Efficacy and safety of conversion of percutaneous cholecystostomy to endoscopic transpapillary gallbladder stenting in high-risk surgical patients.

BACKGROUND: Endoscopic transpapillary gallbladder stenting (ETGBS) has been used as an alternative to percutaneous cholecystostomy in patients with acute cholecystitis who are considered unfit for surgery. However, there are few data on the efficacy and safety of ETGBS replacement of percutaneous cholecystostomy in high-risk surgical patients. This study aimed to evaluate the feasibility, efficacy, and safety of ETGBS to replace percutaneous cholecystostomy in high-risk surgical patients. METHODS: This single center retrospective study reviewed the data of patients who attempted ETGBS to replace percutaneous cholecystostomy between January 2017 and September 2019. The technical success, clinical success, adverse events, and stent patency were evaluated. RESULTS: ETGBS was performed in 43 patients (24 male, mean age 80.7 ± 7.4 years) to replace percutaneous cholecystostomy due to high surgical risk. The technical success rate and clinical success rate were 97.7% (42/43) and 90.5% (38/42), respectively. Procedure-related adverse events and stent-related late adverse events occurred in 7.0% (3/43) and 11.6% (5/43), respectively. Of the patients who successfully underwent ETGBS (n = 42), only one had recurrent acute cholecystitis during follow-up. The median stent patency was 415 days (interquartile range 240-528 days). CONCLUSIONS: ETGBS, as a secondary intervention for the purpose of internalizing gallbladder drainage in patients following placement of a percutaneous cholecystostomy, is safe, effective, and technically feasible. Thus, conversion of percutaneous cholecystostomy to ETGBS may be considered as a viable option in high-risk surgical patients.

Comparison of Virtual Unenhanced Images Derived From Dual-Energy CT With True Unenhanced Images in Evaluation of Gallstone Disease.

OBJECTIVE: The aim of this study was to compare gallstones on virtual unenhanced images and true unenhanced images acquired with dual-energy CT (DECT). MATERIALS AND METHODS: We enrolled 112 patients with right upper quadrant pain and clinically suspected acute cholecystitis or gallstone who underwent DECT--including unenhanced, arterial, and portal phases. Eighty-three gallstones with composition proven by semiquantitative Fourier transform infrared spectroscopy from 45 patients who had undergone cholecystectomy (40 cholesterol gallstones from 21 patients, 43 calcium gallstones from 24 patients) were included. CT images were retrospectively evaluated for stone size, contrast-to-noise ratio (CNR) of gallstone to bile, and visibility and density of gallstones for each image set. The visibility of each type of stone was compared with a paired t test. RESULTS: Both cholesterol and calcium stones measured smaller on virtual unenhanced images than on true unenhanced images, yielding a lower sensitivity of virtual unenhanced images for detecting small gallstones. Mean CNR of cholesterol stones was 2.45 ± 1.32 versus 1.67 ± 1.55 (p < 0.032) and that of calcium stones was 10.59 ± 7.15 and 14.11 ± 9.81 (p < 0.001) for virtual unenhanced and true unenhanced images, respectively. For calcium stones, two readers found 43 of 43 (100%) on true unenhanced images; one reader found 41 of 43 (95%) and the other, 37 of 43 (86%) on virtual unenhanced images. For cholesterol stones, one reader found 20 of 40 (50%) and the other 19 of 40 (47%) on true unenhanced images versus 34 of 40 (85%) and 30 of 40 (75%), respectively, on virtual unenhanced images. The visibility of cholesterol stones was higher on virtual unenhanced images, but that of calcium stones was lower. CONCLUSION: Virtual unenhanced images at DECT allow better visualization of cholesterol gallstones, but true unenhanced images allow better visualization of calcium and small gallstones.

USP47 and C terminus of Hsp70-interacting protein (CHIP) antagonistically regulate katanin-p60-mediated axonal growth.

Katanin is a heterodimeric enzyme that severs and disassembles microtubules. While the p60 subunit has the enzyme activity, the p80 subunit regulates the p60 activity. The microtubule-severing activity of katanin plays an essential role in axonal growth. However, the mechanisms by which neuronal cells regulate the expression of katanin-p60 remains unknown. Here we showed that USP47 and C terminus of Hsp70-interacting protein (CHIP) antagonistically regulate the stability of katanin-p60 and thereby axonal growth. USP47 was identified as a katanin-p60-specific deubiquitinating enzyme for its stabilization. We also identified CHIP as a ubiquitin E3 ligase that promotes proteasome-mediated degradation of katanin-p60. Moreover, USP47 promoted axonal growth of cultured rat hippocampal neurons, whereas CHIP inhibited it. Significantly, treatment with basic fibroblast growth factor (bFGF), an inducer of axonal growth, increased the levels of USP47 and katanin-p60, but not CHIP. Consistently, bFGF treatment resulted in a marked decrease in the level of ubiquitinated katanin-p60 and thereby in the promotion of axonal growth. On the other hand, the level of USP47, but not CHIP, decreased concurrently with that of katanin-p60 as axons reached their target cells. These results indicate that USP47 plays a crucial role in the control of axonal growth during neuronal development by antagonizing CHIP-mediated katanin-p60 degradation.

c-Cbl regulates αPix-mediated cell migration and invasion.

c-Cbl, a RING-type ubiquitin E3 ligase, down-regulates receptor tyrosine kinases, including EGF receptor, and inhibits cell proliferation. Moreover, c-Cbl mutations are frequently found in patients with myeloid neoplasm. Therefore, c-Cbl is known as a tumor suppressor. αPix is expressed only in highly proliferative and mobile cells, including immune cells, and up-regulated in certain invasive tumors, such as glioblastoma multiforme. Here, we showed that c-Cbl serves as an ubiquitin E3 ligase for proteasome-mediated degradation of αPix, but not ßPix. Remarkably, the rat C6 and human A172 glioma cells were unable to express c-Cbl, which leads to a dramatic accumulation of αPix. Depletion of αPix by shRNA markedly reduced the ability of the glioma cells to migrate and invade, whereas complementation of shRNA-insensitive αPix promoted it. These results indicate that c-Cbl negatively regulates αPix-mediated cell migration and invasion and the lack of c-Cbl in the C6 and A172 glioma cells is responsible for their malignant behavior.

Retropancreatic fascia is absent along the pancreas facing the superior mesenteric artery: a histological study using elderly donated cadavers.

To determine the fascial configuration between the superior mesenteric artery and vein and the posterior aspect of the pancreas, we examined histological sections of 10 elderly donated cadavers without pathology in the abdomen. The retropancreatic fascia was absent along the pancreatic parenchyma facing the artery and vein. Abundant nerves along the artery were separated from the pancreas by loose tissue almost 10 mm in thickness. In addition, anterior renal fasciae facing the pancreatic body were not evident in these specimens, possibly due to the degeneration of the left adrenal gland with age. Thus, a definite renal fascia was restricted on the lateral and posterior sides of the left kidney. These findings suggest that interactions between a pancreatic tumor and nerves would require migration of cancer cells over a long distance. Conversely, attachment of the enlarged tumor mass to the nerves may be necessary for the invasion. The anterior renal fascia may fuse with the retropancreatic fascia.

2',4',6'-Tris(methoxymethoxy) chalcone (TMMC) attenuates the severity of cerulein-induced acute pancreatitis and associated lung injury.

Acute pancreatitis (AP) is an inflammatory disease involving acinar cell injury and rapid production and release of inflammatory cytokines, which play a dominant role in local pancreatic inflammation and systemic complications. 2',4',6'-Tris (methoxymethoxy) chalcone (TMMC), a synthetic chalcone derivative, displays potent anti-inflammatory effects. Therefore, we aimed to investigate whether TMMC might affect the severity of AP and pancreatitis-associated lung injury in mice. We used the cerulein hyperstimulation model of AP. Severity of pancreatitis was determined in cerulein-injected mice by histological analysis and neutrophil sequestration. The pretreatment of mice with TMMC reduced the severity of AP and pancreatitis-associated lung injury and inhibited several biochemical parameters (activity of amylase, lipase, trypsin, trypsinogen, and myeloperoxidase and production of proinflammatory cytokines). In addition, TMMC inhibited pancreatic acinar cell death and production of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-6 by inhibiting NF-κB and extracellular signal-regulated protein kinase 1/2 (ERK1/2) activation. Neutralizing antibodies for TNF-α, IL-1ß, and IL-6 inhibited cerulein-induced cell death in isolated pancreatic acinar cells. Moreover, pharmacological blockade of NF-κB/ERK1/2 reduced acinar cell death and production of TNF-α, IL-1ß, and IL-6 in isolated pancreatic acinar cells. In addition, posttreatment of mice with TMMC showed reduced severity of AP and lung injury. Our results suggest that TMMC may reduce the complications associated with pancreatitis.

Ruptured Pancreaticoduodenal Artery Aneurysm with Pancreatitis Treated Using Endovascular and Endoscopic Methods.

Pancreaticoduodenal artery aneurysm (PDAA) is a rare form of abdominal visceral aneurysm that accounts for approximately 2% of all cases. Most cases of PDAA are associated with celiac artery stenosis (CAS). Regardless of the size, there is a risk of rupture. Therefore, treatment should be performed immediately after discovery, even though the need to treat the accompanying CAS, if present, is controversial. The authors report a case of ruptured PDAA and accompanying pancreatitis treated using endovascular and endoscopic methods without treatment of CAS. A 50-year-old man was admitted to the emergency department of Wonkwang University Hospital with epigastric pain and hypovolemic shock. CT revealed a ruptured PDAA and a large volume hemoperitoneum. Emergency angiography was performed, and angioembolization of the PDAA was performed successfully. Follow-up CT revealed infection and pancreatitis, which were treated by surgical drainage and pancreatic duct stenting with ERCP. Because the degree of stenosis was not severe, it was decided to follow-up the accompanying CAS. After discharge, the patient was followed up without complications.

Endoscopic transpapillary gallbladder drainage for the management of acute calculus cholecystitis patients unfit for urgent cholecystectomy.

OBJECTIVES: Endoscopic transpapillary gallbladder drainage (ETGBD) has been proposed as an alternative to surgery or percutaneous cholecystostomy in patients with acute calculus cholecystitis (ACC). We aimed to evaluate the safety and efficacy of ETGBD via endoscopic transpapillary gallbladder stenting (ETGBS) or endoscopic naso-gallbladder drainage (ENGBD) as either a bridging or a definitive treatment option for patients with ACC when a cholecystectomy is delayed or cannot be performed. METHODS: From July 2014 to December 2018, 171 patients with ACC in whom ETGBD were attempted were retrospectively reviewed. The technical and clinical success rates and adverse events were evaluated. Moreover, the predictive factors for technical success and the stent patency in the ETGBS group with high surgical risk were examined. RESULTS: The technical and clinical success rates by intention-to-treat analysis for ETGBD were 90.6% (155/171) and 90.1% (154/171), respectively. Visible cystic duct on cholangiography were significant technical success predictor (adjusted odds ratio: 7.099, 95% confidence interval: 1.983-25.407, P = 0.003) as per logistic regression analysis. Adverse events occurred in 12.2% of patients (21/171: mild pancreatitis, n = 9; acute cholangitis, n = 6; post-endoscopic sphincterotomy bleeding, n = 4; and stent migration, n = 1; ACC recurrence, n = 1), but all patients were treated with conservative management and endoscopic treatment. Among the ETGBS group, the median stent patency in 70 patients with high surgical risk was 503 days (interquartile range: 404.25-775 days). CONCLUSIONS: ETGBD, using either ETGBS or ENGBD, may be a suitable bridging option for ACC patients unfit for urgent cholecystectomy. In high surgical risk patients, ETGBS may be a promising and useful treatment modality with low ACC recurrence.

[A case of hepatocellular carcinoma invading the gallbladder misdiagnosed as a primary gallbladder carcinoma].

Extrahepatic metastasis of hepatocellular carcinoma (HCC) is occasionally seen in the lung, bone, adrenal gland, and lymph nodes. It is well known that HCC sometimes invades the biliary system. Since there is no peritoneum between the gallbladder and the liver fossa, a gallbladder cancer easily invades the liver; however, HCC seldom invades the gallbladder because it rarely destroys the muscle layer or the collagen fibers of the gallbladder wall. Routes of gallbladder metastasis of HCC include direct invasion, extension to the biliary system, and invasion of the adjacent hepatic vascular system. Some cases of gallbladder metastasis of HCC without direct invasion have been reported. We report here a case of HCC that directly invaded the gallbladder, and that resembled gallbladder carcinoma invading the liver.

Mucinous Non-neoplastic Cyst of the Pancreas.

Cystic neoplasms of the pancreas consist of a wide range of pathological entities and are being detected more frequently due to advances in cross-sectional imaging modalities and increasing numbers of periodic health checkups. The majority of pancreatic cystic neoplasms are intraductal papillary mucinous neoplasms, serous neoplasms, and mucinous cystic neoplasms, but recently, rare cases of mucinous non-neoplastic cyst of the pancreas (MNCP) have been reported, and despite the availabilities of modern imaging systems, such as MRI and CT, the differentiation of non-neoplastic and neoplastic cysts remains challenging. Herein, we report our experience of a 65-year-old male case with an MNCP.

Increased lysine N-methylation of a 23-kDa protein during hepatic regeneration.

The methylation of a 23-kDa nuclear protein increased after partial hepatectomy and methylation returned to basal levels after the initial stage of regeneration. The methylating enzyme was partially purified from rat liver by ammonium sulfate precipitation, DEAE-anion exchange chromatography and Butyl-Sepharose chromatography. The 23-kDa protein was purified from a nuclear fraction of liver tissue with SP-Sepharose. When the 23-kDa protein was methylated with the partially purified methyltransferase and analyzed on C(18) high performance liquid chromatography (HPLC), the methylated acceptor amino acid was monomethyl lysine (MML). Previously, only arginine N-methylation of specific substrate proteins has been reported during liver regeneration. However, in this report, we found that lysine N-methylation increased during early hepatic regeneration, suggesting that lysine N-methylation of the 23-kDa nuclear protein may play a functional role in hepatic regeneration. The methyltransferase did not methylate other proteins such as histones, hnRNPA1, or cytochrome C, suggesting the enzyme is a 23-kDa nuclear protein- specific lysine N-methyltransferase.

Timing of Cholecystectomy after Percutaneous Cholecystostomy for Acute Cholecystitis.

BACKGROUND/AIMS: Laparoscopic cholecystectomy is the standard treatment for acute cholecystitis. Percutaneous cholecystostomy is an alternative treatment to resolve acute inflammation in patients with severe comorbidities. The purpose of this study is to determine the optimal timing of laparoscopic cholecystectomy after percutaneous cholecystostomy for the patients with acute cholecystitis. METHODS: This retrospective study was conducted in patients who underwent cholecystectomy after percutaneous cholecystostomy from January 2010 through November 2014. Seventy-four patients were included in this study. The patients were divided into two groups by the operation timing. Group I patients underwent cholecystectomy within 10 days after percutaneous cholecystostomy (n=30) and group II patients underwent cholecystectomy at more than 10 days after percutaneous cholecystostomy (n=44). RESULTS: There was no significant difference between groups in conversion rate to open surgery, operation time, perioperative complications rate, and days of hospital stay after operation. However, complications related to cholecystostomy such as catheter dislodgement occurred significantly more often in group II than group I (group I:group II=0%:18.2%; p=0.013). CONCLUSIONS: Timing of laparoscopic cholecystectomy after percutaneous cholecystostomy did not influence postoperative outcomes. However, late surgery caused more complications related to cholecystostomy than early surgery. Therefore, early laparoscopic cholecystectomy should be considered over late surgery after percutaneous cholecystostomy insertion.

Overexpression of betaPix-a in human breast cancer tissues.

Pak interacting exchange factor (betaPix) is a recently cloned protein that contains a multidomain with many potential binding sites and is known to be involved in the regulation of Cdc42/Rac GTPases and Pak kinase activity. These domains of betaPix appear to play a critical role in the regulation of the cytoskeletal organization. The overexpression of betaPix enhances the activation of p38, which is thought to be an important downstream effector of the Rho GTPase family (Rac, Cdc42), which are involved in increased membrane ruffling and cell motility. This increase of cell mobility is an important feature of cancer invasion. We examined the expression of betaPix-a in human breast cancer tissues and adjacent normal tissues obtained from 39 breast cancer patients. Immunoblot analysis and RT-PCR revealed that betaPix-a expression was significantly increased in 37 of the 39 breast cancer tissues (94.9%) versus normal breast tissues. Immunohistochemical analysis showed that breast cancer tissues have consistently stronger immunoreactivity to betaPix-a antibodies than normal tissues. betaPix-a overexpression was inversely associated with extensive intraductal component (P<0.001). In conclusion, betaPix-a expression was found to be higher in human breast cancer tissues than in normal breast tissues, which implies a role for betaPix-a in human breast tumorigenesis. We suggest that betaPix-a may be a useful marker of malignant disease in the breast.

Management of inferior vena cava thrombosis after blunt liver injury.

Inferior vena cava (IVC) thrombosis after traumatic liver injury is an extremely rare condition, and only 12 cases have been reported in the English literature since 1911. We report a case of a 26-year-old man who presented with IVC thrombosis after blunt liver injury. IVC thrombosis was incidentally detected by computed tomography 15 days after conservative management of blunt liver injury. The patient denied any symptoms of thrombophlebitis and did not have any evidence of hypercoagulable state. We placed an IVC filter via the right jugular vein and started the anticoagulation treatment. The patient recovered successfully without operative treatment and IVC thrombosis disappeared completely two months later. We suggest that that the possibility of IVC thrombosis should be considered in patients with a large hematoma of the liver, which may cause compression of the IVC.

Effect of quercetin on apoptosis of PANC-1 cells.

PURPOSE: To investigate the chemotherapeutic effect of quercetin against cancer cells, signaling pathway of apoptosis was explored in human pancreatic cells. METHODS: Various anticancer drugs including adriamycin, cisplatin, 5-fluorouracil (5-FU) and gemcitabine were used. Cell viability was measured by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphe-nyltetra zolium bromide assay. Apoptosis was determined by 4'-6-diamidino-2-phenylindole nuclei staining and flow cytometry in PANC-1 cells treated with 50 µg/mL quercetin for 24 hours. Expression of endoplas mic reticulum (ER) stress mediators including, Grp78/Bip, p-PERK, PERK, ATF4, ATF6 and GADD153/CHOP proteins were measured by Western blot analysis. Mitochondrial membrane potential was measured by fluorescence staining with JC-1, rhodamine 123. Quercetin induced the apoptosis of PANC-1, which was characterized as nucleic acid and genomic DNA fragmentation, chromatin condensation, and sub-G0/G1 fraction of cell cycle increase. But not adriamycin, cisplatin, gemcitabine, and 5-FU. PANC-1 cells were markedly sensitive to quercetin. RESULTS: Treatment with quercetin resulted in the increased accumulation of intracellular Ca(2+) ion. Treatment with quercetin also increased the expression of Grp78/Bip and GADD153/CHOP protein and induced mitochondrial dysfunction. Quercetin exerted cytotoxicity against human pancreatic cancer cells via ER stress-mediated apoptotic signaling including reactive oxygen species production and mitochondrial dysfunction. CONCLUSION: These data suggest that quercetin may be an important modulator of chemosensitivity of cancer cells against anticancer chemotherapeutic agents.

Successful percutaneous management of bronchobiliary fistula after radiofrequency ablation of metastatic cholangiocarcinoma in a patient who has a postoperative stricture of hepaticojejunostomy site.

Bronchobiliary fistula (BBF) is a rare condition that is defined as an abnormal communication between the biliary system and bronchial tree. Furthermore, a BBF is an extremely rare complication of radiofrequency ablation (RFA). A 54 year-old man with a history of extrahepatic biliary cancer had been suffering with a benign stricture of hepaticojejunostomy site and was treated with RFA for metastatic cholangicarcinoma. In this report, we describe a patient with BBF complicated by an abscess which occurred after RFA. He was treated by placement of external drainage catheter into the liver abscess and percutaneous transhepatic biliary drainage (PTBD) into the right intrahepatic duct. After 6 weeks, a complete obliteration of the BBF was confirmed by a repeated follow-up of computed tomography scan and cholangiography through PTBD.

Clinical results between single incision laparoscopic cholecystectomy and conventional 3-port laparoscopic cholecystectomy: prospective case-matched analysis in single institution.

PURPOSE: The aim of our study was to compare single incision laparoscopic cholecystectomy (SILC) and conventional laparoscopic cholecystectomy (CLC) with respect to clinical outcomes. METHODS: Patients with less than a 28 body mass index (BMI) and a benign gall bladder disease were enrolled in this study. From January 2011 to February 2012, 30 consecutive patients who underwent SILC were compared with 30 patients who underwent CLC during the same period. In this study, all operations were performed by one surgeon. In each group, patient characteristics and perioperative data were collected. RESULTS: There was no significant difference in the preoperative characteristics. There was no significant difference in the postoperative laboratory result (alanine aminotransferase, aspartate aminotransferase, and alanine aminotransferase), number of conversion and complication cases, and length of hospital stay. The operation time was significantly longer in the SILC group (78.5 ± 17.8 minutes in SILC group vs. 34.9 ± 5.75 minutes in CLC group, P < 0.0001). The total nonsteroidal antiinflammatory drug usage during perioperative period showed significantly higher in SILC groups (162 ± 51 mg in the SILC group vs. 138 ± 30 mg in the CLC group), but there was no statistically significant difference in opioid usage between two groups. The postoperative pain score was significantly higher in the SILC group at second, third, and tenth postoperative day. Satisfaction of postoperative wound showed superiority in SILC group. CONCLUSION: SILC seems to be an acceptable alternative to CLC with acceptable results. However, it is not enough to propose any real benefits of SILC when compared with CLC in terms of operation time and postoperative pain.

Huge subcapsular hematoma caused by intrahepatic sarcomatoid cholangiocarcinoma.

Intrahepatic sarcomatoid cholangiocarcinomais is a very rare disease with a poor prognosis due to its biologically aggressive tumor behavior. We report a patient who presented with subcapsular hemorrhage and a rapidly growing liver mass. A 57 year-old man was admitted with severe abdominal pain. CT and MRI images showed the presence of a 10 cm-sized subcapsular hemorrhage connected with a multi-lobulated mass with hemorrhage and necrotic foci in the right liver. The patients underwent right hemihepatectomy with caudate lobectomy and lymphadenectomy. The operation findings revealed metastatic nodules to the diaphragm and omentum. Detailed histopathological analysis through immunohistochemistry confirmed the diagnosis of sarcomatoid cholangiocarcinoma with a poorly undifferentiated sarcomatous component. The patient underwent chemotherapy. To date, the patient is doing well for 8 months after initial diagnosis.

Application of single incision laparoscopic surgery for appendectomy in children.

PURPOSE: Recently, single incision laparoscopic surgery (SILS) has been popular in use with its progress studied for more minimally invasive surgery and cosmetic improvement. We investigated the feasibility and efficacy of SILS for appendectomy (SILS-A) in children and compare it with conventional laparoscopic appendectomy (C-LA). METHODS: We studied, retrospectively, adolescent patients who underwent C-LA or SILS-A. There were 25 patients in the C-LA group and 30 patients in the SILS-A group. The clinical outcomes were compared between the groups. RESULTS: The SILS-A procedures were performed successfully in adolescent patients . There were no significant difference between the C-LA and SILS-A group with respect to demographic data and post-operative outcomes. There was one complication (4%) in the C-LA group and two complications (6.6%) in the SILS-A group, but there was no significant difference. CONCLUSION: SILS-A was technically feasible and safe in children. Considering little postoperative scar and no difference in post-operative outcomes compared to C-LA, SILA could be applicable in adolescent patients. Larger studies and further technical implements will be necessary to assess the true benefit of this approach.

Chylous ascites caused by acute pancreatitis with portal vein thrombosis.

Chylous ascites is defined as the accumulation of chyle in the peritoneum due to obstruction or rupture of the peritoneal or retroperitoneal lymphatic glands. Chylous ascites that arises from acute pancreatitis with portal vein thrombosis is very rare. We report here on a case of chylous ascite that was caused by acute pancreatitis with portal vein thrombosis, in which the patient showed an impressive response to conservative therapy with total parenteral nutrition and octerotide. We also review the relevant literature about chylous ascites with particular reference to the management of this rare disease.