Clinical significance of cathepsin E in pancreatic juice in the diagnosis of pancreatic ductal adenocarcinoma

BACKGROUND: It has been reported that cathepsin E (CTSE) is a non-secretory and intracellular aspartic proteinase found in the superficial epithelial cells of the stomach and that it is also expressed in pancreatic ductal adenocarcinoma. We evaluated the diagnostic value of CTSE in the pancreatic juice in the diagnosis of pancreatic ductal adenocarcinoma compared with that of CA19-9, carcinoembryonic antigen (CEA) and K-ras mutations. METHODS: One hundred and one patients (25 with pancreatic ductal adenocarcinoma and 76 with chronic pancreatitis) were examined for the diagnostic significance of CTSE in the pancreatic juice in the diagnosis of pancreatic ductal adenocarcinoma. Forty of 101 patients (15 with pancreatic ductal adenocarcinoma and 25 with chronic pancreatitis) were examined to compare the diagnostic value of various tumor markers in the pancreatic juice, namely CA19-9, CEA, K-ras mutations and CTSE. RESULTS: The detection frequency of CTSE was significantly higher in patients with pancreatic ductal adenocarcinoma (64.0%) than in patients with chronic pancreatitis (7.9%; chi2 = 34.76; P < 0.0001). The sensitivity, specificity and diagnostic accuracy of CTSE in the pancreatic juice for pancreatic ductal adenocarcinoma was 66.7, 92.0 and 82.5%, respectively. These values were more efficient in comparison with those of CA19-9, CEA and K-ras mutations. The main cause of the detection failure of CTSE in pancreatic ductal adenocarcinoma was obstruction of the main pancreatic duct. Sensitivity was 85.7% in patients without obstruction of the main pancreatic duct. CONCLUSIONS: Cathepsin E in the pancreatic juice is a novel marker for a definitive diagnosis of pancreatic ductal adenocarcinoma.     

双向凝胶电泳技术在胰腺癌蛋白质组学研究中的应用及条件优化

目的将双向凝胶电泳技术用于胰腺癌蛋白质组学研究并对其条件进行优化。方法对胰腺癌组织、癌旁组织、胰液等标本在组织研磨、裂解、蛋白抽提及双向凝胶电泳等各个环节进行调整和优化。结果液氮研磨法可得到更多的蛋白质点;超声方法去除组织中核酸效果较好;二硫苏糖醇（DTT）平衡时间12—15min,碘乙酰胺（IAA）平衡时间应等同或略长于DTT平衡时间时可得到高质量图谱;丙酮沉淀法可获得较多的胰液生物标志物蛋白点;将2—3根长度〈13cm的IPG胶条在1块凝胶上进行十二烷基硫酸钠-聚丙烯酰胺凝胶电泳（SDS-PAGE）的方法（Msoc）使双向电泳的重复性和通量显著提高。结论本研究成功建立了双向凝胶电泳技术平台,所获得的电泳图谱分辨率高、重复性好,能够较好地用于胰腺癌蛋白质组学研究。     

Genomics of pancreatic ductal adenocarcinoma

Pancreatic cancer is one of the worst prognostic cancers because of the late diagnosis and the absence of effective treatment. Within all subtypes of this disease, ductal adenocarcinoma has the shortest survival time. In recent years, global genomics profiling allowed the identification of hundreds of genes that are perturbed in pancreatic cancer. The integration of different omics sources in the study of pancreatic cancer has revealed several molecular mechanisms, indicating the complex history of its development. However, validation of these genes as biomarkers for early diagnosis, prognosis or treatment efficacy is still incomplete but should lead to new approaches for the treatment of the disease in the future.     

Molecular analysis to detect pancreatic ductal adenocarcinoma in high-risk groups

BACKGROUND & AIMS: Screening of high-risk groups for pancreatic cancer has not been adopted because of concerns regarding specificity and sensitivity. Suitability of a combination of 3 novel molecular screening techniques was investigated. METHODS: Pancreatic juice was extracted from 146 patients with pancreatic ductal adenocarcinoma, chronic pancreatitis, or biliary tract stones. p53 mutations were analyzed by using a modified yeast functional assay, K-ras status was analyzed using mutation-specific real-time PCR and the proportion of p16(INK4a) promoter methylation was estimated using comparative methylation-specific real-time PCR. RESULTS: p53 mutations were detected in 20 of 48 (42%) cancer cases, none of 49 controls, and 2 of 49 (4%) patients with pancreatitis. K-ras mutations were detected in 31 of 57 (54%) cancer patients, 13 of 61 (21%) controls, and 23 of 67 (34%) patients with pancreatitis. Twenty-six of 42 (62%) cancer patients had promoter methylation levels > 12%, compared with 3 of 24 (13%) controls, and 2 of 26 (8%) with pancreatitis. Mutations in p53 or high-level p16(INK4a) promoter methylation occurred in 29 of 36 (80%) patients with cancer, 3 of 24 (13%) controls, and 3 of 22 (13%) with pancreatitis. Three patients (8%) of 36 with cancer; 14 of 24 (58%) controls, and 13 of 22 (59%) patients with pancreatitis had no marker. The gallstone disease patients had a high rate of positive K-ras mutations, possibly reflecting the fact that they were not disease free. CONCLUSIONS: Combination molecular analysis increased the discrimination between patients with malignant and benign disease. This level of discrimination would allow patients in high-risk groups to be stratified from negligible risk to over 50% probability of an early cancer.     

Predictive factors in pancreatic ductal adenocarcinoma: Role of the inflammatory response

Objective. Pancreatic ductal adenocarcinoma is a highly lethal disease and most patients are not eligible for curable resection. Estimation of prognosis is essential in order to provide the best individual treatment for patients with pancreatic adenocarcinoma. Prediction of survival by current methods is limited, therefore the objective of this study was to determine possible prognostic factors identified at the time of diagnosis. Material and methods. All 119 consecutive patients with pancreatic ductal adenocarcinoma receiving palliative treatment at the Department of Surgery, Lund University Hospital from 1999 through 2002 were reviewed retrospectively. Prognostic factors and interventions were analysed statistically. C-reactive protein (CRP) at the time of diagnosis was measured in 109 patients. Results. The overall median survival was 4.4 months. By means of a multivariate analysis it was shown that CRP (p<0.001) and tumour size (p=0.018) were independent predictors of survival. The median survival of patients with normal CRP at the time of diagnosis was 10.8 months versus 4.2 months for those with raised CRP levels (≥5 mg/l; p<0.001). Chemotherapy was the only intervention associated with a longer survival time (p<0.001 versus no chemotherapy). Conclusions. The poor prognosis for patients with pancreatic ductal adenocarcinoma was confirmed. CRP proved to be a strong independent predictor of survival. Together with previous reported factors, CRP could serve as a potential tool to determine future treatment strategies for optimal individual palliation.     

腹腔镜胰十二指肠切除术在老年胰腺导管腺癌患者中的肿瘤学疗效研究

目的 研究腹腔镜胰十二指肠切除术在老年胰腺导管腺癌患者中的肿瘤学疗效.方法 回顾性分析自2015年1月-2017年12月在复旦大学附属华东医院普外科完成胰十二指肠切除术治疗的胰腺导管腺癌、年龄≥60岁患者的临床资料.根据其手术方式分为腹腔镜(LPD)组与开放(OPD)组,并对2组的手术及肿瘤学资料进行比较.结果 共入组...     

Perioperative transfusion for pancreaticoduodenectomy and its impact on prognosis in resected pancreatic ductal adenocarcinoma

Background and aims: Pancreaticoduodenectomy (PD) is a major operative intervention performed most commonly for malignancy in the head of pancreas. The aim of this study was to evaluate the utilization of blood transfusion for PD and to determine whether this had prognostic significance in a subset of patients with pancreatic ductal adenocarcinoma (PDAC). Material and methods: Data on blood transfusion requirement were retrospectively collected for patients undergoing PD from 1998 to 2005. Standard prognostic factors and survival data were also collected in patients with PDAC. Results: One-hundred-and-seventy patients underwent PD. Seventy-six patients (45%) received transfusion. The median (interquartile range) number of units of red cell concentrate (RCC) transfused perioperatively (intraoperatively and within 24 h of surgery) was 1.5 (0.5–2.5). The median preoperative haemoglobin (Hb) was 126 g/dl. The median number of units of RCC transfused perioperatively in patients with Hb <126 g/dl was 2 (1–3); for those with Hb ≥ 126 g/dl the median was 0 (0–1); p=0.003. Forty-nine patients who were resected for PDAC were subjected to survival analysis. Univariate and multivariate analyses showed that only posterior resection margin invasion was associated with an adverse outcome (margin positive 198 [143–470] days vs margin negative 398 [303–859] days; p=0.02). Perioperative RCC transfusion requirement was not a significant predictor of survival (transfusion 408 [214–769] days vs no transfusion 331 [217–391] days; p=0.18). Furthermore, RCC transfusion within 30 days of operation was not a significant predictor of poor survival (transfusion 331 [201–459] days vs no transfusion 317 [196–769] days; p=0.43). Conclusions: PD can be performed with a moderately low requirement for RCC transfusion; however, low preoperative haemoglobin is a predictor for the requirement of RCC transfusion. Administration of RCC transfusion does not appear to be a significant adverse prognostic factor in patients with resected PDAC.     

Clinical significance of serum Wisteria floribunda agglutinin-positive Mac-2 binding protein in pancreatic ductal adenocarcinoma

BackgroundWisteria floribunda agglutinin-positive mac-2 binding protein (WFA⁺-M2BP) is an excellent biomarker for predicting hepatic fibrosis. We hypothesized WFA⁺-M2BP might be a serum biomarker for the diagnosis of chronic pancreatitis (CP) and pancreatic ductal adenocarcinoma (PDAC) with dense fibrosis.MethodsIn this study, we included 16 CP and 24 PDAC patients. Serum levels of WFA⁺-M2BP (cut-off index [COI]) were compared between the 2 groups. To confirm the cellular production of WFA⁺-M2BP, we investigated the presence of WFA⁺-M2BP in HEK293 cells, 3 established human PDAC cell lines and a recently generated human PDAC cell line derived from a liver metastasis (MDA-PATC53). The bio-physiological effects of MDA-PATC53 supernatant were evaluated. Finally, the difference in the expression of glycosylation enzymes between MDA-PATC53 and Panc-1 were analyzed by cDNA microarray.ResultsWe found that the serum WFA⁺-M2BP level could distinguish the 2 groups. The median serum COI of WFA⁺-M2BP was 0.98 and 0.51 in PDAC and CP, respectively. Additionally, WFA⁺-M2BP positive PDACs were more frequently associated with metastatic lesions than the WFA⁺-M2BP negative PDACs (91.6% vs. 41.7%, P = 0.009). The MDA-PATC53 cells alone produced WFA⁺-M2BP. However, we found that MDA-PATC53 supernatant containing WFA⁺-M2BP (1.0 COI) did not alter the biological behavior of cancer cell lines. The results of cDNA microarray revealed that several glycosylation enzymes with pro-oncologic function were highly expressed in MDA-PATC53 compared to Panc-1.ConclusionsSerum WFA⁺-M2BP can be a useful biomarker for the diagnosis of PDAC and the prediction of disease progression since it potentially reflects altered pro-oncologic glycosylation enzymes.     

Serum endocannabinoids in assessing pain in patients with chronic pancreatitis and in those with pancreatic ductal adenocarcinoma

Background: The endocannabinoid system plays a substantial role in analgesia.

Aim: To analyze N-arachidonoylethanolamine (AEA), N-oleoylethanolamine (OEA), linoleoyl ethanolamide (LEA), α-linoleoyl ethanolamine (α-LNEA), N-palmitoylethanolamine (PEA) and N-stearoyl ethanolamine (SEA) in two groups of patients having chronic pancreatic diseases.

Patients and methods: Twenty-six patients with chronic pancreatitis, 26 patients with pancreatic ductal adenocarcinoma and 36 healthy subjects were studied. The visual analogic scale (VAS) was used for assessing pain immediately before the venipuncture to obtain blood in all subjects. Six endocannabinoids were measured in serum of the patients enrolled.

Results: Only OEA, LEA and PEA serum levels were significantly higher in patients with pain as compared to those without. Using the cutoff values, the sensitivity and specificity of the various endocannabinoids in evaluating pain in patients with chronic pancreatitis and in those with pancreatic ductal adenocarcinoma were: 44.2% and 95.6% for AEA, 83.7% and 73.3% for LEA, 88.4% and 91.1% for LNEA, 81.4% and 82.2% for OEA, 81.4% and 88.9% for PEA, 86.0% and 88.9% for SEA, respectively.

Conclusion: Endocannabinoids are not useful in assessing pain in patients with chronic pancreatic diseases and they cannot replace a simple method such as VAS for assessing the pain and its intensity.     

Recent advances in artificial intelligence for pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) remains the most lethal type of cancer. The 5-year survival rate for patients with early-stage diagnosis can be as high as 20%, suggesting that early diagnosis plays a pivotal role in the prognostic improvement of PDAC cases. In the medical field, the broad availability of biomedical data has led to the advent of the “big data” era. To overcome this deadly disease, how to fully exploit big data is a new challenge in the era of precision medicine. Artificial intelligence (AI) is the ability of a machine to learn and display intelligence to solve problems. AI can help to transform big data into clinically actionable insights more efficiently, reduce inevitable errors to improve diagnostic accuracy, and make real-time predictions. AI-based omics analyses will become the next alterative approach to overcome this poor-prognostic disease by discovering biomarkers for early detection, providing molecular/genomic subtyping, offering treatment guidance, and predicting recurrence and survival. Advances in AI may therefore improve PDAC survival outcomes in the near future. The present review mainly focuses on recent advances of AI in PDAC for clinicians. We believe that breakthroughs will soon emerge to fight this deadly disease using AI-navigated precision medicine.     

Expression of fibroblast activation protein in human pancreatic adenocarcinoma and its clinicopathological significance

AIM: To examine fibroblast activation protein (FAP) expression in pancreatic ductal adenocarcinoma (PDAC) and to analyze its relationship with the clinicopathology of PDAC.METHODS: FAP expression was examined in 134 PDAC specimens by immunohistochemistry, and in four pancreatic cancer cell lines (SW1990, Miapaca-2, AsPC-1 and BxPC-3) by Western blotting assay. We also analyzed the association between FAP expression in PDAC cells and the clinicopathology of PDAC patients.RESULTS: The results showed that the FAP was ex-pressed in both stromal fibroblast cells (98/134, 73.1%) and carcinoma cells (102/134, 76.1%). All 4 pancreatic cancer cell lines expressed FAP protein at different levels. Protein bands corresponding to the proteolytically active 170-kDa seprase dimer and its 88-kDa seprase subunit were identified. Higher FAP expression in carcinoma cells was associated with tumor size (P < 0.001), fibrotic focus (P = 0.003), perineural invasion (P = 0.009) and worse clinical outcome (P = 0.0085).CONCLUSION: FAP is highly expressed in carcinoma cells and fibroblasts in PDAC tissues, and its expression is associated with desmoplasia and worse prognosis.     

Role of endoscopic retrograde pancreatography for early detection of pancreatic ductal adenocarcinoma concomitant with intraductal papillary mucinous neoplasm of the pancreas

Background

Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is often found with distinct pancreatic ductal adenocarcinoma (PDAC) in the same pancreas. The aim of this study was to clarify whether endoscopic retrograde pancreatography (ERP) would be useful for the early detection of concomitant PDACs in patients with IPMNs.

Methods

Medical records of 179 patients who were histologically confirmed to have IPMNs after resection between 1987 and 2011 were reviewed. The patients having concomitant PDACs were selected, and the diagnostic abilities to detect concomitant PDACs of computed tomography (CT), magnetic resonance imaging (MRI), endoscopic ultrasonography (EUS), and ERP were compared between early (stages 0–I according to Japanese General Rules for Pancreatic Cancer) and advanced (stages II–IV) PDACs.

Results

A total of 23 PDACs developed synchronously or metachronously in 20 patients, and the prevalence of PDACs concomitant with IPMNs was 11.2 % (20/179). Sensitivities of CT (16 vs. 87 %), MRI (29 vs. 93 %), and EUS (29 vs. 92 %) in the early group were significantly lower than those in the advanced group (p < 0.01). On the other hand, the sensitivity of ERP in the early group was as high as that in the advanced group (86 vs. 82 %, respectively, p > 0.99). Among 7 early PDACs, 3 were diagnosed only by ERP.

Conclusions

ERP has an important role in the early diagnosis of distinct PDACs in patients with IPMNs. Further investigation is necessary to clarify the indication and the timing of ERP during management of IPMNs in term of early detection of concomitant PDACs.     

IL2RA is a prognostic indicator and correlated with immune characteristics of pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive and incurable cancer with a dismal prognosis. In this study, we aimed to explore potential predictors for the prognosis and immunological characteristics of PDAC.Estimation of stromal and immune cells in malignant tumors, using expression data (ESTIMATE) method was applied to calculate the immune and stromal scores of 206 PDAC samples from {"type":"entrez-geo","attrs":{"text":"GSE71729","term_id":"71729"}}GSE71729. R package of “limma” was utilized to identify differentially expressed genes (DEGs). Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses were conducted for functional exploration. Protein-protein interaction (PPI) network and Univariate Cox analysis were conducted to select key prognostic genes of PDAC. Gene set enrichment analysis (GSEA) was applied to investigate the roles of IL2RA in PDAC. Single sample GSEA (ssGSEA) was performed to evaluate the immunological characteristics of PDAC samples. Wilcoxon rank sum test was conducted to compare the difference of immunological characteristics of PDAC samples between low IL2RA and high IL2RA. Spearman correlation analysis was used to explore the correlations of IL2RA expression and immune checkpoint genes.A total of 747 DEGs were identified between low and high immune/stromal groups. Functional exploration revealed upregulated DEGs were associated with immune-related activities, whereas downregulated DEGs were involved in inflammatory-related activities. IL2RA was selected as the critical gene by overlapping the hub genes in PPI network and prognostic genes. Significantly, IL2RA expression was significantly elevated in PDAC and patients with higher IL2RA expression had worse prognoses. The immunological and oncogenic roles of IL2RA in PDAC were evidenced by GSEA. Furthermore, PDAC samples with high IL2RA expression exhibited increased immune infiltration and better immunotherapy responses. IL2RA expression was positively correlated with PDCD1, CD274, CTLA4, IDO1, TDO2, and TIGT.Higher expression of IL2RA predicts worse survival outcomes and increased immune infiltration in PDAC. PDAC patients with high IL2RA expression might potentially benefit from immunotherapy.     

Ablation of sensory neurons in a genetic model of pancreatic ductal adenocarcinoma slows initiation and progression of cancer

Pancreatic ductal adenocarcinoma (PDAC) is characterized by an exuberant inflammatory desmoplastic response. The PDAC microenvironment is complex, containing both pro- and antitumorigenic elements, and remains to be fully characterized. Here, we show that sensory neurons, an under-studied cohort of the pancreas tumor stroma, play a significant role in the initiation and progression of the early stages of PDAC. Using a well-established autochthonous model of PDAC (PKC), we show that inflammation and neuronal damage in the peripheral and central nervous system (CNS) occurs as early as the pancreatic intraepithelial neoplasia (PanIN) 2 stage. Also at the PanIN2 stage, pancreas acinar-derived cells frequently invade along sensory neurons into the spinal cord and migrate caudally to the lower thoracic and upper lumbar regions. Sensory neuron ablation by neonatal capsaicin injection prevented perineural invasion (PNI), astrocyte activation, and neuronal damage, suggesting that sensory neurons convey inflammatory signals from Kras-induced pancreatic neoplasia to the CNS. Neuron ablation in PKC mice also significantly delayed PanIN formation and ultimately prolonged survival compared with vehicle-treated controls (median survival, 7.8 vs. 4.5 mo; P = 0.001). These data establish a reciprocal signaling loop between the pancreas and nervous system, including the CNS, that supports inflammation associated with oncogenic Kras-induced neoplasia. Thus, pancreatic sensory neurons comprise an important stromal cell population that supports the initiation and progression of PDAC and may represent a potential target for prevention in high-risk populations.Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers with a median survival of ∼6 mo from diagnosis (National Cancer Institute). A number of unique features distinguish PDAC from other carcinomas, but the most striking is the exuberant desmoplastic infiltrate within tumors. This compartment exhibits an array of cell types, including activated myofibroblasts and myeloid-derived cells. Indeed, this inflammatory infiltrate is present at the inception of neoplasia and accumulates at a near exponential rate during progression to carcinoma and tumor formation. It provides a complex balance of pro- and antitumorigenic signals to neoplastic cells (and also to each other) that is a focus of intense investigation. The pancreas tumor microenvironment has been studied previously, but new tools [genetically engineered mouse models (GEMs) that faithfully recapitulate the salient features of human PDAC] now allow for a careful dissection of the stroma. Using these models, we showed that generalized inflammation is required for the development of precancerous pancreatic intraepithelial neoplasias (1) and that Hedgehog-dependent stromal elements, including activated myofibroblasts, serve to constrain tumor growth and spread (2). Other cellular components of the pancreatic inflammatory stroma have not been examined, and it is possible they also contribute to the complex balance of inputs, supportive and inhibitory, which underlie tumorigenesis and progression.Previous reports indicate sensory neurons have a central role in benign inflammatory disease of the pancreas. Like most abdominal organs, the pancreas is innervated by sensory fibers from both the nodose (via the vagal nerve) and spinal ganglia (via splanchnic nerves) (3–7). In rodent models of acute or chronic pancreatitis, blockade of primary afferents from both nodose and spinal ganglia can moderate or prevent inflammation (8, 9) as well as associated pathology, even if done after the inciting injury (10, 11). In addition, autonomic neurons (sympathetic, parasympathetic, and enteric) (12) innervate the pancreas and interact with sensory fibers.Because of the documented role of sensory neurons in the pathogenesis of pancreatitis (8–11, 13–15), a known contributor to the pathogenesis of PDAC, we hypothesized that sensory neurons innervating the pancreas provide key proinflammatory inputs that support the early stages of tumorigenesis. Here, using GEMs of PDAC, we provide evidence that bidirectional communication between the pancreas and sensory neurons is active well before the establishment of tumors. We detected inflammation in the spinal cord when histologically only precancerous lesions (pancreatic intraepithelial neoplasia, PanIN) were present. This was accompanied by perineural invasion (PNI) of sensory ganglia and spinal cord and evidence of injury to pancreatic sensory and sympathetic neurons. Ablation of sensory neurons at postnatal days 1–2 prevented injury to peripheral neurons and spinal cord inflammation. Surprisingly, sensory neuron ablation was associated with a dose-dependent and dramatic prolongation of survival in PDAC mice. The animals with the greatest degree of capsaicin-induced neuronal ablation (>80%) did not develop cancer (up to 18 mo when they were euthanized for analysis), whereas more than 90% of untreated mice succumbed to PDAC within 6 mo. These studies indicate that sensory neurons contribute significantly to the initiation and progression of PDAC and may be required for the development of this disease.     

Semi-quantitative analysis of telomerase in pancreatic ductal adenocarcinoma

Using a polymerase chain reaction-based amplification assay, we measured telomerase activity in surgically resected pancreatic ductal carcinomas (n=16 cases) and normal ducts (n=6), comparing findings with the telomerase activity of a human pancreatic cancer cell line, MIA PaCa-2, as a standard, i.e., relative telomerase activity was determined. Telomerase activity was expressed as the equivalent telomerase intensity of the number of cells of MIA PaCa-2 per μg protein of tissue samples. The median value for telomerase activity in normal pancreatic ducts was 0.13 and the 25th and 75th percentile were 0.01 and 0.76. The median value for telomerase activity in pancreatic ductal adenocarcinoma was 34.7 (25th percentile, 4.98; and 75th percentile, 296), significantly higher than that of normal ducts (P<0.001). When the cut-off value was set at 1.0 and 3.0, the telomerase positivity rate of pancreatic ductal adenocarcinomas was 100% and 81.3%, respectively. Telomerase may be a specific marker for pancreatic ductal carcinomas.     

Neurotensin receptors: a new marker for human ductal pancreatic adenocarcinoma

Background/Aims—New imaging possibilities forearly diagnosis of the devastating exocrine pancreatic adenocarcinomaswould be highly welcome. Recently, pancreatic neuroendocrine tumours have been successfully visualised in vivo on the basis of their highdensity of receptors for the regulatory peptide somatostatin. Unfortunately, exocrine pancreatic tumours do not express sufficient amounts of somatostatin receptors. Therefore overexpression of other regulatory peptide receptors in these tumours needs to be found.
Methods—Receptors for the regulatory peptideneurotensin were evaluated in vitro by receptor autoradiography in 24 ductal pancreatic adenocarcinomas, 20 endocrine pancreatic cancers, 18cases of chronic pancreatitis, and 10 normal pancreatic glands.
Results—Some 75% of all ductal pancreaticadenocarcinomas, most of them differentiated, were neurotensin receptorpositive, whereas endocrine pancreatic cancers did not expressneurotensin receptors. No neurotensin receptors were found in chronicpancreatitis or normal pancreatic tissues, including pancreatic acini,ducts, and islets.
Conclusions—The selective and high expression ofneurotensin receptors in ductal pancreatic adenocarcinomas could formthe molecular basis for potential clinical applications, such as in vivo neurotensin receptor scintigraphy for early tumour diagnosis, radiotherapy with radiolabelled neurotensin analogues, and chemotherapy with neurotensin receptor antagonists.

Keywords:neurotensin receptors; ductal pancreatic carcinomas; chronic pancreatitis; endocrine pancreatic tumours; in vivoscintigraphy; regulatory peptides