Economic evaluation of suture versus clip anastomosis in arteriovenous fistula creation.

OBJECTIVE: Techniques such as the use of nonpenetrating vascular clips for arteriovenous fistula (AVF) anastomotic creation have been developed in an effort to reduce fistula-related complications. However, the outcomes data for the use of clips have remained equivocal, and the cost evaluations to support their use have been largely theoretical. Therefore, the present study aimed to determine both the clinical and the cost outcomes of AVFs created with nonpenetrating vascular clips compared with the continuous suture technique during a 10-year period at a single institution. METHODS: All patients undergoing AVF creation in the upper extremity from 2009 through 2018 were retrospectively analyzed. The patient demographics and AVF outcomes were collected and compared stratified by the surgical technique used. A cost analysis was performed of a subgroup of patients from 2013 to 2018. RESULTS: During the 10-year study period, 916 AVFs were created (79% using the continuous suture technique and 21% using nonpenetrating vascular clips). Patient demographics and comorbid conditions did not differ between the two groups, and no differences were present in maturation, primary patency, assisted primary patency, or complication rates between the two groups at 1 year. The suture group had a shorter time to maturation (4.3 months vs 5.5 months; P < .01) and improved secondary patency compared with the clip group (77.13% vs 69.59%; P = .03) The cost analysis of the procedures revealed a significant difference in direct costs (suture, $1389.26 vs clip, $1716.51; P < .01) and contribution margin (suture, $1770.19 vs clip, $1128.36; P < .01) for the two groups. CONCLUSIONS: Both suture and clip techniques in AVF creation demonstrated equivalent rates of maturation, primary patency, assisted primary patency, and complications at 1 year with higher expense associated with the use of clips. Thus, in an effort to reduce the economic burden of healthcare in the United States, the findings from the present study support the preferential use of the standard polypropylene suture technique when creating upper extremity AVFs.

Comparative incidence and outcomes of COVID-19 in kidney or kidney-pancreas transplant recipients versus kidney or kidney-pancreas waitlisted patients: A single-center study.

BACKGROUND: COVID-19 epidemiologic studies comparing immunosuppressed and immunocompetent patients may provide insight into the impact of immunosuppressants on outcomes. METHODS: In this retrospective cohort study, we assembled kidney or kidney-pancreas transplant recipients who underwent transplant from January 1, 2010, to June 30, 2020, and kidney or kidney-pancreas waitlisted patients who were ever on the waitlist from January 1, 2019, to June 30, 2020. We identified laboratory-confirmed COVID-19 until January 31, 2021, and tracked its outcomes by leveraging informatics infrastructure developed for an outcomes research network. RESULTS: COVID-19 was identified in 62 of 887 kidney or kidney-pancreas transplant recipients and 20 of 434 kidney or kidney-pancreas waitlisted patients (7.0% vs. 4.6%, p = .092). Of these patients with COVID-19, hospitalization occurred in 48 of 62 transplant recipients and 8 of 20 waitlisted patients (77% vs. 40%, p = .002); intensive care unit admission occurred in 18 of 62 transplant recipients and 2 of 20 waitlisted patients (29% vs. 10%, p = .085); and 7 transplant recipients were mechanically ventilated and died, whereas no waitlisted patients were mechanically ventilated or died (11% vs. 0%, p = .116). CONCLUSIONS: Our study provides single-center data and an informatics approach that can be used to inform the design of multicenter studies.

Outcomes after combined liver-kidney transplant vs. kidney transplant followed by liver transplant.

INTRODUCTION: The decision for isolated kidney transplant (KT) vs. combined liver-kidney transplant (CLKT) in patients with end-stage renal disease (ESRD) with compensated cirrhosis remains controversial. We sought to determine outcomes of patients requiring listing for a liver transplant (LT) following either a cadaveric or living donor KT and compare these outcomes to similar patients receiving a CLKT. METHODS: Our dataset included the United Network for Organ Sharing (UNOS)/Standard Transplant and Analysis and Research (STAR) kidney files from 1987 to 2012 after being joined with the liver files from 2002 to 2012. Outcomes of patients who received a CLKT with an international normalized ratio (INR) ≤1 and total bilirubin ≤1 were compared to patients who received a primary KT and subsequently required listing for LT between zero and five yr or after five yr. RESULTS: For the three groups, 244 patients had a CLKT, 216 were wait-listed for LT between zero and five yr after KT (0-5 WL), and 320 were wait-listed five yr after KT (+5 WL). From the time of KT, the 0-5 WL group had significantly worse survival than the CLKT group and the +5 WL group. The +5 WL had the best survival of all groups. For the 0-5 WL group, 45% underwent LT and 40% died while waiting compared to the +5 WL group with 53% having LT and 26% died while waiting. At the time of LT, the 0-5 WL group had a higher model for end-stage liver disease (MELD) score, higher incidence of being in the ICU at the time of transplant, and higher incidence of requiring life support. From the time of LT, the CLKT trended toward better survival (p = 0.0549) than both the 0-5 WL and +5 WL groups, which had equivalent survival. CONCLUSION: The 0-5 WL group is a higher risk group with poorer survival due to a higher incidence of dying on the waitlist. Better identification of patients with a high risk for hepatic decompensation following KT and agreement for regional exception for LT in the event of decompensation may improve utilization of organs and better survival for those patients.

Balloon-assisted over-the-wire technique for placement of the venous outflow component of the Hemodialysis Reliable Outflow (HeRO) device.

A modified technique for placement of the venous outflow component (VOC) of the Hemodialysis Reliable Outflow (HeRO) device (Hemosphere Inc, Minneapolis, Minn) is described. The purpose of the technique is to improve the system's trackability and facilitate device insertion in patients with central venous occlusion. Device preparation requires placement of a 6-mm × 4-cm angioplasty balloon within the leading end of the VOC. The leading 2 cm of the balloon are placed just distal to the radiopaque marker of the VOC. The balloon is inflated to profile and locked in this position within the leading end of the VOC. The VOC and balloon combination is advanced over the wire through the 20F peel-away sheath provided by the manufacturer. The described technique was used to successfully implant the HeRO device in 12 patients with central venous occlusion. This technique is recommended for placement of the VOC of the HeRO device in patients with central venous occlusions.

Early Experience Using Donor-derived Cell-free DNA for Surveillance of Rejection Following Simultaneous Pancreas and Kidney Transplantation.

Background: Allograft biopsy is the gold standard for diagnosing graft rejection following simultaneous pancreas and kidney (SPK) transplant. Intraperitoneal biopsies are technically challenging and can be burdensome to patients and the healthcare system. Donor-derived cell-free DNA (dd-cfDNA) is well-studied in kidney transplant recipients; however, it has not yet been studied in the SPK population. Methods: We hypothesized that dd-cfDNA could be utilized for rejection surveillance following SPK transplant. We prospectively collected dd-cfDNA in 46 SPK patients at a single institution. Results: There were 10 rejection events, 5 of which were confirmed with biopsy. The other 5 were treated based on dd-cfDNA and clinical data alone with favorable outcomes. Among all patients who did not have rejection, 97% had dd-cfDNA <0.5%. Dd-cfDNA may also help differentiate rejection from graft injury (ie, pancreatitis) with median values in rejection 2.25%, injury 0.36%, and quiescence 0.18% (P = 0.0006). Conclusions: Similar to kidneys, dd-cfDNA shows promise for rejection surveillance in SPK transplant recipients.

Graft repair of arteriovenous fistula aneurysms is associated with decreased long-term patency.

INTRODUCTION: Arteriovenous fistula (AVF) aneurysms are a chronic complication which can be disfiguring, painful, and can rupture. Here, we compare the outcomes between three different methods of AVF aneurysm repair. METHODS: One-way ANOVA, Chi-square, and Fisher Exact analyses were used to compare demographics. Multivariate logistic regression compared outcomes. Kaplan-Meier estimate illustrated long-term fistula patency. RESULTS: There were no differences between demographics in the aneurysmorrhaphy, end-to-end anastomosis, and synthetic graft groups. The odds of patients who received graft repair losing primary patency within one year compared to the aneurysmorrhaphy group was 3.5 (p = 0.025). Graft repair patients were 6.7 times more likely to develop an infection compared to aneurysmorrhaphy (p = 0.014). Synthetic grafts also exhibited accelerated rates of complete access loss compared to autogenous methods (p = 0.034). CONCLUSIONS: Graft repair of AVF aneurysms results in higher rates of infection and decreased primary and ultimate patency compared to autogenous repair techniques. Therefore, synthetic grafts should be avoided whenever possible.

Can Donor-Derived Cell-Free DNA Detect Graft-Versus-Host Disease in Solid Organ Transplantation: A Case Report.

Graft-versus-host disease (GVHD) is a rare complication after solid organ transplant. We present a case of GVHD after simultaneous pancreas kidney transplant. The patient was diagnosed with a cutaneous biopsy after developing the classic symptoms of maculopapular rash, diarrhea, and pancytopenia. However, this patient had unexplained elevations in donor-derived cell-free DNA (dd-cfDNA) for months before the onset of GVHD symptoms. We hypothesize that GVHD may be associated with elevated dd-cfDNA as a result of massive donor lymphocyte proliferation and turnover. Further investigation is warranted because earlier diagnosis and treatment could improve outcomes in an otherwise lethal disease.

End-to-end anastomosis as a superior repair type to prevent recurrence of arteriovenous fistula aneurysms and improve patency outcomes.

BACKGROUND: Arteriovenous fistulae (AVF) complicated by aneurysms are repaired through several mechanisms. Little is known about risk factors for aneurysm recurrence or the efficacy of subsequent repair of recurring aneurysms. METHODS: About 291 patients underwent AVF aneurysm repair between 2009 and 2019 at a large urban medical center. Patients who underwent staged repair, had a primary graft with pseudoaneurysm, were status-post kidney transplant, or using other dialysis access at the time of repair were excluded. One hundred sixty-two patients were included in the study, of which 52 developed a secondary aneurysm. Chi-square and t-test analyses were used to compare demographics. Multivariate logistic regression was used to examine independent risk factors for aneurysm recurrence. Of the 52 patients with recurrent aneurysms, 41 were repaired again. Patency was examined for each group 1 year postoperatively. RESULTS: Patients without secondary aneurysms were more likely to have a Charlson Comorbidity Index score ⩾5 (p = 0.045). Males were 2.8 times more likely to develop a secondary aneurysm compared to females (p = 0.023). Patients who underwent elective compared to emergent or urgent surgery for primary aneurysms were significantly less likely to recur (OR = 0.222; p = 0.016). Primary aneurysms repaired by end-to-end anastomosis, compared to aneurysmorrhaphy or graft, were significantly less likely to recur (OR = 0.239; p = 0.041). Among patients with secondary aneurysms, those repaired via end-to-end anastomosis had a significantly higher primary patency rate 1 year postoperatively (p = 0.024). Secondary aneurysm repairs exhibited 1-year primary and secondary patency rates of 51.2% and 82.9%, respectively. CONCLUSIONS: End-to-end anastomosis reduces risk of recurrence and demonstrates superior patency rates when repairing recurrent aneurysms. It remains unclear why some patients are prone to aneurysm recurrence, however continued attempts to repair existing vascular access are proven to be successful.

No difference in clinical transplant outcomes for local and imported liver allografts.

In the United States, liver allograft allocation is strictly regulated. Local centers have the first option to accept a donor liver; this is followed by regional allocation for those donor livers not used locally and then by national allocation for those donor livers not accepted regionally. This study reviews the outcomes of all liver allografts used over 6 years (2001-2007) and evaluates initial and long-term function stratified by the geographic source of the donor liver allograft. The records for 845 consecutive deceased donor liver transplants at a single center were reviewed. The geographic origin of the allograft was recorded along with donor and graft characteristics to determine the probable reason for graft refusal. Within our local organ procurement organization, there is 1 liver transplant center, and within the region, there are 8 active centers. Early graft failure included any graft loss within 7 days of transplant, and initial function was measured with liver enzymes 30 days post-transplant. Graft survival and patient survival were evaluated with Kaplan-Meier and Cox survival modeling. Median follow-up was 43 months. The geographic distribution of organs included local organs (562, 66%), regionally imported organs (126, 15%), and nationally imported organs (157, 19%). There were no differences between the 3 groups in initial graft function, intraoperative death, or early graft loss. Survival curves for the 3 study groups demonstrated no difference in survival up to 5 years post-transplant. In conclusion, liver allografts rejected for use by a large number of transplant centers can still be successfully used without early graft function or long-term survival being affected.

A new vascular approach to the modified multivisceral graft procurement.

Modified multivisceral (MMV) transplantation including the stomach, pancreaticoduodenal complex and intestine requires preservation of the left gastric and splenic arteries. The previously described techniques require division of the hepatic artery proximal to the gastroduodenal artery leaving the liver transplant team with a very short and small caliber vessel. To increase MMV graft availability and provide the liver transplant team with an appropriate quality vessel, we developed the following technique. We also describe two cases where we used this method to support the technical feasibility of this procedure.

The case for pancreas after kidney transplantation.

Pancreas after kidney (PAK) transplantation has historically demonstrated inferior pancreas allograft survival compared to simultaneous pancreas and kidney (SPK) transplantation. Under our current immunosuppression protocol, we have noted excellent outcomes and rare immunological graft loss. The goal of this study was to compare pancreas allograft survival in PAK and SPK recipients using this regimen. This was a single center retrospective review of all SPK and PAK transplants performed between January 2003 and November 2007. All transplants were performed with systemic venous drainage and enteric exocrine drainage. Immunosuppression included induction with rabbit anti-thymocyte globulin (thymoglobulin), early steroid withdrawal, and maintenance with tacrolimus and sirolimus or mycophenolate mofetil. Study end points included graft and patient survival and immunosuppression related complications. Transplants included PAK 61 (30%) and SPK 142 (70%). One-yr patient survival was PAK 98% and SPK 95% (p = 0.44) and pancreas graft survival was PAK 95% and SPK 90% (p = 0.28). Acute cellular rejection was uncommon with 2% requiring treatment in each group. Survival for PAK using thymoglobulin induction, early steroid withdrawal and tacrolimus-based immunosuppression is at least comparable to SPK and should be pursued in the recipient with a potential living donor.

Comparison of histidine-tryptophan-ketoglutarate solution and University of Wisconsin solution in intestinal and multivisceral transplantation.

BACKGROUND: Previous studies have failed to demonstrate a clinical difference between histidine-tryptophan-ketoglutarate (HTK) and University of Wisconsin (UW) preservation solutions in clinical transplant outcomes for liver, pancreas, and kidney transplantation. This study compares HTK and UW in bowel transplantation with primary outcomes being graft and patient survival, early graft function, and episodes of rejection. METHODS: Data were extracted using a retrospective chart and medical record review of all bowel transplants between 2003 and 2007, and included both pediatric and adult grafts. Transplanted organs included isolated small bowel, modified multivisceral (bowel, pancreas, and stomach) and multivisceral (bowel, pancreas, stomach, and liver). Immunosuppression included induction with a steroid taper and antithymocyte globulin and anti-CD20 monoclonal antibody (rituximab), followed by maintenance with prograf monotherapy. Bowel surveillance was performed with twice weekly zoom endoscopy and biopsy. RESULTS: There were 54 patients transplanted with 57 grafts, 22 preserved in UW, and 37 in HTK. No differences were noted between the two solutions in initial graft function, appearance of bowel on initial endoscopy, and number of rejection episodes. There were no episodes of pancreatitis in the 44 multivisceral grafts which included a transplant pancreas (14 UW and 30 HTK). Kaplan-Meier survival analysis did not demonstrate a significant difference in graft or patient survival at 30- or 90-days posttransplant. CONCLUSIONS: Intestinal grafts preserved in UW and HTK demonstrate no difference in graft and patient survival at 30- and 90-days posttransplant. There were no differences noted in initial function, endoscopic appearance, rejection episodes, or transplant pancreatitis.

Initiation of an intestinal transplant program: the Indiana experience.

INTRODUCTION: Establishment of a new intestinal transplant (Itx) program in the United States entails significant programmatic costs and a steep learning curve. We report results of the first 4 years of the program at Indiana University. METHODS: Forty-six intestinal and multivisceral transplants (MVtx) were performed between 2003 and 2007. All organ procurements were performed by our team. Immunosuppression included an induction protocol combined with maintenance tacrolimus monotherapy. Scheduled rejection surveillance was with magnification endoscopy. RESULTS: Forty-three patients (13 children and 30 adults) received 10 Itx (22%), 5 modified MVtxs (11%), and 31 (MVtx, 67%). Recipient ages ranged from 3 months to 66 years, with median follow-up time of 15 months. Thirty-five patients are currently alive (81%). Patient and graft survival at 30 days was 85%/86% in pediatric and 93%/91% in adult; overall survival was 69%/64% in pediatric and 87%/75% in adult. Thirty patients (69%) experienced episodes of rejection. Multivisceral transplanted patients experienced less episodes of severe rejection (2/31, 6%) when compared with patients with isolated Itx and modified MVtxs. Retransplantation was performed in three patients with nonresponsive severe acute rejection. CONCLUSION: The Indiana University Intestinal and Multivisceral Transplant program experienced significant early graft loss and mortality among pediatric patients, but not among adults. This discrepancy resolved within 2 years of program initiation. After 4 years, adult and pediatric graft and patient survival statistics are similar to those at other programs.

Safe inclusion of the entire pancreas as a component of the multivisceral graft.

BACKGROUND: Multivisceral transplantation (MVtx) involves simultaneous transplantation of the intestine with other organs, often including the pancreas. The pancreas portion of the graft has always been approached with caution because allograft pancreatitis, rejection or technical complications may be devastating in this setting. We reviewed our experience with multivisceral grafts that included the entire pancreas. METHODS: Twenty-five patients received 27 MVtx that included the entire pancreas between July 2003 and November 2006. In five, a modified MVtx with preservation of the native liver was performed. Two patients required retransplantation for severe rejection. Insulin requirements, graft and patient survival were determined at 6-months posttransplant. Serum amylase and lipase levels were analyzed on postoperative days 3, 7, 30, and 180. RESULTS: Twenty of 25 patients with a transplant pancreas graft were alive at 6-months posttransplant. Median serum amylase and lipase levels posttransplant were normal at all time points. One patient exhibited elevation of amylase and lipase at the time of severe acute cellular rejection of the intestinal graft, likely representing simultaneous pancreas allograft rejection, although this was not confirmed by biopsy. There were no episodes of allograft pancreatitis or technical complications. Once weaned from hyperalimentation, all patients remained normoglycemic and insulin-independent 6-months posttransplant. CONCLUSION: In this series, there were no postoperative pancreatic complications, no episode of isolated pancreas allograft rejection, and no loss of pancreatic graft function. None of the five deaths were related to pancreatic graft complications.

Addition of a total pancreatectomy and pancreas transplantation in a liver transplant recipient with intraductal papillary mucinous neoplasm of the pancreas.

BACKGROUND: Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas are increasingly recognized in clinical practice. There are no published data suggesting a management approach for the potential organ transplant recipient with the incidental finding of this pre-malignant lesion. METHODS: The recipient was a 65-yr-old man with hepatocellular carcinoma in a background of Laennec's cirrhosis. During evaluation for transplant, he was found to have diffuse IPMN. This patient underwent liver transplantation with a planned simultaneous total native pancreatectomy and pancreas transplant from the same donor. RESULTS: The patient has had normal liver function and has been free of diabetes and exocrine insufficiency at 18 months post-transplant. CONCLUSION: IPMN in the potential transplant recipient should be managed more aggressively than in the general population because these patients will be committed to life-long immunosuppression. If a total pancreatectomy is contemplated, this is a unique opportunity to replace the pancreas with an allograft at the time of transplantation.

Bilateral sequential lung and simultaneous pancreas transplant: a new approach for the recipient with cystic fibrosis.

UNLABELLED: Cystic fibrosis (CF) is an inherited disorder that presents in childhood as a multisystem disease. Pulmonary failure and pancreatic insufficiency, including CF related diabetes (CFRD) and exocrine insufficiency, are common complications of this disease. In this report we review the first three simultaneous lung and pancreas transplantations in CF patients with diabetes. METHODS: All three CF patients presented for evaluation for lung transplantation and had pancreatic insufficiency requiring enzyme supplementation and CFRD requiring insulin. All were severely malnourished and required nutritional supplementation. SURGICAL TECHNIQUE: In each case, the allografts were procured from a single cadaveric donor. Bilateral lung transplantation was performed first using two separate thoracic incisions. The pancreas transplant was performed with systemic venous drainage and enteric exocrine drainage. RESULTS: The pancreas allografts all functioned normally with normoglycemia independent of insulin. As a result of the enteric drainage of the pancreas allograft, supplemental pancreatic enzymes were no longer required. Despite several complications detailed in the manuscript, all three remain independent of supplemental oxygen, insulin and pancreatic enzyme replacement at 4, 6 and 14 months of follow-up. CONCLUSION: Simultaneous lung and pancreas transplantation in patients with CF can be performed successfully and provides the advantages of normoglycemia and improves nutrition for patients requiring lung transplantation.

The Usage of Mock Oral Examinations for Program Improvement.

OBJECTIVE: Mock oral examinations are often used to prepare residents for the American Board of Surgery certifying examination. Another potential use of these examinations is to identify programmatic weaknesses. Results from a multi-institutional mock oral examination were evaluated to determine if specific areas of weakness within each of the participating programs could be identified to facilitate program development. DESIGN: A mock oral examination was administered annually consisting of 3 examination rooms per resident with 3 cases in each room. Case categories included core general surgery and subspecialties and cases were changed yearly. Each case included facets of patient management from history and physical examination, and differential diagnosis to postoperative care and professional behaviors. SETTING: General Surgery programs at 3 academic medical centers-Northwestern University, Rush University, and University of Illinois at Chicago. PARTICIPANTS: A total of 259 resident examinations of fourth- and fifth-year general surgery residents over a 7-year period. RESULTS: A total of 2331 individual resident cases were evaluated with an overall case pass rate of 50.2% across all 3 programs. The weakest case category for each program was different (A = vascular 40.0% pass, B = trauma 41.4% pass, and C = breast 30.0% pass). All programs scored above their mean in gastrointestinal and abdominal surgery and below their mean in vascular surgery. Within vascular surgery, the weakest facet of patient management also differed between programs (A = select tests 44.3% pass, B = complications 57.0% pass, and C = history and physical 55.4% pass). CONCLUSIONS: A standardized mock oral examination is able to identify topic areas of relative strength and weakness that differ between programs. These results can be used to define focused areas for improvement within training programs, guide rotation schedules, and improve didactic curricula.

The utility of mock oral examinations in preparation for the American Board of Surgery certifying examination.

BACKGROUND: Determine the utility of mock oral examinations in preparation for the American Board of Surgery certifying examination (ABS CE). METHODS: Between 2002 and 2012, blinded data were collected on 63 general surgery residents: 4th and 5th-year mock oral examination scores, first-time pass rates on ABS CE, and an online survey. RESULTS: Fifty-seven residents took the 4th-year mock oral examination: 30 (52.6%) passed and 27 (47.4%) failed, with first-time ABS CE pass rates 93.3% and 81.5% (P = .238). Fifty-nine residents took the 5th-year mock oral examination: 28 (47.5%) passed and 31 (52.5%) failed, with first-time ABS CE pass rates 82.1% and 93.5% (P = .240). Thirty-eight responded to the online survey, 77.1% ranked mock oral examinations as very or extremely helpful with ABS CE preparation. CONCLUSIONS: Although mock oral examinations and ABS CE passing rates do not directly correlate, residents perceive the mock oral examinations to be helpful.

Vascular complications associated with pancreaticoduodenectomy adversely affect clinical outcome.

BACKGROUND: Early survival after pancreaticoduodenectomy has improved, but its morbidity remains high. The purpose of this study is to determine how the intra-operative (OR) occurrence of major vascular complications affects the outcome of pancreaticoduodenectomy. METHODS: The medical records of 180 consecutive patients having pancreaticoduodenectomy from 1991 to 2001 were reviewed. Vascular complications were defined as "an unanticipated injury or thrombosis of a major vessel necessitating intervention." Age, sex, type of pancreaticoduodenectomy, tumor size, estimated blood loss, OR time, time in intensive care, post-OR hospitalization, and survival were compared. RESULTS: Eighteen vascular complications were identified. Differences in age, sex, and type of resection between patients with or without vascular complications were not significant. OR time, estimated blood loss, blood transfusions, tumor size, time in intensive care, and post-OR hospitalization were all significantly greater in patients with vascular complications. Median survival for patients with vascular complications was significantly shorter than for patients without vascular complications. Thirty-day mortality was greater in patients with vascular complications. CONCLUSION: Vascular complications significantly affect the outcome of pancreaticoduodenectomy increasing OR time, estimated blood loss, blood transfusion requirements, time in intensive care, post-OR hospitalization, and mortality.

Human heparanase-1 gene expression in pancreatic adenocarcinoma.

Extracellular matrix degradation is an essential step that allows tumor cells to penetrate a tissue barrier and become metastatic. Heparanase-1 (HPR1) is an endoglycosidase that specifically degrades heparan sulfate proteoglycans, a chief component of the extracellular matrix. HPR1 is not expressed in normal epithelial cells but can be detected in a variety of malignancies. In the present study, we examined HPR1 expression in pancreatic cancer by using in situ hybridization and tested whether HPR1 expression correlated with any clinicopathlogic parameters. HPR1 was not detected in the ductal cells of normal pancreas samples obtained from 10 patients at autopsy. However, HPR1 was detected in 77 (78%) of 99 pancreatic adenocarcinomas. Among them, 69 (78%) of 89 primary pancreatic adenocarcinomas and 8 (80%) of the 10 metastases were HPR1 positive. Age, sex, tumor stage, and lymph node status were not predictive of HPR1 expression. Log-rank test of the Kaplan-Meier survival curves revealed that HPR1 expression in early-stage tumors was associated with decreased survival. HPR1 expression was frequent in pancreatic adenocarcinomas and was associated with decreased survival in early-stage tumors. This suggests that HPR1 may contribute to the highly invasive and early metastatic behavior of pancreatic cancer.