphologic evaluation of pancreatic ductal system brushings: potential augmentation for diagnostic sensitivity

Malignancies arising from the pancreatic and biliary ductal systems present the gastroenterologist and pathologist with diagnostic challenges. Tumors of the pancreatic and/or biliary ductal system may present as either duct strictures or mass lesions. When lesions present as strictures without associated demonstrable masses, brushing cytology may represent the only reasonable diagnostic technique aside from open biopsy. Diagnostic sensitivities for brushing cytology have ranged from 18 to 90%. Positive diagnoses of malignancy are of great clinical value but a negative result is of relatively little clinical aid when the radiographic or clinical findings are suspicious for a malignancy.A variety of techniques have been used in an attempt to improve diagnostic sensitivity for brushing cytology. These have included immunohistochemistry and various molecular diagnostic techniques. Using the high resolution melting curve technique, we performed mutational analysis on 20 bile duct brushing specimens for mutations in p53, K-ras, BRAF, and EGFR genes. Eleven specimens had corresponding surgical specimens, which were similarly analyzed. Our series included twelve adenocarcinomas, one islet cell tumor, one case of dysplasia, and six benign cases. K-ras mutations were found in cytology specimens of 3 out of 12 malignancies. No EGFR or B-raf mutations were detected and only a single p53 mutation in an adenocarcinoma was detected in the corresponding cytology specimen. No mutations were detected in benign lesions or in the dysplasia. Only 8% of specimens from adenocarcinomas had p53 mutations and only 33% of cases had K-ras mutations. Mutational analysis did not appear to improve the cytologic detection of adenocarcinoma by bile duct brushings.     

EGFR expression in pancreatic intraepithelial neoplasia and ductal adenocarcinoma

Pancreatic ductal adenocarcinoma (PDA) is an aggressive malignant tumor with poor prognosis. Epidermal growth factor receptor (EGFR) is an important cell adhesion and signaling pathway mediator. The aim of this study was to evaluate the expression of EGFR in both pancreatic intraepithelial neoplasia (PanIN) and PDA and their relationship to clinicopathologic characteristics. Formalin-fixed, paraffin-embedded tissues including 81 cases with pancreatic ductal adenocarcinoma, 27 with normal pancreas, 16 with PanIN-1A, 18 with PanIN-1B, 11 with PanIN-2, and 24 with PanIN-3 were used for construction of tissue microarrays. Imunohistochemistry for EGFR was performed. Normal pancreatic ducts, PanIN-1A, and PanIN-1B did not show EGFR overexpression. EGFR overexpression was observed in 18.2% (2/9) of PanIN-2, 41.7% (10/14) of PanIN-3, and 64.2% (52/81) of PDA, respectively. Significantly higher EGFR overexpression was observed in PDAs than in PanIN lesions (P<0.05). No statistically significant correlation was observed between EGFR overexpression and patient age, sex, tumor location, size, histological grade, vascular invasion, lymph node metastasis and stage at presentation, respectively. In conclusion, EGFR expression increased from PanIN to PDA. EGFR may be involved in early stage in development of PDA.     

Molecular pathogenesis of pancreatic ductal adenocarcinoma

The statistics are alarming; pancreatic ductal adenocarcinoma (PDA) will be the second leading cause of death amongst all cancers by 2020. More worrisome is that incidence is on the rise, and without more effective cancer control of this disease, the trajectory of the virtually indistinguishable rates of incidence and mortality will remain the reality for years to come. Advances in genomics are beginning to clarify the key issues about the pathogenesis of this aggressive tumour type. New insights into classic pathogenic driver genes, such as KRAS, CDKN2A, TP53 and SMAD4, are portraying alternative roles for these genes beyond their function at the preneoplastic level including metastatic dissemination and chemoresistance. Clinically relevant molecular subtypes have recently emerged, which will aid oncologists in making more informed treatment decisions to improve outcomes in the future. A wealth of data surrounding these issues has been generated over the last 5 years. Below, we attempt to bring readers up to speed on recent research findings in PDA.     

Pancreaticoduodenectomy of pancreatic ductal adenocarcinoma in the elderly

PURPOSE: Pancreatic ductal adenocarcinoma has the highest incidence between the ages of 60 and 70 years. As the elderly population has been increasing in the last several decades, the proportion of patients older than 70 years of age with resectable pancreatic cancer is expected to increase in our society. This retrospective observation was performed to evaluate surgical value of pancreaticoduodenectomy for the elderly patients with pancreatic ductal adenocarcinoma. MATERIALS AND METHODS: From January 1990 to June 2005, among the patients who underwent pancreaticoduodenectomy for pancreatic ductal adenocarcinoma, the elder patients older than 70 years of age were retrospectively reviewed. Perioperative surgical outcomes, including general clinicopathologic features, morbidity, mortality, and survival outcomes, were investigated based on available medical records. RESULTS: Seventy-seven patients underwent pancreaticoduodenectomy (PD) for pancreatic ductal adenocarcinoma. Among them, 11 patients (14.3%) were 70 years older. More frequent incidences of morbidity (8 out of 11 vs. 25 out of 65, p=0.049), especially delayed gastric emptying (3 out of 8 vs. 3 out of 66, p=0.035), were observed and overall length of hospital stay was also longer in the elderly (49.2 +/- 13.9 days vs. 36.1 +/- 13.2, p=0.012). However, no significant differences in mortality rate and survival outcomes were noted when comparing with those of the younger patients (p > 0.05). CONCLUSION: We agree with the opinion that age factor can not be absolute contraindication for pancreaticoduodenectomy, however, appropriate preoperative evaluations, proper patient selection considering life expectancy, advanced surgical techniques and detailed perioperative management are mandatory to guarantee the safety of pancreaticoduodenectomy performed in the elderly with pancreatic ductal adenocarcinoma.     

Expression of urocortin in pancreatic ductal adenocarcinoma and pancreatic intraepithelial neoplasia

Urocortin (UCN) is a 40‐aminoacid neuropeptide that regulates angiogenesis and inhibits cell proliferation. Our aim was to examine the relationship of UCN expression to the clinicopathological parameters of pancreatic ductal adenocarcinoma (PDAC) and histological grade of pancreatic intraepithelial neoplasia (PanIN). Tissue microarray was used to analyze UCN protein expression in 89 surgical specimens including 21 PanIN, 3 PDAC arising from PanIN, and 65 PDAC without PanIN. UCN immunoscores ranging from 0 to 12 were obtained by multiplying intensity (scored on a 3‐point scale) by the percentage of stained cells (scored on a 4‐point scale). Strong expression of UCN was detected in 5 specimens of non‐neoplastic pancreatic ductal epithelia. UCN immunoscore was significantly higher in PanIN‐1 than in PanIN‐2 and PanIN‐3 (p = 0.038) and significantly higher in well‐differentiated PDAC or early American Joint Committee on Cancer (AJCC) stage PDAC than in poorly differentiated or advanced stage PDAC (p = 0.025, p = 0.018). Higher expression of UCN correlates with PDAC tumor grade and AJCC pathologic stage as well as PanIN grade. Immunohistochemical assessment of UCN may help clinicians predict tumor recurrence rate and help pathologists make a proper diagnosis.     

Concentrations of trace elements and KRAS mutations in pancreatic ductal adenocarcinoma

Trace elements are a possible risk factor for pancreatic ductal adenocarcinoma (PDAC). However, their role in the occurrence and persistence of KRAS mutations remains unstudied. There appear to be no studies analyzing biomarkers of trace elements and KRAS mutations in any human cancer. We aimed to determine whether patients with KRAS mutated and nonmutated tumors exhibit differences in concentrations of trace elements. Incident cases of PDAC were prospectively identified in five hospitals in Spain. KRAS mutational status was determined through polymerase chain reaction from tumor tissue. Concentrations of 12 trace elements were determined in toenail samples by inductively coupled plasma mass spectrometry. Concentrations of trace elements were compared in 78 PDAC cases and 416 hospital-based controls (case–control analyses), and between 17 KRAS wild-type tumors and 61 KRAS mutated tumors (case–case analyses). Higher levels of iron, arsenic, and vanadium were associated with a statistically nonsignificant increased risk of a KRAS wild-type PDAC (OR for higher tertile of arsenic = 3.37, 95% CI 0.98–11.57). Lower levels of nickel and manganese were associated with a statistically significant higher risk of a KRAS mutated PDAC (OR for manganese = 0.34, 95% CI 0.14–0.80). Higher levels of selenium appeared protective for both mutated and KRAS wild-type PDAC. Higher levels of cadmium and lead were clear risk factors for both KRAS mutated and wild-type cases. This is the first study analyzing biomarkers of trace elements and KRAS mutations in any human cancer. Concentrations of trace elements differed markedly between PDAC cases with and without mutations in codon 12 of the KRAS oncogene, thus suggesting a role for trace elements in pancreatic and perhaps other cancers with such mutations. Environ. Mol. Mutagen., 60:693–703, 2019. © 2019 Wiley Periodicals, Inc.     

Vascular and ductal elastotic changes in pancreatic cancer

This study aims to identify and define the type and frequency of elastotic alterations of vessels and ducts in pancreatic ductal carcinoma (PDAC) and evaluate its diagnostic significance. Representative tissue from 36 Whipple specimens, stained with Verhoeff's Van‐Gieson, was studied focusing on the density and distribution of elastic fibers in walls of vessels and ducts, in perivascular and periductal tissue and in tumor stroma. Vessels and ducts within the carcinoma, at tumor periphery and in non‐tumoral pancreas were grouped and examined separately. Vimentin and α‐SMA immunostains were used for the depiction of fibroblasts and myofibroblasts. Histochemistry revealed mild to severe elastotic changes of vessels and ducts in all examined cases. Vascular and ductal elastosis was more prominent within the tumor and diminished at tumor periphery. In tumor stroma and non‐tumoral pancreatic tissue mild or no elastosis was identified. α‐SMA+ cells were observed in large numbers in tumor stroma and as a ring around carcinomatous structures. There were scant α‐SMA+ cells around elastotic and non‐elastotic vessels. Conclusively, vascular and ductal elastosis is a tumor‐associated phenomenon in PDAC. Its presence is indicative of benignity acquiring a possible diagnostic role.     

Metastatic cancer involving pancreatic duct epithelium and its mimicry of primary pancreatic cancer

We investigated 47 autopsy cases of metastatic cancer involving the pancreas. Metastatic disease in nine cases involved the pancreatic duct epithelium. In two cases, metastatic cancer cells showed Pagetoid features. In three cases, pancreatic metastatic disease showed solitary proliferation with focal in situ carcinoma-like lesions mimicking primary pancreatic cancers. Each of these three cases had primary lung adenocarcinomas. Serial sections revealed abrupt borders between the in situ carcinoma-like lesions and the non-cancerous epithelium. Primary pancreatic cancers did not show Pagetoid features or abrupt borders between the cancerous and non-cancerous epithelium. We conclude that the possible diagnosis of pancreatic metastasis should be carefully ruled out in the histological detection of latent primary pancreatic cancer.     

Minute pancreatic adenocarcinoma presenting with stenosis of the main pancreatic duct

We describe a case of minute pancreatic ductal adenocarcinoma featuring stenosis of the main pancreatic duct (MPD) and associated with histological findings of periductal elastosis and fibroblast proliferation. A 53-year-old Japanese man with preoperative radiological evidence of MPD stricture and dilation of the distal MPD, and suspected of having pancreatic cancer, underwent successful resection. Neither radiological nor macroscopic examination directly disclosed any tumorous lesions, and a small focus of carcinoma (8 x 8 mm) was only revealed on microscopic examination. The tumor was a poorly differentiated, invasive ductal adenocarcinoma that had invaded the intrapancreatic nerves and veins. Interestingly, the MPD located at the edges of the tumor had not been destroyed by the carcinoma, but its wall had been thickened by elastic tissue and fibroblast proliferation, resulting in stenosis. The peripheral pancreas exhibited secondary obstructive pancreatitis. To date, the detection of small pancreatic tumor masses using imaging procedures remains difficult, and most patients are diagnosed on the basis of pancreatic ductal changes. However, the published work on small pancreatic cancers contains little information about the histological features of the affected MPD. The present findings suggest that MPD strictures are not always provoked by destruction or filling with cancer cells, and that they can be caused by periductal elastosis and fibroblast proliferation in a minute carcinoma. Such changes in the MPD may therefore be of clinical importance in the detection of early stage cancers.     

Concepts of variation and normality in morphology: Important issues at risk of neglect in modern undergraduate medical courses

In anatomy, normality embraces a range of morphologies and includes those that are most common and others called variations which are less frequent but not considered abnormal. Variations ranging from subtle to remarkable affect every part of the human body. They may have important influences on predisposition to illness, symptomatology, clinical examination and investigation, and patient management including operative surgery. Recognition of variations enables clinicians to distinguish features which merit further investigation or treatment from those which do not. We believe the concepts of normality and variation should be introduced early in the medical course and that the dissecting laboratory is the ideal venue. Students who are able to examine several specimens or are privileged to dissect soon realize that each cadaver is unique. Knowledge of variations should be reinforced in several components of the medical course where physical examination, imaging investigations, surgical procedures, and autopsies are studied. Appreciation of the range of normality including variations matures as experience is gained over several years. Current trends in undergraduate courses—including reduced exposure to dissection and dissected specimens, increased use of plastic bones, models and computer‐generated images, loss of experienced teachers, especially those who are medically qualified, and loss of morphological approach—all conspire to defer the stage when students encounter variation. We are concerned that these trends will compromise the knowledge and understanding of variation required to start practicing medicine safely and competently. Clin. Anat. 12:186–190, 1999. © 1999 Wiley‐Liss, Inc.     

胰腺癌中主要的基因改变

胰腺导管腺癌是胰腺癌中最常见的组织学类型,其发病隐匿,预后差,死亡率高,治疗手段有限。目前对其致病机制的研究很多,遗传因素和环境因素所造成的分子遗传学改变在其中凸显重要,越来越多的发现都深入到了基因分子水平。对于这些已发现的基因改变,有些已通过体内体外实验予以验证,有些仍未明确,现对其中4个主要通路的特征性分子改变以及相关途径的认识做一简要概括,进一步明确这些基因改变在胰腺癌发病过程中的作用及其研究的现状。     

The role of 64‐slice CT following perfusion with iohexol via the hepatopancreatic ampulla in assessing pancreaticobiliary junctions

The aim of this study was to delineate the structure of the pancreatic and biliary ducts in premature infants using a novel imaging method. The duodenal papillae of 30 premature infant cadavers were dissected. The pancreatic and biliary ducts were visualized using 64‐detector multislice spiral computed tomography (MSCT). Contrast agent was injected into the duodenal papilla via the hepatopancreatic ampulla of Vater. MSCT scanning revealed both the pancreatic and biliary ducts as well as the common channel in 18 cases. The bile duct was visualized in the remaining 12 cases. Four patterns of the pancreaticobiliary ductal junction were noted: Y‐type (73.3%), U‐type (13.3%), V‐type (6.7%), and II‐type (6.7%). The results showed that MSCT and three‐dimensional reconstruction can be used to visualize the junction pattern and common channel of the pancreatic and biliary ducts, and the structure of the surrounding tissue, in premature infants. Clin. Anat. 28:645–648, 2015. © 2015 Wiley Periodicals, Inc.     

浅述P物质与胰腺疾病

P物质是一种脑肠肽，它广泛地分布在中枢神经系统和外周组织器官，在不同的部位发挥不同的生物学效应。在中枢它作为神经递质发挥作用且与痛觉传导有关，在外周神经它作为诱导神经源炎症的物质发挥作用。近年来发现P物质与胰腺的疾病如胰腺炎、糖尿病和胰腺癌关系密切。     

后腹腔镜胰体尾外科手术入路及解剖学标志

目的:探讨后腹腔镜胰体尾外科手术入路和解剖学标志。方法:对陈旧及新鲜成人尸体腹部标本进行解剖观测,在对新鲜尸体进行解剖观测前模拟后腹腔镜行胰体尾分离和暴露。第1个trocar位置在左腋中线髂嵴上方2cm交点处插入,第2个trocar在左腋后线第12肋缘下2cm交点处插入,第3个trocar在左腋前线与肋弓下2cm交点处插入。在腹膜后间隙内加压注水制造操作空间。结果:12例全部成功分离出肾旁前间隙。2例模拟操作成功,但在模拟操作过程中均有轻微的后腹膜损伤。完全分离胰体尾后肾旁前间隙内平均能一次性注水1.68L。结论:后腹腔镜胰体尾外科手术经左肾旁前间隙入路是安全可行的,能获得足够的操作空间,且有良好的解剖学标志。