Fairly rare clear cell adenocarcinoma mimicking liver cancer: a case report.

BACKGROUND: Clear cell carcinoma commonly occurs in the ovary and kidney, and clear cell cholangiocarcinoma was rarely reported. Differential diagnosis which the origin of the tumor located on the liver surface is intrahepatic or extrahepatic was difficult. Herein, we report a case of clear cell adenocarcinoma mimicking liver cancer. CASE PRESENTATION: This was a 55-year-old female who had the tumor with cystic component in the liver. She was performed hepatectomy and diagnosed as clear cell adenocarcinoma. Histopathological evaluation revealed intra-cystic clear cell adenocarcinoma. The tumor has ductal structure including mucin and atypical nuclear with clear cytoplasm. The tumor was separated from the liver and the diaphragm. The expression of Pax8 was positive, but the expression CK7 and HNF1ß was positive and that of CD10 and ER was negative, which indicate that the tumor has the feature of clear cell carcinoma of ovary, not renal cell carcinoma nor cholangiocarcinoma. CONCLUSIONS: Our experience with this patient suggests that this tumor may originate from the endometriosis onto the diaphragm from the detailed results of immunohistochemical staining.

Interplay of neuropilin-1 and semaphorin 3A after partial hepatectomy in rats.

AIM: To elucidate the role of neuropilin-1 (Nrp-1) and semaphorin 3A (Sema3A) in sinusoidal remodeling during liver regeneration in rats. METHODS: Male Wistar/ST rats at 7 wk of age, weighing about 200 g, were used for all animal experiments. In vivo, at 24, 48, 72, 96, 144 and 192 h after two-thirds partial hepatectomy (PHx), the remnant livers were removed. Liver tissues were immunohistochemically stained for Nrp-1, Sema3A and SE-1, a liver sinusoidal endothelial cell (SEC) marker. Total RNA of the liver tissue was extracted and reversely transcribed into cDNA. The mRNA expression of Sema3A was analyzed by quantitative real-time polymerase chain reaction and normalized to that of ribosomal protein S18. In vitro, SECs were isolated from rat liver and cultured in endothelial growth medium containing 20 ng/mL vascular endothelial cell growth factor. Migration of SECs in primary culture was assessed by cell transwell assay with or without recombinant Sema3A. Apoptotic cells were determined by a terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling method. RESULTS: In vitro, immunohistochemistry study revealed that Sema3A and Nrp-1 were constitutively expressed in hepatocytes and SECs, respectively, in normal rat liver tissues. Nrp-1 expression in SECs was quantified by the percentage of immunostained area with anti-Nrp-1 antibody in relation to the area stained with SE-1. Between 24 h and 96 h following resection of liver, Nrp-1 expression in SECs was transiently increased. Compared with the baseline (5.2% ± 0.1%), Nrp-1 expression in SECs significantly increased at 24 h (17.3% ± 0.7%, P < 0.05), 48 h (39.1% ± 0.6%, P < 0.01), 72 h (46.9% ± 4.5%, P < 0.01) and 96 h (29.9% ± 3.8%, P < 0.01) after PHx, then returned to the basal level at termination of liver regeneration. Interestingly, the expression of Sema3A was inversely associated with that of Nrp-1 in liver after PHx. Sema3A mRNA expression was significantly reduced by about 75% over the period 24-144 h after PHx (P < 0.05), and returned to basal levels at 192 h after PHx. In vitro, SECs isolated from rats after PHx (PHx-SECs) were observed to migrate to the lower chamber of the cell transwell system after incubation for 24 h, but not cells from normal rats (CONT-SECs), indicating that mobility of PHx-SECs increases as compared with that of CONT-SECs. Moreover, recombinant Sema3A significantly attenuated migration in PHx-SECs in primary culture (vehicle-treated 100% ± 7.9% vs Sema3A-treated 42.6% ± 5.4%, P < 0.01), but not in CONT-SECs. Compared with CONT-SECs, the apoptotic rate of PHx-SECs decreased by 78.3% (P < 0.05). There was no difference in apoptosis between CONT-SECs that were treated with vehicle and Sema3A. However, in PHx-SECs, apoptosis was induced by the presence of 5 nmol Sema3A for 24 h (vehicle-treated 21.7% ± 7.6% vs Sema3A-treated 104.3% ± 8.9%, P < 0.05). In addition, immunohistochemistry confirmed the increased expression of Nrp-1 in PHx-SECs, while it was noted to a lesser extent in CONT-SECs. CONCLUSION: The interplay of Nrp-1 and Sema3A shown in our results may lead to a better understanding of interaction between sinusoidal remodeling and SECs during liver regeneration.

Japanese clinical practice guidelines for pancreaticobiliary maljunction.

There have been no clinical guidelines for the management of pancreaticobiliary maljunction (PBM). The Japanese Study Group on Pancreaticobiliary Maljunction (JSPBM) has proposed to establish clinical practice guidelines on how to deal with PBM, with the support of the Japan Biliary Association (JBA). Because the body of evidence-based literature is relatively small, we decided to create guidelines based on the consensus of experts, using the medical literature for reference. A total of 46 clinical questions (CQs) were considered by the members of the editorial committee responsible for the guidelines. The CQs covered distinct aspects of PBM: (1) Concepts and Pathophysiology (10 CQs); (2) Diagnosis (10 CQs); (3) Pancreatobiliary complications (9 CQs); and (4) Treatments and prognosis (17 CQs). Statements and comments for each CQ were prepared by the guidelines committee members and collaborating partners. The CQs were completed after review by members of the editorial committee, meetings of this committee, public comments on the homepages of the JSPBM and the JBA, public hearings, and assessment and approval by the guidelines evaluation board. PBM includes cases where the bile duct is dilated (PBM with biliary dilatation) and those in which it is not (PBM without biliary dilatation). In these guidelines, PBM with biliary dilatation is defined as being identical to congenital biliary dilatation of Todani type I (except for type Ib) and type IV-A, both of which are accompanied by PBM in almost all cases. These guidelines are created to provide assistance in the clinical practice of PBM management; their contents focus on clinical utility, and they include general information on PBM to make this disease more widely recognized.

Randomized phase II study of gemcitabine and S-1 combination versus gemcitabine alone in the treatment of unresectable advanced pancreatic cancer (Japan Clinical Cancer Research Organization PC-01 study).

PURPOSE: To evaluate the efficacy and safety of the combination of gemcitabine (GEM) and S-1 (GS) in comparison to GEM alone (G) for unresectable pancreatic cancer. METHODS: In this multicenter randomized phase II study, we randomly assigned unresectable pancreatic cancer patients to either the GS group or the G group. The GS group regimen consists of intravenous 1,000 mg/m(2) GEM during 30 min on days 1 and 8, combined with 80 mg/m(2) oral S-1 twice daily on days 1-14, repeated every 3 weeks. On the other hand, the G group regimen consists of intravenous 1,000 mg/m(2) GEM on days 1, 8, and 15, repeated every 4 weeks. The primary endpoint was objective response rate (ORR). Secondary end points included treatment toxicity, clinical response benefit, progression-free survival (PFS), and overall survival. RESULTS: We registered 117 patients from 16 institutions between June 2007 and August, 2010. The ORR of the GS group was 28.3%, whereas that of the G group was 6.8%. This difference was statistically significant (P = 0.005). The disease control rate was 64.2% in the GS group and 44.1% in the G group. Median PFS was 6.15 months in the GS group and 3.78 month in the G group. This was also statistically significant (P = 0.0007). Moreover, the median overall survival (OS) of the GS group was significantly longer than that of the G group (13.7 months vs. 8.0 months; P = 0.035). The major grade 3-4 adverse events were neutropenia (54.7% in the GS group and 22.0% in the G group), thrombocytopenia (15.1% in the GS group and 5.1% in the G group), and skin rash (9.4% in the GS group). CONCLUSIONS: The GS group showed stronger anticancer activity than the G group, suggesting the need for a large randomized phase III study to confirm GS advantages in a specific subset.

Reactive lymphoid hyperplasia of the liver associated with primary biliary cirrhosis.

BACKGROUND: Although reactive lymphoid hyperplasia (RLH) can be found in various organs, including the gastrointestinal tract, orbit, lung, and skin, its occurrence in the liver is rare. CASE REPORT: We report the case of a 47-year-old RLH woman who was identified with RLH of the liver during clinical follow- up of primary biliary cirrhosis. The mass, found incidentally during a medical examination, appeared on ultrasonogram as a hypoechoic mass in the 7th segment of the liver. Further analyses using composed tomography, magnetic resonance imaging, and angiography suggested malignancy, and we performed lateral segmentectomy of the liver. Histologically, the tumor was composed of lymphoid follicles with germinal centers that expressed kappa and lambda light-chain B-cell markers at equal frequency, and no IgH gene rearrangements were detected in Southern blots. Based on these results, we identified the lesion as RLH. CONCLUSIONS: We suggest that this diagnosis be taken into consideration in other cases involving a space-occupying liver mass associated with autoimmune disease.

Pancreatobiliary reflux and the length of a common channel.

BACKGROUND/PURPOSE: Gallbladder cancer occurs frequently in patients with pancreaticobiliary maljunction due to pancreatobiliary reflux. Pancreatobiliary reflux is also detected in some patients with a relatively long common channel. This study aimed to clarify the correlation between pancreatobiliary reflux and the length of a common channel. METHODS: Two hundred and three patients, in whom both the length of a common channel and amylase level in the bile were measured, were enrolled from nine centers. RESULTS: Bile amylase level was correlated with the length of a common channel (P < 0.01). The minimum length of a common channel that could induce a markedly elevated amylase level in the bile (>1,000 mg/dl) was determined as 5 mm. We redefined high confluence of pancreatobiliary ducts (HCPBD) as cases with a common channel > or = 5 mm, in which the communication between the pancreatic and bile ducts was occluded with the sphincter contraction. Gallbladder cancer was found in 20% of 56 redefined HCPBD patients. Bile amylase level >1,000 mg/dl and biliopancreatic reflux were detected in 79 and 95% of the patients, respectively. CONCLUSIONS: Patients with a common channel > or = 5 mm (redefined HCPBD) should be monitored for the development of gallbladder cancer, as they frequently showed significant pancreatobiliary reflux.

Identification of cerebral response to balloon distention of the bile duct.

AIM: To identify the brain loci that process human biliary sensation. METHODS: In 6 patients (age range: 42-74 years; 4 men), who underwent percutaneous transhepatic biliary drainage (PTBD), the distal biliary tract was stimulated by repeatedly inflating the balloon of the PTBD catheter so that it reached volumes that produced a definite painless sensation. The functional magnetic resonance imaging (fMRI) of the cortical response to biliary sensation was examined. RESULTS: Biliary balloon stimulation elicited activation of the insular cortex, prefrontal cortex, and somatosensory cortex (P < 0.001). CONCLUSION: Biliary balloon stimulation evoked a cerebral cortical response detectable by fMRI.

Antitumor activity of anti-C-ERC/mesothelin monoclonal antibody in vivo.

Mesothelioma is an aggressive cancer often caused by chronic asbestos exposure, and its prognosis is very poor despite the therapies currently used. Due to the long latency period between asbestos exposure and tumor development, the worldwide incidence will increase substantially in the next decades. Thus, novel effective therapies are warranted to improve the prognosis. The ERC/mesothelin gene (MSLN) is expressed in wide variety of human cancers, including mesotheliomas, and encodes a precursor protein cleaved by proteases to generate C-ERC/mesothelin and N-ERC/mesothelin. In this study, we investigated the antitumor activity of C-ERC/mesothelin-specific mouse monoclonal antibody, 22A31, against tumors derived from a human mesothelioma cell line, ACC-MESO-4, in a xenograft experimental model using female BALB/c athymic nude mice. Treatment with 22A31 did not inhibit cell proliferation of ACC-MESO-4 in vitro; however, therapeutic treatment with 22A31 drastically inhibited tumor growth in vivo. 22A31 induced antibody-dependent cell-mediated cytotoxicity by natural killer (NK) cells, but not macrophages, in vitro. Consistently, the F(ab')(2) fragment of 22A31 did not inhibit tumor growth in vivo, nor did it induce antibody-dependent cell mediated cytotoxicity (ADCC) in vitro. Moreover, NK cell depletion diminished the antitumor effect of 22A31. Thus, 22A31 induced NK cell-mediated ADCC and exerted antitumor activity in vivo. 22A31 could have potential as a therapeutic tool to treat C-ERC/mesothelin-expressing cancers including mesothelioma.

Efficacy of camostat mesilate against dyspepsia associated with non-alcoholic mild pancreatic disease.

BACKGROUND: The aim of the present study was to examine the potential efficacy of camostat mesilate, a protease inhibitor, against dyspepsia associated with non-alcoholic mild pancreatic disease. METHODS: Patients with upper abdominal pain suggesting pancreatic disease (persistent over hours, pain aggravated by ingestion of food, epigastric pain radiating to the back), without a history of alcohol consumption and who exhibited no abnormalities regarding serum amylase and lipase, ultrasonography, CT and upper gastrointestinal endoscopy, were prescribed 200 mg camostat mesilate three times daily for 2 weeks. The patients were subjected to endoscopic ultrasonography (EUS) while under treatment and were distributed into those who had 4 or more suggestive findings of chronic pancreatitis (suspected pancreatic disease group), 2 or 3 (equivalent group) and those with 1 or no findings (control group). Symptom severity was recorded before and after treatment using a 10-cm visual analog scale (VAS). RESULTS: Among 95 patients, 40 were in the suspected pancreatic disease group, 30 were in the equivalent group and 25 served as controls. A significant intra- and intergroup improvement of symptoms was observed not only in the suspected pancreatic disease group but also in the equivalent group. CONCLUSIONS: Camostat mesilate may serve as a therapeutic agent for patients with dyspepsia associated with mild pancreatic disease, who do not habitually drink alcohol.

Early detection of extrahepatic bile-duct carcinomas in the nonicteric stage by using MRCP followed by EUS.

BACKGROUND: Most extrahepatic bile-duct carcinomas are usually diagnosed when they are already in an advanced stage, which is the main reason for the poor prognosis of this tumor. OBJECTIVE: To examine the usefulness of MRCP followed by EUS in the early diagnosis of extrahepatic bile-duct carcinoma in the nonicteric stage. PATIENTS: This study included patients who were nonicteric, who had abnormal serum concentrations of alkaline phosphatase and gamma glutamyl transpeptidase, and whose common hepatic duct was more than 8 mm in diameter on abdominal US because of unknown reasons. DESIGN: A single-center, prospective study. SETTING: An academic medical center. MAIN OUTCOME MEASUREMENTS: The sensitivity and specificity of MRCP followed by EUS for the early diagnosis of extrahepatic bile duct carcinoma in the nonicteric stage. RESULTS: A total of 142 patients who were nonicteric underwent prospective MRCP, and 26 of them underwent EUS. Ten patients (5 with stricture, 4 with filling defect, and 1 with no stricture or filling defect) had extrahepatic bile-duct carcinoma, including 5 patients with an incidentally diagnosed T1 stage tumor. The sensitivity and specificity of MRCP followed by EUS were 90% and 98%, respectively. LIMITATIONS: A single center and small number of patients. CONCLUSIONS: MRCP followed by EUS was highly sensitive and specific for the early diagnosis of extrahepatic bile-duct carcinoma in the nonicteric stage, including T1 stage tumors. Filling defects, as well as stenosis in the bile duct, are important MRCP findings of T1 stage carcinoma.

Pancreatic-duct-lavage cytology in candidates for surgical resection of branch-duct intraductal papillary mucinous neoplasm of the pancreas: should the International Consensus Guidelines be revised?

BACKGROUND: The International Consensus Guidelines are helpful for the management of branch-duct intraductal papillary mucinous neoplasms (IPMNs), because they allow us to exclude malignancy. However, it is not possible to predict malignancy with certainty, and further preoperative differentiation between benign and malignant IPMNs is required to avoid the false-positive results. OBJECTIVE: To examine the usefulness of pancreatic-duct-lavage cytology by using an originally designed double-lumen catheter for discriminating benign and malignant IPMNs of the branch-duct type in candidates for surgical resection based on the International Consensus Guidelines. PATIENTS: Pancreatic-duct-lavage cytology was investigated in 24 patients with branch-duct IPMNs who underwent surgical resection based on the International Consensus Guidelines, namely, they either had intramural nodules or the ectatic branch duct was >30 mm in diameter. DESIGN: Single-center retrospective study. SETTING: Academic medical center. MAIN OUTCOME MEASUREMENTS: The sensitivity and specificity of pancreatic-duct-lavage cytology for discriminating benign from malignant IPMNs. RESULTS: More than 30 mL of pancreatic-duct-lavage fluid was obtained from each patient, and there were no patients with noninformative results. The sensitivity, specificity, positive predictive value, and negative predictive value of the cytologic diagnosis were 78%, 93%, 88%, and 88%, respectively. LIMITATIONS: Single-center and small number of patients. CONCLUSIONS: Pancreatic-duct-lavage cytology can improve differentiation between benign and malignant IPMNs of the branch-duct type in candidates for surgical resection based on the International Consensus Guidelines.

Secretion of N-ERC/mesothelin and expression of C-ERC/mesothelin in human pancreatic ductal carcinoma.

ERC/mesothelin gene (MSLN) encodes a precursor protein, which is cleaved by proteases to generate N-ERC/mesothelin and C-ERC/mesothelin. N-ERC/mesothelin is a soluble protein, also known as megakaryocyte-potentiating factor, which is released into extracellular space. N-ERC/mesothelin is known to be a serum marker of mesothelioma. We have previously developed an enzyme-linked immunosorbent assay system for N-ERC/mesothelin, which can detect mesothelioma. C-ERC/mesothelin is expressed in normal mesothelial cell, pancreatic cancers, ovarian cancers, mesotheliomas and some other cancers. Pancreatic ductal carcinoma remains a fatal disease because its diagnosis often occurs very late. In this study, we examined ERC/mesothelin expression in human pancreatic cancer cell lines (MIA-PaCa2, PK-1, KP-3, TCC-PAN2, PK-59 and PK-45H) by reverse transcription-polymerase chain reaction and immunoblotting and N-ERC/mesothelin concentration in the supernatant of cultured cancer cells by the ELISA system. We also investigated C-ERC/mesothlein expression in human pancreatic ductal carcinoma tissues by immunostaining using 5B2 anti-mesothelin monoclonal antibody and N-ERC/mesothelin concentration in sera obtained from patients with pancreatic ductal carcinoma via ELISA. In vitro, N-ERC/mesothelin concentration in cell culture medium nearly correlated with the expression level of C-ERC/mesothelin. Although C-ERC/mesothelin was frequently expressed in human pancreatic ductal carcinoma, serum N-ERC/mesothelin concentration of cancer patients was equivalent to healthy controls. N-ERC/mesothelin was not useful as a serum marker of pancreatic ductal carcinoma, but because of frequent expression, C-ERC/mesothelin might be useful as a target of molecular imaging and immunotherapy.

Diagnosis of mild chronic pancreatitis (Cambridge classification): comparative study using secretin injection-magnetic resonance cholangiopancreatography and endoscopic retrograde pancreatography.

AIM: To investigate the usefulness of secretin injection-MRCP for the diagnosis of mild chronic pancreatitis. METHODS: Sixteen patients having mild chronic pancreatitis according to the Cambridge classification and 12 control subjects with no abnormal findings on the pancreatogram were examined for the diagnostic accuracy of secretin injection-MRCP regarding abnormal branch pancreatic ducts associated with mild chronic pancreatitis (Cambridge Classification), using endoscopic retrograde cholangiopancreatography (ERCP) for comparison. RESULTS: The sensitivity and specificity for abnormal branch pancreatic ducts determined by two reviewers were respectively 55%-63% and 75%-83% in the head, 57%-64% and 82%-83% in the body, and 44%-44% and 72%-76% in the tail of the pancreas. The sensitivity and specificity for mild chronic pancreatitis were 56%-63% and 92%-92%, respectively. Interobserver agreement (kappa statistics) concerning the diagnosis of an abnormal branch pancreatic duct and of mild chronic pancreatitis was good to excellent. CONCLUSION: Secretin injection-MRCP might be useful for the diagnosis of mild chronic pancreatitis.

Stenting and interventional radiology for obstructive jaundice in patients with unresectable biliary tract carcinomas.

Together with biliary drainage, which is an appropriate procedure for unresectable biliary cancer, biliary stent placement is used to improve symptoms associated with jaundice. Owing to investigations comparing percutaneous transhepatic biliary drainage (PTBD), surgical drainage, and endoscopic drainage, many types of stents are now available that can be placed endoscopically. The stents used are classified roughly as plastic stents and metal stents. Compared with plastic stents, metal stents are of large diameter, and have long-term patency (although they are expensive). For this reason, the use of metal stents is preferred for patients who are expected to survive for more than 6 months, whereas for patients who are likely to survive for less than 6 months, the use of plastic stents is not considered to be improper. Obstruction in a metal stent is caused by a tumor that grows within the stent through the mesh interstices. To overcome such problems, a covered metal stent was developed, and these stents are now used in patients with malignant distal biliary obstruction. However, this type of stent has been reported to have several shortcomings, such as being associated with the development of acute cholecystitis and stent migration. In spite of these shortcomings, evidence is expected to demonstrate its superiority over other types of stent.

Two distinct pathways of p16 gene inactivation in gallbladder cancer.

AIM: To examine the mechanism of inactivation of the p16 gene in gallbladder cancer, and to investigate p16 alterations and their correlation with clinicopathological features. METHODS: Specimens were collected surgically from 51 patients with gallbladder cancer. We evaluated the status of protein expression, loss of heterozygosity (LOH), homozygous deletion and promoter hypermethylation using immunohistochemistry, microsatellite analysis, quantitative real-time polymerase chain reaction (PCR) and methylation-specific PCR, respectively. In addition, mutations were examined by direct DNA sequencing. RESULTS: Homozygous deletions of the p16 gene exon2, LOH at 9p21-22, p16 promoter hypermethylation, and loss of p16 protein expression were detected in 26.0% (13/50), 56.9% (29/51), 72.5% (37/51) and 62.7% (32/51), respectively. No mutations were found. LOH at 9p21 correlated with the loss of p16 protein expression (P < 0.05). Homozygous deletion of the p16 gene, a combination LOH and promoter hypermethylation, and multiple LOH at 9p21 were significantly correlated with the loss of p16 protein expression (P < 0.05). LOH at 9p21 and promoter hypermethylation of the p16 gene were detected in 15.4% (2/13) and 92.3% (12/13) of the tumors with homozygous deletion of the p16 gene, respectively. P16 alterations were not associated with clinicopathological features. CONCLUSION: Our results suggest that LOH and homozygous deletion may be two distinct pathways in the inactivation of the p16 gene. Homozygous deletion, a combination of LOH and promoter hypermethylation, and multiple LOH are major mechanisms of p16 inactivation in gallbladder cancer.

Gallbladder carcinoma associated with pancreatobiliary reflux.

AIM: To detect the patients with and without pancreaticobiliary maljunction who had pancreatobiliary reflux with extremely high biliary amylase levels. METHODS: Ninety-six patients, who had diffuse thickness (>3 mm) of the gallbladder wall and were suspected of having a pancreaticobiliary maljunction on ultrasonography, were prospectively subjected to endoscopic retrograde cholangiopancreatography, and bile in the common bile duct was sampled. Among them, patients, who had extremely high biliary amylase levels (>10000 IU/L), underwent cholecystectomy, and the clinicopathological findings of those patients with and without pancreaticobiliary maljunction were examined. RESULTS: Seventeen patients had biliary amylase levels in the common bile duct above 10000 IU/L, including 11 with pancreaticobiliary maljunction and 6 without pancreaticobiliary maljunction. The occurrence of gallbladder carcinoma was 45.5% (5/11) in patients with pancreaticobiliary maljunction, and 50% (3/6) in those without pancreaticobiliary maljunction. CONCLUSION: Pancreatobiliary reflux with extremely high biliary amylase levels and associated gallbladder carcinoma could be identified in patients with and without pancreaticobiliary maljunction, and those patients might be detected by ultrasonography and bile sampling.

A case of gallbladder carcinoma associated with pancreatobiliary reflux in the absence of a pancreaticobiliary maljunction: A hint for early diagnosis of gallbladder carcinoma.

A 62-year-old man with progressive thickening of the gallbladder wall visited our outpatient clinic. The biliary amylase level in the common bile duct was 19,900 IU/L and that of the gallbladder was 127,000 IU/L, although endoscopic retrograde cholangiopancreatography revealed no pancreaticobiliary maljunction. Histology demonstrated a moderately differentiated adenocarcinoma of the gallbladder. Pancreatobiliary reflux and associated gallbladder carcinoma were confirmed in the present case, in the absence of a pancreaticobiliary maljunction. Earlier detection of the pancreatobiliary reflux and progressive thickening of the gallbladder wall might have led to an earlier resection of the gallbladder and improved this patient's poor prognosis.