Increased incidence of indeterminate pancreatic cysts and changes of management pattern: Evidence from nationwide data.

BACKGROUND: Pancreatic cysts are common. However, most studies are based on data collected from individual centers. The present study aimed to evaluate the changes of management patterns for pancreatic cystic lesions (PCLs) by analyzing large epidemiologic data. METHODS: Between January 2007 and December 2018, information regarding pancreatic cystic lesions was acquired from the nationwide Health Insurance Review and Assessment Service database in Korea. RESULTS: The final number of patients with pancreatic cysts was 165 277 among the total claims for reimbursement of 855 983 associated with PCLs over 12 years. The total number of claims were increased from 19 453 in 2007 to 155 842 in 2018 and the prevalence increased from 0.04% to 0.23%. For 12 years, 2874 (1.7%) had pancreatic cancer and 8212 (5.0%) underwent surgery, and 36 had surgery for twice (total 8248 pancreatectomy). After ruling out claims from the first 3 years of washout period, the incidence increased from 9891 to 24 651 and the crude incidence rate of PCLs expanded from 19.96 per 100 000 to 47.77 per 100 000. Compared to specific neoplasm codes (D136 or D377), the use of pancreatic cyst code (K862) has been remarkably increased and the most common since 2010. The annual number of pancreatectomies increased from 518 to 861 between 2007 and 2012, and decreased to 596 until 2018. The percentage of pancreatic cancer in patients who received pancreatectomy increased from 5.6% in 2007 to 11.7% in 2018. CONCLUSIONS: The incidence of PCLs is rapidly increasing. Among PCLs, indeterminate cyst is increasing outstandingly. A trend of decreasing in the number of resections and increasing cancer rates among resected cysts may be attributed to the updated international guidelines.

Prediction model using clinical factors for radiation exposure during endoscopic retrograde cholangiopancreatography.

BACKGROUND AND AIM: Endoscopic retrograde cholangiopancreatography (ERCP) requires radiation. This study aimed to assess the clinical factors influencing radiation exposure and devise a scoring model for predicting high-dose radiation exposure. METHODS: Endoscopic retrograde cholangiopancreatography cases recorded between 2016 and 2019 in a single tertiary teaching hospital were retrospectively reviewed. A scoring model was created by bootstrap method in a derivation cohort (2016-2018) and was assessed in a validation cohort (2019). RESULTS: Out of 4223 ERCPs, 2983 and 1240 cases were included in the derivation and validation cohorts, respectively. In the derivation cohort, 746 cases (top 25%) comprised the high-dose exposure group, and 2237 cases (bottom 75%) comprised the low-dose exposure group. Nine clinical parameters associated with high-dose exposure were male, pancreatic sphincterotomy, balloon dilatation, biliary or pancreatic drainage, procedures with contrast dye, endoscopist, in-hospital ERCP, and spot image. Stone removal was included by bootstrap analysis. As presented in a nomogram, the weight score of each variable was as follows: male, 1; pancreatic sphincterotomy, 3; balloon dilatation, 7; stone removal, 3; biliary or pancreatic drainage, 5; procedures with contrast dye, 1; endoscopist B, 4; endoscopist C, 5; in-hospital procedure, 3; and spot image, 3. A total score ≥ 15 suggested a high-dose radiation exposure. The sensitivity and specificity of the model for high-dose exposure were 0.562 and 0.813, respectively. In the validation cohort, the model showed reasonable predictability. CONCLUSIONS: Various factors were associated with radiation exposure. The simple scoring system in this study could guide endoscopists in predicting the risk of high-dose radiation exposure.

Confined growth of Ag nanogap shells emitting stable Raman label signals for SERS liquid biopsy of pancreatic cancer.

To develop a reliable surface-enhanced Raman scattering (SERS) immunoassay as a new liquid biopsy modality, SERS nanoprobes emitting strong and stable signals are necessary. However, Ag nanoparticles used as SERS nanoprobes are prone to rapid fading of SERS signals by oxidation. This has driven the development of a new strategy for Ag-based SERS nanoprobes emitting stable and strong SERS signals over time. Herein, Ag nanogap shells entrapping Raman labels are created in the confined pores of mesoporous silica nanoparticles (AgNSM) through a rapid single-step reaction for SERS liquid biopsy. Each AgNSM nanoprobe possesses multiple nanogaps of 1.58 nm to entrap Raman labels, allowing superior long-term SERS signal stability and large enhancement of 1.5 × 106. AgNSM nanoprobes conjugated with an antibody specific for carbohydrate antigen (CA)19-9 are employed in the SERS sandwich immunoassay including antibody-conjugated magnetic nanoparticles for CA19-9 detection, showing a two orders of magnitude lower limit of detection (0.025 U mL-1) than an enzyme-linked immunosorbent assay (0.3 U mL-1). The AgNSM nanoprobe immunoassay accurately quantifies CA19-9 levels from clinical serum samples of early and advanced pancreatic cancer. AgNSM nanoprobes with stable SERS signals provide a new route to SERS liquid biopsy for effective detection of blood biomarkers.

Analysis of Recent Improvement of Survival Outcomes in Patients with Pancreatic Cancer Who Underwent Upfront Surgery.

Background/Aims: : Recently, patients with pancreatic cancer (PC) who underwent resection have exhibited improved survival outcomes, but comprehensive analysis is limited. We analyzed the trends of contributing factors. Methods: : Data of patients with resected PC were retrospectively collected from the Korean Health Insurance Review and Assessment Service (HIRA) database and separately at our institution. Cox regression analysis was conducted with the data from our institution a survival prediction score was calculated using the ß coefficients. Results: : Comparison between the periods 2013-2015 (n=3,255) and 2016-2018 (n=3,698) revealed a difference in the median overall survival (25.9 months vs not reached, p<0.001) when analyzed with the HIRA database which was similar to our single-center data (2013-2015 [n=119] vs 2016-2018 [n=148], 20.9 months vs 32.2 months, p=0.003). Multivariable analyses revealed six factors significantly associated with better OS, and the scores were as follows: age >70 years, 1; elevated carbohydrate antigen 19-9 at diagnosis, 1; R1 resection, 1; stage N1 and N2, 1 and 3, respectively; no adjuvant treatment, 2; FOLFIRINOX or gemcitabine plus nab-paclitaxel after recurrence, 4; and other chemotherapy or supportive care only after recurrence, 5. The rate of R0 resection (69.7% vs 80.4%), use of adjuvant treatment (63.0% vs 74.3%), and utilization of FOLFIRINOX or gemcitabine plus nab-paclitaxel (25.2% vs 47.3%) as palliative chemotherapeutic regimen, all increased between the two time periods, resulting in decreased total survival prediction score (mean: 7.32 vs 6.18, p=0.004). Conclusions: : Strict selection of surgical candidates, more use of adjuvant treatment, and adoption of the latest combination regimens for palliative chemotherapy after recurrence were identified as factors of recent improvement.

Impact of histopathological type on the prognosis of ampullary carcinoma: A systematic review and meta-analysis.

Histologically, ampullary carcinomas (ACs) can be classified into intestinal (INT-AC) and pancreatobiliary (PB-AC) subtypes. However, the prognostic implications of these subtypes remain unclear. This study aimed to evaluate the impact of the histopathologic phenotype of ACs on survival following pancreaticoduodenectomy. We searched PubMed, Embase, and Medline for studies published in English from 1994 to 2021. A meta-analysis was performed using Review Manager 5.3. The primary endpoint was overall survival (OS). We identified 3,890 articles; of these, 37 articles involving 3,455 participants (1,659 INT-ACs and 1,796 PB-ACs) were included. Patients in the PB-ACs group had significantly shorter OS than those in the INT-ACs group (hazard ratio [HR]: 1.79, 95% confidence interval [95% CI]: 1.51-2.13, p < 0.001, I2 = 61%). A similar tendency was observed in the immunohistochemistry staining group (HR: 1.76, 95% CI: 1.33-2.33, p < 0.001, I2 = 67%), which included 24 studies and 1,638 patients, and the non-immunohistochemistry group (HR: 1.84, 95% CI: 1.53-2.22, p = 0.04, I2 = 46%), which included 13 studies and 1,817 patients. Subgroup analysis revealed that patients with PB-AC had higher frequencies of advanced (III, IV) and pT3-4 stage AC, lymph node metastasis, poorly differentiated tumor, positive surgical margins, lymphovascular invasion, and perineural invasion, than those with INT-AC. Patients with PB-AC had a significantly shorter OS than those with INT-AC due to a higher aggressiveness. Because the histopathologic subtype is a major prognostic factor in patients with resected AC, routine histopathologic classification should be considered even in clinical settings without immunohistochemistry.

Real-world dose reduction of standard and modified FOLFIRINOX in metastatic pancreatic cancer: a systematic review, evidence-mapping, and meta-analysis.

Background: FOLFIRINOX, used in metastatic pancreatic cancer (MPC), is highly efficacious but also toxic. Various dose modifications for FOLFIRINOX have been introduced to reduce toxicity. However, these studies lack a unified pattern for 'planned' dose modification, and the 'actually administered' dose varied more. Objective: To map a 10-year trend for 'planned' and 'actual' doses of FOLFIRINOX and investigate the clinical outcomes according to dose modification. Data sources and methods: A comprehensive systematic literature search was conducted from January 2011 to September 2021. All studies for FOLFIRINOX as first-line treatment in MPC were considered. Selected studies were firstly classified according to prospective versus retrospective research, secondly standard versus modified FOLFIRINOX, and thirdly 'planned' versus 'actual' dose. For evidence-mapping for the trend of dose modification, we developed a web-based interactive bubble-plot program (www.RDI-map.com). Objective response rate (ORR) and hematologic toxicity were set as endpoints for the comparison of clinical outcomes according to dose modification. Results: A total of 37 studies were identified for evidence-mapping (11 prospective and 26 retrospective studies). There were 12 different types of 'planned' dose modification in FOLFIRINOX ranging 75-100% oxaliplatin, 75-100% irinotecan, 0-100% 5-fluorouracil (5-FU) bolus, and 75-133% 5-FU continuous injection. The 'actual' dose further decreased to 54-96%, 61-88%, 0-92%, and 63-98%, respectively. For the standard versus modified FOLFIRINOX, the ORR was 28.2% (95% CI: 22.5-33.9%) and 33.8% (95% CI: 30.3-37.3%), respectively (p = 0.100), and the incidence of febrile neutropenia was 11.6% (95% CI: 0-16.0%) and 5.5% (95% CI: 0-8.9%), respectively (p = 0.030). Conclusions: RDI-map.com enables multifactorial evidence-mapping for practical FOLFIRINOX dose reduction. The pattern of dose modification was not consistent across studies, and there was a significant gap between the 'planned' and 'actual' doses. Modified FOLFIRINOX showed similar efficacy to the standard regimen with reduced incidence of febrile neutropenia.

Efficacy improvement in searching MEDLINE database using a novel PubMed visual analytic system: EEEvis.

PubMed is the most extensively used database and search engine in the biomedical and healthcare fields. However, users could experience several difficulties in acquiring their target papers facing massive numbers of search results, especially in their unfamiliar fields. Therefore, we developed a novel user interface for PubMed and conducted three steps of study: step A, a preliminary user survey with 76 medical experts regarding the current usability for the biomedical literature search task at PubMed; step B is implementing EEEvis, a novel interactive visual analytic system for the search task; step C, a randomized user study comparing PubMed and EEEvis. First, we conducted a Google survey of 76 medical experts regarding the unmet needs of PubMed and the user requirements for a novel search interface. According to the data of preliminary Google survey, we implemented a novel interactive visual analytic system for biomedical literature search. This EEEvis provides enhanced literature data analysis functions including (1) an overview of the bibliographic features including publication date, citation count, and impact factors, (2) an overview of the co-authorship network, and (3) interactive sorting, filtering, and highlighting. In the randomized user study of 24 medical experts, the search speed of EEEvis was not inferior to PubMed in the time to reach the first article (median difference 3 sec, 95% CI -2.1 to 8.5, P = 0.535) nor in the search completion time (median difference 8 sec, 95% CI -4.7 to 19.1, P = 0.771). However, 22 participants (91.7%) responded that they are willing to use EEEvis as their first choice for a biomedical literature search task, and 21 participants (87.5%) answered the bibliographic sorting and filtering functionalities of EEEvis as a major advantage. EEEvis could be a supplementary interface for PubMed that can enhance the user experience in the search for biomedical literature.

Real-World Outcomes of Gemcitabine, Cisplatin, and Nab-Paclitaxel Chemotherapy Regimen for Advanced Biliary Tract Cancer: A Propensity Score-Matched Analysis.

Background/Aims: Advanced biliary tract cancer (BTC) is associated with poor survival. A recent phase II study of triplet combination chemotherapy, including gemcitabine, cisplatin, and nanoparticle albumin-bound (nab)-paclitaxel, has shown promising results. This study aimed to compare the efficacy of triplet and standard doublet chemotherapy in a real-world setting. Methods: Patients with advanced BTC treated with triplet and doublet chemotherapy regimens were recruited. The propensity-score nearest neighbor matching method with a ratio of one-to-one was used to create a matched cohort for comparison. Progression-free survival (PFS), overall survival (OS), and safety profiles were examined in both groups. Results: A total of 68 patients (n=34 per group) were included in the matched cohort, and their baseline characteristics were well balanced. Survival outcomes in the triplet chemotherapy group were not better than those in the doublet chemotherapy group, with a median PFS of 7.5 months (95% confidence interval [CI], 4.1 to 10.9) versus 7.2 months (95% CI, 5.6 to 8.9) (hazard ratio [HR], 0.93; 95% CI, 0.53 to 1.62; p=0.793) and a median OS of 13.7 months (95% CI, 8.8 to 18.7) versus 12.2 months (95% CI, 8.4 to 16.0) (HR 0.73; 95% CI, 0.38 to 1.41; p=0.354), respectively. In addition, the treatment-related severe adverse events, such as neutropenia, were more common in the triplet chemotherapy group. Conclusions: Gemcitabine, cisplatin, and nab-paclitaxel did not improve the PFS or OS compared to that achieved by standard chemotherapy in patients with advanced BTC. The benefits of triplet chemotherapy in advanced BTC require examination in large randomized controlled trials.

Induction FOLFIRINOX followed by stereotactic body radiation therapy in locally advanced pancreatic cancer.

Introduction: FOLFIRINOX (the combination of 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin) is the preferred systemic regimen for locally advanced pancreatic cancer (LAPC). Furthermore, stereotactic body radiation therapy (SBRT) is a promising treatment option for achieving local control in these patients. However, clinical outcomes in patients with LAPC treated using FOLFIRINOX followed by SBRT have not been clarified. Therefore, we aimed to evaluate clinical outcomes of induction FOLFIRINOX treatment followed by SBRT in patients with LAPC. Methods: To this end, we retrospectively reviewed the medical records of patients with LAPC treated with induction FOLFIRINOX followed by SBRT in a single tertiary hospital. We evaluated overall survival (OS), progression-free survival (PFS), resection rate, SBRT-related adverse events, and prognostic factors affecting survival. Results: Fifty patients were treated with induction FOLFIRINOX for a median of 8 cycles (range: 3-28), which was followed by SBRT. The median OS and PFS were 26.4 (95% confidence interval [CI]: 22.4-30.3) and 16.7 months (95% CI: 13.0-20.3), respectively. Nine patients underwent conversion surgery (eight achieved R0) and showed better OS than those who did not (not reached vs. 24.1 months, p = 0.022). During a follow-up period of 23.6 months, three cases of grade 3 gastrointestinal bleeding at the pseudoaneurysm site were noted, which were managed successfully. Analysis of the factors affecting clinical outcomes revealed that a high radiation dose (≥ 35 Gy) resulted in a higher rate of conversion surgery (25% [8/32] vs. 5.6% [1/18], respectively) and was an independent favorable prognostic factor for OS in the adjusted analysis (hazard ratio: 2.024, 95% CI: 1.042-3.930, p = 0.037). Conclusion: Our findings suggest that induction FOLFIRINOX followed by SBRT in patients with LAPC results in better survival with manageable toxicities. A high total SBRT dose was associated with a high rate of conversion surgery and could afford better survival.

NGS-based targeted gene mutational profiles in Korean patients with pancreatic cancer.

According to molecular profiling studies, a considerable number of patients with pancreatic cancer harbor potentially actionable mutations. However, there are limited relevant data from the Korean population. We assessed the molecular profiles of patients with pancreatic cancer in Korea. This study collected molecular profiling data from patients with pancreatic cancer who visited Seoul National University Bundang Hospital between March 2018 and August 2020. Formalin-fixed, paraffin-embedded tumor specimens were sequenced using a targeted next-generation sequencing (NGS) platform. Cancer-associated mutations were analyzed, and potentially actionable mutations were identified. Potentially actionable mutations were classified into "highly actionable" and "modifies options" based on the Know Your Tumor registry study. In total, 87 patients with NGS tumor panel data were identified. Sixty-one patients (70.1%) had metastatic disease at the time of tissue acquisition. Tissues were obtained from the primary tumors and metastatic sites in 41 (47.1%) and 46 (52.9%) patients, respectively. At least one pathogenic mutation was reported in 86 patients (98.9%). The frequencies of four common mutations in our cohort were similar to those in The Cancer Genome Atlas data. Potentially actionable mutations were identified in 27 patients (31.0%). Of these, mutations categorized as highly actionable and modifies options were identified in 12 (13.8%) and 18 patients (20.7%), respectively. The most frequent highly actionable mutations were located in DNA damage response genes, such as BRCA1, BRCA2, or ATM (n = 6, 6.9%). Two patients with germline BRCA1 mutations received maintenance poly(adenosine diphosphate-ribose) polymerase inhibitor therapy. One patient has been receiving maintenance treatment for 18 months while remaining in radiologically complete remission. Mutational profiles using targeted NGS in Korean patients with pancreatic cancer were similar to those in Western patients. The present study supports the clinical potential and possible expanded clinical use of genetic profiling.

Association between progression-free survival and metal stent patency in patients with advanced pancreatic cancer.

Background: Chemotherapy reportedly affects the patency of self-expandable metal stents (SEMSs) in patients with cancer. However, knowledge regarding the association between SEMS patency and progression-free survival (PFS) remains limited. This study aimed to assess PFS and SEMS patency in patients with advanced pancreatic cancer. Methods: Between January 2012 and June 2021, 74 patients with locally advanced or metastatic pancreatic cancer (MPC) were enrolled in the study. Patients received gemcitabine plus nab-paclitaxel (GnP) or fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFIRINOX) as initial chemotherapy and SEMS within 1 month before or after the initial chemotherapy. Longer PFS was defined as PFS ≥7 months. Results: This study enrolled 38 male patients (51.4%); the mean age was 66.2 [95% confidence interval (CI), 63.7-68.6] years. Of the patients, 46 (62.2%) had MPC and 58 (78.4%) received FOLFIRINOX as the initial chemotherapy. Of the patients, 61 (82.4%) underwent endoscopic SEMS insertion. The median stent patency and PFS were 6.9 [interquartile range (IQR), 4.5-12.9] and 6.4 (IQR, 4.2-12.5) months, respectively; the median overall survival (OS) was 10.5 (IQR, 6.7-16.5) months. Of the clinical parameters assessed using multivariate analysis, shorter PFS [PFS <7 months; hazard ratio (HR), 2.117; 95% CI, 1.020-4.393; P=0.044] and metastatic cancer (HR, 2.414; 95% CI, 1.159-5.018; P=0.019) were found to be associated with shorter SEMS patency. The median SEMS patency in patients with longer PFS and those with shorter PFS was 14.3 and 7.0 months (P=0.012), respectively, and that in patients with locally advanced cancer and those with metastatic cancer was 16.7 and 7.0 months (P=0.006), respectively. The coefficient of determination between stent patency and PFS was 0.624. Conclusions: SEMS patency may be associated with PFS in patients with advanced pancreatic cancer who receive GnP or FOLFIRINOX.

Gender Differences in Patients with Metastatic Pancreatic Cancer Who Received FOLFIRINOX.

BACKGROUND: The combination of 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) is a very effective chemotherapeutic regimen for unresectable pancreatic cancer. Previous studies have reported that female gender may be a predictor of a better response to FOLFIRINOX. This study was aimed at investigating the clinical outcomes and dose modification patterns of FOLFIRINOX by gender. METHODS: Patients with metastatic pancreatic cancer (MPC) who began FOLFIRINOX as the first-line therapy at Seoul National University Bundang Hospital between 2013 and 2018 were enrolled. The patients received at least four chemotherapy cycles. Local regression and a linear mixed model were used to analyze dose modification patterns by gender. RESULTS: Ninety-seven patients with MPC (54 men; 43 women) were enrolled. In the first FOLFIRINOX cycle, there were significant differences in age and body surface area between the genders (58.8 (men) and 64.9 years (women), p = 0.005; 1.7 (men) and 1.6 m2 (women), p < 0.001, respectively). The median progression-free survival (PFS) and overall survival (OS) were 10.8 and 18.0 months, respectively. There was a trend of longer PFS (10.3 (men) and 11.9 months (women), p = 0.153) and a significantly longer OS (17.9 (men) and 25.9 months (women), p = 0.019) in female patients. During the first year of FOLFIRINOX treatment, there was a significant difference of the age-corrected dose reduction pattern by gender (a mean of 95.6% dose at the initial cycle and -0.35% of dose reduction per week in men versus a mean of 90.7% dose at the initial cycle and -0.53% of dose reduction per week in women, p-value of the slope: <0.001). There was no difference in the adverse event rates between the genders. CONCLUSIONS: Female patients showed longer OS despite a more rapid dose reduction during each cycle. Gender differences should be considered during FOLFIRINOX treatment.

Clinical Impact of Unexpected Para-Aortic Lymph Node Metastasis in Surgery for Resectable Pancreatic Cancer.

Radiologically identified para-aortic lymph node (PALN) metastasis is contraindicated for pancreatic cancer (PC) surgery. There is no clinical consensus for unexpected intraoperative PALN enlargement. To analyze the prognostic role of unexpected PALN enlargement in resectable PC, we retrospectively reviewed data of 1953 PC patients in a single tertiary center. Patients with unexpected intraoperative PALN enlargement (group A1, negative pathology, n = 59; group A2, positive pathology, n = 13) showed median overall survival (OS) of 24.6 (95% CI: 15.2-33.2) and 13.0 (95% CI: 4.9-19.7) months, respectively. Patients with radiological PALN metastasis without other metastases (group B, n = 91) showed median OS of 8.6 months (95% CI: 7.4-11.6). Compared with group A1, groups A2 and B had hazard ratios (HRs) of 2.79 (95% CI, 1.4-5.7) and 2.67 (95% CI: 1.8-4.0), respectively. Compared with group A2, group B had HR of 0.96 (95% CI: 0.5-1.9). Multivariable analysis also showed positive PALN as a negative prognostic factor (HR 2.57, 95% CI: 1.2-5.3), whereas positive regional lymph node did not (HR 1.32 95% CI: 0.8-2.3). Thus, unexpected malignant PALN has a negative prognostic impact comparable to radiological PALN metastasis. This results suggests prompt pathologic evaluation for unexpected PALN enlargements is needed and on-site modification of surgical strategy would be considered.

Acute liver failure caused by occupational exposure to HCFC-123: Two case reports.

RATIONALE: Hydrochlorofluorocarbon 123 (HCFC-123, Freon123; 2,2-dichloro-1,1,1-trifluoroethane) has been widely used in refrigeration and heat-transfer applications as a substitute for chlorofluorocarbons due to its lower ozone-depleting potentials. Occupational exposure to HCFC-123 may cause mild reversible hepatoxicity, but no fatal cases have been reported yet. PATIENT CONCERNS: In this report, we present cases of severe hepatitis with fatal outcome by HCFC-123. Two industrial workers from a manufacturing factory of fire extinguishers which use HCFC-123 were presented with diarrhea, fever, myalgia, and jaundice. Patients had been repeatedly exposed to the liquid form of HCFC-123 for the past three weeks before flare of symptoms. DIAGNOSIS: The blood biochemistry tests showed acute cholestatic hepatitis and liver biopsy findings indicated inflammatory hepatocellular injury. The diagnosis of HCFC-123 induced hepatitis was made. INTERVENTIONS: The treatment for both patients were generally supportive. The second patient went through hemodialysis, ventilatory care, and artificial liver support therapy (molecular adsorbent recirculating system) at intensive care unit. OUTCOMES: One patient recovered uneventfully, whereas the other patient showed rapid deterioration leading to acute liver failure complicated with cerebral edema, subdural hemorrhage, and death on hospital day 10. LESSONS: The HCFC-123-induced hepatitis showed similarities with halothane hepatitis, both of which may share pathophysiologic mechanisms. Exposure to HCFC-123 needs to be listed as a potential cause of acute liver failure, and to be considered in patients with acute hepatitis of uncertain etiology and negative viral serology.