Optimized nerve block techniques while performing percutaneous hepatic ablation: Literature review and practical use.

Percutaneous image guided thermal ablation has become a cornerstone of therapy for patients with oligometastatic disease and primary liver malignancies. Evolving from percutaneous ethanol injection (PEI), thermal ablation utilizing radiofrequency ablation (RFA) and microwave ablation (MWA) have become the standard approach in the treatment of isolated lesions that fit within the size criteria for curative intent therapy (typically 3-4cm). With the evolution of more intense thermal ablation, such as MWA, the dramatic increase in both the size of ablation zone and intensity of heat generation have extended the limits of this technique. As a result of these innovations, intra-procedural and post-procedural pain have also significantly increased, requiring either higher levels of intravenous sedation or, in some institutions, general anesthesia. In addition to the increase in therapeutic intensity, the use of intravenous sedation during aggressive ablation procedures carries the risk of over-sedation when the noxious insult (i.e. the ablation) is removed, adding further difficulty to post-procedural recovery and management. Furthermore, high subdiaphragmatic lesions become challenging in this setting due to issues relating to sedation and compliance with breath hold/breathing instructions. Although general anesthesia may mitigate these complications, the added resources associated with providing general anesthesia during ablation is not cost effective and may result in substantial delays in treatment. The reduction of Aerosol Generating Medical Procedures (AGMP), such as intubation due to the COVID-19 Pandemic, must also be taken into consideration. Due to the potential increased risk of infection transmission, alternatives to general anesthesia should be considered when safe and possible. Upper abdominal regional nerve block techniques have been used to manage pain related to trauma, surgery, and cancer; however, blocks of this nature are not well described in the interventional radiology literature. The McGill University group has developed experience in using such blocks as splanchnic, celiac and hepatic hilar nerve blocks to provide peri-procedural pain control [1]. Since incorporating these techniques (along with hydrodissection with tumescent anesthesia), we have also observed in our high volume ablation center a dramatic decrease in the amount of sedatives administered during the procedure, a decrease in patient discomfort during localization and ablation, as well as decreased pain post-procedure. Faster time to discharge and overall reduction in room procedural time serve as added benefits. The purpose of this publication is to outline and illustrate the practical application and use of nerve block/regional anesthesia techniques with respect to percutaneous hepatic thermal ablation.

Inducible T-cell co-stimulator ligand (ICOSL) blockade leads to selective inhibition of anti-KLH IgG responses in subjects with systemic lupus erythematosus.

OBJECTIVES: To evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of single-dose and multiple-dose administration of AMG 557, a human anti-inducible T cell co-stimulator ligand (ICOSL) monoclonal antibody, in subjects with systemic lupus erythematosus (SLE). METHODS: Patients with mild, stable SLE (n=112) were enrolled in two clinical trials to evaluate the effects of single (1.8-210 mg subcutaneous or 18 mg intravenous) and multiple (6 -210 mg subcutaneous every other week (Q2W)×7) doses of AMG 557. Subjects received two 1 mg intradermal injections 28 days apart of keyhole limpet haemocyanin (KLH), a neoantigen, to assess PD effects of AMG 557. Safety, PK, target occupancy, anti-KLH antibody responses, lymphocyte subset analyses and SLE-associated biomarkers and clinical outcomes were assessed. RESULTS: AMG 557 demonstrated an acceptable safety profile. The PK properties were consistent with an antibody directed against a cell surface target, with non-linear PK observed at lower concentrations and linear PK at higher concentrations. Target occupancy by AMG 557 was dose dependent and reversible, and maximal occupancy was achieved in the setting of this trial. Anti-AMG 557 antibodies were observed, but none were neutralising and without impact on drug levels. A significant reduction in the anti-KLH IgG response was observed with AMG 557 administration without discernible changes in the anti-KLH IgM response or on the overall IgG levels. No discernible changes were seen in lymphocyte subsets or in SLE-related biomarkers and clinical measures. CONCLUSIONS: The selective reduction in anti-KLH IgG demonstrates a PD effect of AMG 557 in subjects with SLE consistent with the biology of the ICOS pathway and supports further studies of AMG 557 as a potential therapeutic for autoimmune diseases. TRIAL REGISTRATION NUMBERS: NCT02391259 and NCT00774943.

A novel disposable, transnasal esophagoscope: a pilot trial of feasibility, safety, and tolerance.

A novel disposable transnasal esophagoscope, the E.G. Scan (IntroMedic Co. Ltd., Seoul, Korea), was developed for the evaluation of esophageal diseases while eliminating the inconvenience associated with sterilization, portability, patient monitoring, complications, and the economic burden of sedation. The feasibility, safety, and tolerability of the first version of the E.G. Scan was evaluated in this pilot study. Nasal esophagoscopy was performed successfully in 46 patients with known or suspected esophageal diseases. At least 50% of the Z-line was visualized by the E.G. Scan in 38 (82.6%) of 46 patients. Abnormalities were identified in 27 patients: erosive esophagitis (n=18), Barrett's esophagus (n=1), esophageal varices (n=7), and esophageal candidiasis (n=1). Nasal pain was absent or mild in most patients, and adverse events were not observed. Further technical improvement of the E.G. Scan would increase the diagnostic usefulness in future clinical practice.

The efficacy of portal vein embolization prior to right extended hemihepatectomy for hilar cholangiocellular carcinoma: a retrospective cohort study.

BACKGROUND/PURPOSE: Preoperative portal vein embolization was introduced to minimize complications after extended hepatectomy. This retrospective cohort study was conducted to compare outcomes with and without portal vein embolization before hepatectomy for hilar cholangiocellular carcinoma. METHODS: This study was conducted with 35 patients who underwent right extended hemihepatectomy for hilar cholangiocellular carcinoma from 2001 to 2008. Preoperative portal vein embolization was performed in 14 patients (embolization group) and not performed in 21 patients (non-embolization group). RESULTS: The groups did not differ in terms of sex, age, operative time, transfusion, postoperative serum bilirubin level, prothrombin time, and length of intensive care unit (ICU) stay. Although blood loss was higher in the embolization group than in the non-embolization group (P = .009), no major complications were observed between embolization and resection. At presentation, future liver remnant was smaller in the embolization group (19.8%, range 16-35%) than in non-embolization group (28.3%, 15-47%; P = .001). After embolization, the volume of the future liver remnant increased significantly to 27.2% (range, 23-42%; P = .001). Future liver remnants just before operation were similar in both groups (P > .99). There was no significant difference in terms of the rate of morbidity and in-hospital mortality. No statistically significant differences were observed in disease-free survival (P = .52) and overall survival (P = .30). CONCLUSIONS: Portal vein embolizations do not increase the rate of morbidity, in-hospital mortality, local recurrence and system metastasis. Therefore it can be considered safe and effective for patients with small future liver remnants. Embolization can lessen postoperative liver failure and widen the indication of the surgical resection, especially in patients with marginal future liver remnants.

Histologic diagnosis based on forceps biopsy is not adequate for determining endoscopic treatment of gastric adenomatous lesions.

BACKGROUND AND STUDY AIMS: Controversy persists around the treatment of gastric low-grade dysplasia (LGD). The aim of this study was to investigate possible indications for the endoscopic resection of gastric LGD through analysis of the histologic discrepancies between specimens of gastric LGD obtained by forceps biopsy and by endoscopic mucosal resection (EMR), and of their clinicopathologic characteristics. PATIENTS AND METHODS: The study involved 293 gastric LGD that were histologically proven on the basis of forceps biopsy in Severance Hospital between January 2004 and December 2007. Twenty cases were regularly followed up, and the remaining 273 were resected by EMR. We performed univariate and multivariate analyses of clinical and endoscopic characteristics including lesion size, number of biopsy fragments, and endoscopic appearance, in order to analyze the factors affecting histologic discrepancies. RESULTS: Of the 273 lesions resected by EMR, 207 (75.8 %) showed concordant histology, whereas for 51 (18.7 %) the histology was upgraded after endoscopic resection. Lesion size, absence of whitish discoloration, and the presence of spontaneous bleeding were found by univariate analysis to be statistically significant factors predicting an upgraded histology after EMR ( P = 0.026, P < 0.001, and P = 0.025, respectively). Multivariate analysis also showed absence of whitish discoloration to be a statistically significant factor influencing histologic discrepancies ( P = 0.001, odds ratio 5.29, 95 % confidence interval 1.95 - 14.37). Perforation and bleeding rates associated with EMR for LGD were 0.7 % and 6.2 %, respectively. Twenty patients who did not undergo EMR were followed up for a mean of 22 months, and 3 were revealed to have adenocarcinoma and 1 high-grade dysplasia on the latest histologic exam. CONCLUSIONS: We should consider endoscopic resection for gastric LGD that are 2 cm or more in size and do not have whitish discoloration.

Mangafodipir trisodium-enhanced MRI of hepatocellular carcinoma: correlation with histological characteristics.

AIM: To define histopathological factors related to the degree of mangafodipir trisodium (MnDPDP) uptake in hepatocellular carcinomas (HCCs) on magnetic resonance imaging (MRI). MATERIALS AND METHODS: In-phase and opposed-phase gradient-echo MRI images were obtained preoperatively in 37 patients with 38 HCCs before and 15-30 min after intravenous injection of MnDPDP. Subjective ratings of the enhancement degree, the signal-to-noise ratio (SNR) of the lesion and the liver, and the contrast enhancement ratios (CER) were compared with histopathological factors. RESULTS: The mean SNR of HCCs increased from 59.6 to 95.0 (CER=59.5%), whereas that of the liver increased from 75.1 to 108.7 (CER=45.2%). Eight HCCs showed mild enhancement, 11 moderate enhancement, and 15 strong enhancement. There was no visually perceptible enhancement in four HCCs (10.3%). The degree of MnDPDP enhancement was significantly related with the cell density ratio (p<.05) and monoclonal hepatocyte antibody positivity (p<0.005), but not with size, growth type, cell type, histological type, cytokeratin 7, or cytokeratin 19. Well-differentiated HCC showed higher MnDPDP enhancement compared with higher grade HCCs, but the differences were not statistically significant. CONCLUSION: The uptake of MnDPDP by HCC was correlated with hepatocyte antibody expression and the cellular density ratio. Well-differentiated HCC tended to show higher MnDPDP enhancement.

Weekly full-dose gemcitabine and single-dose cisplatin with concurrent radiotherapy in patients with locally advanced pancreatic cancer.

The aim of this study was to evaluate the efficacy and the toxicity of a full dose of gemcitabine and a single dose of cisplatin with concurrent radiotherapy in patients with locally advanced pancreatic cancer. Forty-one patients with locally advanced pancreatic cancer were enrolled. Patients received gemcitabine (1000 mg m(-2) on days 1, 8, 15, 29, and 36) and cisplatin (70 mg m(-2) on days 1 and 29) with concurrent radiotherapy (45 Gy in 25 fractions). Treatment was completed in 38 out of 41 patients (92.7%). The overall response rate was 24.4% (two complete and eight partial). Six patients (14.6%) underwent definite pancreatic resection and four had negative surgical margins. The intention of the treatment analysis showed that the median survival time and median time to tumour progression were 16.7 and 8.9 months. The 1- and 2-year survival rates were 63.3 and 27.9%, respectively. Overall survival was significantly longer in the low baseline CA19-9 group and therapeutic responders. Toxicities were tolerable and successfully managed by conservative treatments. The therapeutic scheme of a weekly full dose of gemcitabine and a single dose of cisplatin combined with external radiation is effective and might prolong the survival of patients with locally advanced pancreatic cancer.

Treatment outcomes of 70 cases of early esophageal carcinoma: 12 years of experience.

Early esophageal cancer (EEC) has an excellent prognosis compared to advanced esophageal cancer. Nowadays, endoscopic mucosal resection (EMR) may offer another alternative to cure early cancers of the gastrointestinal tract. We aimed to evaluate the clinical outcomes of EEC in Korea after curative treatments; EMR or surgery. We retrospectively reviewed the medical records of patients diagnosed as EEC from January 1994 to August 2005 at Yonsei University Medical Center, Seoul, Korea. Among 888 patients diagnosed with esophageal cancer, 70 (7.9%) were included as EEC. Among them, 10 patients (14.3%) were treated by EMR, and 50 (71.4%) by operation. The treatment outcomes of EEC in relation to various clinicopathologic factors along with survival rates were analyzed. There were 18 cases (30%) of mucosal lesions and 42 cases (70%) of submucosal lesions. Overall 5-year survival rate was 84.3%. When comparing treatment outcomes between EMR-treated and operated groups, there were no significant differences in complete remission (80%vs. 84%), recurrence (20%vs. 16%) and 5-year survival rate (100%vs. 78.3%). EEC is a potentially curable entity with a good clinical prognosis. EMR can be considered as another treatment arm for EEC, along with surgical resection.

Endoscopic resection of benign tumors of the papilla of vater.

Most benign papillary tumors are adenomas which can potentially undergo the adenoma-carcinoma-sequence making complete removal mandatory for curative therapy. Endoscopic resection (papillectomy) of these lesions is being increasingly performed as a less traumatic alternative to surgery. Available data shows endoscopic papillectomy to be effective and safe in experienced hands with usually little morbidity and virtually no mortality. Success rates are around 80 % for lesions without intraductal involvement. Selected cases of limited distal intraductal involvement accessible after sphincterotomy may also be managed curatively by endoscopic resection. Endoscopic snare resection of entire lesions should be primarily regarded as a diagnostic procedure. It allows for an accurate histological diagnosis based on examination of the entire specimen rather than forceps biopsies and thus a reliable assessment of the need for surgical therapy. Subsequent surgery in operable patients is not precluded by previous endoscopic resection. Surgery is indicated in case of incomplete removal and if malignancy is present. The curative role of endoscopic papillectomy for early invasive carcinoma needs to be established. Histological features and individual risk for surgery are factors to be considered. Inoperable patients may still benefit from palliative endoscopic stenting. After endoscopic papillectomy has been completed, regular follow-up examinations including biopsies are warranted because of the risk of local recurrence. For benign looking papillary tumors, endoscopic papillectomy serves as a diagnostic tool and should be considered as first line procedure regardless of age. The following article details the approach to patients with benign papillary tumor and the technique of endoscopic papillectomy.

The experiences of hilar skeletonization for the treatment of locally advanced proximal bile duct cancer.

BACKGROUND/AIMS: Because proximal bile duct cancer easily involves the surrounding tissue, tumor cells often remain after apparent macroscopically complete radical resection. We evaluated the effect of resective modality of these tumors on prognosis and the effect of postoperative radiotherapy on survival of patients with microscopic residual tumor following local resection in locally advanced proximal bile duct cancer. METHODOLOGY: From November, 1990 to October, 1993, 45 proximal bile duct cancer patients who received local excision were entered onto this prospective, nonrandomized study. The patients were divided into three groups after operation, 16 patients with curative resection; 15 noncurative resection; and 14 nonresection. Patients who had positive lymph nodes or microscopic cancer cells in resection margin or adjacent major vessels, were treated with postoperative external radiotherapy, 5040 cGy for 40 days. RESULTS: The overall 1-, 2-, and 5-year survival of the patients was 62.2%, 24.4%, and 15.6%, respectively. The overall mean and median survival of patients was 24.1 +/- 3.98 (mean +/- SE) months and 13 +/- 0.74 months, respectively. Survival rates between resection and nonresection showed a statistically significant difference (P < 0.05). However, survival rates between curative resection and noncurative resection with postoperative radiotherapy were not statistically significant (P > 0.05). CONCLUSIONS: The resection is the treatment of choice for locally advanced proximal bile duct cancer, if resectable and the noncurative resection followed by postoperative external radiotherapy may be beneficial to the patients with locally advanced proximal bile duct cancer.

Cutting edge: differential sequestration of plasma membrane-associated B cell antigen receptor in mature and immature B cells into glycosphingolipid-enriched domains.

Glycosphingolipid-enriched domains (GEDs) are believed to act as platforms for transduction of B cell Ag receptor (BCR)-induced signals from the cell surface. We sought to study whether differential sequestration of BCR into GEDs may contribute to the described intrinsic signaling differences between mature and immature B cells. In this study we found that mature B cells copolarize the BCR with GEDs following BCR aggregation, whereas transitional immature B cells do not. Although anti-BCR treatment leads to receptor aggregation by immature stage B cells, the aggregated complexes do not colocalize with GEDs. We found this difference to be independent of the isotype of the receptor, thereby associating this difference in BCR-GED colocalization to the developmental stage of the B cell. These findings suggest a structural basis for the developmentally regulated differences observed in Ag receptor-mediated signal transduction.

Loss of pendimethalin in runoff and leaching from turfgrass land under simulated rainfall.

A field study was undertaken to investigate runoff and leaching loss of the herbicide pendimethalin in turfgrass land of loamy sand soil. A series of plots constructed in a golf course fairway were surface-applied with pendimethalin SC formulation at the rate of 2. 25 or 4.50 kg a.i./ha and subjected to simulated rainfall at 2.0 cm/day for 10 consecutive days. Runoff losses of pendimethalin were the highest at the first rainfall and then gradually decreased with time. The first runoff event contained pendimethalin in its highest concentration, and in subsequent runoff samples the concentration decreased exponentially. The ranges of pendimethalin concentration were 80.9-18.2 and 177.4-48.6 microgram/L in the standard and double doses, respectively. Total losses by 20 cm of rainfall for 10 days reached 0.81 and 1.22% of the initial deposits at 2.25 and 4.50 kg a. i./ha, respectively. Pendimethalin concentration in the leachate collected at 30-cm soil depth was quite lower than that in the runoff, and the concentration rapidly decreased from 4.3-4.7 to 0. 2-0.4 microgram/L during the 10 days of rainfall treatment. Soil residue analysis at 45 and 90 days after pendimethalin treatment showed that more than 90% of the residue remained at the top 10 cm of soil depth. Low runoff and leaching confirmed that lateral and downward movement of the herbicide should be limited in turf soil. The half-life of pendimethalin under field conditions was 23-30 days and was not affected by application dose and rainfall treatment, but longer persistence was observed under laboratory conditions. Considering low runoff and leaching, as well as relatively short persistence in soil, it is concluded that little environmental carryover of pendimethalin would be expected in turfgrass land.

A case of minute intraductal papillary mucinous tumor of the pancreas presenting with recurrent acute pancreatitis.

Intraductal papillary mucinous tumor (IPMT) of the pancreas, a lesion consisting of mucin-producing cells with neoplastic potential, is characterized by duct ectasia, mucin hypersecretion, often extensive papillary intraductal growth, varying degrees of cytologic atypia, and relatively indolent growth. The clinical presentation of IPMT of the pancreas is characterized by chronic or recurrent attacks of abdominal discomfort often in association with low level pancreatic enzyme elevations. Less commonly these lesions may be detected as asymptomatic radiographic abnormalities. Interestingly, a case of a minute IPMT (2 mm in height and 7 mm in length, adenoma) in the main pancreatic duct presenting with acute pancreatitis in a 55 year-old man has been reported in the Japanese literature. Recently, we also experienced a case of a minute IPMT in a branch pancreatic duct causing repeated bouts of acute pancreatitis in a 75 year-old man. A filling defect at the neck of the main pancreatic duct seen on an endoscopic retrograde pancreatogram performed after recovery of the second attack of acute pancreatitis led the patient to undergo an exploratory laparotomy. After a near-total pancreatectomy was carried out, a minute (3 x 7 mm) IPMT of borderline malignancy was discovered in a branch duct at the head portion near the pancreatic neck without any lesions in the main pancreatic duct. Surprisingly, despite the resective surgery the patient died of carcinomatosis 8.5 months after the operation. We herein report a case of a minute but aggressive IPMT of the pancreas with a review of the literature.

Cost-effectiveness of prophylaxis against Pneumocystis carinii pneumonia in patients with Wegner's granulomatosis undergoing immunosuppressive therapy.

OBJECTIVE: To assess the incremental cost-effectiveness of 3 Pneumocystis carinii pneumonia (PCP) prophylaxis strategies in patients with Wegener's granulomatosis (WG) receiving immunosuppressive therapies: 1) no prophylaxis; 2) trimethoprim/sulfamethoxazole (TMP/SMX) 160 mg/800 mg 3 times a week, which is discontinued if patients experience an adverse drug reaction (ADR); and 3) TMP/SMX 160 mg/800 mg 3 times a week, which is replaced by monthly aerosolized pentamidine (300 mg) if patients experience an ADR. METHODS: A Markov state-transition model was developed to follow a hypothetical cohort of WG patients over their lifetimes starting from the time of initial exposure to the immunosuppressive therapy. The effect of PCP prophylaxis on life expectancy, quality-adjusted life expectancy, average discounted lifetime cost (ADLC), and incremental cost-effectiveness was estimated based on data obtained from a literature review. Direct medical costs were examined from a societal perspective, and costs and benefits were discounted at 3% annually. RESULTS: No prophylaxis resulted in a life expectancy of 13.36 quality-adjusted life years (QALY) at an ADLC of $4,538. In comparison, prophylaxis with TMP/ SMX alone increased the QALY to 13.54 and was cost saving, with an ADLC of $3,304. The addition of pentamidine in patients who had an ADR to TMP/SMX resulted in 13.61 QALY, with an ADLC of $7,428. Compared with TMP/SMX alone, TMP/SMX followed by pentamidine increased the QALY by 0.07 at an incremental cost of $58,037 per QALY. Both TMP/SMX alone and TMP/SMX followed by pentamidine prophylaxis strategies dominated the no prophylaxis strategy until the incidence of PCP fell below 0.2% and 2.25%, respectively. Institution of pentamidine therapy for patients with a TMP/SMX ADR increased quality-adjusted life expectancy compared with that with TMP/ SMX alone until the incidence of PCP rose above 7.5%. CONCLUSION: Prophylaxis using TMP/SMX alone increased life expectancy and reduced cost for patients with WG receiving immunosuppressive therapy. Replacing TMP/SMX with monthly aerosolized pentamidine in cases of ADR further increased life expectancy, although at an increased cost.

Endoscopic snare resection for tumors of the ampulla of Vater.

Though surgical resection has been the traditional treatment for tumors of the ampulla of Vater, endoscopic maneuvers such as snare resection, laser photodestruction and electrofulguration have recently been introduced to avoid operation-related morbidity and mortality. From 1994 to 1996, 6 patients with ampullary tumor were managed by endoscopic snare resection and regularly followed. Endoscopic snare resection of the ampullary tumor was technically feasible in all patients and each procedure was performed in a single session. Histologic diagnoses of the resected specimens were adenoma in 4 patients and adenoma with coexistent adenocarcinoma in 2 patients. Resection margins were negative in all patients except 1 with coexistent adenocarcinoma and a radical pancreaticoduodenectomy was performed in that case. For the other patient with adenocarcinoma foci, no further treatment was persued since he was 72-year-old and refused operation. Acute pancreatitis developed in 2 patients after endoscopic therapy, but was resolved with conservative management. There was no procedure-related death. Surveillance duodenoscopy performed at 1 and 6 months after endoscopic resection revealed no evidence of recurrent tumor in 4 patients with adenoma. Among them, 3 patients are alive without evidence of recurrence at 16-37 months after resection, but 1 patient was lost after 9 months of follow-up. The patient with adenocarcinoma in whom a pancreaticoduodenectomy was performed, has been alive without recurrence for 12 months. Oral 5-fluorouracil was administered for the other patient with adenocarcinoma foci. Though he experienced local recurrence at 13 months after the procedure, he has been alive for 28 months after resection. In conclusion, endoscopic snare resection may be applied as a viable alternative to surgery in selected patients with small ampullary tumors.

Tissue plasminogen activator and plasminogen activator inhibitor-1 in human choledochal bile.

Fibrinolytic properties have been detected in animal and human gallbladder (GB) bile. Plasminogen activator inhibitor-1 (PAI-1) has been reported in greater concentration in GB stone bile and may be a nucleating factor in the pathogenesis of GB stone formation. It is unknown whether or not human choledochal bile has similar properties, which could have a role in choledocholithiasis. The aims of this study were to determine the presence of fibrinolytic properties of human choledochal bile and to compare those properties among normal, acalculous, and calculous-infected choledochal bile. Tissue plasminogen activator (t-PA) and PAI-1 of choledochal bile were measured by enzyme linked immunosorbent assay in patients with cholangitis due to acalculous bile duct obstructions (n = 9), choledocholithiasis with cholangitis (n = 20), and normal bile (n = 7). The t-PA concentration of choledochal bile was no different among the three groups (acalculous-infected bile, median 4.61 ng/ml, and calculous-infected bile, 4.61 ng/ml, versus normal bile, 7.33 ng/ml). PAI-1 was detected in choledochal bile in significantly greater concentrations in patients with acalculous cholangitis due to bile duct obstructions and choledocholithiasis with cholangitis (acalculous-infected bile, median 0.36 ng/ml, and calculous-infected bile, 0.1 ng/ml, versus normal bile, 0.02 ng/ml, p < 0.05), but the bile concentration of PAI-1 was no different between the acalculous and calculous-infected choledochal bile. Human choledochal bile possesses t-PA and PAI-1. PAI-1 was present in greater concentrations in both acalculous and calculous-infected choledochal bile. Increased levels of PAI-1 may be an epiphenomenon of cholangitis rather than a factor in the pathogenesis of choledocholithiasis.