Infection among adult small bowel and multivisceral transplant recipients in the 30-day postoperative period.

BACKGROUND: Intestinal transplantation is a potential option for patients with short gut syndrome (SGS), and infection is common in the postoperative period. The aim of our study was to identify the incidence and characteristics of bacterial and fungal infections of adult small bowel or multivisceral (SB/MV) transplantation recipients in the 30-day postoperative period. METHODS: This retrospective chart review assessed the incidence and characteristics of bacterial and fungal infections in patients who underwent SB/MV transplant at our center between April 2004 and November 2008. Patient data were retrieved from computerized databases, flow-charts, and medical records. RESULTS: A total of 40 adult patients with a mean age of 38.7 ± 13.4 years received transplants during this period: 27 patients received isolated SB, 12 received MV, and 1 received SB and kidney. Our immunosuppressive regimen included basiliximab for induction, and tacrolimus, sirolimus, and methylprednisolone for maintenance therapy. The most common indications for transplant were SGS, intestinal ischemia, Crohn's disease, trauma, motility disorders, and Gardner's syndrome. We report a 30-day postoperative infection rate of 57.5% and mean time to first infection of 10.78 ± 8.99 days. A total of 36 infections were documented in 23 patients. Of patients who developed infections, 56.5% developed 1 infection, 30.4% developed 2 infections, and 13% developed 3 infections. The most common site of infection was the abdomen, followed by blood, urine, lung, and wound infection. The isolates were gram-negative bacteria in 49.3%, gram-positive bacteria in 39.4%, and 11.3% were fungi. The most common organisms were Pseudomonas (19%), Enterococcus (15%), and Escherichia coli (13%). Overall, 47% of infections were due to drug-resistant pathogens; 31% of E. coli and Klebsiella species were extended-spectrum beta-lactamase-producing organisms, 36% of Pseudomonas was multidrug resistant (MDR), 75% of Enterococcus was vancomycin resistant, and 100% of Staphylococcus aureus was methicillin resistant. CONCLUSION: These findings demonstrate that bacterial and fungal infections remain an important complication in SB/MV transplant recipients within the early postoperative period. Infections due to MDR organisms have emerged as an important clinical problem in this patient population.

Abnormal CX3CR1⁺ lamina propria myeloid cells from intestinal transplant recipients with NOD2 mutations.

Although progress has been made in intestinal transplantation, chronic inflammation remains a challenge. We have reported that the risk of immunological graft loss is almost 100-fold greater in recipients who carry any of the prevalent NOD2 polymorphisms associated with Crohn's disease, and have shown that the normal levels of a key antimicrobial peptide produced by the Paneth cells of the allograft, fall as the graft becomes repopulated by hematopoietic cells of the NOD2 mutant recipient. These studies are extended in this report. Within several months following engraftment into a NOD2 mutant recipient the allograft loses its capacity to prevent adherence of lumenal microbes. Despite the significantly increased expression of CX3CL1, a stress protein produced by the injured enterocyte, NOD2 mutant CX3CR1(+) myeloid cells within the lamina propria fail to exhibit the characteristic morphological phenotype, and fail to express key genes required expressed by NOD2 wild-type cells, including Wnt 5a. We propose that the CX3CR1(+) myeloid cell within the lamina propria supports normal Paneth cell function through expression of Wnt 5a, and that this function is impaired in the setting of intestinal transplantation into a NOD2 mutant recipient. The therapeutic value of Wnt 5a administration in this setting is proposed.

Metabolomics of human intestinal transplant rejection.

Surveillance endoscopy with biopsy is the standard method to monitor intestinal transplant recipients but it is invasive, costly and prone to sampling error. Early noninvasive biomarkers of intestinal rejection are needed. In this pilot study we applied metabolomics to characterize the metabolomic profile of intestinal allograft rejection. Fifty-six samples of ileostomy fluid or stool from 11 rejection and 45 nonrejection episodes were analyzed by ultraperformance liquid chromatography in conjunction with Quadrupole time-of-flight mass spectrometry (UPLC-QTOFMS). The data were acquired in duplicate for each sample in positive ionization mode and preprocessed using XCMS (Scripps) followed by multivariate data analysis. We detected a total of 2541 metabolites in the positive ionization mode (mass 50-850 Daltons). A significant interclass separation was found between rejection and nonrejection. The proinflammatory mediator leukotriene E4 was the metabolite with the highest fold change in the rejection group compared to nonrejection. Water-soluble vitamins B2, B5, B6, and taurocholate were also detected with high fold change in rejection. The metabolomic profile of rejection was more heterogeneous than nonrejection. Although larger studies are needed, metabolomics appears to be a promising tool to characterize the pathophysiologic mechanisms involved in intestinal allograft rejection and potentially to identify noninvasive biomarkers.

Successful isolated intestinal transplantation in sensitized recipients with the use of virtual crossmatching.

We evaluated virtual crossmatching (VXM) for organ allocation and immunologic risk reduction in sensitized isolated intestinal transplantation recipients. All isolated intestine transplants performed at our institution from 2008 to 2011 were included in this study. Allograft allocation in sensitized recipients was based on the results of a VXM, in which the donor-specific antibody (DSA) was prospectively evaluated with the use of single-antigen assays. A total of 42 isolated intestine transplants (13 pediatric and 29 adult) were performed during this time period, with a median follow-up of 20 months (6-40 months). A sensitized (PRA ≥ 20%) group (n = 15) was compared to a control (PRA < 20%) group (n = 27) to evaluate the efficacy of VXM. With the use of VXM, 80% (12/15) of the sensitized patients were transplanted with a negative or weakly positive flow-cytometry crossmatch and 86.7% (13/15) with zero or only low-titer (≤ 1:16) DSA. Outcomes were comparable between sensitized and control recipients, including 1-year freedom from rejection (53.3% and 66.7% respectively, p = 0.367), 1-year patient survival (73.3% and 88.9% respectively, p = 0.197) and 1-year graft survival (66.7% and 85.2% respectively, p = 0.167). In conclusion, a VXM strategy to optimize organ allocation enables sensitized patients to successfully undergo isolated intestinal transplantation with acceptable short-term outcomes.

Complex arterial reconstruction in multivisceral transplantation.

We report the case of a successful multivisceral transplant in which both donor and recipient presented aberrant anatomy of the celiac-mesenteric axis requiring five separate arterial anastomoses to reconstruct the blood inflow to the graft.

Long term outcomes of abdominal wall reconstruction using open component separation and biologic mesh in the liver, kidney, and small bowel transplant population.

PURPOSE: The aim of this study is to critically examine the multidisciplinary approach to abdominal wall reconstruction (AWR) in the solid organ transplant (SOT) population at our institution, MedStar Georgetown University Hospital, using a modified component separation technique (CST). METHODS: A retrospective review of AWR utilizing modified open CST with biologic mesh in SOT patients was performed from January 2010 to June 2018. Patient demographics, comorbidities, operative details, complications, and outcomes were recorded. Descriptive statistics, logistic and linear regression analyses were performed to appraise outcomes. RESULTS: Thirty-five patients were included; mean age was 53 years. Patient demographics and comorbidities were: 82.9% male, 45.7% history of tobacco use, and 28.6% diabetes. Fifty-one percent had undergone prior hernia repair. Transplant types were: kidney (9), liver (16), liver/kidney (1), small bowel (7), multivisceral (2). All were on an immunosuppressive regimen at time of surgery; 22.9% included steroids. Average defect size was 361 cm2. Additional soft tissue procedures were performed in 65.7% (n = 23) of patients. Median time to healing was 29.0 days. Complication rate was 31.4% (n = 11); six patients required reoperation within 90 days. Recurrence rate was 5.7% (n = 2) at mean of follow up of 3.0 years. Additional soft tissue procedures were statistically significant for healing time (p = 0.037). Steroid use was statistically significant for reoperation within 90 days (OR = 12.500; 95% CI 1.694-92.250); however, steroid use was not significant after correction for confounders. CONCLUSION: Modified open CST with biologic mesh is a safe, efficacious approach to complex AWR in the SOT population with recurrence rates comparable to the general population.

Rejection reversibly alters enteroendocrine cell renewal in the transplanted small intestine.

Acute small intestinal allograft rejection presents clinically as an abrupt increase in ileal fluid output in the absence of extensive inflammation. We questioned whether acute intestinal rejection might be accompanied by a disturbance of normal intestinal stem cell differentiation. We examined the intestinal epithelial secretory cell lineage among patients experiencing early rejection before and during rejection as well as following corrective therapy. Lineage-specific progenitors were identified by their expression of stage-specific transcription factors. Progenitors of the enteroendocrine cell (EEC) expressing neurogenin-3 (NEUROG3) were found to be disproportionately reduced in numbers, along with their more mature EEC derivatives expressing neuro D; the enteric hormone PYY was the most profoundly depleted of all the EEC products evaluated. No change in the numbers of goblet or Paneth cells was observed. Steroid treatment resulted in resolution of clinical symptoms, restoration of normal patterns of EEC differentiation and recovery of normal levels of enteric hormones. Acute intestinal rejection is associated with a loss of certain subtypes of EEC, most profoundly, those expressing PYY. Deficiency of the mature EECs appears to occur as a consequence of a mechanism that depletes NEUROG3 EEC progenitors. Our study highlights the dynamics of the EEC lineage during acute intestinal rejection.

Nonhemolytic passenger lymphocyte syndrome: donor-derived anti-M in an M+ recipient of a multiorgan transplant.

Passenger lymphocyte syndrome (PLS) is a well-recognized complication that may follow a hematopoietic progenitor cell or solid-organ transplant. Typically, the syndrome presents as acute hemolysis of the recipient's RBCs, which have become serologically incompatible with blood group antibodies formed by passively transfused donor-origin B lymphocytes. Most cases involve anti-A or anti-B. However, there are cases involving non-ABO serologic incompatibility, as well as cases in which the serologic incompatibility was not associated with clinical evidence of hemolysis. This report describes a case of passenger lymphocyte syndrome in an M+ recipient who developed anti-M after receiving a multiorgan transplant from an M- cadaver donor. Although the temporal events and serologic findings were consistent with a diagnosis of PLS, there was no evidence of in vivo hemolysis associated with the identification of a newly formed anti-M. This report includes a literature review of other case reports of PLS associated with non-ABO antibodies in solid-organ and hematopoietic progenitor cell transplant recipients.

Unusual Cystic Fibrosis Transmembrane Conductance Regulator Mutations and Liver Disease: A Case Series and Review of the Literature.

Cystic fibrosis (CF) is caused by a mutation in the CF transmembrane conductance regulator (CFTR) gene, deranging the activity of chloride channels on the epithelial cell surface. Herein we describe end-stage liver disease in 3 infants with rare CFTR gene mutations; 2 of them were heterozygous. Case 1 was a premature male infant with negative CF screening at birth who developed a small bowel obstruction in the neonatal period requiring an ileostomy, with subsequent cholestatic liver disease and portal hypertension. In addition, he was noted to have frequent respiratory infections prompting a sweat test, which was positive. Genetic testing revealed that he was heterozygous for P.1177F. He then underwent a successful liver transplant. Case 2 was a female infant who developed progressive cholestasis with poor weight gain and was found to have neonatal hepatitis on liver biopsy. A sweat test was negative and genetic testing revealed she was heterozygous for CFTR and PEX26 gene mutations. She subsequently developed pneumatosis involving the cecum that was treated conservatively, followed by a successful liver transplant. Case 3 was a male infant who developed progressive liver disease, with liver biopsy showing neonatal hepatitis. He was extensively investigated but had a negative sweat test on repeated studies. Genetic testing revealed that the patient was heterozygous P.K186N-variant in the AKRID1 gene and homozygous P.R75Q-variant in the CFTR gene. Unfortunately, he succumbed to an acute upper gastrointestinal hemorrhage. Rare and unusual CFTR mutations, even in the heterozygous form, may be a feature in otherwise undiagnosed end-stage liver disease of infancy.

Impact of positive preoperative surveillance blood cultures from chronic indwelling catheters in cadaveric intestinal transplant recipients.

Recurrent bloodstream infections are a common indication for intestinal transplantation (ITx). Often, clinical symptoms may be absent in the setting of bacteremia, especially in patients with chronic liver disease. This study investigated the incidence and impact of positive blood cultures (BCx) obtained from central venous catheters used for total parenteral nutrition (TPN) in asymptomatic patients immediately prior to cadaveric ITx. Of 13 consecutive patients transplanted between November 2003 and November 2004, 12 underwent preoperative surveillance BCx with four positives (33%). Isolates included Staphylococcus epidermidis (n = 2), methicillin-resistant Staphylococcus aureus, and Citrobacter freundii. All four patients with positive BCx displayed liver dysfunction at the time of transplant (> or = grade 2 fibrosis, total bilirubin >8.0 g/dL), three of whom were inpatients. In contrast, only three of eight nonbacteremic patients showed liver disease of comparable severity. Liver dysfunction and inpatient status at the time of transplant appear to predict positive blood cultures. Postoperative length of stay and time on the ventilator were significantly longer among bacteremic as compared with nonbacteremic patients, but there were no differences in intraoperative blood use, time to total parenteral nutrition independence, or operative time between bacteremic and nonbacteremic patients. Our study showed that occult bacteremia in asymptomatic pre-intestinal transplant patients was not uncommon and may increase postoperative morbidity. Preemptive removal of long-term central venous catheters should be considered prior to ITx.

Multi-Visceral Transplantation in a 21-Year-Old Man with Prior Pancreatoblastoma.

Organ transplantation in patients with prior malignancy increases the risk of tumor recurrence post-transplantation due to immunosuppression. Only two cases of liver transplantation have so far been reported in children with hepatic metastases from pancreatoblastoma, a rare malignant neoplasm originating from the epithelial exocrine cells of the pancreas. Herein, we describe a case of a successful multi-visceral transplant in a man with intestinal failure after surgical resection of pancreatoblastoma.

Hospital Readmissions After Intestinal and Multivisceral Transplantation.

BACKGROUND: Intestinal transplant recipients require frequent hospital readmission after a successful transplantation, but the reasons for readmission have not been characterized in detail. METHODS: We reviewed our single-center experience to characterize the patterns of readmissions and to identify preventable causes. Among 87 adult patients who received an intestinal or multivisceral transplant, 65 patients (35 males, 30 females; median age, 42 years [range, 19-66]) with a follow-up of at least 1 year were included in this study. Readmissions were defined as any unplanned inpatient hospital stay of 24 hours or longer occurring within 1 year after discharge from the transplantation admission and were classified as early (<1 month) and late (months 2-12) readmissions. RESULTS: Forty-four (68%) patients required early, and 59 (91%) patients required late readmission. A total of 333 readmissions (median, 4 readmissions/patient [0-20]) occurred within the first year post-transplantation; 69 were early (21%) and 264 were late (79%), resulting in a total of 4089 days of hospital stay (median, 7 days/readmission [2-136]). The three most frequent causes of readmission were dehydration, infection, and surgical complications. CONCLUSIONS: These findings suggest that the rate of hospital readmission after intestinal transplantation could potentially be reduced by optimizing fluid balance and hydration status after discharge.

Developments in immunotherapy for gastrointestinal cancer.

Gastrointestinal (GI) cancers are the most commonly occurring cancer worldwide. Colorectal cancer (CRC) is the second and third most commonly diagnosed cancer in women and men, respectively. Despite the advent of screening and the declining incidence of CRC overall, most patients are not diagnosed at an early, localized stage. Due to resistance to chemotherapy, recurrence, and metastatic disease, those diagnosed with advanced disease have only a 12% 5-year survival rate. Given the overwhelming global impact of CRC, the need for advanced therapy is crucial. Targeted immunotherapy in addition to surgical resection, traditional chemotherapy, and radiation therapy is on the rise. For the purpose of this review, we focused on the advances of immunotherapy, particularly in CRC, with mention of research pertaining to particular advances in immunotherapy for other aspects of the GI system. We review basic immunology and the microenvironment surrounding colorectal tumors that lead to immune system evasion and poor responses to chemotherapy. We also examined the way these obstacles are proving to be the targets of tumor specific immunotherapy. We will present current FDA approved immunotherapies such as monoclonal antibodies (mAb) targeting tumor specific antigens, as well as vaccines, adoptive cell therapy, cytokines, and check-point inhibitors. A summation of prior research, current clinical trials, and prospective therapies in murine models help delineate our current status and future strategies on CRC immunotherapy.

National sharing of cadaveric isolated intestinal allografts for human transplantation: a feasibility study.

UNLABELLED: Most isolated intestinal graft losses are immunological. We conducted a pilot study to evaluate the feasibility of national sharing of HLA no-mismatch allografts for cadaveric isolated intestinal transplantation. METHODS: UNOS data were analyzed in a theoretical model. Part I: All solid organ donors between 1/95-8/97 who would have met criteria for bowel donation were considered potential donors for all recipients who actually received isolated intestinal transplants during this period. We then determined how many donor intestines could have been directed to no-mismatch candidates had national sharing been in place. Donor exclusion criteria were CMV+ donors to CMV- recipients, hemodynamic instability, age >50, size mismatch (donor weight greater than recipient), and obesity. Mean and median waits for transplants, as well as theoretical mean and median waits for transplants that would have occurred given national sharing, were calculated. Part II: We estimated, based on registry graft survival data, the number of intestinal transplants necessary to demonstrate a no-mismatch graft survival advantage at 2 years. RESULTS: Part I: Although no actual cadaveric no-mismatch transplant was performed, 12-17% of patients could have received no-mismatch allografts had sharing been in place, using various donor acceptance criteria. The impact on waiting time was variable. Part II: Accepting a 15% rate of no-mismatch cases and a survival advantage of 10% at 2 years, 793 transplants would be required to prove an advantage to HLA matching at P<0.05. If the graft survival advantage were 20% at 2 years, the time to show significance would be approximately 5 years. Using early acute rejection as an endpoint could require fewer transplants (93), and only a few years to complete the study. CONCLUSIONS: National sharing of cadaveric isolated intestinal allografts is feasible. Median waits would not be significantly increased. The time necessary to prove graft survival advantage would be considerable, but a difference in the rate of acute rejection could be seen within 2 years. Additionally, a national sharing arrangement might improve the overall outcome of isolated intestinal transplantation.

Use of livers with microvesicular fat safely expands the donor pool.

BACKGROUND: The safety of transplanting livers with moderate to severe microvesicular steatosis is unknown. Livers that appear fatty are often abandoned at the donor hospital. We have recently used frozen-section biopsy to distinguish between microvesicular and macrovesicular steatosis. We present here our single-center experience with transplantation of 40 allografts with moderate or severe microvesicular steatosis. METHODS: We reviewed our data on 426 transplants and identified 40 cases in which the donor liver contained at least 30% microvesicular steatosis. Early graft function, patient and graft survival, and donor risk factors for steatosis were examined, and results in this cohort were compared with results in all other patients who received liver transplants at our center during the same time period. We also analyzed the reliability of donor frozen-section biopsies in quantitating microsteatosis. Persistence of steatosis was assessed on the basis of 1-year follow-up biopsies. RESULTS: The incidence of primary nonfunction and poor early graft function was 5% and 10%, respectively. One-year patient and graft survival rates were 80% and 72.5%, respectively. Donor obesity and traumatic death were commonly identified risk factors for microvesicular steatosis. Frozen-section biopsy was reliable for pretransplant decision-making about the use of potential grafts, and the steatosis had disappeared from the graft at 1 year in the majority of cases. CONCLUSIONS: Livers with even severe microvesicular steatosis can be reliably used for transplantation without the fear of high rates of primary nonfunction. There was a significant incidence of poor early graft function, but this did not affect outcome. Microsteatosis is usually associated with some underlying risk factor in the donor and is reversible, as demonstrated by follow-up biopsies after transplant.

Safe transplantation of blood type A2 livers to blood type O recipients.

BACKGROUND: Transplantation of blood type A subgroup 2 (A2) livers into non-A recipients has not been reported previously. A2 to O renal transplantation has been reported, with early results including some accelerated rejections and graft losses. This has led some to selectively offer A2 renal transplantation only for patients with low anti-A titers. Given the different clinical behavior of liver allografts to preformed antibody, we felt that such restriction was unnecessary. METHODS: We performed six cases of A2 to O liver transplantation with no augmented immunomodulation or restriction with regard to antibody titers. Clinical courses, anti-A titers, rejection rates, and graft and patient survival were evaluated. RESULTS: All six patients had high pretransplant anti-A titers (>1:8), and all six grafts functioned normally. There were nine rejections in the six patients, of which three were severe (steroid-resistant) and five were late (>90 days). No rejection was vascular, and no grafts were lost, with mean follow-up of 665 days. In one patient who had anti-A antibody measured at the time of rejection IGM titers increased from baseline. Currently all patients are home with normal function. CONCLUSIONS: We found that transplantation of blood group A2 livers into blood group O recipients is safe and can be performed without graft loss and without regard to anti-A titer level. The rate of acute cellular rejection is high in this small series, and a significant proportion of these events were late or required OKT-3. We did not rely on plasmapheresis or anti-A titer determinations. However, the potential for late rejection prompts us to consider the addition of a third immunosuppressive agent. The transplantation of A2 livers into O recipients can partially compensate for the more frequent use of O livers in recipients from other blood groups.

Unsuspected bile duct paucity in donors for living-related liver transplantation: two case reports.

Alagille's syndrome is a common cause of liver disease in children and may lead to the need for orthotopic liver transplantation. Alagille's syndrome is inherited in an autosomal dominant manner, with variable penetration, and may also be present in patients' parents, who may be considered potential donors for living-related transplantation. We report here on two cases in which the living-related donors for children with Alagille's syndrome had no liver function abnormalities or characteristic features of Alagille's syndrome. In both cases, the operation for living-related donation had to be aborted because of a paucity of bile ducts discovered intraoperatively. Given the variable presentation of Alagille's syndrome, we believe that it is necessary preoperatively to evaluate the biliary system of family members who are potential living-related donors for patients with this condition.

Long-term medical complications in patients surviving > or = 5 years after liver transplant.

BACKGROUND: Short-term outcomes of liver transplantation are well reported. Little is known, however, about long-term results in liver recipients surviving > or =5 years. We sought to analyze long-term complications in liver recipients surviving > or =5 years after transplant, to assess their medical condition and to compare findings to the general population. METHODS: We analyzed the chart and database records of all patients (n=139) who underwent liver transplantation at a major transplant center before January 1, 1991. Outcome measures included the presence of diabetes, hypertension, heart, renal or neurological disease, osteoporosis, incidence of de novo malignancy or fracture, or other pathology, body mass index, serum cholesterol and glucose, liver function, blood pressure, frequency of laboratory and clinic follow-up, current pharmacological regimen, and late rejection episodes. RESULTS: Ninety-six patients (70%) survived > or =5 years. Compared to numbers expected based on U.S. population rates, transplant recipients had significantly higher overall prevalences of hypertension (standardized prevalence ratio [SPR]=3.07, 95% confidence interval [CI], 2.35-3.93) and diabetes (SPR=5.99, 95% CI, 4.15-8.38), and higher incidences of de novo malignancy (standardized incidence ratio [SIR]=3.94, 95% CI, 2.09-6.73), non-Hodgkin's lymphoma (SIR=28.56, 95% CI, 7.68-73.11), non-melanoma skin cancer (estimated SIR> or =3.16) and fractures in women (SIR=2.05, 95% CI, 1.12-3.43). Forty-one of 87 (47.1%) patients were obese, and 23 patients (27.4%) had elevated serum cholesterol levels (> or =240 mg/dl, 6.22 mmol/L), compared to 33% and 19.5% of U.S. adults, respectively. Prevalences of heart or peptic ulcer disease were not significantly higher. CONCLUSIONS: Liver transplantation is being performed with excellent 5-year survival. Significant comorbidities exist, however, which appear to be related to long-term immunosuppression.

Aggressive surgical treatment of intrahepatic cholangiocarcinoma: predictors of outcomes.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver cancer and constitutes 10% of primary liver malignancies. Surgery is the optimal therapy; the majority of the patients will require extensive resections that are associated with significant morbidity. METHODS: We retrospectively studied the records of 26 patients who underwent exploratory laparotomy for intrahepatic cholangiocarcinoma between June 1991 and December 1997 at the Mount Sinai Hospital. Patients with perihilar (Klatskin) tumors were excluded. All patients were considered resectable based on CT or MRI findings. Patients with positive margins or nodal invasion received adjuvant chemotherapy and radiation. RESULTS: Sixteen patients underwent 18 resections; in 10 patients the tumors were unresectable at laparotomy and only biopsy was performed. The mean age (62 versus 53 years) was significantly higher, and the mean total bilirubin level (0.71 versus 6.17 mg/dL) was significantly lower in the resected group (p=0.031 and 0.017, respectively). No patient with a total bilirubin over 1.2 mg/dL was found to be resectable. Median actuarial survivals were 42.9+/-8.9 months for resectable and 6.7+/-3.6 months for unresectable patients (p=0.005). Positive margins were associated with significantly shorter disease-free survival. But resected patients with positive margins survived significantly longer than those who were unresectable. Tumor size, presence of satellite nodules, and degree of tumor necrosis on histologic examination were significant predictors of outcomes. Survival among patients receiving adjuvant therapy was not significantly altered. CONCLUSIONS: We conclude that an aggressive surgical approach is warranted in patients with ICC because resection offers the only hope for longterm survival. Our findings emphasize the importance of achieving tumor-free margins. Noncurative resection offers a survival advantage over no resection. Histologic examination of resected specimens can help select patients with poor prognoses.