Search

Herein, we describe the global comparison of miRNAs in human pancreatic cancer tumors, adjacent normal tissue, and matched patient-derived xenograft models using microarray screening. RNA was extracted from seven tumor, five adjacent normal, and eight FI PDX tumor samples and analyzed by Affymetrix GeneChip miRNA 4.0 array. A transcriptome analysis console (TAC) was used to generate comparative lists of up- and downregulated miRNAs for the comparisons, tumor vs. normal and F1 PDX vs. tumor. Particular attention was paid to miRNAs that were changed in the same direction in both comparisons. We identified the involvement in pancreatic tumor tissue of several miRNAs, including miR4534, miR3154, and miR4742, not previously highlighted as being involved in this type of cancer. Investigation in the parallel mRNA and protein lists from the same samples allowed the elimination of proteins where altered expression correlated with corresponding mRNA levels and was thus less likely to be miRNA regulated. Using the remaining differential expression protein lists for proteins predicted to be targeted for differentially expressed miRNA on our list, we were able to tentatively ascribe specific protein changes to individual miRNA. Particularly interesting target proteins for miRs 615-3p, 2467-3p, 4742-5p, 509-5p, and 605-3p were identified. Prominent among the protein targets are enzymes involved in aldehyde metabolism and membrane transport and trafficking. These results may help to uncover vulnerabilities that could enable novel approaches to treating pancreatic cancer. [ABSTRACT FROM AUTHOR]

The study objective was to determine the incidence of laparoscopically detected metastasis in patients with radiographically staged locally advanced adenocarcinoma of the pancreas. Patients with locally advanced pancreatic cancer are considered candidates for novel treatment protocols. Stratification of patients into locally advanced disease versus metastatic disease is imperative to accurately evaluate treatment outcome. Between 1994 and 2000, 100 consecutive patients undergoing staging laparoscopy with radiologic evidence of unresectable locally advanced pancreatic cancer were identified from a prospective database. All patients had preoperative contrast-enhanced, thin-cut computed tomography scanning or magnetic resonance imaging and had no evidence of detectable metastatic disease. There were 53 men and 47 women, with a median age of 64 years. The disease site was the pancreatic head in 69 cases and the body or tail in 31. Radiographic assessment of nonresectability was due to encasement of the celiac or hepatic artery in 37 patients, of the portal vein and superior mesenteric vessels in 56, and extrapancreatic extension in 7. Laparoscopy identified metastatic disease in 37% of patients, not seen on preoperative imaging. Peritoneal disease was noted in 12 cases and liver metastasis in 18 cases, and 7 patients had both. Neither the primary tumor size nor location influenced the incidence of metastatic disease. Standard imaging modalities failed to detect metastatic disease in 37% of patients who were considered to have locally advanced pancreatic cancer. Patients considered for treatment protocols for locally unresectable pancreatic cancer should be staged laparoscopically before initiation of therapy. [Copyright &y& Elsevier]

Patients with body or tail tumors of the pancreas often have contiguous organ involvement or portal-splenic confluence adherence requiring extensive resection in order to obtain grossly negative margins. The aim of this study was to determine whether long-term survival is possible after contiguous organ or portal vein resection in patients with adenocarcinoma of the body or tail of the pancreas. Between 1983 and 2000, a total of 513 patients with adenocarcinoma of the body or tail of the pancreas were identified from a prospective database. Distal pancreatectomy with or without splenectomy was performed in 57 patients (11%). Extended resection was necessary in 22 patients (39%): 14 (64%) for contiguous organ involvement and eight (36%) for portal vein resection Estimated blood loss, blood transfused, and length of hospital stay were significantly greater in patients requiring extended resection compared to standard resection (P = 0.02, P = 0.01, and P = 0.02, respectively). Median follow-up for patients still alive was 84 months (range 40 to 189 months). Median survival following resection was 15.9 months compared to 5.8 months in patients who were not resected (P<0.0001). Actual 5- and 10-year survival rates were 22% and 18%, respectively, following extended resection, 8% and 8% following standard resection, and 0% and 0% if no resection was attempted because of locally unresectable disease. Patients undergoing extended resection for adenocarcinoma of the pancreatic body or tail have long-term survival rates similar to those for patients undergoing standard resection; they also have markedly improved long-term survival compared to those who are not considered resectable because of locally advanced disease. Extended distal pancreatectomy is justified in this group of patients. [Copyright &y& Elsevier]

Because of the inability to determine benign from malignant, many have recommended that all cystic lesions of the pancreas be resected. Patients evaluated between January 1995 and December 2000 for the ICD-9 diagnosis of pancreatic cyst (577.2) or benign neoplasm of the pancreas (211.6) were reviewed. Patient, cyst, and treatment characteristics were recorded. Comparisons were made between patients who underwent operative and nonoperative management. Over the 5-year period, 209 patients were evaluated. Nonoperative treatment was initially chosen for 144 patients (69%). In this group the average cyst diameter was 2.5 cm (range 0.5 cm to 13.0 cm), and the median change in diameter during follow-up was zero cm (range 1.5 cm to 4.0 cm). In six patients (4%) changes occurred within the cyst that resulted in resection. None of these patients had a malignant diagnosis. Operative treatment was initially chosen for 65 (31%) of the 209 patients. Malignancy was found in six of the operative patients (6 [9%] of 65). Differences in patient and cyst characteristics between groups included the cyst size, septations, a solid component, and the presence of symptoms. Selected patients with cystic lesions of the pancreas may be safely followed radiographically. Selection criteria identified in this study (symptoms, cyst size, solid component, and septations) and the utilization of new imaging techniques allow the creation of treatment plans for these patients that can be prospectively tested. [Copyright &y& Elsevier]

Lymphoplasmacytic sclerosing pancreatitis (LP) is a rare cause of benign mass lesions of the pancreas that can resemble adenocarcinoma. This study evaluates and classifies a series of patients with LP. Patients with benign pancreatic disease were identified from a prospective pancreatic database, and these cases were reviewed to identify patients with LP. Patients were subdivided into two groups: (1) classic LP, which included those patients who had all four of the characteristic histologic features of LP, including lymphoplasmacytic infiltration of the pancreas, interstitial fibrosis, periductal inflammation, and periphlebitis; and (2) intermediate LP, which included patients with at least two of these histologic findings. Patient demographics, pathologic and clinical features, and outcome were analyzed. From 1985 to 2001, a total of 1287 pancreatic resections were performed at our institution, of which 159 were for benign disease. Of these, 31 had pathologic features consistent with LP, and all of these patients had a presumed preoperative diagnosis of pancreatic carcinoma. Most of these patients presented with jaundice (n = 21) or abdominal pain (n = 7). In 29 of 31 patients, curative resection was possible. Of these, 28% (8/29) developed recurrence after resection: seven with jaundice and one with recurrent pancreatitis (median time to recurrence, 11 months; median follow up, 38 months). All patients with recurrent jaundice appeared to have biliary strictures at the time of direct cholangiography and no patient had malignancy. A review of the pathology reports identified 19 patients with classic LP and 12 patients with intermediate LP, and there was no difference between these two groups. LP is a rare cause of pancreatitis that is difficult to differentiate from carcinoma preoperatively. Patients with classic and intermediate LP appear to demonstrate a similar clinical behavior. Nearly one third of patients have a progressive course after resection, with 25% developing recurrent jaundice; thus close follow-up is mandatory for all patients. ( J Gastrointest Surg 2003;7:129–139.) [Copyright &y& Elsevier]

Recent studies suggest that neoadjuvant chemoradiation can downstage locally advanced pancreatic tumors. There is limited evaluable data to support this approach. We review our experience with preoperative chemoradiation for surgically staged, locally advanced pancreatic cancer to determine whether patients are downstaged with multimodal therapy allowing for curative resection. A prospectively collected database from Memorial Sloan-Kettering Cancer Center was reviewed. Patients admitted between January 1993 and March 1999 with locally advanced pancreatic adenocarcinoma were identified (N = 163). Chemoradiation was administered to 87 (53.3%) of 163, and regimens varied from standard 5-fluorouracil/gemcitabine–based therapies to experimental protocols. Only three patients (3/87; 3.4%) had a sufficient clinical response on restaging to warrant reexploration. Of these, two thirds were unresectable on subsequent laparoscopy because of extensive vascular involvement or metastatic disease. Only one patient underwent a potentially curative resection, with a survival of 18 months despite negative margins and no nodal involvement. The overall median survival for all patients with locally advanced disease treated with chemoradiation was 11 months (6.5 months without multimodal therapy; P = 0.004). Although chemoradiation is associated with improved overall survival in locally advanced disease, it rarely leads to surgical “downstaging” allowing for potentially curative pancreatic resections. Novel multimodality approaches are required. (J Gastrointest Surg 2002;6:763–769.) [ABSTRACT FROM AUTHOR]

Laparoscopy identifies radiologically occult advanced disease in patients with pancreatic adenocarcinoma. The value of laparoscopy in the management of peri-ampullary tumors was determined. One hundred forty-four patients with radiologically resectable nonpancreatic adenocarcinoma, periampullary tumors were identified from a prospective database between August 1993 and December 2000. Criteria for laparoscopic unresectability included histologically proved peritoneal or hepatic metastases, distant nodal involvement, arterial involvement, and local extension outside the resection field. Median age at operation was 70 years (range 31 to 87 years) and 56% of the patients were men. An adequate laparoscopy was performed in 134 cases (93%). Laparoscopy identified 13 patients (10%) with unresectable disease. Of 121 patients with laparoscopic resectable disease, 111 (92%) went on to subsequent resection; CT correctly predicted resectability in 82%. Laparoscopy spared 36% of unresectable patients a nontherapeutic laparotomy. Patients with resectable disease were treated by pancreaticoduodenectomy (n = 91, 76%), ampullectomy (n = 12, 10%), duodenal resection (n = 10, 9%), or bile duct excision (n = 6, 5%). The addition of diagnostic laparoscopy to dynamic CT scanning in this selected patient population identifies an additional 10% of patients with unresectable disease. We believe that laparoscopy should be used in a selective manner for preoperative staging of patients suspected of having nonpancreatic periampullary tumors. ( J Gastrointest Surg 2002;6:139–146.) [Copyright &y& Elsevier]

Simple Summary: Pancreatic cancer (PC) is among the most aggressive types of cancer, having caused over 495,000 deaths worldwide in 2020, with increasing annual incidence. Pancreatic cystic lesions (PCLs) are protrusions found within or on the surface of the pancreas, and in many cases have the potential to become malignant. Current methods of characterising PCLs are imperfect and there is a profound need for improved diagnostic algorithms. This review highlights the importance of biological markers in the context of PCLs and PC, with a focus on 'omics'-related work. Successful integration of different 'omics' data could aid in the identification of a novel integrated biomarker profile for the risk stratification of patients with PCLs and PC. Pancreatic cancer (PC) is regarded as one of the most lethal malignant diseases in the world, with GLOBOCAN 2020 estimates indicating that PC was responsible for almost half a million deaths worldwide in 2020. Pancreatic cystic lesions (PCLs) are fluid-filled structures found within or on the surface of the pancreas, which can either be pre-malignant or have no malignant potential. While some PCLs are found in symptomatic patients, nowadays many PCLs are found incidentally in patients undergoing cross-sectional imaging for other reasons—so called 'incidentalomas'. Current methods of characterising PCLs are imperfect and vary hugely between institutions and countries. As such, there is a profound need for improved diagnostic algorithms. This could facilitate more accurate risk stratification of those PCLs that have malignant potential and reduce unnecessary surveillance. As PC continues to have such a poor prognosis, earlier recognition and risk stratification of PCLs may lead to better treatment protocols. This review will focus on the importance of biomarkers in the context of PCLs and PCand outline how current 'omics'-related work could contribute to the identification of a novel integrated biomarker profile for the risk stratification of patients with PCLs and PC. [ABSTRACT FROM AUTHOR]