PURPOSE: This study aimed to determine the prognostic value of new quantitative parameters of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT), including metabolic tumor volume (MTV), in patients with locally advanced and metastatic gallbladder cancer (GBC). MATERIALS AND METHODS: In total, 83 patients initially diagnosed with locally advanced and metastatic GBC and who underwent 18F-FDG PET/CT at the time of initial diagnosis were retrospectively reviewed. The metabolic volume-based PET parameters of primary tumors and metastatic lesions were measured, including maximum and average standardized uptake values (SUV), MTV, and total lesion glycolysis. An overall survival (OS) analysis was performed using the Kaplan-Meier method with PET and clinical parameters. A Cox proportional hazards regression analysis was performed to determine independent prognostic factors. RESULTS: In univariate analysis, pathologic differentiation (p<0.001), performance status (PS; p=0.003), C-reactive protein (CRP) level (p=0.009), and PET-related SUVmt max (the highest SUV among the metastatic lesions) (p=0.040) and MTVtotal (the sum of the MTVs of both the primary and metastatic lesions) (p=0.031), were significant for OS. In multivariate analysis, MTVtotal (hazard ratio: 2.07; 95% confidence interval: 1.23–3.48; p=0.006) remained significant for the prediction of OS, as did differentiation (p=0.001), PS (p=0.001), and CRP (p=0.039). CONCLUSION: In locally advanced and metastatic GBC, volume-based PET/CT parameters of the total tumor burden of malignancy, such as MTVtotal, were found to be useful for the identification of patients with poor prognosis.
C-Reactive Protein ; Diagnosis ; Electrons ; Fluorodeoxyglucose F18 ; Gallbladder Neoplasms ; Gallbladder ; Glycolysis ; Humans ; Methods ; Multivariate Analysis ; Neoplasm Metastasis ; Positron-Emission Tomography and Computed Tomography ; Prognosis ; Retrospective Studies ; Tumor Burden

BACKGROUND/AIMS: Pathological diagnosis of biliary strictures with atypical or suspicious cells on endoscopic retrograde brush cytology and indeterminate strictures on imaging is challenging. The aim of this study was to identify markers for malignant strictures in such cases. METHODS: We retrospectively analyzed data collected from 146 consecutive patients with indeterminate biliary strictures on imaging who underwent endoscopic retrograde brush cytology from 2007 to 2013. Factors associated with malignant strictures in patients with atypical or suspicious cells on brush cytology were identified. RESULTS: Among the 67 patients with a malignant disease (48 cholangiocarcinoma, 6 gallbladder cancer, 5 pancreatic cancer, 5 ampulla of Vater cancer, and 3 other types), 36 (53.7%) had atypical or suspicious cells on brush cytology. Among these, the factors that independently correlated with malignant strictures were stricture length (odds ratio [OR], 5.259; 95% confidence interval [CI], 1.802– 15.294) and elevated carbohydrate antigen 19-9 (CA19-9) (OR, 3.492; 95% CI, 1.242–9.815), carcinoembryonic antigen (CEA) (OR, 4.909; 95% CI, 1.694–14.224), alkaline phosphatase (ALP) (OR, 3.362; 95% CI, 1.207–9.361), and gamma-glutamyl transpeptidase (rGT) (OR, 4.318; 95% CI, 1.512–12.262). CONCLUSIONS: Elevated levels of CA19-9, CEA, ALP, and rGT and stricture length are associated with malignant strictures in patients with indeterminate biliary strictures on imaging and atypical or suspicious cells on brush cytology.
Alkaline Phosphatase ; Ampulla of Vater ; Carcinoembryonic Antigen ; Cholangiocarcinoma ; Constriction, Pathologic ; Diagnosis ; Gallbladder Neoplasms ; gamma-Glutamyltransferase ; Humans ; Pancreatic Neoplasms ; Retrospective Studies

The role of imaging in the evaluation of gallbladder cancer could be detection, differential diagnosis, and staging. Imaging modalities used for gallbladder cancer are transabdominal ultrasonography (US), computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), and endoscopic US(EUS). With the appropriate use of these multi-modalities, we can potentially increase our detection rate of early-stage gallbladder cancer and right differential diagnosis. In this article, we would like to focus on the differential diagnosis of gallbladder cancer, based on the gross morphologic classification.
Classification ; Diagnosis, Differential ; Gallbladder Neoplasms ; Gallbladder ; Magnetic Resonance Imaging ; Positron-Emission Tomography ; Ultrasonography

Adenocarcinoma is the major histology of gallbladder cancer. There are three subtypes of adenocarcinoma of the gallbladder: biliary, intestinal, and gastric foveolar subtypes. Also, there are three premalignant lesions of gallbladder adenocarcinoma: adenoma, biliary intraepithelial neoplasia (BilIN), and intracystic papillary neoplasm (ICPN). Premalignant lesion is hyperplasia of dysplastic epithelial cells with no evidence of stromal invasion. BilIN is invisible in gross inspection but can be microscopically identified around invasive tumor or chronic cholecystitis. ICPN is grossly identified as exophytic polypoid mass or diffuse friable thickening of mucosa and composed of mucinous epithelial cells with papillary and tubular arrangement. Dysplasia of BilIN and ICPN is classified by using a three-tiered system and high grade dysplasia is the same group with carcinoma in situ. Adenoma and ICPN have some ambiguities in definition and re-establishment of diagnostic criteria is needed for reproducibility of diagnosis. KRAS, TP53, and CDKN2A are the representative altered molecules in gallbladder cancer. Molecular alteration during dysplasia-carcinoma sequence is too heterogenous depending to the risk factors and type of premalignant lesion to explain the whole process by single process. Over-expression of COX2, mutation of TP53, impairment of mitochondrial DNA were reported in early hyperplastic or metaplastic epithelium. Loss of heterozygosity (LOH) of 3p, 8p chromosomes and amplification of HER2 were reported in low grade dysplasia and LOH of 9p, 18q, 22q, 17p chromosomes and mutation of CDK2A were reported in high grade dysplasia/carcinoma in situ.
Adenocarcinoma ; Adenoma ; Bile Pigments ; Carcinogenesis ; Carcinoma in Situ ; Cholecystitis ; Diagnosis ; DNA, Mitochondrial ; Epithelial Cells ; Epithelium ; Gallbladder Neoplasms ; Gallbladder ; Hyperplasia ; Loss of Heterozygosity ; Mucins ; Mucous Membrane ; Precancerous Conditions ; Risk Factors

Gallbladder (GB) cancer is asymptomatic in nature, making diagnosis and treatment difficult. The lymph node status is the strongest predictor of long-term survival for patients with GB cancer, and a complete removal of regional lymph nodes is important for patients undergoing radical resection of GB cancer. Unfortunately, lymph node metastases are common in the early stages of GB cancer. However, there have only been a few cases describing the symptoms or complications of metastatic lymph nodes in patients with GB cancer. Although hemoperitoneum caused by metastatic lymph nodes can occur with several cancers, it is very rare. To the best of our knowledge, hemoperitoneum from spontaneous ruptures of metastatic lymph nodes with GB cancer has not yet been reported. Herein, we describe such a case in a patient newly diagnosed with GB cancer.
Diagnosis ; Gallbladder Neoplasms* ; Gallbladder* ; Hemoperitoneum* ; Humans ; Lymph Nodes* ; Neoplasm Metastasis ; Rupture ; Rupture, Spontaneous*

PURPOSE: To present a case of orbital inflammation and optic perineuritis preceding vesicular eruption in herpes zoster ophthalmicus(HZO). CASE SUMMARY: An 84-year-old woman with a history of gall bladder cancer and hypertension complained of left periorbital erythematous edema and discomfort. On examination, visual acuity was 20/25 bilaterally; no tenderness, proptosis or ophthalmoplegia was observed. Pupils were equal, round, and reactive to light without relative afferent pupillary defects. Slit-lamp examination revealed severe conjunctival injection and chemosis without keratitis or uveitis. The remainder of the ocular examination was unremarkable. Magnetic resonance imaging confirmed left-sided preseptal swelling with an enlarged left lacrimal gland, high signal intensity of the retrobulbar fat and optic nerve sheath. Systemic antibiotic therapy with steroids was started under a presumed diagnosis of idiopathic orbital inflammatory disease, but the clinical presentation was unresolved. After 2 days, vesicular lesions confined to the first division of the trigeminal nerve and pseudodendritic keratitis developed on the left side leading to a diagnosis of HZO. Treatment with acyclovir immediately resolved anterior segment inflammation and periorbital edema. While on therapy, visual acuity deteriorated to 20/125 and the pupil became dilated and unresponsive to light over a few days. All signs and symptoms of acute orbitopathy and postherpetic neuralgia had resolved 3 months later with the exception of pupil abnormality and visual acuity. CONCLUSIONS: HZO may present with symptoms and signs of orbital inflammation and optic perineuritis even in the absence of a vesicular rash. Thus, HZO should be considered in the differential diagnosis of unexplained acute orbital syndromes.
Acyclovir ; Aged, 80 and over ; Dacryocystitis ; Diagnosis ; Diagnosis, Differential ; Edema ; Exanthema ; Exophthalmos ; Female ; Gallbladder Neoplasms ; Herpes Zoster Ophthalmicus* ; Herpes Zoster* ; Humans ; Hypertension ; Inflammation* ; Keratitis ; Lacrimal Apparatus ; Magnetic Resonance Imaging ; Neuralgia, Postherpetic ; Ophthalmoplegia ; Optic Nerve ; Orbit* ; Pupil ; Pupil Disorders ; Steroids ; Trigeminal Nerve ; Uveitis ; Visual Acuity

Signet ring cell carcinoma is a rare form of gallbladder cancer and has a worse prognosis. Since few cases have been reported, information regarding the behavior and prognosis of the gallbladder carcinoma is limited. About twenty four cases of gallbladder signet ring cell carcinoma have been reported so far. We present a rare case of primary signet ring cell carcinoma of the gallbladder. A 58-year-old male presented with epigastric pain. Abdominal computed tomography showed diffuse gallbladder wall thickening with enhancement, gallstones, and choledocholithiasis. After endoscopic treatment of choledocholithiasis, laparoscopic cholecystectomy was performed. Pathologic examination of the resected gallbladder revealed adenocarcinoma of signet ring cell type in the epithelium. Immunohistochemical stain for cytokeratin 7 was positive for tumor cells. The final pathologic diagnosis was primary signet ring cell carcinoma of the gallbladder. Lymph node metastasis was detected and he received chemotherapy and radiotherapy. After one year of follow-up, bone metastasis in the lumbar spine and malignant ascites were found. The patient is being provided with palliative care.
Adenocarcinoma ; Ascites ; Carcinoma, Signet Ring Cell* ; Cholangitis ; Cholecystectomy, Laparoscopic ; Cholecystitis* ; Cholecystitis, Acute ; Choledocholithiasis ; Diagnosis ; Drug Therapy ; Epithelium ; Follow-Up Studies ; Gallbladder Neoplasms ; Gallbladder* ; Gallstones ; Humans ; Keratin-7 ; Lymph Nodes ; Male ; Middle Aged ; Neoplasm Metastasis ; Palliative Care ; Prognosis ; Radiotherapy ; Spine

OBJECTIVE: To investigate the feasibility of ex vivo multispectral photoacoustic (PA) imaging in differentiating cholesterol versus neoplastic polyps, and benign versus malignant polyps, of the gallbladder. MATERIALS AND METHODS: A total of 38 surgically confirmed gallbladder polyps (24 cholesterol polyps, 4 adenomas, and 10 adenocarcinomas) from 38 patients were prospectively included in this study. The surgical specimens were set on a gel pad immersed in a saline-filled container. The PA intensities of polyps were then measured, using two separate wavelength intervals (421–647 nm and 692–917 nm). Mann-Whitney U test was performed for the comparison of normalized PA intensities between the cholesterol and neoplastic polyps, and between the benign and malignant polyps. Kruskal-Wallis test was conducted for the comparison of normalized PA intensities among the cholesterol polyps, adenomas, and adenocarcinomas. RESULTS: A significant difference was observed in the normalized PA intensities between the cholesterol and neoplastic polyps at 459 nm (median, 1.00 vs. 0.73; p = 0.032). Comparing the benign and malignant polyps, there were significant differences in the normalized PA intensities at 765 nm (median, 0.67 vs. 0.78; p = 0.013), 787 nm (median, 0.65 vs. 0.77; p = 0.034), and 853 nm (median, 0.59 vs. 0.85; p = 0.028). The comparison of the normalized PA intensities among cholesterol polyps, adenomas, and adenocarcinomas demonstrated marginally significant differences at 765 nm (median, 0.67 vs. 0.66 vs. 0.78, respectively; p = 0.049). CONCLUSION: These preliminary results indicate that benign versus malignant gallbladder polyps might exhibit different spectral patterns on multispectral PA imaging.
Adenocarcinoma ; Adenoma ; Cholesterol ; Diagnosis, Differential* ; Gallbladder Neoplasms ; Gallbladder* ; Humans ; Photoacoustic Techniques ; Polyps* ; Prospective Studies

OBJECTIVE: Efficacy or long-term result of metastasectomy for recurrent or metastatic biliary tract carcinoma (BTC) is not well established. We conducted a retrospective review of the outcomes of metastasectomy for recurrent or metastatic BTCs. METHODS: The clinicopathological features and outcomes of consecutive patients with BTCs who underwent surgical resection for primary and metastatic disease at a tertiary referral hospital from 2003 to 2013 were reviewed retrospectively. RESULTS: We found 19 eligible patients. Median age of patients was 57 years old (range, 27 to 68 years old), and 11 patients (58%) were female. Primary sites were gallbladder cancer (seven patients, 37%), intrahepatic cholangiocarcinoma (five patients, 26%), distal common bile duct cancer (three patients, 16%), proximal common bile duct cancer (two patients, 11%), and ampulla of Vater cancer (two patients, 11%). Eight patients (42%) had synchronous metastasis, while 11 (58%) had metachronous metastasis. The most common metastatic site was liver (nine patients, 47%), lymph node (nine patients, 47%), and peritoneum (three patients, 16%). Nine patients (47%) achieved R0 resection, while four (21%) and six (32%) patients had R1 and R2 resection, respectively. With a median follow-up period of 26.7 months, the estimated median overall survival (OS) was 18.2 months (95% confidence interval [CI], 13.6 to 22.9 months). Lower Eastern Cooperative Oncology Group performance status (P=0.023), metachronous metastasis (P=0.04), absence of lymph node metastasis (P=0.009), lower numbers of metastatic organs (P<0.001), normal postoperative carbohydrate antigen 19-9 level (P=0.034), and time from diagnosis to metastasectomy more than one year (P=0.019) were identified as prognostic factors for a longer OS after metastasectomy. CONCLUSION: For recurrent or metastatic BTCs, metastasectomy can be a viable option for selected patients.
Ampulla of Vater ; Biliary Tract Neoplasms* ; Biliary Tract* ; Cholangiocarcinoma ; Common Bile Duct ; Diagnosis ; Female ; Follow-Up Studies ; Gallbladder Neoplasms ; Humans ; Liver ; Lymph Nodes ; Metastasectomy* ; Neoplasm Metastasis ; Peritoneum ; Prognosis ; Retrospective Studies ; Tertiary Care Centers

Xanthogranulomatous inflammation (XGI) is characterized histologically by the deposition of foamy macrophages and infiltration of inflammatory cells. While XGI is extremely rare, it has been reported in the gallbladder, kidney, stomach, and lymph nodes. A 61-year-old woman presented with epigastric pain for 2 weeks. Abdominal computed tomography and magnetic resonance imaging showed a pancreatic head mass with distal common bile duct wall thickening. Endoscopic ultrasonography followed by fine needle aspiration was performed, and subsequent pathology report revealed a benign disease. Because uncontrolled abdominal pain persisted and possibility of malignancy could not be excluded, Whipple's operation was eventually performed, and pathology report showed xanthogranulomatous pancreatitis (XGP). Herein, we report a case of symptomatic XGP mimicking of pancreas cancer. Although XGP is extremely rare, it should be considered as a differential diagnosis of neoplastic lesions of the pancreas.
Abdominal Pain ; Biopsy, Fine-Needle ; Common Bile Duct ; Diagnosis, Differential ; Endosonography ; Female ; Gallbladder ; Head ; Humans ; Inflammation ; Kidney ; Lymph Nodes ; Macrophages ; Magnetic Resonance Imaging ; Middle Aged ; Pancreas ; Pancreatic Neoplasms* ; Pancreatitis* ; Pathology ; Stomach