Background: The coexistence of intestinal neoplasms with Crohn's disease (CD) has been reported, but the evidence of an increased risk of carcinoid tumor with Crohn's disease has been mixed. We present 4 patients with CD with associated carcinoid tumor.Methods: The charts of I I I patients with CD who had undergone resection between June 2001 and March 2005 were reviewed. The number of incidental carcinoid tumors in patients who underwent an appendectomy was used as a control.Results: Four cases of carcinoid tumor discovered in patients at resection for CD were identified. None had metastatic disease or carcinoid syndrome. These included I cecal (I mm), 2 appendiceal (3 and 7mm), and I transverse colon (7 mm) carcinoid tumors. None of the carcinoid tumors were identified in regions of active Crohn's disease. The incidence of carcinoid tumor in patients with Crohn's disease was 4 of 111 (3.6%). In comparison, 3 of 1199 patients (0.25%) who had appendectornies were identified as having appendiceat carcinoid tumor. Crohn's disease was associated with an increased incidence of carcinoid tumor; OR 14.9 (95% C1 2.5102.5), P < 0.0001.Conclusions: There was a significantly increased incidence of carcinoid tumor in our Crohn's patients compared to the control patients. None of the carcinoid tumors developed in areas of Crohn's disease. This suggests that the development of carcinoid rumors may be secondary to distant proinflarnmatory mediators, rather than a local inflammatory effect from adjacent Crohn's disease. Patients with CD may be at increased risk of developing a carcinoid tumor.

Background: This study was performed to assess if using endoscopic ultrasound (EUS) to assess and guide combination medical and surgical therapy during fistula healing will lead to a high rate of durable fistula closure and a low or absent incidence of perianal abscess formation in patients with Crohn's perianal fistulas. Methods: This is a retrospective analysis of 21 patients who presented with a symptomatic Crohn's perianal fistula. Patients were enrolled in a clinical practice protocol of serial EUS exams. All patients underwent a baseline rectal EUS and were placed on maximal medical treatment with 6‐mercaptopurine (6‐MP) or azathioprine, Cipro, and infliximab (5 mg/kg at 0, 2, and 6 wk and then every 8 wk). Patients were also assessed at baseline by a colorectal surgeon who was aware of the EUS findings. Seton placement and incision and drainage were performed when appropriate. Serial EUS examinations were performed, and the findings were used to guide therapy (i.e., the presence of fistula healing on EUS was used to guide seton removal, discontinuation of infliximab, and Cipro). Results: In the 21 patients enrolled, the median duration of active perianal symptoms was 9 wks (1‐36). 10 patients (48%) had previous perianal surgery and 5 (24%) had received infliximab previously. The fistulas treated included 8 trans‐sphincteric, 2 superficial, 3 recto‐vaginal, and 7 with multiple and horseshoe fistulas. 13 patients (62%) had associated abscesses at presentation. Eighteen of 21 patients (86%) had complete cessation of drainage initially. Median time to cessation of drainage was 10.6 weeks (range, 4‐32 wk). Sixteen of 21 patients (76%) maintained long‐term cessation of drainage. The median length of follow‐up was 68 weeks (range, 35‐101 wk). No abscess developed during treatment in any patient. EUS evidence of persistent fistula activity was seen in 10 patients (48%). Of the 11 patients (52%) in whom EUS showed no persistent fistula activity, 7 (64%) have maintained fistula closure off of infliximab and Cipro. Median duration from last infliximab infusion was 47 weeks (range, 20‐80 wk). The remaining 4 patients continued infliximab to maintain remission of their luminal disease. Only 1 patient with a horseshoe fistula showed complete healing on EUS. Conclusion: In conclusion, using EUS to guide therapy for Crohn's perianal fistulas with infliximab, an immunosuppressive, and an antibiotic is associated with a high short and long‐term fistula response rate. EUS may identify a subset of patients who can discontinue infliximab without recurrence of fistula drainage.

Background: Up to 42% of patients with inflammatory bowel disease (IBD) have significant metabolic bone disease. The current method of screening for osteopenia or osteoporosis involves dual-energy x-ray absorptiometry (DXA). This is relatively costly and involves radiation exposure. What is needed is a safe, inexpensive, and quick screening tool to identify patients who would benefit from DXA testing. This would reduce the number of patients undergoing DXA testing unnecessarily. We tried to determine if calcaneal ultrasound bone densitometry is a useful tool in screening high-risk patients with IBD for metabolic bone disease.Methods: Patients with IBD who presented to the clinic between August 29, 2003 and December 22, 2003 were enrolled in this prospective study. All patients underwent calcaneal ultrasound bone densitometry screening using a GE Lunar Achilles Insight quantitative ultrasound densitometry machine (QUS). Patients who were at high risk for significant metabolic bone disease (i.e., significant previous prednisone use or a long history of severe IBD) or who had a T-score on QUS less than or equal to -0.7 had DXA testing performed. The DXA results and QUS results were compared. The radiologist was blinded to the results of QUS.Results: One hundred twenty-four patients with IBD were enrolled. Fifty (40%) were considered high risk for metabolic bone disease. This cohort was comprised of 29 men (58%), of which 21 (73%) had Crohn's disease (CD). Eighty percent of this high-risk group had CD, and in both groups, the majority had used corticosteroids. The overall risk of significant metabolic bone disease in this high-risk group was 62% (DXA <= -1.0). Heel density (T-score) correlated poorly with DXA (T-score) at either hip or spine at 0.40 even when 2 outlier patients (QUS = -2.9, DXA spine = 0.7, DXA hip = 0.8 and QUS = -3.6, DXA spine = -3, DXA hip = -4) were excluded. Likewise, no association in osteopenia or osteoporosis was seen between multiple variables. These included sex, disease type (ulcerative colitis or CD), smoking, and prior intestinal resection. The sensitivity of QUS to identify patients with significant metabolic bone disease was 74%, and specificity was 63%. A positive predictive value of 81% and negative predictive value of 53% were also less than ideal. The Altman-Bland analysis showed that the agreement between QUS and DXA was poor (-2.0, 2.1). Based on this. analysis, QUS cannot replace DXA in the individual patient with IBD.Conclusions: Calcaneal ultrasound bone densitometry is not a useful tool to screen high-risk patients with IBD for metabolic bone disease.

Common bile duct (CBD) adenomas are rare tumors that often present in a fashion similar to their malignant counterparts. We report a case of a papillary CBD adenoma causing obstructive jaundice. We also present a review of the CBD adenomas found in the English literature through a Medline search (1970-2003). A 74-year-old female presented with a 10-day history of pruritus, progressive painless jaundice, acholic stools, bilirubinuria, and 10-lb weight loss. Abdominal exam showed no masses. Abdominal ultrasound (U/S) showed cholelithiasis without choledocholithiasis. Endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic U/S revealed a shelf-like stricture, 1.5 cm long and 0.9 cm in diameter, located in the distal CBD. At the time of biliary stent placement, fine-needle aspiration showed benign ductal epithelial cells in sheets and clusters. Abdominal CT scan showed a low attenuation 15 x 17 mm lesion in the head of the pancreas that abutted the superior mesenteric vein (SMV) but no metastatic lesions. We performed a standard pancreaticoduodenectomy (Whipple procedure). Final pathology showed a papillary adenoma without evidence of dysplasia in the distal common bile duct proximal to the ampulla of Vater. The incidence of these tumors and their potential for malignant degeneration is unknown. Pancreaticoduodenectomy is an effective means of treatment and cure for CBD adenoma.

Bile leaks occur in up to 27 per cent of liver transplant patients after biliary reconstruction. Synthetic sealants have not been investigated for these biliary procedures. We performed a randomized controlled study to evaluate a novel absorbable polyethylene glycol/collagen bio-polymer sealant (CT3™ Surgical Sealant) after incomplete end-to-end choledochocholedochostomy (CDCD) in pigs. Pigs (n = 18) underwent transection of the common bile duct and incomplete CDCD over a T-tube, leaving a one-sixth circumferential defect anteriorly. Animals were randomly assigned to treatment (CDCD with sealant, n = 9) or control (no sealant, n = 9). Drains were used to monitor leak volume and bilirubin (bili) concentration. Cholangiography was performed on postoperative day 3. Leaks were defined as drain bili/serum bill > 3, total drain output > 10 mL/kg, and/or extravasation on cholangiography. Animals sacrificed at 3 and 8 weeks (n = 4 and n = 5 from each group, respectively) underwent pathologic examination of the CDCD site. Statistical methods included Student's t test, χ2, linear regression, and analysis of variance procedures. The control group had a higher drain output rate over the first 4 postoperative days than the treatment group ( P < 0.05, analysis of variance). Five of nine (56%) control and one of nine (11%) treatment animals had a bile leak ( P < 0.05, χ2). There was no major inflammatory response to the sealant versus controls. We conclude that CT3 is effective in decreasing biliary leaks in an incomplete CDCD porcine model with no major adverse pathologic changes. This sealant should be considered for trials for biliary reconstruction in humans.

BACKGROUND:. The effects of dopamine (DA) on systemic hemodynamics are better understood than its effects on hepatic hemodynamics, especially after liver denervation occurring during liver transplantation. Therefore, a porcine model was used to study DA's effects on hemodynamics after hepatic denervation.MATERIALS AND METHODS:Fifteen pigs underwent laparotomy for catheter and flow probe placement. The experimental group (n = 7) also underwent hepatic denervation. After 1 week, all pigs underwent DA infusion at increasing doses (3-30 mcg/kg/min) while measuring hepatic parameters [portal vein flow (PVF), hepatic artery flow (HAF), total hepatic blood flow (THBF = HAF + PVF), portal and hepatic vein pressures] and systemic parameters [heart rate (HR), mean arterial pressure (MAP)].RESULTS:There was a significant increase in HAF from baseline to the 30 mcg/kg/min DA infusion rate (within-subjects P < 0.01), but the differences between the two groups were not significant. PVF and THBF showed large effects (increases) with denervation, but the increase in flow with DA infusion was not present after denervation. Perihepatic pressures were unchanged by denervation or DA. Heart rate differed significantly between the control and denervated animals at baseline, 3, 6, 12 (all P < 0.05), and 30 mcg/kg/min DA (P = 0.10). Control vs denervation MAP at baseline was 100 +/- 4 vs 98 +/- 4 Torr and at 30 mcg/kg/min it was 110 +/- 3 vs 101 +/- 5 mm Hg.CONCLUSIONS:Hepatic flows tended to be higher after denervation. HAF showed similar increases with DA in both control and denervation groups. Increases in PVF and THBF with DA infusion were not present after denervation. HR was significantly decreased and MAP tended to be lower after denervation. The HR and MAP response to DA was similar in both groups. Therefore, both denervation and DA infusion have an effect on systemic and hepatic hemodynamics.

The accumulation of intracellular calcium ([Ca(2+)](i)) caused by ischemia-reperfusion during liver transplantation has been implicated as a factor leading to primary graft nonfunction. Plasma membrane (PM) and endoplasmic reticulum (ER) Ca(2+)-adenosinetriphosphatases (ATPases) are the primary transporters that maintain [Ca(2+)](i) homeostasis in the liver. We hypothesized that the porcine liver is better than the rat liver as a model for the study of human liver Ca(2+)-ATPase activity. We also hypothesized that cold preservation would depress Ca(2+)-ATPase activity in the porcine liver. Pig and rat livers were harvested, and human liver samples were obtained from surgical resection specimens. All were preserved with University of Wisconsin solution, and porcine livers were also preserved on ice for 2 to 18 hours. Ca(2+)-ATPase activity was measured after incubation with (45)Ca(2+) and adenosine triphosphate in the presence of specific Ca(2+)-ATPase inhibitors. Porcine PM and ER Ca(2+)-ATPase activities were 0.47 +/- 0.03 and 1.57 +/- 0.10 nmol of Ca(2+)/mg of protein/min, respectively. This was not significantly different from human liver, whereas rat liver was significantly greater at 2.60 +/- 0.03 and 9.2 +/- 0.9 nmol of Ca(2+)/mg of protein/min, respectively. We conclude that the Ca(2+)-ATPase activity in the pig liver is equivalent to that of human liver, and thus, the pig liver is a better model than the rat liver. Cold preservation studies showed a significant decrease in porcine hepatic PM Ca(2+)-ATPase activity after 4 hours of storage and near-total inhibition after 12 hours. Porcine hepatic ER Ca(2+)-ATPase activity showed a 45% decrease in activity by 12 hours and a 69% decrease by 18 hours. We conclude that cold ischemia at clinically relevant times depresses PM Ca(2+)-ATPase more than ER Ca(2+)-ATPase activity in pig liver homogenates.

Combined multivisceral transplantation has emerged as a therapeutic option for a select patient cohort; however, clinical decision-making remains complex and controversial. The aim of this study was to examine patient characteristics, operative complications, and long-term outcomes of all patients who have undergone combined heart-lung-liver transplantation (HLLTx) in Australia.In this study, we performed a retrospective analysis of all adult patients who have undergone combined HLLTx in Australia to date. Recipient clinical characteristics, waitlist, and transplant outcomes are described.Eight adult patients have received HLLTx at a single Australian transplant center. Recipients of HLLTx have typically been young (median age, 30.1 years; range, 24-37), underweight (median body mass index, 19.8 kg/m2; range, 16.2-30.4) patients with cystic fibrosis (n = 8, 100%) with severe airflow obstruction (median forced expiratory volume in the first second of expiration, 24% predicted; range, 17%-48%) accompanied by liver cirrhosis confirmed on histopathology (n = 8, 100%). Despite relative preservation of synthetic function and low model for end-stage liver disease scores (median, 8; range, 6-17), all recipients had complications of portal hypertension prior to transplantation, with many patients having suffered life-threatening variceal hemorrhage. In this cohort, HLLTx was associated with overall posttransplant survival of 87.5% at 30 days, 71.4% at 1 year, and 42.9% at 5 years. Listing for combined HLLTx was associated with prolonged waitlist times relative to bilateral sequential single-lung transplantation (median 556 vs 56 days, respectively), however waitlist mortality and/or delisting was comparable between groups.Taken together, these findings highlight the opportunities and challenges facing combined (heart-) lung and liver transplantation in patients with multiorgan failure.

Radical resection (wedge resection of the gallbladder bed and dissection of the hepatoduodenal ligament, portal, and celiac lymph nodes) has been reported to improve survival from pathologic T-2 gallbladder carcinoma (pT(2) GBCa; invasion through the muscularis without perforation of the serosa). We report our experience and the outcome of patients with pT(2) GBCa. Between 1989 and 2000 at Vanderbilt University Medical Center ten patients were found to have pT2 disease after cholecystectomy. The patients had an average age of 64 +/- 13 years and underwent either radical resection (n = 5) or no further surgical therapy (n = 5). Of the patients who underwent cholecystectomy only, one (20%) is still alive at 27 months and four (80%) died of recurrent GBCa between 6.5 and 21 months. For the patients who underwent radical resection all five are alive at 15 to 83 months with no recurrence. The proportion of patients surviving pT2 GBCa after radical resection was significantly greater than with cholecystectomy alone (P < 0.05). The difference in length of survival between the two groups was also significant (P < 0.05). Morbidity after radical resection was low (pancreatic leak in one patient), and there were no operative mortalities. Radical resection significantly improved survival over cholecystectomy alone for patients with pT(2) GBCa. The procedure has low morbidity and mortality rates. Therefore a radical resection operation is indicated for patients with pT(2) GBCa.

In patients with HCC, recurrence was often seen after curative treatment was done because HCC developed from chronic hepatitis or liver cirrhosis with hepatitis B or C infection.Another HCC lesion sometimes developed in the remnant liver.Risk factors for such development of new HCC lesion elsewhere in the liver were investigated in patients in whom complete ablation was achieved without recurrence in the same subsegment as the primary nodule.92 patients with less than 3 HCC nodules smaller than 3 em in diameter were treated by microwave or radiofrequency ablation percutaneously or laparoscopically from April 1996 to June 1999.Diagnosis of HCC was established by needle biopsy of the nodule in 34, otherwise it was confirmed by hepatic arteriography.Recurrence of HCC in the same subsegment as the primary nodule was observed in 8 patients, thus these patients were excluded from this study.84 patients in whom complete necrosis was achieved without recurrence in the same subsegment as the primary nodule were included in this study.12 possible risk factors were analyzed including age, gender, nodule diameter, HCC localization, number of nodules, therapeutic modalities (microwave or radiofrequency), etiology of the underlying liver disease, serum albumin, total bilirubin, prothrombin time, indocyanin green retention rate, enhancement by CT-arteriography and serum alpha-fetoprotein.Comparing the patients with new HCC nodules in the remnant liver to those without the development of new HCC, statistically significant defference was observed in age(>65 or not, p<0.05), serum alpha-fetoprotein (p<0.05),etiology of the underlying liver disease(HCV or other than HCV, p<0.05), the number of initial nodules (p<0.05),enhancement by CT arteriography (positive vs. iso-or negative enhancement, p<0.05).Multivariate stepwise Cox hazard model revealed that etiology of underlying liver disease of hepatitis C virus infection, the number of primary nodules, and positive enhancement by CT arteriography were statistically independent.In conclusion, patients having more than 2 HCC nodules with positive enhancement by CT arteriography and hepatitis C virus infection should be carefully followed because of high incidence of new HCC lesions in the residual liver, even if ablation by microwave or radiofrequency was complete.79