Staging laparoscopy for proximal pancreatic cancer in a magnetic resonance imaging-driven practice: what's it worth?

AbstractBackgroundPreoperative imaging is often inadequate in excluding unresectable pancreatic cancer. Accordingly, many groups employ staging laparoscopy (SL), although none have evaluated SL after preoperative magnetic resonance imaging (MRI). We performed a retrospective, indirect cost-effectiveness analysis of SL after MRI for pancreatic head lesions.MethodsAll MRI scans administered for proximal pancreatic cancer between 2004 and 2008 were reviewed and the clinical course of each patient determined. We queried our billing database to render average total costs for all inpatients with proximal pancreatic cancer who underwent pancreaticoduodenectomy, palliative bypass or an endoscopic stenting procedure. We then performed an indirect evaluation of the cost of routine SL.ResultsThe average costs of hospitalization for patients undergoing pancreaticoduodenectomy, open palliative bypass and endoscopic palliation were: US$26122.43, US$21957.18 and US$11304.00, respectively. The calculated cost of SL without laparotomy was US$2966.25 or US$1538.61 prior to laparotomy. The calculated cost of treating unresectable disease by outpatient laparoscopy followed by endoscopy was US$5943.17. Routine SL would increase our costs by US$76967.46 (3.6%).ConclusionsStaging laparoscopy becomes cost-effective by diverting unresectable patients from operative to endoscopic palliation. Given the paucity of missed metastases on MRI, the yield of SL is marginal and its cost-effectiveness is poor. Future studies should address the utility of SL by both examining this issue prospectively and investigating the cost-effectiveness of endoscopic vs. surgical palliation in a manner that takes account of survival and quality of life data

Genomic characterization of malignant progression in neoplastic pancreatic cysts

Intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms (MCNs) are non-invasive neoplasms that are often observed in association with invasive pancreatic cancers, but their origins and evolutionary relationships are poorly understood. In this study, we analyze 148 samples from IPMNs, MCNs, and small associated invasive carcinomas from 18 patients using whole exome or targeted sequencing. Using evolutionary analyses, we establish that both IPMNs and MCNs are direct precursors to pancreatic cancer. Mutations in SMAD4 and TGFBR2 are frequently restricted to invasive carcinoma, while RNF43 alterations are largely in non-invasive lesions. Genomic analyses suggest an average window of over three years between the development of high-grade dysplasia and pancreatic cancer. Taken together, these data establish non-invasive IPMNs and MCNs as origins of invasive pancreatic cancer, identifying potential drivers of invasion, highlighting the complex clonal dynamics prior to malignant transformation, and providing opportunities for early detection and intervention

Histopathologic Evidence of Tumor Regression in the Axillary Lymph Nodes of Patients Treated With Preoperative Chemotherapy Correlates With Breast Cancer Outcome

Background: The benefits of primary tumor downstaging and assessment of chemoresponsiveness have resulted in expanded applications for induction chemotherapy. However, the pathologic evaluation and prognostic significance of response in preoperatively treated lymph nodes have not been defined.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41400/1/10434_2003_Article_734.pd

A Phase II study of celecoxib, gemcitabine, and cisplatin in advanced pancreatic cancer

Background . Pancreatic cancer is amongst the most chemoresistant malignancies. Expression of the cyclooxygenase-2 (COX-2) enzyme plays a major role in tumor progression and resistance to therapy. A Phase II study was undertaken to determine the effect of gemcitabine by fixed-dose rate infusion (FDR), cisplatin and the COX-2 inhibitor, celecoxib, on the 6-month survival rate in patients with metastatic pancreatic cancer.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45281/1/10637_2005_Article_1028.pd

Integrated genomic characterization of pancreatic ductal adenocarcinoma

We performed integrated genomic, transcriptomic, and proteomic profiling of 150 pancreatic ductal adenocarcinoma (PDAC) specimens, including samples with characteristic low neoplastic cellularity. Deep whole-exome sequencing revealed recurrent somatic mutations in KRAS, TP53, CDKN2A, SMAD4, RNF43, ARID1A, TGFβR2, GNAS, RREB1, and PBRM1. KRAS wild-type tumors harbored alterations in other oncogenic drivers, including GNAS, BRAF, CTNNB1, and additional RAS pathway genes. A subset of tumors harbored multiple KRAS mutations, with some showing evidence of biallelic mutations. Protein profiling identified a favorable prognosis subset with low epithelial-mesenchymal transition and high MTOR pathway scores. Associations of non-coding RNAs with tumor-specific mRNA subtypes were also identified. Our integrated multi-platform analysis reveals a complex molecular landscape of PDAC and provides a roadmap for precision medicine

Pancreatic endocrine tumour with ductules: further observations of an unusual histological subtype.

AIMS: Pancreatic endocrine tumours (PET) containing ductules are an uncommon histological variant. Considerable conjecture surrounds the origin and histogenesis of the ductules. Opinions range from the ductules being an inherent part of the tumour, to others who feel they are merely entrapped. A study of 21 cases of this variant was undertaken with particular attention paid to the distribution and morphology of the ductules, the presence of entrapped acinar tissue and the surrounding uninvolved pancreatic tissue. METHODS AND RESULTS: Twenty-one cases were detailed occurring in either gender equally and with a wide age range (19-85 years). All cases, except one, were sporadic, the vast majority were located in the tail and were of small size (less than 2.0 cm). All cases were typified by stromal fibrosis, either diffuse (15) or in the form of septae (6). Embedded within the fibrous tissue were ductular structures, some of which were dilated and ectatic. The ductules were centrally located (5), at the periphery of the tumour (9) or diffusely scattered throughout the lesion (7). All cases showed ductulo-insular complexes. Insulin was demonstrated in 15 immunohistochemically. CONCLUSIONS: It is likely that in some cases the ductules are entrapped as the tumour grows into surrounding normal pancreatic tissue and the ductular proliferation is a secondary phenomenon. In a proportion of cases, the ductules are likely to be a part of the tumour arising as part of focal chronic inflammation or as a result of the growth factor effects of insulin, in cases associated with insulin production. There is nothing to suggest that the ductules confer any special biological characteristics to the PET and are merely a histological nuance. However, some cases may have a dominant tubular component, which could present problems at frozen section where the association with fibrosis may invoke a mistaken diagnosis of pancreatic ductal adenocarcinoma or chronic pancreatitis

Mucinous carcinomas of the gallbladder clinicopathologic analysis of 15 cases identified in 606 carcinomas

PubMed: 23106580Context.-There are virtually no data in the literature regarding the incidence, patterns, and clinicopathologic characteristics of mucinous carcinomas (MCs) of the gallbladder (GB). Objective.-To determine the incidence of mucinous differentiation in invasive GB carcinomas and the clinicopathologic characteristics of those that qualify as MC. Design.-Primary invasive GB carcinomas (n = 606) were reviewed for mucinous differentiation. Some degree of mucin production was identified in 40 cases (6.6%); however, only 15 (2.5%) were qualified for the World Health Organization definition of MC (stromal mucin deposition constituting 50% of the tumor). Results.-The mean age was 65 years, and the female to male ratio was 1.1 (versus 3.9 for conventional pancreatobiliary- type GB adenocarcinomas; P = .04). A significant proportion of the cases (8 of 12, 67%) presented with the clinical picture and intraoperative findings that were interpreted as acute cholecystitis. Mean and median tumor sizes were larger than those of conventional adenocarcinomas (4.8 and 3.4 cm versus 2.9 and 2.5 cm, respectively; P = .01). Most (13 of 15, 87%) cases presented with pT3 tumors (versus 48% for ordinary GB carcinomas; P = .01). Two cases had almost an exclusive colloid pattern ( 90% composed of well-defined stromal mucin nodules that contained scanty carcinoma cells, most of which were floating within the mucin). Eight cases were of mixedmucinous type, showing a mixture of colloid and noncolloid patterns. Five others had prominent signet-ring cells, both floating within the mucin (which constituted 50% of the tumor by definition) and infiltrating into the stroma as individual signet-ring cells in some areas. Immunohistochemical analysis performed on the 7 cases that had available tissue revealed CK7 in 4 of 7 (57%), CK20 in 2 of 7 (29%), MUC1 in 4 of 7 (57%), MUC2 in 6 of 7 (86%), CDX2 in 1 of 7 (14%),MUC5AC in 6 of 7 (86%),MUC6 in 0 of 7 (0%), and loss of E-cadherin in 6 of 7 (86%). The MLH1 and MSH2 were retained in 6 of 7 cases (100%). Follow-up information was available for 13 cases: 11 (85%) died of disease (1-37 months) and 2 (15%) were alive (23 months and 1 month). Overall survival of MCs was significantly worse than that of conventional adenocarcinomas (13 versus 26 months; P = .01); however, that did not seem to be independent of stage. Conclusions.-Mucinous carcinomas constitute 2.5% of GB carcinomas. They present with an acute cholecystitis-type picture. Most MCs are a mixed-mucinous, not pure colloid, type. They are typically large and advanced tumors at the time of diagnosis and thus exhibitmore-aggressive behavior than do ordinary GB carcinomas. Immunophenotypically, they differ from conventional GB adenocarcinomas by MUC2 positivity, from intestinal carcinomas by an often inverse CK7/20 profile, from pancreatic mucinous carcinomas by CDX2 negativity, and from mammary colloid carcinomas by a lack of MUC6. Unlike gastrointestinal MCs, they appear to be microsatellite stable