Is surgery justified for elderly patients with extrahepatic cholangiocarcinoma? Reappraisal from a viewpoint of comorbidity and organ function.

PURPOSE: The benefit of surgery for older patients with extrahepatic cholangiocarcinoma (EHCC) has not been established and the differences in the general condition of younger vs. older patients remain unclear. METHODS: Patients who underwent curative surgery for EHCC were divided into two groups according to age: those younger than 75 years old (younger group) and those aged 75 years or older (older group). We analyzed the clinical data of the two groups retrospectively. RESULTS: Among the 116 patients analyzed, 45 (38.8%) were in the older group. Regarding comorbidity, only cardiac disease was significantly more common in the older patients; however, the cardiac function of the two groups was identical. There were no significant differences in the prevalence of kidney and lung disease, but renal function was significantly deteriorated and the incidence of the mixed ventilatory defect was significantly greater in the older group. The overall 5-year survival rates for the younger and older groups were 52.4% vs. 50.4% of all cholangiocarcinoma patients (p = 0.458), 42.4% vs. 51.3% of those with hilar cholangiocarcinoma (p = 0.718), and 69.0% vs. 49.1% of those with distal cholangiocarcinoma (p = 0.534), respectively. CONCLUSIONS: Improved survival after surgery can be expected in well-selected older cholangiocarcinoma patients. Comorbidities were not necessarily reflected in organ function, with precise organ function assessment being more important when selecting surgical candidates.

Primary Sclerosing Cholangitis in a Young Female.

Primary sclerosing cholangitis (PSC) is a liver disease characterized by inflammation and fibrosis of both intrahepatic and extrahepatic bile ducts resulting in cholestasis. Due to nonspecific symptoms it is difficult to diagnose until complication arises. It is common in male and usually associated with other autoimmune diseases. Here, we report a case of PSC in a young female which was initially thought to be drug induced cholestasis without presence of any other autoimmunity.

Repair of extrahepatic bile duct defect using a collagen patch in a Swine model.

Extrahepatic bile duct (EBD) injury can happen during surgery. To repair a defect of the EBD and prevent postoperative biliary complications, a collagen membrane was designed. The collagen material was porous, biocompatible, and degradable and could maintain its shape in bile soaking for about 4 weeks. The goal was to induce rapid bile duct tissue regeneration. Twenty Chinese experimental hybrid pigs were used in this study and divided into a patch group and a control group. A spindle-shaped defect (20 mm × 6 mm) was made in the anterior wall of the lower EBD in the swine model, and then the defect was reconstructed using a collagen patch with a drainage tube and wrapped with greater omentum. Ultrasound was performed at 2, 4, 8, and 12 weeks postoperatively. Liver function tests and white blood cell count (WBC) were measured. Hematoxylin-eosin staining, cytokeratin 7 immunohistochemical staining, and Van Gieson's staining of EBD were used. The diameter and thickness of the EBD at the graft site were measured. There was no significant difference in liver function tests or WBC in the patch group compared with the control group. No evidence of leakage or stricture was observed, but some pigs developed biliary sludge or stone at 4 and 8 weeks. The drainage tube was lost within 12 weeks. The neo-EBD could withstand normal biliary pressure 2 weeks after surgery. Histological study showed the accessory glands and epithelial cells gradually regenerated at graft sites from 4 weeks, with increasing vessel infiltration and decreasing inflammation. The collagen fibers became regular with full coverage of epithelial cells. The statistical analysis of diameter and thickness showed no stricture formation at the graft site, but the EBD wall was slightly thicker than in the normal bile duct due to collagen fiber deposition. The structure of the neo-EBD was similar to that of the normal EBD. The collagen membrane patch associated with a drainage tube and wrapped with greater omentum effectively induced the regeneration of the EBD defect within 12 weeks.

Pacemakers in extrahepatic biliary ducts.

Pacemaker cells in the biliary system were studied by using electromyographic and histological methods. The pacemaker cells of the duodenal-biliary complex are located in the bile duct (predominantly, in its proximal part). They are characterized with enhanced spontaneous spike and slow-wave electrical activity. The pacemaker cells organize the sequential motor activity of the proximal and distal portions of ductus choledochus, with subsequent involvement of the duodenum into this activity.

Ceftriaxone-associated Pseudolithiasis in the Gallbladder and Bile Duct of an Elderly Patient.

A 78-year-old man had been undergoing treatment with Cefamezin for pyogenic spondylitis. Because of complication of a urinary tract infection, the medication was switched to ceftriaxone (CTRX) 2 g/day. On day 18 after starting CTRX, the patient began experiencing abdominal pain. Computed tomography (CT) and endoscopic ultrasound led to the identification of calculi in the gallbladder and extrahepatic bile duct with a peculiar formation. We suspected CTRX-associated pseudo-cholecystolithiasis and pseudo-choledocholithiasis, although CT performed at admission had shown no such findings. Therefore, CTRX was discontinued. By day 17 after CTRX cessation, both the pseudo-cholecystolithiasis and pseudo-choledocholithiasis had disappeared.

Synchronous Double Bile Duct Cancers with Distinct Genetic Features.

A 69-year-old man was referred to our hospital because of appetite loss. Imaging showed a nodular tumor in the perihilar bile duct and a second flat lesion in the distal bile duct. Right hepatopancreaticoduodenectomy was performed, and the histopathological findings demonstrated that the perihilar and distal lesions were moderately and poorly differentiated adenocarcinoma, respectively, and anatomically separated. Furthermore, the resected specimens showed no pancreaticobiliary maljunction. Histological and TP53 gene analyses in a rare case of synchronous double bile duct cancers suggest that there are various genetic pathways through which bile duct cancer develops, highlighting the complexity of its pathogenesis.

Extrahepatic bile duct injury caused by a horse kicking injury.

A 35-year-old man presented to a regional hospital after being kicked by a horse in the right upper quadrant. He was transferred to our hepatobiliary unit with bile peritonitis 8 days post trauma. Laparoscopic cholecystectomy and intraoperative cholangiography were performed, demonstrating distal common bile duct (CBD) obstruction with contrast extravasation from the distal duct. The CBD was drained with a T-tube via laparotomy. On postoperative day 14, T-tube cholangiography demonstrated no extravasation of contrast from the distal CBD and minor stricturing with eventual duodenal drainage. The T-tube was clamped and 5 weeks later, the patient represented with peri-T-tube bile leakage and right upper quadrant pain. A T-tube cholangiogram confirmed a complex distal CBD stricture. Two attempts at ERCP with intent of stenting the stricture were unsuccessful. The patient underwent an end to side Roux-en-Y choledochojejunostomy and was discharged home 4 days postoperatively on simple analgesia.

Primary Langerhans Cell Histiocytosis of the Extrahepatic Bile Duct Occurring in an Adult Patient

Background: Langerhans cell histiocytosis is characterized by an abnormal proliferation of neoplastic Langerhans cells. Langerhans cell histiocytosis commonly affects the pediatric population, whereas presentation in adults remains a rare event. The presentation of Langerhans cell histiocytosis is highly variable, but the involvement of skin, bone, and lung is very common. Langerhans cell histiocytosis presenting as a bile duct mass is rare and usually occurs as part of a multiorgan system disease. Case Report: We present a case of Langerhans cell histiocytosis confined to the extrahepatic bile duct in a 62-year-old female patient with sclerosing cholangitis. The mass was composed of mononuclear cells with cleaved nuclei that were positive for CD68, S100, and CD1a as assessed by immunohistochemistry. Conclusion: This is the first report of Langerhans cell histiocytosis limited to the extrahepatic bile duct in an adult patient. We discuss the clinical manifestations and the challenges encountered in the diagnosis and treatment of this rare entity.

Biogenic amine actions on cholangiocyte function.

Biogenic amines, such as serotonin, histamine, dopamine, and the catecholamines epinephrine and norepinephrine, regulate a multitude of cellular responses. A great deal of effort has been invested into understanding the effects of these molecules and their corresponding receptor systems on cholangiocyte secretion, apoptosis, and growth. This review summarizes the results of these efforts and highlights the importance of these regulatory molecules on the physiology and pathophysiology of cholangiocytes.

Bi-directional regulation of acupuncture on extrahepatic biliary system: An approach in guinea pigs.

Clinically, acupuncture affects the motility of the extrahepatic biliary tract, but the underlining mechanisms are still unknown. We applied manual acupuncture (MA) and electrical acupuncture (EA) separately at acupoints Tianshu (ST25), Qimen (LR14), Yanglingquan (GB34), and Yidan (CO11) in forty guinea pigs (4 groups) with or without atropinization under anesthesia while Sphincter of Oddi (SO) myoelectric activities and gallbladder pressure were monitored. In both MA and EA groups, stimulation at ST25 or LR14 significantly increased the frequency and amplitude of SO myoelectrical activities and simultaneously decreased the gallbladder pressure as compared to the pre-MA and pre-EA (P < 0.05). On the contrary, stimulation at GB34 or CO11 significantly decreased SO myoelectricity and increased the gallbladder pressure (P < 0.05). Pretreatment with atropine could abolish the effect of stimulation at acupoints ST25, GB34 and LR14 (P > 0.05), although significant myoelectricity increases were still inducible with MA or EA stimulation at CO11 (P < 0.05). In summary, acupuncture has bi-directional effects to gallbladder pressure and SO function, which probably due to autonomic reflex and somatovisceral interactions.

Biliary wound healing, ductular reactions, and IL-6/gp130 signaling in the development of liver disease.

Basic and translational wound healing research in the biliary tree lag significantly behind similar studies on the skin and gastrointestinal tract. This is at least partly attributable to lack of easy access to the biliary tract for study. But clinical relevance, more interest in biliary epithelial cell (BEC) pathophysiology, and widespread availability of BEC cultures are factors reversing this trend. In the extra-hepatic biliary tree, ineffectual wound healing, scarring and stricture development are pressing issues. In the smallest intra-hepatic bile ducts either impaired BEC proliferation or an exuberant response can contribute to liver disease. Chronic inflammation and persistent wound healing reactions in large and small bile ducts often lead to liver cancer. General concepts of wound healing as they apply to the biliary tract, importance of cellular processes dependent on IL-6/gp130/STAT3 signaling pathways, unanswered questions, and future directions are discussed.

Biliary carcinoma risk in patients with pancreaticobiliary maljunction and the degree of extrahepatic bile duct dilatation.

BACKGROUND/AIMS: Pancreaticobiliary maljunction (PBM) carries a high risk of biliary carcinoma. This study aimed to examine the biliary complications of patients with PBM in relation to the degree of extra-hepatic bile duct dilatation. METHODOLOGY: Ninety-eight cases of PBM could be divided into 5 groups according to the maximum diameter of the extrahepatic bile duct: < or = 10mm, 11-15mm, 16-20mm, 21-30mm, > or = 31mm. The clinicopathological findings of biliary carcinomas associated with PBM were compared with 232 cases of gallbladder carcinoma and 159 cases of bile duct carcinoma that were not associated with PBM. RESULTS: Gallbladder carcinoma occurred in 36 of 65 patients (55%) with PBM whose maximum diameter of the extrahepatic bile duct was < or = 30mm, but no gallbladder carcinoma occurred in patients with PBM whose diameter was > or = 31mm. Bile duct carcinoma occurred in 6 of 52 patients (12%) with PBM whose diameter was > or = 21mm, but no bile duct carcinoma occurred in patients with PBM whose diameter was < or = 20mm. The age at diagnosis of the patients with gallbladder or bile duct carcinoma associated with PBM was significantly younger than those without PBM (p<0.01). CONCLUSIONS: PBM with an extrahepatic bile duct diameter < or = 30mm is associated with a high risk of gallbladder carcinoma. PBM with an extrahepatic bile duct diameter > or = 21mm is associated with a high risk of bile duct carcinoma. Prophylactic cholecystectomy is recommended for patients with PBM without biliary dilatation.

Overweight, obesity and the risk of gallbladder and extrahepatic bile duct cancers: A meta-analysis of observational studies.

OBJECTIVE: Epidemiological studies have repeatedly investigated the association between excess body weight and the risk of biliary tract cancer with inconsistent results. The objective of this study was to quantitatively assess the associations between overweight and obesity and the risk of biliary tract cancer. METHODS: A comprehensive search of PubMed, Embase, Web of Science, and China National Knowledge Infrastructure databases up to August 2015 was conducted, and the reference lists of retrieved articles for additional relevant studies were manually searched. RESULTS: Fourteen prospective cohort studies and 15 case-control studies were included in this meta-analysis. These studies included 11,448,397 participants (6,733 patients with gallbladder cancer [GBC] and 5,798 patients with extrahepatic bile duct cancer [EBDC]) with follow-up durations ranging from 5 to 23 years. Among overweight adults, the pooled RR was 1.17 (95% CI, 1.07-1.28) for GBC and 1.26 (95% CI, 1.14-1.39) for EBDC, and among people with obesity, the pooled RR was 1.62 (95% CI, 1.49-1.75) for GBC and 1.48 (95% CI, 1.21-1.81) for EBDC. Visual inspection of the funnel plots and the Begg's and the Egger's tests did not show enough evidence of publication bias. CONCLUSIONS: Integrated evidence from this meta-analysis suggests that excess body weight is associated with a significantly increased risk of GBC and EBDC.

Diffusion-weighted imaging of biliopancreatic disorders: correlation with conventional magnetic resonance imaging.

Diffusion-weighted magnetic resonance imaging (DWI) is a well established method for the evaluation of intracranial diseases, such as acute stroke. DWI for extracranial application is more difficult due to physiological motion artifacts and the heterogeneous composition of the organs. However, thanks to the newer technical development of DWI, DWI has become increasingly used over the past few years in extracranial organs including the abdomen and pelvis. Most previous studies of DWI have been limited to the evaluation of diffuse parenchymal abnormalities and focal lesions in abdominal organs, whereas there are few studies about DWI for the evaluation of the biliopancreatic tract. Although further studies are needed to determine its performance in evaluating bile duct, gallbladder and pancreas diseases, DWI has potential in the assessment of the functional information on the biliopancreatic tract concerning the status of tissue cellularity, because increased cellularity is associated with impeded diffusion, as indicated by a reduction in the apparent diffusion coefficient. The detection of malignant lesions and their differentiation from benign tumor-like lesions in the biliopancreatic tract could be improved using DWI in conjunction with findings obtained with conventional magnetic resonance cholagiopancreatography. Additionally, DWI can be useful for the assessment of the biliopancreatic tract in patients with renal impairment because contrast-enhanced computed tomography or magnetic resonance scans should be avoided in these patients.

Computed tomography virtual endoscopy with angiographic imaging for the treatment of type IV-A choledochal cyst.

Type IV-A choledochal cysts (CCs) are a congenital biliary anomaly which involve dilatation of the extrahepatic and intrahepatic bile ducts. We present the case of a 30-year-old woman with type IV-A CC, on whom three-dimensional computed tomography (3D CT) and virtual endoscopy were performed. 3D CT revealed partial dilatation in the posterior branch of the intrahepatic bile duct and a relative stricture between it and the extrahepatic bile duct. Virtual endoscopy showed that this stricture was membrane-like and separated from the surrounding blood vessels. Based on these image findings, complete cyst resection, bile duct plasty for the stricture, and hepaticojejunostomy were safely performed. To the best of our knowledge, there are no reports of imaging by virtual endoscopy of the biliary tract which show the surrounding blood vessels running along the bile duct.

Influence of glutamine on morphological and functional changes of liver in the presence of extrahepatic biliary obstruction in rats.

PURPOSE: To study the influence of glutamine on functional and morphological changes of liver in the extrahepatic biliary obstruction through an experimental model in rats. METHODS: Seventy Wistar rats were divided into four groups: control (group C) fictitious operation, (group FO), submitted to laparotomy with handling of bile ducts, but without hepatic duct ligation, (group EBO) submitted to laparotomy and hepatic duct ligation, one of them submitted to supplementation with glutamine 2% (group G). The control group consisted of 6 animals. The animals from groups FO, EBO and G were divided into three groups consisting of 6 animals each, being sacrificed at 7, 14 and 21 days after operation, respectively. Blood samples were collected for biochemical analysis and a fragment of liver tissue was collected from the middle lobe for histological analysis. RESULTS: Both for biochemical analysis (BT, aspartate and alanine aminotransferase AST, ALT and alkaline phosphatase FAL) and for histopathological changes (fibrosis, portal inflammation, parenchymal inflammation, hepatocytic changes and duct proliferation), no statistical difference between groups submitted to extrahepatic biliary obstruction (EBO) with and without treatment with glutamine (G) was observed. CONCLUSION: Glutamine supplementation did not alter the prognosis of liver enzymes and histopathological changes in animals submitted to extrahepatic biliary obstruction.