Management of complex glottic stenosis in children with recurrent respiratory papillomatosis.

PubMed

Siegel, Bianca; Smith, Lee P

2013-10-01

To describe our management of complex glottic stenosis in tracheotomy dependent children with severe recurrent respiratory papillomatosis. Retrospective chart review at a tertiary care children's hospital. Three children with complex glottic stenosis secondary to severe recurrent respiratory papillomatosis were treated at our institution since 2011. Two patients had complete stenosis, and the third had near-complete stenosis. Two patients were managed using balloon dilation alone, and the third also underwent laryngotracheal reconstruction with posterior costal cartilage grafting. Two patients have been successfully decannulated and the third has been tolerating continuous tracheotomy capping for greater than twelve months. All three patients underwent aggressive debridement of papillomatosis and balloon dilation every 4-6 weeks until their burden of disease was controlled. In two patients, the glottic airway was patent, and the third continued to have complete restenosis between procedures and required laryngotracheoplasty with multiple post-operative dilation procedures to establish an adequate glottic airway. Severe laryngeal stenosis is a well-described complication of recurrent respiratory papillomatosis, but its management is not well-defined. Aggressive management of papillomatosis with frequent debridement is critical in successfully managing laryngeal stenosis. Balloon dilation alone may be surprisingly effective in these patients, and laryngotracheoplasty can be used as an adjunct procedure in those patients who fail balloon dilation. Given the quality of life issues and concerns regarding distal spread of disease with tracheotomies in these patients, we feel that aggressive management and early decannulation is in the patient's best interest. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Polycystic Ovarian Syndrome-associated Confluent and Reticulated Papillomatosis: Report of a Patient Successfully Treated with Azithromycin.

PubMed

Fite, Laura Paul; Cohen, Philip R

2017-09-01

Polycystic ovarian syndrome is a common endocrine disorder with a variety of dermatologic manifestations among young women. Confluent and reticulated papillomatosis is a rare dermatosis of unknown etiology that is seldom reported in patients with polycystic ovarian syndrome. We describe the case of a young woman with obesity, confluent and reticulated papillomatosis, and concurrent acanthosis nigricans. Her history, physical examination, and laboratory evaluation led to the diagnosis of polycystic ovarian syndrome. The proposed etiologies and the various of treatment options for confluent and reticulated papillomatosis are discussed. In our case, the patient had a dramatic response to treatment with azithromycin. The etiology of confluent and reticulated papillomatosis remains to be established. Additionally, the mechanism behind the success of treatment with antibiotics is unclear; however, in this patient, azithromycin was a safe and effective option for the treatment of confluent and reticulated papillomatosis.

Juvenile Papillomatosis of the Breast in a Pre-Pubertal Girl: An Uncommon Diagnosis.

PubMed

Kafadar, Mehmet Tolga; Anadolulu, Zeynep; Anadolulu, Ali İhsan; Tarini, Emine Zeynep

2018-01-01

Juvenile papillomatosis of the breast represents a rare benign proliferative disorder that affects women younger than thirty years of age. Although it is a localized lesion, it does not have well-demarcated margins. These patients tend to have a strong family history for cancer. As it has similar clinical presentation with that of a fibroadenoma, it usually receives the diagnosis of the latter in the preoperative period. Nonetheless, it has distinct microscopic features such as ductal papillomatosis and cysts that are helpful in the diagnosis. In this article, a case of juvenile papillomatosis diagnosed in a young girl who presented due to a mass of the breast was presented. For the fairly rare case, a total mass excision was performed with preserved breast tissue. The exact diagnosis was made by postoperative histopathological examination.

Mucinous Cystic Neoplasm of the Liver or Intraductal Papillary Mucinous Neoplasm of the Bile Duct? A Case Report and a Review of Literature.

PubMed

Kunovsky, Lumir; Kala, Zdenek; Svaton, Roman; Moravcik, Petr; Mazanec, Jan; Husty, Jakub; Prochazka, Vladimir

2018-01-01

Mucinous cystic neoplasm of the liver (MCN-L) and intraductal papillary mucinous neoplasm of the bile duct (IPMN-B) are diagnoses that were classified by the World Health Organization in 2010 as mucin-producing bile duct tumors of the hepatobiliary system. The preoperative differential diagnosis between these two entities is difficult; the presence of a communication with the bile duct is usually considered as a typical sign of IPMN-B. However, the presence of an ovarian-like stroma (OLS) has been established to define the diagnosis of MCN-L. We present the case of a 33-year-old woman with a rapid progression of a cystic tumor of the liver. In 2 years, the lesion increased from 27 to 64 mm and a dilation of the left hepatic duct appeared. Percutaneous transhepatic drainage with a biopsy was performed. No malignant cells were found on biopsy. Because of the rapid progression of the cystic tumor and unclear malignant potential, left hemihepatectomy was performed. Even though tumor masses were present in the biliary duct, on the basis of the presence of OLS, histology finally confirmed MCN-L with intermediate-grade intraepithelial dysplasia to high-grade intraepithelial dysplasia. The patient is currently under oncologic follow-up with no signs of recurrence of the disease. We present a rare case where MCN-L caused a dilation of the left hepatic duct, a sign that is usually a characteristic of IPMN-B.

Hydrogen-rich saline inhibits tobacco smoke-induced chronic obstructive pulmonary disease by alleviating airway inflammation and mucus hypersecretion in rats.

PubMed

Liu, Zibing; Geng, Wenye; Jiang, Chuanwei; Zhao, Shujun; Liu, Yong; Zhang, Ying; Qin, Shucun; Li, Chenxu; Zhang, Xinfang; Si, Yanhong

2017-09-01

Chronic obstructive pulmonary disease induced by tobacco smoke has been regarded as a great health problem worldwide. The purpose of this study is to evaluate the protective effect of hydrogen-rich saline, a novel antioxidant, on chronic obstructive pulmonary disease and explore the underlying mechanism. Sprague-Dawley rats were made chronic obstructive pulmonary disease models via tobacco smoke exposure for 12 weeks and the rats were treated with 10 ml/kg hydrogen-rich saline intraperitoneally during the last 4 weeks. Lung function testing indicated hydrogen-rich saline decreased lung airway resistance and increased lung compliance and the ratio of forced expiratory volume in 0.1 s/forced vital capacity in chronic obstructive pulmonary disease rats. Histological analysis revealed that hydrogen-rich saline alleviated morphological impairments of lung in tobacco smoke-induced chronic obstructive pulmonary disease rats. ELISA assay showed hydrogen-rich saline lowered the levels of pro-inflammatory cytokines (IL-8 and IL-6) and anti-inflammatory cytokine IL-10 in bronchoalveolar lavage fluid and serum of chronic obstructive pulmonary disease rats. The content of malondialdehyde in lung tissue and serum was also determined and the data indicated hydrogen-rich saline suppressed oxidative stress reaction. The protein expressions of mucin MUC5C and aquaporin 5 involved in mucus hypersecretion were analyzed by Western blot and ELISA and the data revealed that hydrogen-rich saline down-regulated MUC5AC level in bronchoalveolar lavage fluid and lung tissue and up-regulated aquaporin 5 level in lung tissue of chronic obstructive pulmonary disease rats. In conclusion, these results suggest that administration of hydrogen-rich saline exhibits significant protective effect on chronic obstructive pulmonary disease through alleviating inflammation, reducing oxidative stress and lessening mucus hypersecretion in tobacco smoke-induced chronic obstructive pulmonary disease rats

Primary mucinous cystadenocarcinoma of the breast with endocervical-like mucinous epithelium.

PubMed

Lin, Dong-Liang; Hu, Ji-Lin; Shao, Shi-Hong; Sun, Dong-Mei; Wang, Ji-Gang

2013-12-01

Primary mucinous cystadenocarcinoma of the breast is an extremely rare entity. To the best of our knowledge, only 17 patients have been described in the PubMed database. Here, we report a primary breast mucinous cystadenocarcinoma with endocervical-like mucinous epithelium in a 62-year-old woman. The patient was followed for 5 months without any adjuvant treatment and she continues to be disease free. Primary breast mucinous cystadenocarcinoma usually displays unique pathologic and immunohistochemical characteristics simulating its ovarian counterparts; it seems to have a good prognosis after complete resection.

Photodynamic therapy for recurrent respiratory papillomatosis.

PubMed

Lieder, Anja; Khan, Muhammad K; Lippert, Burkard M

2014-06-05

Recurrent respiratory papillomatosis (RRP) is a benign condition of the mucosa of the upper aerodigestive tract. It is characterised by recurrent papillomatous lesions and is associated with human papillomavirus (HPV). Frequent recurrence and rapid papilloma growth are common and in part responsible for the onset of potentially life-threatening symptoms. Most patients afflicted by the condition will require repeated surgical treatments to maintain their airway, and these may result in scarring and voice problems. Photodynamic therapy introduces a light-sensitising agent, which is administered either orally or by injection. This substance (called a photo-sensitiser) is selectively retained in hyperplastic and neoplastic tissue, including papilloma. It is then activated by light of a specific wavelength and may be used as a sole or adjuvant treatment for RRP. To assess the effects of photodynamic therapy in the management of recurrent respiratory papillomatosis (RRP) in children and adults. We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL); PubMed; EMBASE; CINAHL; Web of Science; Cambridge Scientific Abstracts; ICTRP and additional sources for published and unpublished trials. The date of the search was 27 January 2014. Randomised controlled trials utilising photodynamic therapy as sole or adjuvant therapy in participants of any age with proven RRP versus control intervention. Primary outcome measures were symptom improvement (respiratory distress/dyspnoea and voice quality), quality of life improvement and recurrence-free interval. Secondary outcomes included reduction in the frequency of surgical intervention, reduction in disease volume and adverse effects of treatment.   We used the standard methodological procedures expected by The Cochrane Collaboration. Meta-analysis was not possible and results are presented descriptively. We included one trial with a total of 23

[Laryngeal papillomatosis: A rare cause of dysphonia in the child. Case series].

PubMed

Cuestas, Giselle; Rodríguez, Verónica; Doormann, Flavia; Bellia Munzón, Patricio; Bellia Munzón, Gastón

2018-06-01

Juvenile laryngeal papillomatosis is an uncommon disease caused by human papilloma virus, mainly types 6 and 11. It is the most common benign laryngeal tumor in children. This condition should be suspected in any children with persistent and progressive dysphonia with or without stridor and respiratory distress. Flexible laryngoscopy under local anesthesia allows to visualize the typical wart-like lesions. The diagnosis is confirmed by pathological anatomy. Existing treatment is palliative and consists mainly of the surgical excision of the papillomas to maintain the airway without obstruction and to improve the quality of the voice, but it has a high rate of relapse. We present 20 patients with juvenile laryngeal papillomatosis. We describe the clinical manifestations, the diagnostic methods and the treatment of this pathology. Sociedad Argentina de Pediatría.

Primary Mucinous Cystadenocarcinoma of the Breast with Endocervical-Like Mucinous Epithelium

PubMed Central

Lin, Dong-Liang; Hu, Ji-Lin; Shao, Shi-Hong; Sun, Dong-Mei; Wang, Ji-Gang

2013-01-01

Summary Background Primary mucinous cystadenocarcinoma of the breast is an extremely rare entity. To the best of our knowledge, only 17 patients have been described in the PubMed database. Case Report Here, we report a primary breast mucinous cystadenocarcinoma with endocervical-like mucinous epithelium in a 62-year-old woman. The patient was followed for 5 months without any adjuvant treatment and she continues to be disease free. Conclusions Primary breast mucinous cystadenocarcinoma usually displays unique pathologic and immunohistochemical characteristics simulating its ovarian counterparts; it seems to have a good prognosis after complete resection. PMID:24550753

Plastic biliary stents for benign biliary diseases.

PubMed

Perri, Vincenzo; Familiari, Pietro; Tringali, Andrea; Boskoski, Ivo; Costamagna, Guido

2011-07-01

Biliary plastic stenting plays a key role in the endoscopic management of benign biliary diseases. Complications following surgery of the biliary tract and liver transplantation are amenable to endoscopic treatment by plastic stenting. Insertion of an increasing number of plastic stents is currently the method of choice to treat postoperative biliary strictures. Benign biliary strictures secondary to chronic pancreatitis or primary sclerosing cholangitis may benefit from plastic stenting in select cases. There is a role for plastic stent placement in nonoperative candidates with acute cholecystitis and in patients with irretrievable bile duct stones. Copyright © 2011 Elsevier Inc. All rights reserved.

Clinicopathological features of benign biliary strictures masquerading as biliary malignancy.

PubMed

Wakai, Toshifumi; Shirai, Yoshio; Sakata, Jun; Maruyama, Tomohiro; Ohashi, Taku; Korira, Pavel V; Ajioka, Yoichi; Hatakeyama, Katsuyoshi

2012-12-01

Discrimination between benign and malignant biliary strictures is difficult, with 5.2 to 24.5 per cent of biliary strictures proving to be benign after histological examination of the resected specimen. This study aimed to evaluate the clinicopathological features of benign biliary strictures in patients undergoing resection for presumed biliary malignancy. From January 1990 to August 2010, 5 of 153 (3.3%) patients who had undergone resection after a preoperative diagnosis of biliary malignancy had a final histological diagnosis of benign biliary stricture. The infiltration of immunoglobulin G4-positive plasma cells was evaluated by immunohistochemistry. None of the five patients had a history of trauma or earlier hepatobiliary surgery and all five underwent hemihepatectomy (combined with extrahepatic bile duct resection in three patients). Postoperative morbidity was recorded in two patients (transient cholangitis and biliary fistula), but there was no postoperative mortality. Histological re-examination identified immunoglobulin G4-related sclerosing cholangitis (n = 2) and nonspecific fibrosis/inflammation (n = 3). No preoperative clinical or radiographic features were identified that could reliably distinguish patients with benign biliary strictures from those with biliary malignancies. Although benign biliary strictures are rare, differentiating benign strictures from malignancy remains problematic. Thus, the treatment approach for biliary strictures should remain surgical resection for presumed biliary malignancy.

Primary Mucinous Cystadenocarcinoma of the Breast: Cytologic Finding and Expression of MUC5 Are Different from Mucinous Carcinoma

PubMed Central

Kim, Sung Eun; Park, Ji Hye; Hong, SoonWon; Koo, Ja Seung; Jeong, Joon

2012-01-01

Mucinous cystadenocarcinoma (MCA) in the breast is a rare neoplasm. There have been 13 cases of primary breast MCA reported. The MCA presents as a large, partially cystic mass in postmenopausal woman with a good prognosis. The microscopic findings resemble those of ovarian, pancreatic, or appendiceal MCA. The aspiration findings showed mucin-containing cell clusters in the background of mucin and necrotic material. The cell clusters had intracytoplasmic mucin displacing atypical nuclei to the periphery. Histologically, the tumor revealed an abundant mucin pool with small floating clusters of mucin-containing tumor cells. There were also small cysts lined by a single layer of tall columnar mucinous cells, resembling those of the uterine endocervix. The cancer cells were positive for mucin (MUC) 5 and negative for MUC2 and MUC6. This mucin profile is different from ordinary mucinous carcinoma and may be a unique characteristic of breast MCA. PMID:23323116

Primary Mucinous Cystadenocarcinoma of the Breast: Cytologic Finding and Expression of MUC5 Are Different from Mucinous Carcinoma.

PubMed

Kim, Sung Eun; Park, Ji Hye; Hong, Soonwon; Koo, Ja Seung; Jeong, Joon; Jung, Woo-Hee

2012-12-01

Mucinous cystadenocarcinoma (MCA) in the breast is a rare neoplasm. There have been 13 cases of primary breast MCA reported. The MCA presents as a large, partially cystic mass in postmenopausal woman with a good prognosis. The microscopic findings resemble those of ovarian, pancreatic, or appendiceal MCA. The aspiration findings showed mucin-containing cell clusters in the background of mucin and necrotic material. The cell clusters had intracytoplasmic mucin displacing atypical nuclei to the periphery. Histologically, the tumor revealed an abundant mucin pool with small floating clusters of mucin-containing tumor cells. There were also small cysts lined by a single layer of tall columnar mucinous cells, resembling those of the uterine endocervix. The cancer cells were positive for mucin (MUC) 5 and negative for MUC2 and MUC6. This mucin profile is different from ordinary mucinous carcinoma and may be a unique characteristic of breast MCA.

McCune-Albright syndrome: growth hormone and prolactin hypersecretion.

PubMed

Christoforidis, Athanasios; Maniadaki, Ilianna; Stanhope, Richard

2006-05-01

McCune-Albright syndrome (MAS) has a special interest for endocrinologists as its pathogenesis results in hypersecretion of hormones in peripheral endocrine tissues. This can be expressed as precocious puberty, mainly in girls, primary hyperthyroidism, growth hormone (GH) and/or prolactin excess, hyperparathyroidism and hypercortisolism. The incidence of GH excess among patients with MAS has been assessed as up to 21%. The pathogenesis of GH hypersecretion in MAS is not completely understood, whereas it seems to be different from the aetiology of acromegaly/gigantism in non-MAS patients. The clinical expression of GH excess can be masked because of precocious puberty or craniofacial fibrous dysplasia, indicating the necessity for screening. Medical treatment is usually the only option in MAS patients with GH excess, as transsphenoidal surgery is usually restricted due to massive thickening of the skull base, whereas radiotherapy is contraindicated due to probable higher predisposition to sarcomatous transformation. The use of bromocriptine, cabergoline and octreotide, or the combination of these, has shown variable results, whereas pegvisomant, a GH receptor antagonist, is a new promising option, although not yet used in patients with MAS.

Low-Grade Appendiceal Mucinous Neoplasm Involving the Endometrium and Presenting with Mucinous Vaginal Discharge.

PubMed

Vavinskaya, Vera; Baumgartner, Joel M; Ko, Albert; Saenz, Cheryl C; Valasek, Mark A

2016-01-01

Primary appendiceal mucinous lesions are uncommon and represent a spectrum from nonneoplastic mucous retention cysts to invasive adenocarcinoma. Low-grade appendiceal mucinous neoplasms (LAMNs) represent an intermediate category on this spectrum and can be classified according to whether or not they are confined to the appendix. Although LAMNs are frequently confined to the appendix, they can also spread to the peritoneum and clinically progress as pseudomyxoma peritonei (i.e., mucinous ascites). Thus, the appropriate classification of appendiceal primary neoplasia is essential for prognosis and influences clinical management. In addition, the precise classification, management, and clinical outcome of patients with disseminated peritoneal disease remain controversial. Here, we report an unusual case of LAMN with pseudomyxoma peritonei that initially presented with mucinous and bloody vaginal discharge. Pathological evaluation revealed low-grade appendiceal mucinous neoplasm with secondary involvement of the peritoneum, ovaries, and endometrial surface. Therefore, LAMN should be considered in the differential diagnosis of mucinous vaginal discharge.

Transmembrane mucins as novel therapeutic targets.

PubMed

Constantinou, Pamela E; Danysh, Brian P; Dharmaraj, Neeraja; Carson, Daniel D

2011-11-01

Membrane-tethered mucin glycoproteins are abundantly expressed at the apical surfaces of simple epithelia, where they play important roles in lubricating and protecting tissues from pathogens and enzymatic attack. Notable examples of these mucins are MUC1, MUC4 and MUC16 (also known as cancer antigen 125). In adenocarcinomas, apical mucin restriction is lost and overall expression is often highly increased. High-level mucin expression protects tumors from killing by the host immune system, as well as by chemotherapeutic agents, and affords protection from apoptosis. Mucin expression can increase as the result of gene duplication and/or in response to hormones, cytokines and growth factors prevalent in the tumor milieu. Rises in the normally low levels of mucin fragments in serum have been used as markers of disease, such as tumor burden, for many years. Currently, several approaches are being examined that target mucins for immunization or nanomedicine using mucin-specific antibodies.

Intraductal Papillary Mucinous Neoplasm (IPMN) with Extra-Pancreatic Mucin: A Case Series and Review of the Literature

PubMed Central

Stein, Louis H.; Witkiewicz, Agnieszka K.; Kennedy, Eugene P.; Yeo, Charles J.

2012-01-01

Background Intraductal papillary mucinous neoplasm (IPMN) is an increasingly recognized pancreatic neoplasm characterized by excessive mucin secretion by ductal epithelial cells resulting in a cystic dilation of the pancreatic duct. Aim The objective of this study was to review Thomas Jefferson University’s experience and the literature to determine the significance of extra-pancreatic mucin when associated with an IPMN. Results A retrospective analysis at our institution revealed only two cases of IPMN associated with extra-pancreatic mucin, which were classic IPMNs with rupture of the pancreatic duct and peritoneal mucin spillage. This specific finding is not previously described, although is assumed as five cases were reported in the literature with IPMN and mucin extension demonstrated by pseudomyxoma peritonei (PMP). We propose IPMN of the pancreas may be grossly compared to a mucocele of the appendix, as both are characterized by excessive secretion of mucin by ductal epithelial cells. A morbid complication of a mucocele is PMP. The presence of extra-pancreatic mucin with an IPMN could present a rare but important marker of the eventual seeding of tumor outside the primary IPMN. This has been documented with cases of iatrogenic spilling of pancreatic mucin, as well as multiple cases of IPMN associated with pseudomyxoma peritonei. Conclusions At this time, there is scant reporting and consensus for the treatment of IPMN with extra-pancreatic mucin. PMID:22258877

Confluent and reticulated papillomatosis: clinical and histopathological study of 10 cases from Lebanon.

PubMed

Tamraz, H; Raffoul, M; Kurban, M; Kibbi, A-G; Abbas, O

2013-01-01

Confluent and reticulate papillomatosis (CRP) is a rare disorder that has mostly been described in case reports and limited case series. Studies on this condition from our region are lacking. To describe the clinical and histopathological findings, as well as response to treatment of all patients diagnosed with CRP at the American University of Beirut Medical Center (AUB-MC) between 1999 and 2009, and to compare our findings with those published in the literature. Confluent and reticulate papillomatosis was diagnosed in 10 patients (five men, five women). Mean age at diagnosis was 19 years. Duration of lesions ranged from few months to several years. Skin lesions mainly consisted of reticulated, pigmented macules, patches and plaques. The most common area of involvement was the chest in five cases. The rash was asymptomatic in eight patients. Skin biopsy specimens from all patients revealed hyperkeratosis, papillomatosis and variable acanthosis. Whereas follicular plugging was observed in nine cases, anastomosis of the rete ridges was noted in three. Periodic acid Schiff stains highlighted yeast forms in six cases. The clinical and histopathological features of the CRP patients in our study are generally comparable to those published in the literature, with minor differences. Clinically, one case had an atypical clinical presentation, and microscopically follicular plugging was seen in the majority of cases. Yeast-like spores were seen in six cases further supporting a role of Malassezia furfur in the pathogenesis of CRP. © 2011 The Authors. Journal of the European Academy of Dermatology and Venereology © 2011 European Academy of Dermatology and Venereology.

Mucin Binding Reduces Colistin Antimicrobial Activity.

PubMed

Huang, Johnny X; Blaskovich, Mark A T; Pelingon, Ruby; Ramu, Soumya; Kavanagh, Angela; Elliott, Alysha G; Butler, Mark S; Montgomery, A Bruce; Cooper, Matthew A

2015-10-01

Colistin has found increasing use in treating drug-resistant bacterial lung infections, but potential interactions with pulmonary biomolecules have not been investigated. We postulated that colistin, like aminoglycoside antibiotics, may bind to secretory mucin in sputum or epithelial mucin that lines airways, reducing free drug levels. To test this hypothesis, we measured binding of colistin and other antibiotics to porcine mucin, a family of densely glycosylated proteins used as a surrogate for human sputum and airway mucin. Antibiotics were incubated in dialysis tubing with or without mucin, and concentrations of unbound antibiotics able to penetrate the dialysis tubing were measured over time using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The percentage of antibiotic measured in the dialysate after 4 h in the presence of mucin, relative to the amount without mucin, was 15% for colistin, 16% for polymyxin B, 19% for tobramycin, 52% for ciprofloxacin, and 78% for daptomycin. Antibiotics with the strongest mucin binding had an overall polybasic positive charge, whereas those with comparatively little binding were less basic. When comparing MICs measured with or without added mucin, colistin and polymyxin B showed >100-fold increases in MICs for multiple Gram-negative bacteria. Preclinical evaluation of mucin binding should become a standard procedure when considering the potential pulmonary use of new or existing antibiotics, particularly those with a polybasic overall charge. In the airways, mucin binding may reduce the antibacterial efficacy of inhaled or intravenously administered colistin, and the presence of sub-MIC effective antibiotic concentrations could result in the development of antibiotic resistance. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Xenograft model for therapeutic drug testing in recurrent respiratory papillomatosis.

PubMed

Ahn, Julie; Bishop, Justin A; Akpeng, Belinda; Pai, Sara I; Best, Simon R A

2015-02-01

Identifying effective treatment for papillomatosis is limited by a lack of animal models, and there is currently no preclinical model for testing potential therapeutic agents. We hypothesized that xenografting of papilloma may facilitate in vivo drug testing to identify novel treatment options. A biopsy of fresh tracheal papilloma was xenografted into a NOD-scid-IL2Rgamma(null) (NSG) mouse. The xenograft began growing after 5 weeks and was serially passaged over multiple generations. Each generation showed a consistent log-growth pattern, and in all xenografts, the presence of the human papillomavirus (HPV) genome was confirmed by polymerase chain reaction (PCR). Histopathologic analysis demonstrated that the squamous architecture of the original papilloma was maintained in each generation. In vivo drug testing with bevacizumab (5 mg/kg i.p. twice weekly for 3 weeks) showed a dramatic therapeutic response compared to saline control. We report here the first successful case of serial xenografting of a tracheal papilloma in vivo with a therapeutic response observed with drug testing. In severely immunocompromised mice, the HPV genome and squamous differentiation of the papilloma can be maintained for multiple generations. This is a feasible approach to identify therapeutic agents in the treatment of recurrent respiratory papillomatosis. © The Author(s) 2014.

Experience with recurrent respiratory papillomatosis in a developing country: impact of tracheostomy.

PubMed

Orji, Foster Tochukwu; Okorafor, Ijeoma A; Akpeh, James O

2013-02-01

The frequent relapses of recurrent respiratory papillomatosis (RRP) sometimes demand repeated surgical excision with tracheostomy. This situation plays a vital role in the management of RRP in developing countries such as ours because of late presentation. This study was conducted to evaluate our experience with RRP and to determine the incidence and impact of tracheostomy in the overall management and outcomes of our patients. The records of 59 patients with histologically confirmed RRP treated between 1994 and 2008 at our tertiary institution were reviewed. We collected data such as age at onset, tracheostomy frequency and duration, number of required surgical excisions, papilloma spread to the lower airways. Patients' characteristics and the course of the disease were compared between a juvenile-onset papillomatosis (JoRRP) group and an adult-onset group (AdRRP). Overall, 68 % of our patients were in the JoRRP group (ages 2-11 years, mean 6 years). The other 32 % were 22-58 years of age (AdRRP group). Two cases of JoRRP continued into adult life. Multiple RRP dominated in the JoRRP group (93 %), whereas solitary papillomas predominated in the AdRRP group (63 %). Tracheostomy was performed because of upper airway obstruction in 42 % of our patients, with children accounting for 72 %. The mean duration of tracheostomy was 3.5 months, with 80 % lasting <4 months. Significantly more JoRRP patients had severe upper airway obstruction, required tracheostomy, and underwent multiple surgical excisions (p = 0.04, 0.02, and 0.009, respectively). Tracheobronchial spread occurred in a patient with prolonged tracheostomy. Multiple laryngeal papillomatosis clearly followed a more severe and less predictable course than the solitary type in both groups. Although there was a high incidence of tracheostomy in this study, short-duration tracheostomies accounted for the low incidence of extralaryngeal spread.

Florid papillomatosis of the nipple. A study of 51 patients, including nine with mammary carcinoma.

PubMed

Rosen, P P; Caicco, J A

1986-02-01

The present study was undertaken to review the pathology of florid papillomatosis (FP) of the nipple and to examine the relationship of FP to breast carcinoma. Clinical features of 49 women studied did not differ appreciably from those noted on prior reports, except that in one instance the lesion was probably congenital. Histologically, three distinct growth patterns were found: sclerosing papillomatosis (17 cases), papillomatosis (12 cases), and adenosis (3 cases). In 17 other cases, mixtures of these proliferative patterns were seen. FP with the sclerosing papillomatosis pattern more frequently had areas of focal necrosis in hyperplastic ducts and scattered mitoses, features that might be interpreted as evidence of carcinoma. No prognostic significance can be attributed to these patterns, since all types were cured by excision with follow-up that averaged 8.3 years. Seven of the 49 women had carcinoma in the same breast as FP: Two women had invasive carcinoma that appeared to arise from FP, and four women had concurrent invasive carcinomas that were separate from the FP; the seventh woman developed diffuse intraductal carcinoma 10 years after FP was excised from the same breast. Three of the seven women were also treated for contralateral breast carcinoma. Also reviewed were lesions from two men who had carcinoma arising in FP. One had intraductal carcinoma with Paget's disease and the other had invasive carcinoma. Appreciation of the diverse histological patterns of FP may be helpful in avoiding an erroneous diagnosis of carcinoma. Features indicative of carcinoma arising in FP are Paget's disease and areas of invasion. FP of the nipple is rarely the substrate for mammary carcinoma and is adequately treated by local excision. Coexistence with carcinoma elsewhere in the same or opposite breast occurs often enough to warrant thorough examination of the breasts when FP of the nipple is diagnosed. The risk of subsequent carcinoma following excision of FP appears to

Entamoeba histolytica-Induced Mucin Exocytosis Is Mediated by VAMP8 and Is Critical in Mucosal Innate Host Defense.

PubMed

Cornick, Steve; Moreau, France; Gaisano, Herbert Y; Chadee, Kris

2017-10-03

Intestinal mucus secretion is critical in maintaining mucosal host defense against a myriad of pathogens by preventing direct association with the epithelium. Entamoeba histolytica specifically binds colonic MUC2 mucin and also induces potent hypersecretion from goblet cells; however, characterization of the nature of the mechanisms controlling mucus release remains elusive. In this report, we identify vesicle SNARE vesicle-associated membrane protein 8 (VAMP8) present on mucin granules as orchestrating regulated exocytosis in human goblet cells in response to the presence of E. histolytica VAMP8 was specifically activated during E. histolytica infection, and ablation of VAMP8 led to impaired mucin secretion. As a consequence, loss of VAMP8 increased E. histolytica adherence to epithelial cells associated with enhanced cell death through apoptosis characterized by caspase 3 and 9 cleavages and DNA fragmentation. With the mucosal barrier compromised in Vamp8 -/- animals, E. histolytica induced an aggressive proinflammatory response with elevated levels of interleukin-1 alpha (IL-1α), IL-1β, and tumor necrosis factor alpha (TNF-α) secretion. This report is the first to characterize regulated mucin exocytosis in intestinal goblet cells in response to a pathogen and the downstream consequences of improper mucin secretion in mucosal barrier defense. IMPORTANCE The intestinal tract is exposed to countless substances and pathogens, and yet homeostasis is maintained, in part by the mucus layer that houses the microbiota and spatially separates potential threats from the underlying single layer of epithelium. Despite the critical role of mucus in innate host defense, characterization of the mechanisms by which mucus is secreted from specialized goblet cells in the gut remains elusive. Here, we describe the machinery that regulates mucus secretion as well as the consequence during infection with the colonic pathogen Entamoeba histolytica Abolishment of the key

The tear film and ocular mucins.

PubMed

Davidson, Harriet J; Kuonen, Vanessa J

2004-01-01

Abstract The trilaminar tear film, composed of the lipid, aqueous and mucin layers, has many functions including defending the ocular surface. The aqueous layer has several soluble antimicrobial factors that protect the ocular surface. Ocular mucins have recently been studied with regard to their role in the defense of the eye as well as in dry eye syndromes. To date, 15 mucin genes have been identified, and six of these mucin genes are localized to or secreted by ocular glands or epithelia. Understanding the production, secretion and function of ocular mucins will aid in the treatment of dry eye syndromes and ocular surface microbial infections.

[Lysozyme in the treatment of juvenile laryngeal papillomatosis. A new concept in its etiopathogenesis].

PubMed

Altamar-Ríos, J

1990-01-01

The A. inform about the results achieved with lysozyme chlorhydrate in the treatment of 15 patients with juvenile laryngeal papillomatosis. The lysozyme is an electropositive enzyme which synthesis is related to the degree of proteins and vitamin B complex ingestion. Lysozyme is a component of the immunitary inespecific system, serving to prevent against HPV-DNA at the level of the secretory film of the mucociliary apparatus of the respiratory mucous membrane. Furthermore, lysozyme hydrolyzes the mucopolysaccharide of the connective tissue and inhibits the virus-DNA replication. 100-300 mgr daily during 30-60 days simultaneously with hyperproteic diet and vitamin B complex (after correction of the nutrimental deficiencies) brought about the evanishment of papillomatosis. The A. suggest that the predisposition to infection by virus DNA is primarily of immunitary origin, because of lysozyme deficiency, and secondary due to a low intake of proteins and vitamin B complex.

Hypersecretion of mucus glycoprotein by the gallbladder epithelium in experimental cholelithiasis.

PubMed

Lee, S P

1981-07-01

In three models of cholelithiasis (dihydrocholesterol-fed rabbits, cholesterol-cholic acid-fed mice, and Lincomycin-treated guinea pigs), the quantity and chemical composition of gallbladder epithelial mucin have been studied using (1) a spectrum of histochemical glycoprotein stains, and (2) biochemical extraction, purification and analysis of the carbohydrate components of epithelial mucin. Despite the diverse mechanism of stone induction and difference in stone composition, a common pattern of response by the epithelial mucin was observed in all three models. There was a quantitative increase in epithelial mucus production at a time before stones were formed and this increase persisted till stones were formed. There was no difference, qualitatively, between mucus produced by normal and stone-forming gallbladders.

Significance of mucin on the ocular surface.

PubMed

Watanabe, Hitoshi

2002-03-01

To review the significance of mucin in the tear film and the ocular surface epithelium. Summary of the information on how mucin derived from the corneal and conjunctival epithelia and from goblet cells plays a role in the stability of the tear film over the ocular surface. The change in mucin expression derived from the ocular surface epithelium is also discussed with reference to ocular surface disease. The corneal and conjunctival epithelia produce transmembrane mucins such as MUC1, MUC2, and MUC4. In contrast, goblet cells produce the gel-forming secretory mucin, MUC5AC. The lacrimal gland produces MUC7. On the ocular surface, cooperation between transmembrane mucin and secretory mucin is necessary for the stability of the tear film. The expression of mucin from the ocular surface epithelium is coordinated from the time of eyelid opening and is altered in conditions such as squamous metaplasia and dry eye. This alteration may result in instability of the tear film. CONCLU SION: The induction of mucin from the ocular surface may facilitate the stability of the tear film, and increased knowledge may lead to the development of a new modality for the treatment of dry eye.

Membrane-associated mucins in normal human conjunctiva.

PubMed

Berry, M; Ellingham, R B; Corfield, A P

2000-02-01

To examine the presence of specific membrane-associated mucins in normal human conjunctiva. Glycoconjugates were extracted from membranes with two detergents: octylglucoside and Triton X114. Mucins were separated by cesium chloride density gradient centrifugation. Size was assessed by gel filtration on Sepharose CL2B and charge by ion-exchange chromatography on MonoQ. Cross reaction with antibodies against mucin gene products was assessed in blots of electrophoresis gels. Extraction of total tissue membranes yielded material with a buoyant density typical of mucins. Gel filtration showed material reacting with antimucin antibodies in a range of molecular sizes. Agarose electrophoresis confirmed the presence of MUC1 and MUC4 and the absence of MUC2 or MUC5AC. Isolation of membrane mucins by sequential, exhaustive extraction with octylglucoside followed by Triton X114 suggested the existence of mucins in different membrane environments. Reagents to carbohydrate epitopes revealed high mobility material, comigrating with MUC1 and MUC4. Low mobility membrane-bound mucins did not cross-react with any antibodies to mucin genes known to be expressed in human conjunctiva. Membrane-associated mucins are distinct from secreted mucins in normal human conjunctiva. MUC1 and MUC4 mature products decorate the membranes of conjunctival epithelial cells. Their segregation between octyl glucoside and the detergent and aqueous phases of Triton X114 suggests a variety of membrane anchoring modes.

Biliary sphincteroplasty facilitates retrieval of proximally migrated plastic biliary stent.

PubMed

Shah, Dharmesh K; Jain, Samit S; Somani, Piyush O; Rathi, Pravin M

2014-01-01

Proximal migration of biliary stents presents a technical challenge for the therapeutic endoscopist. It may require multiple, complicated corrective procedures resulting in significant morbidity to the patients. In this study we evaluated the utility of balloon biliary sphincteroplasty with CRE (Controlled Radial Expansion) Balloon Dilator on retrieval of proximally migrated biliary stents. We identified patients from our ERCP database who presented with proximal migration of biliary stent, between August 2011 and October 2013. Patients in whom the stent could not be retrieved with conventional methods, balloon sphincteroplasty was performed with a 12 mm CRETM Balloon Dilator (Boston Scientific). Stent removal was attempted with extraction balloon or basket thereafter. We identified 28 patients with proximal migration of biliary stents, placed for benign diseases of the common bile duct. Stent removal was successful in 18 patients (64.28%) with help of an extraction balloon or basket. Of the remaining 10 patients, balloon sphincteroplasty was successfully followed by stent removal in eight patients. Balloon biliary sphincteroplasty increases the success rate of retrieving proximally migrated biliary stents. The procedure is safe, technically easy and yields a good success rate in our experience.

Pancreatobiliary fistula associated with intraductal papillary mucinous carcinoma accompanying obstructive jaundice: A case report.

PubMed

Komo, Toshiaki; Oishi, Koichi; Kohashi, Toshihiko; Hihara, Jun; Kanou, Mikihiro; Nakashima, Akira; Kaneko, Mayumi; Mukaida, Hidenori; Hirabayashi, Naoki

2018-06-04

Intraductal papillary mucinous neoplasms (IPMNs) occasionally involve formation of fistulas with other adjacent organs. Pancreatobiliary fistulas associated with IPMNs are rare, but affected patients often develop obstructive jaundice and cholangitis. A 79-year-old man was referred to our hospital for evaluation of abnormal biliary enzymes. Contrast-enhanced computed tomography and endoscopic retrograde cholangiopancreatography demonstrated multiple cystic lesions with septa in the pancreatic head and fistulas between the cystic lesions and common bile duct. The clinical diagnosis was pancreatobiliary fistula associated with a mixed-type IPMN and accompanying obstructive jaundice. The patient underwent subtotal stomach-preserving pancreaticoduodenectomy. The resected specimen showed fistulas between the cystic lesions and common bile duct. Histopathological examination showed that the main and branch ducts of the pancreatic head were dilated and filled with mucus. The epithelia of the pancreatic ducts revealed papillary proliferation and an invasive adenocarcinoma arising from an intraductal neoplasm. Immunohistochemistry examination showed CDX2- and MUC2-positive reactions. The final diagnosis was an intraductal papillary mucinous carcinoma of the intestinal-type. The patient remained disease-free for 9 months postoperatively. The causes of death in patients who have pancreatobiliary fistulas associated with IPMNs without resection are cholangitis or hepatic insufficiency. Nonoperative treatment is limited for cases with obstructive jaundice. It is necessary to prevent obstructive jaundice and cholangitis due to a large quantity of mucinous material. Surgical resection should be considered, if possible, in patients with pancreatobiliary fistulas associated with IPMNs. A better prognosis is expected with prevention of obstructive jaundice or cholangitis. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Mucin gene expression in human male urogenital tract epithelia

PubMed Central

Russo, Cindy Leigh; Spurr-Michaud, Sandra; Tisdale, Ann; Pudney, Jeffrey; Anderson, Deborah; Gipson, Ilene K.

2010-01-01

BACKGROUND Mucins are large, hydrophilic glycoproteins that protect wet-surfaced epithelia from pathogen invasion as well as provide lubrication. At least 17 mucin genes have been cloned to date. This study sought to determine the mucin gene expression profile of the human male urogenital tract epithelia, to determine if mucins are present in seminal fluid, and to assess the effect of androgens on mucin expression. METHODS AND RESULTS Testis, epididymis, vas deferens, seminal vesicle, prostate, bladder, urethra and foreskin were assessed for mucin expression by RT-PCR and immunohistochemistry. Epithelia of the vas deferens, prostate and urethra expressed the greatest number of mucins, each expressing 5–8 mucins. Messenger RNA of MUC1 and MUC20, both membrane-associated mucins, were detected in most tissues analyzed. Conversely, MUC6 was predominantly detected in seminal vesicle. MUC1, MUC5B and MUC6 were detected in seminal fluid samples by immunoblot analysis. Androgens had no effect on mucin expression by cultured human prostatic epithelial cells. CONCLUSIONS Each region of urogenital tract epithelium expressed a unique mucin gene repertoire. Secretory mucins are present in seminal fluid, and androgens do not appear to regulate mucin gene expression. PMID:16997931

Laryngopharyngeal reflux and herpes simplex virus type 2 are possible risk factors for adult-onset recurrent respiratory papillomatosis (prospective case-control study).

PubMed

Formánek, M; Jančatová, D; Komínek, P; Matoušek, P; Zeleník, K

2017-06-01

The human papillomavirus (HPV) causes recurrent respiratory papillomatosis (RRP). Although HPV prevalence is high, the incidence of papillomatosis is low. Thus, factors other than HPV infection probably contribute to RRP. This study investigated whether patients with papillomatosis are more often infected with herpes simplex virus type 2 and chlamydia trachomatis (ChT) and whether laryngopharyngeal reflux (LPR) occurs in this group of patients more often. Prospective case-control study. Department of Otorhinolaryngology of University Hospital. The study included 20 patients with adult-onset RRP and 20 adult patients with vocal cord cyst and no pathology of laryngeal mucosa (control group). Immunohistochemical analysis of pepsin, HPV, herpes simplex virus type 2 and ChT was performed in biopsy specimens of laryngeal papillomas and of healthy laryngeal mucosa (control group) obtained from medial part of removed vocal cord cyst during microlaryngoscopy procedures. Pathologic LPR (pepsin in tissue) was diagnosed in 8/20 (40.0%) patients with papillomatosis and in 0/20 control patients (P = .003). Herpes simplex virus type 2 was present in 9/20 (45.0%) patients with papillomatosis and in 0/20 control patients (P = .001). Five specimens were positive for both pepsin and herpes simplex virus type 2. No samples were positive for ChT. There were no significant differences between groups for age, body mass index, diabetes mellitus and gastrooesophageal reflux disease. Tobacco exposure was not more frequent in RRP group either (P = .01). Results show that LPR and herpes simplex virus type 2 are significantly more often present in patients with RRP. LPR and herpes simplex virus type 2 might activate latent HPV infection and thereby be possible risk factors for RRP. © 2016 John Wiley & Sons Ltd.

Lubiprostone stimulates small intestinal mucin release

PubMed Central

2012-01-01

Background Lubiprostone is a synthetic bicyclic fatty acid derivative of prostaglandin E1 (PGE1) used for chronic constipation. The best known action of lubiprostone is simulation of Cl- dependent fluid secretion. In a mouse model of the genetic disease cystic fibrosis, we previously showed that in vivo administration of lubiprostone resulted in greater mucus accumulation in the small intestine. The aim of this study was to directly test whether lubiprostone stimulates intestinal mucin release. Methods Mucin release was measured by mounting segments (4-5 cm) of mouse proximal-mid small intestine in an organ bath, allowing access to the perfusate (luminal) and the bath (serosal) solutions. Nifedipine (10-6 M) and indomethacin (10-5 M) were included in all solutions to inhibit smooth muscle activity and endogenous prostaglandin production, respectively. The tissue was equilibrated under flow for 30 min, using the perfusate collected during the final 10 min of the equilibration period to measure unstimulated release rate. Stimulus was then added to either the perfusate or the bath and the perfusate was collected for another 30 min to measure the stimulated mucin release rate. Mucin in perfusates was quantified by periodic acid-Schiff's base dot-blot assay, using purified pig gastric mucin as a standard. Results When applied luminally at 1 μM lubiprostone was ineffective at stimulating mucin release. When added to the serosal solution, 1 μM lubiprostone stimulated mucin release to ~300% of the unstimulated rate. As a positive control, serosal 1 μM prostaglandin E2 increased mucin release to ~400% of the unstimulated rate. Conclusions These results support the idea that lubiprostone has prostaglandin-like actions on the intestine, which includes stimulation of mucin release. Stimulation of mucin release by lubiprostone may be protective in gastrointestinal conditions where loss of mucus is believed to contribute to pathogenesis. Thus, in addition to chronic

Lubiprostone stimulates small intestinal mucin release.

PubMed

De Lisle, Robert C

2012-11-06

Lubiprostone is a synthetic bicyclic fatty acid derivative of prostaglandin E1 (PGE1) used for chronic constipation. The best known action of lubiprostone is simulation of Cl- dependent fluid secretion. In a mouse model of the genetic disease cystic fibrosis, we previously showed that in vivo administration of lubiprostone resulted in greater mucus accumulation in the small intestine. The aim of this study was to directly test whether lubiprostone stimulates intestinal mucin release. Mucin release was measured by mounting segments (4-5 cm) of mouse proximal-mid small intestine in an organ bath, allowing access to the perfusate (luminal) and the bath (serosal) solutions. Nifedipine (10-6 M) and indomethacin (10-5 M) were included in all solutions to inhibit smooth muscle activity and endogenous prostaglandin production, respectively. The tissue was equilibrated under flow for 30 min, using the perfusate collected during the final 10 min of the equilibration period to measure unstimulated release rate. Stimulus was then added to either the perfusate or the bath and the perfusate was collected for another 30 min to measure the stimulated mucin release rate. Mucin in perfusates was quantified by periodic acid-Schiff's base dot-blot assay, using purified pig gastric mucin as a standard. When applied luminally at 1 μM lubiprostone was ineffective at stimulating mucin release. When added to the serosal solution, 1 μM lubiprostone stimulated mucin release to ~300% of the unstimulated rate. As a positive control, serosal 1 μM prostaglandin E2 increased mucin release to ~400% of the unstimulated rate. These results support the idea that lubiprostone has prostaglandin-like actions on the intestine, which includes stimulation of mucin release. Stimulation of mucin release by lubiprostone may be protective in gastrointestinal conditions where loss of mucus is believed to contribute to pathogenesis. Thus, in addition to chronic constipation, there is greater potential for the

Case report: human papilloma virus type 120-related papillomatosis mimicking laryngeal carcinoma.

PubMed

Belvisi, Valeria; Martellucci, Salvatore; Garbuglia, Anna Rosa; Del Borgo, Cosmo; Martellucci, Stanislao; Baiocchini, Andrea; Manicone, Anna Maria; Bagni, Oreste; Mastroianni, Claudio Maria; Gallo, Andrea

2017-10-01

The relationship between human papilloma virus (HPV) and upper respiratory tract pathology was better understood in recent years and represents now an issue of particular interest in carcinogenesis and in immunocompromised host. We describe a case in which a rare genotype HPV-related papillomatosis mimics laryngeal carcinoma in an immunocompromised host. A 54-year-old woman with a history of HIV-HCV coinfection and anal and laryngeal cancer successfully treated some years before was hospitalized for severe dyspnea, cough and dysphagia. Fiberoptic endoscopic evaluation raised the suspicion of tumor relapse showing the presence of a large glottic-supraglottic ulcerated mass. Several laryngeal biopsies demonstrated koilocytosis and p16 expression, according to a possible HPV infection, and focal figures of mild dysplasia of epithelium. 18 F-FDG PET/CT did not show high glycolytic activity at laryngeal level. An invasive upper respiratory tract papillomatosis in an immunocompromised host was suspected because of the patient's clinical improvement after antiretroviral therapy. Pharyngeal swab and oral rinse harboured the same HPV120 genotype sequence, a betapapillomavirus of recent description and not yet related to any similar clinical presentations.

Mapping the protein domain structures of the respiratory mucins: a mucin proteome coverage study.

PubMed

Cao, Rui; Wang, T Tiffany; DeMaria, Genevieve; Sheehan, John K; Kesimer, Mehmet

2012-08-03

Mucin genes encode a family of the largest expressed proteins in the human genome. The proteins are highly substituted with O-linked oligosaccharides that greatly restrict access to the peptide backbones. The genomic organization of the N-terminal, O-glycosylated, and C-terminal regions of most of the mucins has been established and is available in the sequence databases. However, much less is known about the fate of their exposed protein regions after translation and secretion, and to date, detailed proteomic studies complementary to the genomic studies are rather limited. Using mucins isolated from cultured human airway epithelial cell secretions, trypsin digestion, and mass spectrometry, we investigated the proteome coverage of the mucins responsible for the maintenance and protection of the airway epithelia. Excluding the heavily glycosylated mucin domains, up to 85% coverage of the N-terminal region of the gel-forming mucins MUC5B and MUC5AC was achieved, and up to 60% of the C-terminal regions were covered, suggesting that more N- and sparsely O-glycosylated regions as well as possible other modifications are available at the C-terminus. All possible peptides from the cysteine-rich regions that interrupt the heavily glycosylated mucin domains were identified. Interestingly, 43 cleavage sites from 10 different domains of MUC5B and MUC5AC were identified, which possessed a non-tryptic cleavage site on the N-terminal end of the peptide, indicating potential exposure to proteolytic and/or "spontaneous cleavages". Some of these non-tryptic cleavages may be important for proper maturation of the molecule, before and/or after secretion. Most of the peptides identified from MUC16 were from the SEA region. Surprisingly, three peptides were clearly identified from its heavily glycosylated regions. Up to 25% coverage of MUC4 was achieved covering seven different domains of the molecule. All peptides from the MUC1 cytoplasmic domain were detected along with the three non

Structure and interactions of human respiratory mucin

NASA Astrophysics Data System (ADS)

Purdy, Kirstin; Sheehan, John; Rubinstein, Michael; Wong, Gerard

2006-03-01

Human respiratory mucin plays a crucial role in the pathology of Cystic Fibrosis lung infections. Mucin is a flexible, linear polyelectrolyte, characterized by its many charged oligo-carbohydrate side chains that give it its bottle-brush structure. The macroscopic properties of a mucin suspension are known to change drastically with changes in ion concentration and solution pH, but little is known about the effect of these variables on individual mucin structure. We present preliminary results on the structural response of individual human respiratory mucin molecules to variations in concentration of ions of different valences via small angle x-ray diffraction.

Influence of microemulsion-mucin interaction on the fate of microemulsions diffusing through pig gastric mucin solutions.

PubMed

Zhang, Jianbin; Lv, Yan; Wang, Bing; Zhao, Shan; Tan, Mingqian; Lv, Guojun; Ma, Xiaojun

2015-03-02

Mucus layer, a selective diffusion barrier, has an important effect on the fate of drug delivery systems in the gastrointestinal tract. To study the fate of microemulsions in the mucus layer, four microemulsion formulations with different particle sizes and lipid compositions were prepared. The microemulsion-mucin interaction was demonstrated by the fluorescence resonance energy transfer (FRET) method. Moreover, the microemulsions were observed aggregated into micron-sized emulsions by laser confocal microscopy. We concluded the microemulsion-mucin interaction not only led to microemulsions closely adhered to mucins but also destroyed the structure of microemulsions. At last, the diffusion of blank microemulsions and microemulsion-carried drugs (resveratrol and hymecromone) through mucin solutions was determined by the fluorescence recovery after photobleaching (FRAP) method and the Franz diffusion cell method. The results demonstrated the diffusion of microemulsions was significantly hindered by mucin solutions. The particle size of microemulsions had a negligible effect on the diffusion coefficients. However, the type of lipid played an important role, which could form hydrophobic interactions with mucins. Interestingly, microemulsion-carried drugs with different core/shell locations seemed to suffer different fates in the mucin solutions. The drug incorporated in the oil core of microemulsions, resveratrol, was transported through the mucus layer by the carriers, while the drug incorporated in the surfactant shell of microemulsions, hymecromone, was separated from the carriers and diffused toward the epithelium in the form of free molecules.

Mitogen-activated protein kinase inhibition reduces mucin 2 production and mucinous tumor growth.

PubMed

Dilly, Ashok K; Song, Xinxin; Zeh, Herbert J; Guo, Zong S; Lee, Yong J; Bartlett, David L; Choudry, Haroon A

2015-10-01

Excessive accumulation of mucin 2 (MUC2) protein (a gel-forming secreted mucin) within the peritoneal cavity is the major cause of morbidity and mortality in pseudomyxoma peritonei (PMP), a unique mucinous malignancy of the appendix. Mitogen-activated protein kinase (MAPK) signaling pathway is upregulated in PMP and has been shown to modulate MUC2 promoter activity. We hypothesized that targeted inhibition of the MAPK pathway would be a novel, effective, and safe therapeutic strategy to reduce MUC2 production and mucinous tumor growth. We tested RDEA119, a specific MEK1/2 (MAPK extracellular signal-regulated kinase [ERK] kinase) inhibitor, in MUC2-secreting LS174T cells, human PMP explant tissue, and in a unique intraperitoneal murine xenograft model of PMP. RDEA119 reduced ERK1/2 phosphorylation and inhibited MUC2 messenger RNA and protein expression in vitro. In the xenograft model, chronic oral therapy with RDEA119 inhibited mucinous tumor growth in an MAPK pathway-dependent manner and this translated into a significant improvement in survival. RDEA119 downregulated phosphorylated ERK1/2 and nuclear factor κB p65 protein signaling and reduced activating protein 1 (AP1) transcription factor binding to the MUC2 promoter in LS174T cells. This study provides a preclinical rationale for the use of MEK inhibitors to treat patients with PMP. Copyright © 2015 Elsevier Inc. All rights reserved.

Human lacrimal gland mucins.

PubMed

Paulsen, Friedrich; Langer, Gesa; Hoffmann, Werner; Berry, Monica

2004-05-01

The objective of this study was to determine whether the lacrimal gland synthesizes mucins and whether they are changed with age or in cases of dry eye. Expression of mucins in human lacrimal glands was monitored by reverse transcription-polymerase chain reaction analysis. Furthermore, the presence and distribution of MUC1, -2, -4, -5AC, -5B, -6 and -7 in epithelia of the human lacrimal gland and its excretory duct system were assessed with antisera to mucin peptide cores. Thirty normal tissues from cadavers of different ages were tested, plus four with dry eye treated with artificial tears. Expression studies detected mRNAs for mucins MUC1, -4, -5AC, -5B, -6 and -7; whereas the MUC2 message was absent. The message for MUC4 was present in all four cases of dry eye, but only in six out of the 30 normal glands from individuals who did not receive artificial tears. MUC6 mRNA was detected only in about half of the investigated samples. Immunohistochemistry revealed membrane-bound MUC1 at the apical surface of acinar cells, absence of MUC2, MUC5AC associated with goblet cells of excretory ducts, MUC5B and -7 in the cytoplasm of acinar cells, and MUC7 also in epithelial cells of excretory ducts. MUC4 mucin was detected only in those individuals in which message was identified. In dry eyes, MUC5AC and -5B were localized in the same acinar cells; whereas MUC2 and MUC6 were not detectable. Dot-blot analysis clearly revealed increased amounts of MUC4, -5AC, and -5B in the glands of elderly women who received treatment for dry eyes. These results confirm that the human lacrimal gland synthesizes a spectrum of mucins; part of them might be correlated with age. Copyright 2004 Springer-Verlag

Targeting Src in Mucinous Ovarian Carcinoma

PubMed Central

Matsuo, Koji; Nishimura, Masato; Bottsford-Miller, Justin N.; Huang1, Jie; Komurov, Kakajan; Armaiz-Pena, Guillermo N.; Shahzad, Mian M. K.; Stone, Rebecca L.; Roh, Ju Won; Sanguino, Angela M.; Lu, Chunhua; Im, Dwight D.; Rosenshien, Neil B.; Sakakibara, Atsuko; Nagano, Tadayoshi; Yamasaki, Masato; Enomoto, Takayuki; Kimura, Tadashi; Ram, Prahlad T.; Schmeler, Kathleen M.; Gallick, Gary E.; Wong, Kwong K.; Frumovitz, Michael; Sood, Anil K.

2014-01-01

PURPOSE Mucinous ovarian carcinomas have a distinct clinical pattern compared to other subtypes of ovarian carcinoma. Here, we evaluated (i) stage-specific clinical significance of mucinous ovarian carcinomas in a large cohort and (ii) the functional role of src kinase in pre-clinical models of mucinous ovarian carcinoma. EXPERIMENTAL DESIGN 1302 ovarian cancer patients including 122 (9.4%) cases of mucinous carcinoma were evaluated for survival analyses. Biological effects of src kinase inhibition were tested in a novel orthotopic mucinous ovarian cancer model (RMUG-S-ip2) using dasatinib-based therapy. RESULTS Patients with advanced-stage mucinous ovarian cancer had significantly worse survival compared to those with serous histology: median overall survival, 1.67 versus 3.41 years, p=0.002; and median survival time after recurrence of 0.53 versus 1.66 years, p<0.0001. Among multiple ovarian cancer cell lines, RMUG-S-ip2 mucinous ovarian cancer cells showed the highest src kinase activity. Moreover, oxaliplatin treatment induced phosphorylation of src kinase. This induced activity by oxaliplatin therapy was inhibited by concurrent administration of dasatinib. Targeting src with dasatinib in vivo showed significant anti-tumor effects in the RMUG-S-ip2 model, but not in the serous ovarian carcinoma (SKOV3-TR) model. Combination therapy of oxaliplatin with dasatinib further demonstrated significant effects on reducing cell viability, increasing apoptosis, and in vivo anti-tumor effects in the RMUG-S-ip2 model. CONCLUSIONS Our results suggest that poor survival of women with mucinous ovarian carcinoma is associated with resistance to cytotoxic therapy. Targeting src kinase with combination of dasatinib and oxaliplatin may be an attractive approach in this disease. PMID:21737505

Age of onset of recurrent respiratory papillomatosis: a distribution analysis.

PubMed

San Giorgi, M R M; van den Heuvel, E R; Tjon Pian Gi, R E A; Brunings, J W; Chirila, M; Friedrich, G; Golusinski, W; Graupp, M; Horcasitas Pous, R A; Ilmarinen, T; Jackowska, J; Koelmel, J C; Ferran Vilà, F; Weichbold, V; Wierzbicka, M; Dikkers, F G

2016-10-01

Distribution of age of onset of recurrent respiratory papillomatosis (RRP) is generally described to be bimodal, with peaks at approximately 5 years and 30 years. This assumption has never been scientifically confirmed, and authors tend to refer to an article that does not describe distribution. Knowledge of the distribution of age of onset is important for virological and epidemiological comprehension. The objective of this study was to determine the distribution of age of onset of RRP in a large international sample. Cross-sectional distribution analysis. Laryngologists from 12 European hospitals provided information on date of birth and date of onset of all their RRP patients treated between 1998 and 2012. Centers that exclusively treated either patients with juvenile onset RRP or patients with adult onset RRP, or were less accessible for one of these groups, were excluded to prevent skewness. A mixture model was implemented to describe distribution of age of onset. The best fitting model was selected using the Bayesian information criterion. Six hundred and thirty-nine patients were included in the analysis. Age of onset was described by a three component mixture distribution with lognormally distributed components. Recurrent respiratory papillomatosis starts at three median ages 7, 35 and 64 years. Distribution of age of onset of RRP shows three peaks. In addition to the already adopted idea of age peaks at paediatric and adult age, there is an additional peak around the age of 64. © 2015 John Wiley & Sons Ltd.

Mucin profiles in signet-ring cell carcinoma.

PubMed

Nguyen, Minh D; Plasil, Brian; Wen, Ping; Frankel, Wendy L

2006-06-01

Signet-ring cell carcinoma (SRCC) is a poorly differentiated mucin-producing adenocarcinoma that may arise from many different organs, but all SRCCs share identical morphology. It is not possible to differentiate sites of origin for metastatic SRCC based on morphology alone. Mucins are high-molecular-weight glycoproteins differentially expressed in glandular epithelia and in adenocarcinomas. To identify mucin profiles of primary and metastatic SRCCs using immunohistochemistry to determine whether mucin staining could help distinguish sites of origin. Forty-seven SRCCs, including 38 primary (21 stomach, 11 colorectum, and 6 breast) and 9 metastases from these primary sites were retrieved from archival files. Consecutive tissue sections were immunostained with monoclonal antibodies against MUC1, MUC2, MUC4, MUC5AC (MUC5), and MUC6 on separate slides. Cytoplasmic staining was scored based on proportion of positive tumor cells as follows: 0+ (<5%), 1+ (5%-25%), 2+ (26%-50%), and 3+ (>50%). Mucin profiles were recorded as MUC+, MUCv, and MUC- for consistent, variable, and negative expression, respectively. The mucin profiles for gastric, colorectum, and breast SRCCs are MUC1.2.4.5.6v, MUC2.4+/MUC5v/ MUC1.6-, and MUC1+/MUC2.5.6v/MUC4-, respectively. Mucin profiles of metastatic cases shared profiles with their respective primaries. Signet-ring cell carcinomas of the stomach, colorectum, and breast have distinct mucin expression patterns that are maintained in metastases. Mucin profiling may be useful to identify the origin of a metastatic SRCC of unknown primary.

Mucinous breast carcinoma with tall columnar cells.

PubMed

Tsoukalas, N; Kiakou, M; Tolia, M; Kostakis, I D; Galanopoulos, M; Nakos, G; Tryfonopoulos, D; Kyrgias, G; Koumakis, G

2018-05-01

Mucinous carcinoma of the breast represents 1%-4% of all breast cancers. The World Health Organization classification divides this type of tumour into three different subtypes: mucinous carcinoma, mucinous carcinoma with tall columnar cells (mucinous cystadenocarcinoma and columnar cell mucinous carcinoma) and signet ring cell carcinoma. A 74-year-old woman presented a tumour with inflammatory features in the upper outer quadrant of her left breast, 7 cm in diameter. The core biopsy showed infiltrating ductal carcinoma of no specific type. The tumour-node-metastasis clinical staging was T4cN3M0 (Stage IIIC). She received neoadjuvant chemotherapy, underwent left mastectomy with radical axillary resection and subsequently received radiotherapy and chemotherapy. The histological examination of the surgical specimen revealed two solid tumors in the tail of Spence, which corresponded to adenocarcinoma with high columnar cells. The patient died 16 months after the diagnosis, suffering from pulmonary metastases and anterior chest wall infiltration. A review of the literature revealed only 21 reports of mucinous carcinoma of the breast with tall columnar cells, including our case. This is only the third time that the specific histological type of columnar cell mucinous carcinoma has been reported in the literature.

Biliary system

MedlinePlus

The biliary system creates, moves, stores, and releases bile into the duodenum . This helps the body digest food. It also assists ... from the liver to the duodenum. The biliary system includes: The gallbladder Bile ducts and certain cells ...

Molecular Pathways: Mucins and Drug Delivery in Cancer.

PubMed

Rao, Chinthalapally V; Janakiram, Naveena B; Mohammed, Altaf

2017-03-15

Over the past few decades, clinical and preclinical studies have clearly demonstrated the role of mucins in tumor development. It is well established that mucins form a barrier impeding drug access to target sites, leading to cancer chemoresistance. Recently gained knowledge regarding core enzyme synthesis has opened avenues to explore the possibility of disrupting mucin synthesis to improve drug efficacy. Cancer cells exploit aberrant mucin synthesis to efficiently mask the epithelial cells and ensure survival under hostile tumor microenvironment conditions. However, O-glycan synthesis enzyme core 2 beta 1,6 N-acetylglucosaminyltransferase (GCNT3/C2GnT-2) is overexpressed in Kras-driven mouse and human cancer, and inhibition of GCNT3 has been shown to disrupt mucin synthesis. This previously unrecognized developmental pathway might be responsible for aberrant mucin biosynthesis and chemoresistance. In this Molecular Pathways article, we briefly discuss the potential role of mucin synthesis in cancers, ways to improve drug delivery and disrupt mucin mesh to overcome chemoresistance by targeting mucin synthesis, and the unique opportunity to target the GCNT3 pathway for the prevention and treatment of cancers. Clin Cancer Res; 23(6); 1373-8. ©2016 AACR . ©2016 American Association for Cancer Research.

Mucin-based targeted pancreatic cancer therapy.

PubMed

Torres, Maria P; Chakraborty, Subhankar; Souchek, Joshua; Batra, Surinder K

2012-01-01

The prognosis of pancreatic cancer (PC) patients is very poor with a five-year survival of less than 5%. One of the major challenges in developing new therapies for PC is the lack of expression of specific markers by pancreatic tumor cells. Mucins are heavily Oglycosylated proteins characterized by the presence of short stretches of amino acid sequences repeated several times in tandem. The expression of several mucins including MUC1, MUC4, MUC5AC, and MUC16 is strongly upregulated in PC. Recent studies have also demonstrated a link between the aberrant expression and differential overexpression of mucin glycoproteins to the initiation, progression, and poor prognosis of the disease. These studies have led to increasing recognition of mucins as potential diagnostic markers and therapeutic targets in PC. In this focused review we present an overview of the therapies targeting mucins in PC, including immunotherapy (i.e. vaccines, antibodies, and radioimmunoconjugates), gene therapy, and other novel therapeutic strategies.

Cellular and Molecular Biology of Airway Mucins

PubMed Central

Lillehoj, Erik P.; Kato, Kosuke; Lu, Wenju; Kim, Kwang C.

2017-01-01

Airway mucus constitutes a thin layer of airway surface liquid with component macromolecules that covers the luminal surface of the respiratory tract. The major function of mucus is to protect the lungs through mucociliary clearance of inhaled foreign particles and noxious chemicals. Mucus is comprised of water, ions, mucin glycoproteins, and a variety of other macromolecules, some of which possess anti-microbial, anti-protease, and anti-oxidant activities. Mucins comprise the major protein component of mucus and exist as secreted and cell-associated glycoproteins. Secreted, gel-forming mucins are mainly responsible for the viscoelastic property of mucus, which is crucial for effective mucociliary clearance. Cell-associated mucins shield the epithelial surface from pathogens through their extracellular domains and regulate intracellular signaling through their cytoplasmic regions. However, neither the exact structures of mucin glycoproteins, nor the manner through which their expression is regulated, are completely understood. This chapter reviews what is currently known about the cellular and molecular properties of airway mucins. PMID:23445810

Functions of ocular surface mucins in health and disease

PubMed Central

Mantelli, Flavio; Argüeso, Pablo

2009-01-01

Purpose of review The purpose of the present review is to describe new concepts on the role of mucins in the protection of corneal and conjunctival epithelia and to identify alterations of mucins in ocular surface diseases. Recent findings New evidence indicates that gel-forming and cell surface-associated mucins contribute differently to the protection of the ocular surface against allergens, pathogens, extracellular molecules, abrasive stress, and drying. Summary Mucins are high molecular weight glycoproteins characterized by their extensive O-glycosylation. Major mucins expressed by the ocular surface epithelia include cell surface-associated mucins MUC1, -4 and -16, and the gel-forming mucin MUC5AC. Recent advances using functional assays have allowed the examination of their roles in the protection of corneal and conjunctival epithelia. Alterations in mucin and mucin O-glycan biosynthesis in ocular surface disorders, including allergy, non-autoimmune dry eye, autoimmune dry eye, and infection, are presented. PMID:18769205

Risk factors for recurrent symptomatic pigmented biliary stones after percutaneous transhepatic biliary extraction.

PubMed

Kim, Dong Won; Lee, Sang Yun; Cho, Jin-Han; Kang, Myong Jin; Noh, Myung Hwan; Park, Byeong-Ho

2010-07-01

To evaluate risk factors for the recurrence of biliary stones after a percutaneous transhepatic biliary stone extraction. The procedures were performed on 339 patients between July 2004 and December 2008 (54 months). Medical records and images were retrospectively reviewed for 135 patients (mean age, 66.4 years; 83 men and 52 women) who had undergone follow-up for a mean of 13.2 months (range, 3-37 months). To evaluate risk factors for the recurrence of biliary stones, variables were evaluated with univariate and multivariate analyses. Variables included sex, age, stone location, number of stones, stone size, presence of a peripapillary diverticulum, application of antegrade sphincteroplasty, presence of a biliary stricture, largest biliary diameter before the procedure, and gallbladder status. Thirty-three of the 135 patients (24%) had recurrent symptomatic biliary stones and underwent an additional extraction. The mean time to recurrence was 17.2 months +/- 8.7. Univariate analysis of risk factors for recurrence of biliary stones demonstrated that location, number of stones, stone size, application of antegrade sphincteroplasty, presence of a biliary stricture, and biliary diameter were significant factors (P < .05). With use of multivariate analysis, the number of stones (> or =6; relative risk, 64.8; 95% confidence interval: 5.8, 717.6) and stone size (> or =14 mm; relative risk, 3.8; 95% confidence interval: 1.138, 13.231) were determined to be significant risk factors. The independent risk factors for recurrence of symptomatic biliary stones after percutaneous transhepatic biliary stone extraction were a stone size of at least 14 mm and the presence of at least six stones. Copyright 2010 SIR. Published by Elsevier Inc. All rights reserved.

Human preocular mucins reflect changes in surface physiology.

PubMed

Berry, M; Ellingham, R B; Corfield, A P

2004-03-01

Mucin function is associated with both peptide core and glycosylation characteristics. The authors assessed whether structural alterations occurring during mucin residence in the tear film reflect changes in ocular surface physiology. Ocular surface mucus was collected from normal volunteers as N-acetyl cysteine (NAcCys) washes or directly from the speculum after cataract surgery. To assess the influence of surface health on mucins, NAcCys washings were also obtained from patients with symptoms, but no clinical signs of dry eye (symptomatics). Mucins were extracted in guanidine hydrochloride (GuHCl) with protease inhibitors. Buoyant density of mucin species, a correlate of glycosylation density, was followed by reactivity with anti-peptide core antibodies. Mucin hydrodynamic volume was assessed by gel filtration on Sepharose CL2B. Surface fluid and mucus contained soluble forms of MUC1, MUC2, MUC4, and MUC5AC and also the same species requiring DTT solubilisation. Reactivity with antibodies to MUC2 and MUC5AC peaked at 1.3-1.5 g/ml in normals, while dominated by underglycosylated forms in symptomatics. Surface mucins were predominantly smaller than intracellular species. MUC2 size distributions were different in symptomatics and normals, while those of MUC5AC were similar in these two groups. A reduction in surface mucin size indicates post-secretory cleavage. Dissimilarities in surface mucin glycosylation and individual MUC size distributions in symptomatics suggest changes in preocular mucin that might precede dry eye signs.

Gd-EOB-DTPA-enhanced magnetic resonance imaging for bile duct intraductal papillary mucinous neoplasms

PubMed Central

Ying, Shi-Hong; Teng, Xiao-Dong; Wang, Zhao-Ming; Wang, Qi-Dong; Zhao, Yi-Lei; Chen, Feng; Xiao, Wen-Bo

2015-01-01

AIM: To investigate gadolinium-ethoxybenzyl-diethylenetriamine-pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) of intraductal papillary mucinous neoplasms of the bile duct (IPMN-B). METHODS: The imaging findings of five cases of IPMN-B which were pathologically confirmed at our hospital between March 2012 and May 2013 were retrospectively analyzed. Three of these cases were diagnosed by duodenal endoscopy and biopsy pathology, and two cases were diagnosed by surgical pathology. All five patients underwent enhanced and non-enhanced computed tomography (CT), magnetic resonance cholangiopancreatography, and Gd-EOB-DTPA-enhanced MRI; one case underwent both Gd-EOB-DTPA-enhanced MRI and positron emission tomography-CT. The clinical data and imaging results for these cases were compared and are presented. RESULTS: Conventional imaging showed diffuse dilatation of bile ducts and multiple intraductal polypoid and papillary neoplasms or serrated changes along the bile ducts. In two cases, Gd-EOB-DTPA-enhanced MRI revealed dilated biliary ducts and intraductal tumors, as well as filling defects caused by mucin in the dilated bile ducts in the hepatobiliary phase. Gd-EOB-DTPA-enhanced MRI in one case clearly showed a low-signal tumor in the hepatobiliary phase, similar to what was seen by positron emission tomography-CT. In two patients, routine inspection was unable to discern whether the lesions were inflammation or tumors. However, Gd-EOB-DTPA-enhanced MRI revealed a pattern of gradual enhancement during the hepatobiliary phase, and the signal intensity of the lesions was lower than the surrounding liver parenchyma, suggesting tissue inflammation in both cases, which were confirmed by surgical pathology. CONCLUSION: Gd-EOB-DTPA-enhanced MRI reveals the intraductal mucin component of IPMN-B in some cases and the extent of tumor infiltration beyond the bile ducts in invasive cases. PMID:26167082

Gd-EOB-DTPA-enhanced magnetic resonance imaging for bile duct intraductal papillary mucinous neoplasms.

PubMed

Ying, Shi-Hong; Teng, Xiao-Dong; Wang, Zhao-Ming; Wang, Qi-Dong; Zhao, Yi-Lei; Chen, Feng; Xiao, Wen-Bo

2015-07-07

To investigate gadolinium-ethoxybenzyl-diethylenetriamine-pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) of intraductal papillary mucinous neoplasms of the bile duct (IPMN-B). The imaging findings of five cases of IPMN-B which were pathologically confirmed at our hospital between March 2012 and May 2013 were retrospectively analyzed. Three of these cases were diagnosed by duodenal endoscopy and biopsy pathology, and two cases were diagnosed by surgical pathology. All five patients underwent enhanced and non-enhanced computed tomography (CT), magnetic resonance cholangiopancreatography, and Gd-EOB-DTPA-enhanced MRI; one case underwent both Gd-EOB-DTPA-enhanced MRI and positron emission tomography-CT. The clinical data and imaging results for these cases were compared and are presented. Conventional imaging showed diffuse dilatation of bile ducts and multiple intraductal polypoid and papillary neoplasms or serrated changes along the bile ducts. In two cases, Gd-EOB-DTPA-enhanced MRI revealed dilated biliary ducts and intraductal tumors, as well as filling defects caused by mucin in the dilated bile ducts in the hepatobiliary phase. Gd-EOB-DTPA-enhanced MRI in one case clearly showed a low-signal tumor in the hepatobiliary phase, similar to what was seen by positron emission tomography-CT. In two patients, routine inspection was unable to discern whether the lesions were inflammation or tumors. However, Gd-EOB-DTPA-enhanced MRI revealed a pattern of gradual enhancement during the hepatobiliary phase, and the signal intensity of the lesions was lower than the surrounding liver parenchyma, suggesting tissue inflammation in both cases, which were confirmed by surgical pathology. Gd-EOB-DTPA-enhanced MRI reveals the intraductal mucin component of IPMN-B in some cases and the extent of tumor infiltration beyond the bile ducts in invasive cases.

Mucinous cystadenocarcinoma of the breast.

PubMed

Koenig, C; Tavassoli, F A

1998-06-01

Four unusual cases of primary mammary mucinous cystadenocarcinoma composed predominantly of tall columnar cells with abundant intracytoplasmic mucin are reported; they were multicystic and appeared virtually identical to mucinous cystadenocarcinomas of the ovary and pancreas. Three of the women were white and one was black, they ranged in age from 49 to 67 years (average 58), and they had tumors that ranged from 0.8 to 19 cm in diameter. Microscopically, the tumors were characterized by cystic spaces lined by predominantly bland-appearing columnar mucinous cells with stratification, tufting, and papillary formations. Varying degrees of cytologic atypia were focally evident, with gradual loss of the intracytoplasmic mucin and transformation to an eosinophilic squamoid cell population. Multifocal invasion generally emanated from these eosinophilic, squamoid areas in all cases. All four tumors displayed immunoreactivity for MIB-1 (Ki-67) in a relatively high percentage of cells and failed to show immunoreactivity for estrogen receptors and progesterone receptors. All four stained positively with cytokeratin 7 (CK7) but were negative with cytokeratin 20 (CK20). Mastectomy and axillary lymph node dissection were performed in three cases and lumpectomy with lymph node dissection in the remaining case. Lymph node metastases, identified in only one patient, retained the distinctive morphology. Three of the patients are alive without evidence of disease 11, 22, and 24 months after the diagnosis; the fourth is a recent case. These tumors are a rare, clinicopathologically distinct type of primary breast carcinoma that should be distinguished from typical mucinous (colloid) carcinomas of the breast and, more importantly, metastases from other sites.

Endoscopic Biliary Stenting Versus Percutaneous Transhepatic Biliary Stenting in Advanced Malignant Biliary Obstruction: Cost-effectiveness Analysis.

PubMed

Sun, Xin Rong; Tang, Cheng Wu; Lu, Wen Ming; Xu, Yong Qiang; Feng, Wen Ming; Bao, Yin; Zheng, Yin Yuan

2014-05-01

This study aims to compare the clinical outcomes and costs between endoscopic biliary stenting (EBS) and percutaneous transhepatic biliary stenting (PTBS). We randomly assigned 112 patients with unresectable malignant biliary obstruction 2006 and 2011 to receive EBS or PTBS with self-expandable metal stent (SEMS) as palliative treatment. PTBS was successfully performed in 55 patients who formed the PTBS group (failed in 2 patients). EBS was successfully performed in 52 patients who formed the EBS group (failed in 3 patients). The effectiveness of biliary drainage, hospital stay, complications, cost, survival time and mortality were compared. Patients in PTBS group had shorter hospital stay and lower initial and overall expense than the BBS group (P < 0.05). There was no significant difference in effectiveness of biliary drainage (P = 0.9357) or survival time between two groups (P = 0.6733). Early complications occurred in PTBS group was significantly lower than in EBS group (3/55 vs 11/52, P = 0.0343). Late complications in the EBS group did not differ significantly from PTBS group (7/55 vs 9/52, P = 0.6922). The survival curves in the two groups showed no significant difference (P = 0.5294). Conclusions: 3.

Sequence of a second gene encoding bovine submaxillary mucin: implication for mucin heterogeneity and cloning.

PubMed

Jiang, W; Woitach, J T; Gupta, D; Bhavanandan, V P

1998-10-20

Secreted epithelial mucins are extremely large and heterogeneous glycoproteins. We report the 5 kilobase DNA sequence of a second gene, BSM2, which encodes bovine submaxillary mucin. The determined nucleotide and deduced amino acid sequences of BSM2 are 95.2% and 92. 2% identical, respectively, to those of the previously described BSM1 gene isolated from the same cow. Further, the five predicted protein domains of the two genes are 100%, 94%, 93%, 77%, and 88% identical. Based on the above results, we propose that expression of multiple homologous core proteins from a single animal is a factor in generating diversity of saccharides in mucins and in providing resistance of the molecules to proteolysis. In addition, this work raises several important issues in mucin cloning such as assembling sequences from seemingly overlapping clones and deducing consensus sequences for nearly identical tandem repeats. Copyright 1998 Academic Press.

Malignant biliary disease: percutaneous interventions.

PubMed

Morgan, R A; Adam, A N

2001-09-01

Interventional radiologists have an important role in the management of patients with malignant biliary obstruction. This article describes the techniques for percutaneous biliary drainage, insertion of biliary endoprostheses, and the management of occluded biliary endoprostheses. Most procedures are performed by using fluoroscopic guidance alone. Ultrasound is also a useful modality for guiding biliary drainage, particularly drainage of the left biliary ducts. Patients should be treated by internal drainage if possible. Metallic endoprostheses can be inserted at the time of the initial biliary drainage procedure. Plastic tubes should be inserted a few days after biliary drainage because of their relatively large size compared with metallic stents. Occluded plastic stents should be replaced. Blocked metallic stents should be treated either by placement of additional overlapping metallic stents or by placement of plastic stents within the metallic stent lumen. Copyright 2001 by W.B. Saunders Company

Human preocular mucins reflect changes in surface physiology

PubMed Central

Berry, M; Ellingham, R B; Corfield, A P

2004-01-01

Background/aims: Mucin function is associated with both peptide core and glycosylation characteristics. The authors assessed whether structural alterations occurring during mucin residence in the tear film reflect changes in ocular surface physiology. Methods: Ocular surface mucus was collected from normal volunteers as N-acetyl cysteine (NAcCys) washes or directly from the speculum after cataract surgery. To assess the influence of surface health on mucins, NAcCys washings were also obtained from patients with symptoms, but no clinical signs of dry eye (symptomatics). Mucins were extracted in guanidine hydrochloride (GuHCl) with protease inhibitors. Buoyant density of mucin species, a correlate of glycosylation density, was followed by reactivity with anti-peptide core antibodies. Mucin hydrodynamic volume was assessed by gel filtration on Sepharose CL2B. Results: Surface fluid and mucus contained soluble forms of MUC1, MUC2, MUC4, and MUC5AC and also the same species requiring DTT solubilisation. Reactivity with antibodies to MUC2 and MUC5AC peaked at 1.3–1.5 g/ml in normals, while dominated by underglycosylated forms in symptomatics. Surface mucins were predominantly smaller than intracellular species. MUC2 size distributions were different in symptomatics and normals, while those of MUC5AC were similar in these two groups. Conclusions: A reduction in surface mucin size indicates post-secretory cleavage. Dissimilarities in surface mucin glycosylation and individual MUC size distributions in symptomatics suggest changes in preocular mucin that might precede dry eye signs. PMID:14977773

Assay of mucins in human tear fluid.

PubMed

Spurr-Michaud, Sandra; Argüeso, Pablo; Gipson, Ilene

2007-05-01

Mucin genes, both secreted (MUC2, MUC5AC, MUC5B, MUC7) and membrane associated (MUC1, MUC4, MUC16), have been reported to be expressed by ocular surface epithelia. The purpose of this study was to comprehensively assay the mucin content of human tear fluid using multiple antibodies for each mucin and to develop a sensitive, semi-quantitative method for the assay of mucins in tears. Tear washes were obtained by instillation of saline onto the ocular surface, followed by collection from the inferior fornix. Tear proteins were separated in 1% agarose gels, transferred to nitrocellulose membrane by vacuum blotting and probed with multiple antibodies recognizing MUC1, MUC2, MUC4, MUC5AC, MUC5B, MUC7 and MUC16. Binding was detected using chemiluminescence, and quantity was determined by densitometry. Serial dilutions of pooled tears from normal individuals were assayed to determine the linear range of detectability. MUC1, MUC4, MUC16, MUC5AC and low levels of MUC2 were consistently detected in human tear fluid, while MUC5B and MUC7 were not. Use of several antibodies recognizing different epitopes on the same mucin confirmed these findings. The antibodies to mucins bound to serial dilutions of tears in a linear fashion (r2 > 0.9), indicating the feasibility of semi-quantitation. MUC5AC in tear fluid had an increased electrophoretic mobility compared to MUC5AC isolated from conjunctival tissue. This study provides clear evidence that the mucin component of tears is a mixture of secreted and shed membrane-associated mucins, and for the first time demonstrates MUC16 in tear fluid. Immunoblots of tears using agarose gel electrophoresis and chemiluminescence detection provide a semi-quantitative assay for mucin protein that will be useful for comparisons with tears from diseased eyes or after pharmacological intervention.

Assay of Mucins in Human Tear Fluid

PubMed Central

Spurr-Michaud, Sandra; Argüeso, Pablo; Gipson, Ilene

2007-01-01

Mucin genes, both secreted (MUC2, MUC5AC, MUC5B, MUC7) and membrane associated (MUC1, MUC4, MUC16), have been reported to be expressed by ocular surface epithelia. The purpose of this study was to comprehensively assay the mucin content of human tear fluid using multiple antibodies for each mucin and to develop a sensitive, semi-quantitative method for the assay of mucins in tears. Tear washes were obtained by instillation of saline onto the ocular surface, followed by collection from the inferior fornix. Tear proteins were separated in 1% agarose gels, transferred to nitrocellulose membrane by vacuum blotting and probed with multiple antibodies recognizing MUC1, MUC2, MUC4, MUC5AC, MUC5B, MUC7 and MUC16. Binding was detected using chemiluminescence, and quantity was determined by densitometry. Serial dilutions of pooled tears from normal individuals were assayed to determine the linear range of detectability. MUC1, MUC4, MUC16, MUC5AC and low levels of MUC2 were consistently detected in human tear fluid, while MUC5B and MUC7 were not. Use of several antibodies recognizing different epitopes on the same mucin confirmed these findings. The antibodies to mucins bound to serial dilutions of tears in a linear fashion (r2 >0.9), indicating the feasibility of semi-quantitation. MUC5AC in tear fluid had an increased electrophoretic mobility compared to MUC5AC isolated from conjunctival tissue. This study provides clear evidence that the mucin component of tears is a mixture of secreted and shed membrane-associated mucins, and for the first time demonstrates MUC16 in tear fluid. Immunoblots of tears using agarose gel electrophoresis and chemiluminescence detection provide a semi-quantitative assay for mucin protein that will be useful for comparisons with tears from diseased eyes or after pharmacological intervention. PMID:17399701

Biomimetic oral mucin from polymer micelle networks

NASA Astrophysics Data System (ADS)

Authimoolam, Sundar Prasanth

Mucin networks are formed by the complexation of bottlebrush-like mucin glycoprotein with other small molecule glycoproteins. These glycoproteins create nanoscale strands that then arrange into a nanoporous mesh. These networks play an important role in ensuring surface hydration, lubricity and barrier protection. In order to understand the functional behavior in mucin networks, it is important to decouple their chemical and physical effects responsible for generating the fundamental property-function relationship. To achieve this goal, we propose to develop a synthetic biomimetic mucin using a layer-by-layer (LBL) deposition approach. In this work, a hierarchical 3-dimensional structures resembling natural mucin networks was generated using affinity-based interactions on synthetic and biological surfaces. Unlike conventional polyelectrolyte-based LBL methods, pre-assembled biotin-functionalized filamentous (worm-like) micelles was utilized as the network building block, which from complementary additions of streptavidin generated synthetic networks of desired thickness. The biomimetic nature in those synthetic networks are studied by evaluating its structural and bio-functional properties. Structurally, synthetic networks formed a nanoporous mesh. The networks demonstrated excellent surface hydration property and were able capable of microbial capture. Those functional properties are akin to that of natural mucin networks. Further, the role of synthetic mucin as a drug delivery vehicle, capable of providing localized and tunable release was demonstrated. By incorporating antibacterial curcumin drug loading within synthetic networks, bacterial growth inhibition was also demonstrated. Thus, such bioactive interfaces can serve as a model for independently characterizing mucin network properties and through its role as a drug carrier vehicle it presents exciting future opportunities for localized drug delivery, in regenerative applications and as bio

The O-Linked Glycome and Blood Group Antigens ABO on Mucin-Type Glycoproteins in Mucinous and Serous Epithelial Ovarian Tumors

PubMed Central

Vitiazeva, Varvara; Kattla, Jayesh J.; Flowers, Sarah A.; Lindén, Sara K.; Premaratne, Pushpa; Weijdegård, Birgitta; Sundfeldt, Karin; Karlsson, Niclas G.

2015-01-01

Background Mucins are heavily O-glycosylated proteins where the glycosylation has been shown to play an important role in cancer. Normal epithelial ovarian cells do not express secreted mucins, but their abnormal expression has previously been described in epithelial ovarian cancer and may relate to tumor formation and progression. The cyst fluids were shown to be a rich source for acidic glycoproteins. The study of these proteins can potentially lead to the identification of more effective biomarkers for ovarian cancer. Methods In this study, we analyzed the expression of the MUC5AC and the O-glycosylation of acidic glycoproteins secreted into ovarian cyst fluids. The samples were obtained from patients with serous and mucinous ovarian tumors of different stages (benign, borderline, malignant) and grades. The O-linked oligosaccharides were released and analyzed by negative-ion graphitized carbon Liquid Chromatography (LC) coupled to Electrospray Ionization tandem Mass Spectrometry (ESI-MSn). The LC-ESI-MSn of the oligosaccharides from ovarian cyst fluids displayed differences in expression of fucose containing structures such as blood group ABO antigens and Lewis-type epitopes. Results The obtained data showed that serous and mucinous benign adenomas, mucinous low malignant potential carcinomas (LMPs, borderline) and mucinous low-grade carcinomas have a high level of blood groups and Lewis type epitopes. In contrast, this type of fucosylated structures were low abundant in the high-grade mucinous carcinomas or in serous carcinomas. In addition, the ovarian tumors that showed a high level of expression of blood group antigens also revealed a strong reactivity towards the MUC5AC antibody. To visualize the differences between serous and mucinous ovarian tumors based on the O-glycosylation, a hierarchical cluster analysis was performed using mass spectrometry average compositions (MSAC). Conclusion Mucinous benign and LMPs along with mucinous low-grade carcinomas

Mucinous Cystic Neoplasms Lined by Abundant Mucinous Epithelium Frequently Involve KRAS Mutations and Malignant Progression.

PubMed

Shibata, Hideki; Ohike, Nobuyuki; Norose, Tomoko; Isobe, Tomohide; Suzuki, Reika; Imai, Hideyuki; Shiokawa, Akira; Aoki, Takeshi; Murakami, Masahiko; Mizukami, Hiroki; Tanaka, Jun-Ichi; Takimoto, Masafumi

2017-12-01

Pancreatic and hepatic mucinous cyst neoplasms (MCNs) have a malignant potential, but indolent MCNs are not uncommon. The pathological and genetic characteristics of resected MCNs (n=15) categorized by the amount of mucin of the lining epithelium were investigated. MCNs were divided into two groups: (i) a rich (r)-MCN group (n=6), in which more than half of the epithelium was lined by abundant mucinous epithelium; and (ii) a poor (p)-MCN group (n=9), which consisted of the remaining cases. Three patients in the r-MCN group showed invasive carcinoma or high-grade dysplasia, whereas all patients in the p-MCN group showed low-grade dysplasia. Mutations of Kirsten rat sarcoma viral oncogene homolog (KRAS) were more frequent in the r-MCN group (83%) (p-MCN; 11%, p<0.05). Mucinous MCNs more frequently have KRAS mutations and higher risk of malignant progression. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Mucin gene expression in intraductal papillary-mucinous pancreatic tumours and related lesions.

PubMed

Terris, Benoît; Dubois, Sylvie; Buisine, Marie-Pierre; Sauvanet, Alain; Ruszniewski, Philippe; Aubert, Jean-Pierre; Porchet, Nicole; Couvelard, Anne; Degott, Claude; Fléjou, Jean-Francois

2002-08-01

Intraductal papillary-mucinous tumours (IPMTs) of the pancreas are heterogeneous proliferations characterized by a malignant potential. The molecular mechanisms underlying the tumourigenesis process are not well understood. Recently, it has been shown that IPMTs secreting the mucin antigen MUC2 have a better prognosis, but the complete pattern of MUC gene expression has not yet been established. The aims of this study were to evaluate the mucin gene expression in 57 IPMTs and eight related lesions surgically resected and to relate MUC gene expression to the histological diagnosis. In situ hybridization (ISH) was performed in 28 cases with probes specific for the MUC1, MUC2, MUC3, MUC4, MUC5AC, MUC5B, MUC6, and MUC7 genes. An immunohistochemical analysis was carried in all 65 cases and in 90 conventional ductal adenocarcinomas of the pancreas using MUC1, MUC2, and MUC5AC antibodies. IPMTs of adenoma (dysplasia) type exhibited high expression of MUC2 (93%), MUC5AC (97%), and, to a lesser extent, of MUC4 (71%), all of which were also observed in colloid carcinomas associated with IPMTs. In contrast, IPMTs with simple hyperplasia, intraductal oncocytic papillary neoplasms, and pyloric glandular adenomas exhibited little or no expression of MUC2. The mucin expression profile supports the existence of two types of invasive tumour associated with IPMTs: a colloid and an ordinary form. The latter shows a pattern similar to the conventional ductal adenocarcinomas with a loss of MUC2 and a gain of MUC1 and has a greater tendency to metastasize. In conclusion, the altered expression of mucin, characteristic of IPMT of adenoma type and of colloid carcinomas, may contribute to the better clinical outcome of these neoplasms, compared to conventional pancreatic ductal adenocarcinomas. Copyright 2002 John Wiley & Sons, Ltd.

Rat gastric mucins recognized by monoclonal antibodies RGM21 and HIK1083: isolation of mucin species characteristic of the surface and glandular mucosa.

PubMed

Goso, Y; Ishihara, K; Kurihara, M; Sugaya, T; Hotta, K

1999-08-01

Whole mucins and reduced subunits were extracted from the corpus of the rat stomach. After purification by Sepharose CL-4B chromatography followed by cesium trifluoroacetate equilibrium centrifugation, they were analyzed by Sepharose CL-2B chromatography, rate-zonal sedimentation centrifugation, and Q-Sepharose chromatography. Monoclonal antibodies RGM21 and HIK1083, which histochemically stained mucins in the surface and glandular mucosa of the rat stomach, respectively, were used to detect the site-specific mucins. Although RGM21- and HIK1083-reactive mucins both had a multimerized structure, the density and size of both the whole mucins and reduced subunits differed, thus indicating the presence of distinct mucin species in the surface and glandular mucosa. The mucin subunits were separated into four fractions, UB, B1, B2a, and B2b, by Q-Sepharose chromatography. HIK1083 reacted mainly with UB, while RGM21 reacted with B1, B2a, and B2b. These results, combined with dot-blot, amino acid, and carbohydrate composition analyses, showed that the surface mucins may consist of three kinds of subunits. In contrast, the glandular mucins may consist of one kind of subunit which differs from that of surface mucins.

Lambdapapillomavirus 2 in a gray wolf (Canis lupus) from Minnesota with oral papillomatosis and sarcoptic mange

USGS Publications Warehouse

Knowles, Susan N.; Windels, Steve K.; Adams, Marie; Hall, Jeffrey S.

2017-01-01

Oral papillomatosis was diagnosed in a gray wolf (Canis lupus) with sarcoptic mange from Minnesota, USA found dead in February 2015. Intranuclear inclusion bodies were evident histologically, and papillomaviral antigens were confirmed using immunohistochemistry. Sequencing of the L1 papillomavirus gene showed closest similarity to Lambdapapillomavirus 2.

Stenting in Malignant Biliary Obstruction.

PubMed

Almadi, Majid A; Barkun, Jeffrey S; Barkun, Alan N

2015-10-01

Decompression of the biliary system in patients with malignant biliary obstruction has been widely accepted and implemented as part of the care. Despite a wealth of literature, there remains a significant amount of uncertainty as to which approach would be most appropriate in different clinical settings. This review covers stenting of the biliary system in cases of resectable or palliative malignant biliary obstruction, potential candidates for biliary drainage, technical aspects of the procedure, as well as management of biliary stent dysfunction. Furthermore, periprocedural considerations including proper mapping of the location of obstruction and the use of antibiotics are addressed. Copyright © 2015 Elsevier Inc. All rights reserved.

Altered Mucin and Glycoprotein Expression in Dry Eye Disease.

PubMed

Stephens, Denise N; McNamara, Nancy A

2015-09-01

Mucins are among the many important constituents of a healthy tear film. Mucins secreted and/or associated with conjunctival goblet cells, ocular mucosal epithelial cells, and the lacrimal gland must work together to create a stable tear film. Although many studies have explored the mechanism(s) whereby mucins maintain and protect the ocular surface, the effects of dry eye on the structure and function of ocular mucins are unclear. Here, we summarize current findings regarding ocular mucins and how they are altered in dry eye. We performed a literature review of studies exploring the expression of mucins produced and/or associated with tissues that comprise the lacrimal functional unit and how they are altered in dry eye. We also summarize new insights on the immune-mediated effects of aqueous tear deficiency on ocular surface mucins that we discovered using a mouse model of dry eye. Although consistent decreases in MUC5AC and altered expression of membrane-bound mucins have been noted in both Sjögren and non-Sjögren dry eye, many reports of altered mucins in dry eye are contradictory. Mechanistic studies, including our own, suggest that changes in the glycosylation of mucins rather than the proteins themselves may occur as the direct result of local inflammation induced by proinflammatory mediators, such as interleukin-1. Altered expression of ocular mucins in dry eye varies considerably from study to study, likely attributed to inherent difficulties in analyzing small-volume tear samples, as well as differences in tear collection methods and disease severity in dry eye cohorts. To better define the functional role of ocular mucin glycosylation in the pathogenesis of dry eye disease, we propose genomic and proteomic studies along with biological pathway analysis to reveal novel avenues for exploration.

Mucin glycan foraging in the human gut microbiome

PubMed Central

Tailford, Louise E.; Crost, Emmanuelle H.; Kavanaugh, Devon; Juge, Nathalie

2015-01-01

The availability of host and dietary carbohydrates in the gastrointestinal (GI) tract plays a key role in shaping the structure-function of the microbiota. In particular, some gut bacteria have the ability to forage on glycans provided by the mucus layer covering the GI tract. The O-glycan structures present in mucin are diverse and complex, consisting predominantly of core 1-4 mucin-type O-glycans containing α- and β- linked N-acetyl-galactosamine, galactose and N-acetyl-glucosamine. These core structures are further elongated and frequently modified by fucose and sialic acid sugar residues via α1,2/3/4 and α2,3/6 linkages, respectively. The ability to metabolize these mucin O-linked oligosaccharides is likely to be a key factor in determining which bacterial species colonize the mucosal surface. Due to their proximity to the immune system, mucin-degrading bacteria are in a prime location to influence the host response. However, despite the growing number of bacterial genome sequences available from mucin degraders, our knowledge on the structural requirements for mucin degradation by gut bacteria remains fragmented. This is largely due to the limited number of functionally characterized enzymes and the lack of studies correlating the specificity of these enzymes with the ability of the strain to degrade and utilize mucin and mucin glycans. This review focuses on recent findings unraveling the molecular strategies used by mucin-degrading bacteria to utilize host glycans, adapt to the mucosal environment, and influence human health. PMID:25852737

New phase II trial of avelumab, a PD-L1 inhibitor, in recurrent respiratory papillomatosis | Center for Cancer Research

Cancer.gov

Dr. Christian Hinrichs, Investigator and Lasker Clinical Research Scholar in the Experimental Transplantation and Immunology Branch (ETIB), is leading a trial of avelumab in patients with recurrent respiratory papillomatosis (RRP). Learn more...

The Cholangiocyte Glycocalyx Stabilizes the 'Biliary HCO3 Umbrella': An Integrated Line of Defense against Toxic Bile Acids.

PubMed

Maillette de Buy Wenniger, Lucas J; Hohenester, Simon; Maroni, Luca; van Vliet, Sandra J; Oude Elferink, Ronald P; Beuers, Ulrich

2015-01-01

Destruction of cholangiocytes is the hallmark of chronic cholangiopathies such as primary biliary cirrhosis. Under physiologic conditions, cholangiocytes display a striking resistance to the high, millimolar concentrations of toxic bile salts present in bile. We recently showed that a 'biliary HCO3(-) umbrella', i.e. apical cholangiocellular HCO3(-) secretion, prevents cholangiotoxicity of bile acids, and speculated on a role for extracellular membrane-bound glycans in the stabilization of this protective layer. This paper summarizes published and thus far unpublished evidence supporting the role of the glycocalyx in stabilizing the 'biliary HCO3(-) umbrella' and thus preventing cholangiotoxicity of bile acids. The apical glycocalyx of a human cholangiocyte cell line and mouse liver sections were visualized by electron microscopy. FACS analysis was used to characterize the surface glycan profile of cultured human cholangiocytes. Using enzymatic digestion with neuraminidase the cholangiocyte glycocalyx was desialylated to test its protective function. Using lectin assays, we demonstrated that the main N-glycans in human and mouse cholangiocytes were sialylated biantennary structures, accompanied by high expression of the H-antigen (α1-2 fucose). Apical neuraminidase treatment induced desialylation without affecting cell viability, but lowered cholangiocellular resistance to bile acid-induced toxicity: both glycochenodeoxycholate and chenodeoxycholate (pKa ≥4), but not taurochenodeoxycholate (pKa <2), displayed cholangiotoxic effects after desialylation. A 24-hour reconstitution period allowed cholangiocytes to recover to a pretreatment bile salt susceptibility pattern. Experimental evidence indicates that an apical cholangiocyte glycocalyx with glycosylated mucins and other glycan-bearing membrane glycoproteins stabilizes the 'biliary HCO3(-) umbrella', thus aiding in the protection of human cholangiocytes against bile acid toxicity. 2015 S. Karger AG, Basel.

Biliary fascioliasis--an uncommon cause of recurrent biliary colics: report of a case and brief review.

PubMed

Al Qurashi, Hesham; Masoodi, Ibrahim; Al Sofiyani, Mohammad; Al Musharaf, Hisham; Shaqhan, Mohammed; All, Gamal Nasr Ahmed Abdel

2012-01-01

Biliary parasitosis is one of the important causes of biliary obstruction in endemic areas, however due to migration and travel the disease is known to occur in non endemic zones as well. The spectrum of biliary fascioliasis ranges from recurrent biliary colics to acute cholangitis. The long term complications are gall stones, sclerosing cholangitis and biliary cirrhosis. We describe fascioliasis as a cause of recurrent biliary colics in a young male necessitating multiple hospitalizations over a period of four years. Investigative profile had been non-contributory every time he was hospitalized for his abdominal pain prior to the current presentation. He never had cholangitis due to the worm in the common bile duct. It was only at endoscopic retrograde cholangiopancreatography (ERCP) biliary fascioliasis was discovered to be the cause of his recurrent biliary colics. After removal of the live Fasciola hepatica from the common bile duct he became symptom free and is attending our clinic for last 11 months now. Clinical spectrum of biliary fascioliasis is discussed in this report.

Physical and chemical characteristics of mucin secreted by pseudomyxoma peritonei (PMP)

PubMed Central

Pillai, Krishna; Akhter, Javed; Mekkawy, Ahmed; Chua, Terence C; Morris, David L

2017-01-01

Background: Pseudomyxoma peritonei (PMP) is a rare disease with excess intraperitoneal mucin secretion. Treatment involves laparotomy, cytoreduction and chemotherapy that is very invasive with patients often acquiring numerous compromises. Hence a mucolytic comprising of bromelain and N-acetyl cystein has been developed to solubilise mucin in situ for removal by catherization. Owing to differences in mucin appearance and hardness, dissolution varies. Therefore the current study investigates the inter-mucin physical and chemical characteristics, in order to reformulate an effective mucolytic for all mucin. Method: PMP mucin, from the three categories (soft, semi hard and hard mucin) was solubilised and then various physical characteristics such as turbidity, density, kinematic viscosity were measured. The water content and the density of solid mucin were also determined. This was followed by the determination of sialic acid, glucose, lipid, Thiol (S-S and S-H) content of the samples. Lastly, the distribution of MUC2, MUC5B and MUC5AC was determined using western blot technique. Results: Both turbidity and kinematic viscosity and sialic acid content increased linearly as the hardness of mucin increased. However, density, hydration, protein, glucose, lipid and sulfhydryl and disulphide content decreased linearly as hardness of mucin increased. The distribution ratio of mucins (MUC2:MUC5B:MUC5AC) in soft mucin is 2.25:1.5:1.0, semi hard mucin is 1:1:1 and hard mucin is 3:2:1. Conclusion: The difference in texture and hardness of mucin may be due to cellular content, hydration, glucose, protein, lipids, thiol and MUC distribution. Soft mucin is solely made of glycoprotein whilst the others contained cellular materials. PMID:28138305

Atraumatic laser treatment for laryngeal papillomatosis

NASA Astrophysics Data System (ADS)

McMillan, Kathleen; Pankratov, Michail M.; Wang, Zhi; Bottrill, Ian; Rebeiz, Elie E.; Shapshay, Stanley M.

1994-09-01

Ten to fifteen thousand new cases of recurrent respiratory papillomatosis (RRP) are diagnosed each year in the United States. RRP is caused by the human papillomavirus (HPV) and is characterized by recurrent, non-malignant, proliferative lesions of the larynx. Patients with RRP undergo numerous microsurgical procedures to remove laryngeal papilloma threatening airway patency and interfering with phonation. The standard surgical technique involves CO2 laser vaporization of laryngeal epithelium affected by the lesions, and requires general anesthesia. The pulsed dye laser operating at 585 nm has previously been demonstrated to be effective in clearing HPV lesions of the skin (verrucae). For treatment of RRP, the fiber- compatible pulsed dye laser radiation may be delivered under local anesthesia using a flexible intranasal laryngoscope. Potential advantages of the pulsed dye laser treatment over CO2 laser surgery include (1) reduced morbidity, especially a lower risk of laryngeal scarring; (2) lower cost; (3) reduced technical difficulty; and (4) reduced risk of viral dissemination or transmission. In vivo studies are underway to determine the effect of pulsed dye laser radiation on normal canine laryngeal tissue.

Purification and characterization of a human pancreatic adenocarcinoma mucin.

PubMed

Khorrami, Ali M; Choudhury, Amit; Andrianifahanana, Mahefatiana; Varshney, Grish C; Bhattacharyya, Sambhu N; Hollingsworth, Michael A; Kaufman, Bernard; Batra, Surinder K

2002-01-01

Pancreatic mucins consist of core proteins that are decorated with carbohydrate structures. Previous studies have identified at least two physically distinct populations of mucins produced by a pancreatic adenocarcinoma cell line (HPAF); one is the MUC1 core protein, which includes an oligosaccharide structure identified by a monoclonal antibody (MAb) recognizing the DU-PAN-2 epitope. In this study, we purified and characterized a second mucin fraction, which also shows reactivity with the DU-PAN-2 antibody, but which has an amino acid composition that is not consistent with the MUC1 core protein. This new mucin was purified by ammonium sulfate precipitation, molecular sieve chromatography, and density gradient centrifugation. It eluted in the void volume of a Sepharose 4B column together with an associated low molecular weight protein, which could be further resolved. The mucin is highly polyanionic due to numerous sulfated and sialylated saccharide chains. Carbohydrate analyses of the purified mucin showed the presence of galactose, glucosamine, galactosamine, and sialic acid, but no mannose, glucose, or uronic acid. The purified and deglycosylated mucin shows no reactivity with anti-MUC1 apomucin antibody, but reacts with antiserum against deglycosylated tracheal mucins and antiserum against the MUC4 tandem repeat peptide. Analysis of mucin expression in HPAF cells revealed high levels of MUC1 and MUC4 mRNA, and moderate levels of MUC5AC and MUC5B mRNA. The amino acid composition of the purified mucin shows a high degree of similarity to the MUC4 core protein.

Mucins in contact lens wear and dry eye conditions.

PubMed

Ramamoorthy, Padmapriya; Nichols, Jason J

2008-08-01

Ocular mucins are thought to play integral roles in ocular surface lubrication, anchoring of the aqueous, stabilizing the lipid components of the tear film, eliminating foreign bodies and pathogens, and with potential involvement in cell cycle mediation and apoptotic activity of ocular surface epithelia. Ocular mucins are of secreted and membrane-associated types. Secreted mucins may be of large gel-forming type or small soluble mucins (e.g., MUC5AC and MUC7). Membrane-associated mucins such as MUCs 1 and 4 are a major component of the glycocalyx. They are thought to render structural support to the microplicae and mediate epithelial cell cycle and apoptotic activity. The alterations in ocular mucins with contact lens wear are unclear. Recent work shows mucin expression may be up-regulated during the early years of contact lens wear, and with long-term lens wear, mucin expression may return to normal levels or sub-normal levels, although this is not well understood. Further, the polar nature of mucins may be associated with their affinity for contact lens surfaces making them a component of contact lens deposition. This has potential implications in the wettability and tolerability of contact lenses, and may be impacted by surface coatings, polymer characteristics, or care solutions. Conjunctival mucin gene expression and secretion may be deficient in several ocular surface disorders associated with dry eye. Deficiency and alterations in glycosylation characteristics of MUC5AC and MUC2 have been reported in both Sjögren and non-Sjögren dry eye types. Decreased binding of the membrane-associated mucin MUC16 to the conjunctival epithelium has been reported in Sjögren dry eye while MUC1 alterations have been reported in Sjögren and non-Sjögren dry eye states. In view of the mucin involvement in dry eye conditions, stimulation of mucus secretion pathways may hold promise in the pharmaceutical treatment of dry eye.

Endoscopic ultrasound-guided biliary drainage

PubMed Central

Chavalitdhamrong, Disaya; Draganov, Peter V

2012-01-01

Endoscopic ultrasound (EUS)-guided biliary drainage has emerged as a minimally invasive alternative to percutaneous and surgical interventions for patients with biliary obstruction who had failed endoscopic retrograde cholangiopancreatography (ERCP). EUS-guided biliary drainage has become feasible due to the development of large channel curvilinear therapeutic echo-endoscopes and the use of real-time ultrasound and fluoroscopy imaging in addition to standard ERCP devices and techniques. EUS-guided biliary drainage is an attractive option because of its minimally invasive, single step procedure which provides internal biliary decompression. Multiple investigators have reported high success and low complication rates. Unfortunately, high quality prospective data are still lacking. We provide detailed review of the use of EUS for biliary drainage from the perspective of practicing endoscopists with specific focus on the technical aspects of the procedure. PMID:22363114

Lambdapapillomavirus 2 in a Gray Wolf ( Canis lupus ) from Minnesota, USA with Oral Papillomatosis and Sarcoptic Mange.

PubMed

Knowles, Susan; Windels, Steve K; Adams, Marie; Hall, Jeffrey S

2017-10-01

Oral papillomatosis was diagnosed in a gray wolf ( Canis lupus ) with sarcoptic mange from Minnesota, US found dead in February 2015. Intranuclear inclusion bodies were evident histologically, and papillomaviral antigens were confirmed using immunohistochemistry. Sequencing of the L1 papillomavirus gene showed closest similarity to Lambdapapillomavirus 2.

Studying Mucin Secretion from Human Bronchial Epithelial Cell Primary Cultures

PubMed Central

Abdullah, Lubna H.; Wolber, Cédric; Kesimer, Mehmet; Sheehan, John K.; Davis, C. William

2016-01-01

Mucin secretion is regulated by extracellular signaling molecules emanating from local, neuronal, or endocrine sources. Quantifying the rate of this secretion is important to understanding how the exocytic process is regulated, and also how goblet/mucous cells synthesize and release mucins under control and pathological conditions. Consequently, measuring mucins in a quantitatively accurate manner is the key to many experiments addressing these issues. This paper describes procedures used to determine agonist-induced mucin secretion from goblet cells in human bronchial epithelial (HBE) cell cultures. It begins with primary epithelial cell culture, offers methods for purifying MUC5AC and MUC5B mucins for standards, and describes five different microtiter plate binding assays which use various probes for mucins. A polymeric mucin-specific antibody is used in standard and sandwich ELISA formats for two assays while the others target the extensive glycosylated domains of mucins with lectin, periodate oxidation, and antibody-based probes. Comparing the data derived from the different assays applied to the same set of samples of HBE cell cultures indicates a qualitative agreement between baseline and agonist stimulated mucin release; however, the polymeric mucin-specific assays yield substantially lower values than the assays using nonspecific molecular reporters. These results indicate that the more non-specific assays are suitable to assess overall secretory responses by goblet cells, but are likely unsuited for specific measurements of polymeric mucins, per se. PMID:22259142

Chemically tunable mucin chimeras assembled on living cells

DOE PAGES

Kramer, Jessica R.; Onoa, Bibiana; Bustamante, Carlos; ...

2015-09-29

Mucins are a family of secreted and transmembrane glycoproteins characterized by a massive domain of dense O-glycosylation on serine and threonine residues. Mucins are intimately involved in immunity and cancer, yet elucidation of the biological roles of their glycodomains has been complicated by their massive size, domain polymorphisms, and variable glycosylation patterns. Here we developed a synthetic route to a library of compositionally defined, high-molecular weight, dual end-functionalized mucin glycodomain constructs via N-carboxyanhydride polymerization. These glycopolypeptides are the first synthetic analogs to our knowledge to feature the native α-GalNAc linkage to serine with molecular weights similar to native mucins, solvingmore » a nearly 50-year synthetic challenge. Physical characterization of the mimics revealed insights into the structure and properties of mucins. The synthetic glycodomains were end-functionalized with an optical probe and a tetrazine moiety, which allowed site-specific bioorthogonal conjugation to an engineered membrane protein on live mammalian cells. Lastly, this strategy in protein engineering will open avenues to explore the biological roles of cell surface mucins.« less

Chemically tunable mucin chimeras assembled on living cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kramer, Jessica R.; Onoa, Bibiana; Bustamante, Carlos

Mucins are a family of secreted and transmembrane glycoproteins characterized by a massive domain of dense O-glycosylation on serine and threonine residues. Mucins are intimately involved in immunity and cancer, yet elucidation of the biological roles of their glycodomains has been complicated by their massive size, domain polymorphisms, and variable glycosylation patterns. Here we developed a synthetic route to a library of compositionally defined, high-molecular weight, dual end-functionalized mucin glycodomain constructs via N-carboxyanhydride polymerization. These glycopolypeptides are the first synthetic analogs to our knowledge to feature the native α-GalNAc linkage to serine with molecular weights similar to native mucins, solvingmore » a nearly 50-year synthetic challenge. Physical characterization of the mimics revealed insights into the structure and properties of mucins. The synthetic glycodomains were end-functionalized with an optical probe and a tetrazine moiety, which allowed site-specific bioorthogonal conjugation to an engineered membrane protein on live mammalian cells. Lastly, this strategy in protein engineering will open avenues to explore the biological roles of cell surface mucins.« less

Depletion of mucin in mucin-producing human gastrointestinal carcinoma: Results from in vitro and in vivo studies with bromelain and N-acetylcysteine.

PubMed

Amini, Afshin; Masoumi-Moghaddam, Samar; Ehteda, Anahid; Liauw, Winston; Morris, David L

2015-10-20

Aberrant expression of membrane-associated and secreted mucins, as evident in epithelial tumors, is known to facilitate tumor growth, progression and metastasis, and to provide protection against adverse growth conditions, chemotherapy and immune surveillance. Emerging evidence provides support for the oncogenic role of MUC1 in gastrointestinal carcinomas and relates its expression to an invasive phenotype. Similarly, mucinous differentiation of gastrointestinal tumors, in particular increased or de novo expression of MUC2 and/or MUC5AC, is widely believed to imply an adverse clinicopathological feature. Through formation of viscous gels, too, MUC2 and MUC5AC significantly contribute to the biology and pathogenesis of mucin-secreting gastrointestinal tumors. Here, we investigated the mucin-depleting effects of bromelain (BR) and N-acetylcysteine (NAC), in nine different regimens as single or combination therapy, in in vitro (MKN45, KATOIII and LS174T cell lines) and in vivo (female nude mice bearing intraperitoneal MKN45 and LS174T) settings. The inhibitory effects of the treatment on cancer cell growth and proliferation were also evaluated in vivo. Our results suggest that a combination of BR and NAC with dual effects on growth and mucin products of mucin-expressing tumor cells is a promising candidate towards the development of novel approaches to gastrointestinal malignancies with the involvement of mucin pathology. This capability supports the use of this combination formulation in locoregional approaches for reducing the adverse effects of the aberrantly secreted gel-forming mucins, as in pseudomyxoma peritonei and similar pathologies with ectopic production of mucin.

Depletion of mucin in mucin-producing human gastrointestinal carcinoma: Results from in vitro and in vivo studies with bromelain and N-acetylcysteine

PubMed Central

Amini, Afshin; Masoumi-Moghaddam, Samar; Ehteda, Anahid; Liauw, Winston; Morris, David L.

2015-01-01

Aberrant expression of membrane-associated and secreted mucins, as evident in epithelial tumors, is known to facilitate tumor growth, progression and metastasis, and to provide protection against adverse growth conditions, chemotherapy and immune surveillance. Emerging evidence provides support for the oncogenic role of MUC1 in gastrointestinal carcinomas and relates its expression to an invasive phenotype. Similarly, mucinous differentiation of gastrointestinal tumors, in particular increased or de novo expression of MUC2 and/or MUC5AC, is widely believed to imply an adverse clinicopathological feature. Through formation of viscous gels, too, MUC2 and MUC5AC significantly contribute to the biology and pathogenesis of mucin-secreting gastrointestinal tumors. Here, we investigated the mucin-depleting effects of bromelain (BR) and N-acetylcysteine (NAC), in nine different regimens as single or combination therapy, in in vitro (MKN45, KATOIII and LS174T cell lines) and in vivo (female nude mice bearing intraperitoneal MKN45 and LS174T) settings. The inhibitory effects of the treatment on cancer cell growth and proliferation were also evaluated in vivo. Our results suggest that a combination of BR and NAC with dual effects on growth and mucin products of mucin-expressing tumor cells is a promising candidate towards the development of novel approaches to gastrointestinal malignancies with the involvement of mucin pathology. This capability supports the use of this combination formulation in locoregional approaches for reducing the adverse effects of the aberrantly secreted gel-forming mucins, as in pseudomyxoma peritonei and similar pathologies with ectopic production of mucin. PMID:26436698

Penile warty mucoepidermoid carcinoma with features of stratified mucin-producing intra-epithelial lesion and invasive stratified mucin-producing carcinoma.

PubMed

Yorita, Kenji; Kuroda, Naoto; Naroda, Takushi; Tamura, Masato; Ohe, Chisato; Divatia, Mukul; Amin, Mahul B; Cubilla, Antonio L; Kazakov, Dimitry V; Hes, Ondrej; Michal, Michael; Michal, Michal

2018-04-01

Stratified mucin-producing intra-epithelial lesion (SMILE) and invasive stratified mucin-producing carcinoma (ISMC) are recently described cervical and penile lesions. We report an unusual case of mixed variant of penile squamous cell carcinomas with warty, usual and mucoepidermoid SMILE/ISMC features. A 62-year-old Japanese man had a glans penis lesion of one-and-a-half years' duration, suggesting malignancy. Partial penectomy and left inguinal lymphadenectomy were performed. Pathological evaluation revealed a mixed squamous cell carcinoma with warty, mucinous and usual features. The mucinous component resembled mucoepidermoid carcinoma (MEC) and SMILE/ISMC. Glandular differentiation was absent. All the diverse tumour components were negative for p16, which was confirmed by negative human papillomavirus (HPV) genotyping. The mucinous component was diffusely positive for cytokeratin 7 and largely negative for cytokeratin 5 and p63. Fluorescence in-situ hybridisation did not detect rearrangement in the MAML2 or EWSR1 genes. The tumour was pathological stage pT2, pN1 (AJCC prognostic stage group IIIA) and was disease-free 26 months after surgery. The lack of glands in the mucinous areas suggested that MEC should be separated from adenosquamous carcinoma (ASC). Penile SMILE/ISMC may occur without dependence upon HPV status. Further studies will be necessary to determine the pathogenesis and definition of penile SMILE/ISMC, the presence of true MEC arising from the glans penis and the clinicopathological differences of penile ASC, MEC and SMILE/ISMC. Herein, we refer to the SMILE-like penile lesion as 'mucinous penile intra-epithelial neoplasia'. © 2017 John Wiley & Sons Ltd.

Acromegaly and papillomatosis: difficult intubation and use of the airway exchange catheter.

PubMed

Hulme, G J; Blues, C M

1999-08-01

We describe the anaesthetic management of a patient with acromegaly scheduled for transsphenoidal resection of a pituitary tumour who was found at intubation to have coexisting laryngeal papillomatosis. Oral intubation was impossible using both direct and fibreoptic techniques. Nasal fibreoptic intubation was successful but precluded the transsphenoidal approach to surgery. A Cook Airway Exchange Catheter [Cook (UK) Ltd, Monroe House, Letchworth SG6 1LN] was used with a Negus bronchoscope to convert to oral intubation and allow completion of surgery without resort to tracheostomy.

Future developments in biliary stenting

PubMed Central

Hair, Clark D; Sejpal, Divyesh V

2013-01-01

Biliary stenting has evolved dramatically over the past 30 years. Advancements in stent design have led to prolonged patency and improved efficacy. However, biliary stenting is still affected by occlusion, migration, anatomical difficulties, and the need for repeat procedures. Multiple novel plastic biliary stent designs have recently been introduced with the primary goals of reduced migration and improved ease of placement. Self-expandable bioabsorbable stents are currently being investigated in animal models. Although not US Food and Drug Administration approved for benign disease, fully covered self-expandable metal stents are increasingly being used in a variety of benign biliary conditions. In malignant disease, developments are being made to improve ease of placement and stent patency for both hilar and distal biliary strictures. The purpose of this review is to describe recent developments and future directions of biliary stenting. PMID:23837001

Novel Biliary Reconstruction Techniques During Liver Transplantation

PubMed Central

Carmody, Ian C.; Romano, John; Bohorquez, Humberto; Bugeaud, Emily; Bruce, David S.; Cohen, Ari J.; Seal, John; Reichman, Trevor W.; Loss, George E.

2017-01-01

Background: Biliary complications remain a significant problem following liver transplantation. Several surgical options can be used to deal with a significant size mismatch between the donor and recipient bile ducts during the biliary anastomosis. We compared biliary transposition to recipient biliary ductoplasty in cadaveric liver transplant. Methods: A total of 33 reconstructions were performed from January 1, 2005 to December 31, 2013. In the biliary transposition group (n=23), 5 reconstructions were performed using an internal stent (5 or 8 French pediatric feeding tube), and 18 were performed without. Of the 10 biliary ductoplasties, 2 were performed with a stent. All patients were managed with standard immunosuppression and ursodiol. Follow-up ranged from 2 months to 5 years. Results: No patients in the biliary transposition group required reoperation; 1 patient had an internal stent removed for recurrent unexplained leukocytosis, and 2 patients required endoscopic retrograde cholangiography and stent placement for evidence of stricture. Three anastomotic leaks occurred in the biliary ductoplasty group, and 2 patients in the biliary ductoplasty group required reoperation for biliary complications. Conclusion: Our results indicate that biliary reconstruction can be performed with either biliary transposition or biliary ductoplasty. These techniques are particularly useful when a significant mismatch in diameter exists between the donor and recipient bile ducts. PMID:28331447

Study on Mucin in Normal-Appearing Leg Skin.

PubMed

Fernandez-Flores, Angel

2017-03-01

Dermal deposits of mucin in the legs have been described associated with venous insufficiency. However, some degree of stasis dermatitis is generally common in aged individuals. Therefore, some amount of mucin is expected a priori in the reticular dermis of aged patients, even in the absence of clinical lesions. To test this hypothesis, the authors investigated the mucin in the legs of aged individuals without any dermatologic disease. Cutaneous samples were taken from the legs of 15 autopsy cases. A sample of the skin of the legs (either from the left or the right leg without any distinction being made) was randomly taken (without selecting any specific area or attending to macroscopical features). The skin samples were fixed in formaldehyde, and sections obtained from all samples were stained with hematoxylin and eosin, iron, and Alcian blue. Iron deposits were graded as 0/4 in 7 cases, as 1/4 in 4 cases, as 2/4 in 2 cases, and as 4/4 in 2 cases. Cases with greater deposits of iron also had other signs of stasis, such as neovascularization. All the samples scored 0 for dermal mucin deposits in the reticular dermis. The authors conclude that mucin deposits in the legs are not inherent to aging. Therefore, any mucin deposit in the reticular dermis, as well as expansion of the periadnexal dermis by mucin deposits, should be considered abnormal.

A Potential Role for Drosophila Mucins in Development and Physiology

PubMed Central

Syed, Zulfeqhar A.; Härd, Torleif; Uv, Anne; van Dijk-Härd, Iris F.

2008-01-01

Vital vertebrate organs are protected from the external environment by a barrier that to a large extent consists of mucins. These proteins are characterized by poorly conserved repeated sequences that are rich in prolines and potentially glycosylated threonines and serines (PTS). We have now used the characteristics of the PTS repeat domain to identify Drosophila mucins in a simple bioinformatics approach. Searching the predicted protein database for proteins with at least 4 repeats and a high ST content, more than 30 mucin-like proteins were identified, ranging from 300–23000 amino acids in length. We find that Drosophila mucins are present at all stages of the fly life cycle, and that their transcripts localize to selective organs analogous to sites of vertebrate mucin expression. The results could allow for addressing basic questions about human mucin-related diseases in this model system. Additionally, many of the mucins are expressed in selective tissues during embryogenesis, thus revealing new potential functions for mucins as apical matrix components during organ morphogenesis. PMID:18725942

Newborn Screening for Biliary Atresia.

PubMed

Wang, Kasper S

2015-12-01

Biliary atresia is the most common cause of pediatric end-stage liver disease and the leading indication for pediatric liver transplantation. Affected infants exhibit evidence of biliary obstruction within the first few weeks after birth. Early diagnosis and successful surgical drainage of bile are associated with greater survival with the child's native liver. Unfortunately, because noncholestatic jaundice is extremely common in early infancy, it is difficult to identify the rare infant with cholestatic jaundice who has biliary atresia. Hence, the need for timely diagnosis of this disease warrants a discussion of the feasibility of screening for biliary atresia to improve outcomes. Herein, newborn screening for biliary atresia in the United States is assessed by using criteria established by the Discretionary Advisory Committee on Heritable Disorders in Newborns and Children. Published analyses indicate that newborn screening for biliary atresia by using serum bilirubin concentrations or stool color cards is potentially life-saving and cost-effective. Further studies are necessary to evaluate the feasibility, effectiveness, and costs of potential screening strategies for early identification of biliary atresia in the United States. Copyright © 2015 by the American Academy of Pediatrics.

The structure of tracheobronchial mucins from cystic fibrosis and control patients.

PubMed

Gupta, R; Jentoft, N

1992-02-15

Tracheobronchial mucin samples from control and cystic fibrosis patients were purified by gel filtration chromatography on Sephacryl S-1000 and by density gradient centrifugation. Normal secretions contained high molecular weight (approximately 10(7] mucins, whereas the cystic fibrosis secretions contained relatively small amounts of high molecular weight mucin together with larger quantities of lower molecular weight mucin fragments. These probably represent products of protease digestion. Reducing the disulfide bonds in either the control or cystic fibrosis high molecular weight mucin fractions released subunits of approximately 2000 kDa. Treating these subunits with trypsin released glycopeptides of 300 kDa. Trypsin treatment of unreduced mucin also released fragments of 2000 kDa that could be converted into 300-kDa glycopeptides upon disulfide bond reduction. Thus, protease-susceptible linkages within these mucins must be cross-linked by disulfide bonds so that the full effects of proteolytic degradation of mucins remain cryptic until disulfide bonds are reduced. Since various combinations of protease treatment and disulfide bond reduction release either 2000- or 300-kDa fragments, these fragments must represent important elements of mucin structure. The high molecular weight fractions of cystic fibrosis mucins appear to be indistinguishable from control mucins. Their amino acid compositions are the same, and various combinations of disulfide bond reduction and protease treatment release products of identical size and amino acid composition. Sulfate and carbohydrate compositions did vary considerably from sample to sample, but the limited number of samples tested did not demonstrate a cystic fibrosis-specific pattern. Thus, tracheobronchial mucins from cystic fibrosis and control patients are very similar, and both share the same generalized structure previously determined for salivary, cervical, and intestinal mucins.

External biliary drainage following major liver resection for perihilar cholangiocarcinoma: impact on development of liver failure and biliary leakage

PubMed Central

Olthof, Pim B.; Coelen, Robert J.S.; Wiggers, Jimme K.; Besselink, Marc G.H.; Busch, Olivier R.C.; van Gulik, Thomas M.

2016-01-01

Background Preoperative biliary drainage is considered essential in perihilar cholangiocarcinoma (PHC) requiring major hepatectomy with biliary-enteric reconstruction. However, evidence for postoperative biliary drainage as to protect the anastomosis is currently lacking. This study investigated the impact of postoperative external biliary drainage on the development of post-hepatectomy biliary leakage and liver failure (PHLF). Methods All patients who underwent major liver resection for suspected PHC between 2000 and 2015 were retrospectively analyzed. Biliary leakage and PHLF was defined as grade B or higher according to the International Study Group of Liver Surgery (ISGLS) criteria. Results Eighty-nine out of 125 (71%) patients had postoperative external biliary drainage. PHLF was more prevalent in the drain group (29% versus 6%; P = 0.004). There was no difference in the incidence of biliary leakage (32% versus 36%). On multivariable analysis, postoperative external biliary drainage was identified as an independent risk factor for PHLF (Odds-ratio 10.3, 95% confidence interval 2.1–50.4; P = 0.004). Conclusions External biliary drainage following major hepatectomy for PHC was associated with an increased incidence of PHLF. It is therefore not recommended to routinely use postoperative external biliary drainage, especially as there is no evidence that this decreases the risk of biliary anastomotic leakage. PMID:27037204

Mucin Agarose Gel Electrophoresis: Western Blotting for High-molecular-weight Glycoproteins.

PubMed

Ramsey, Kathryn A; Rushton, Zachary L; Ehre, Camille

2016-06-14

Mucins, the heavily-glycosylated proteins lining mucosal surfaces, have evolved as a key component of innate defense by protecting the epithelium against invading pathogens. The main role of these macromolecules is to facilitate particle trapping and clearance while promoting lubrication of the mucosa. During protein synthesis, mucins undergo intense O-glycosylation and multimerization, which dramatically increase the mass and size of these molecules. These post-translational modifications are critical for the viscoelastic properties of mucus. As a result of the complex biochemical and biophysical nature of these molecules, working with mucins provides many challenges that cannot be overcome by conventional protein analysis methods. For instance, their high-molecular-weight prevents electrophoretic migration via regular polyacrylamide gels and their sticky nature causes adhesion to experimental tubing. However, investigating the role of mucins in health (e.g., maintaining mucosal integrity) and disease (e.g., hyperconcentration, mucostasis, cancer) has recently gained interest and mucins are being investigated as a therapeutic target. A better understanding of the production and function of mucin macromolecules may lead to novel pharmaceutical approaches, e.g., inhibitors of mucin granule exocytosis and/or mucolytic agents. Therefore, consistent and reliable protocols to investigate mucin biology are critical for scientific advancement. Here, we describe conventional methods to separate mucin macromolecules by electrophoresis using an agarose gel, transfer protein into nitrocellulose membrane, and detect signal with mucin-specific antibodies as well as infrared fluorescent gel reader. These techniques are widely applicable to determine mucin quantitation, multimerization and to test the effects of pharmacological compounds on mucins.

Apocrine hidradenocarcinoma showing Paget's disease and mucinous metaplasia.

PubMed

Wahl, Carter E; Todd, Douglas H; Binder, Scott W; Cassarino, David S

2009-05-01

A 54-year-old man presented with a solitary, erythematous, rapidly growing 1-cm nodule on his scalp that had arisen over the previous 3 months. He had no history of skin cancer. An excisional biopsy of the lesion showed a fairly well-circumscribed but focally invasive tumor consisting of areas of typical-appearing clear cell hidradenoma as well as areas with mucinous goblet-type cells and cells with eosinophilic cytoplasm and decapitation-type secretion. There was marked cellular atypia, numerous atypical mitotic figures and focal necrosis. The tumor cells focally involved the overlying epidermis (Paget's disease). Large areas of mucin were identified throughout the lesion. The tumor cells stained with markers for cytokeratin 7 and focally for EMA and CEA, confirming ductal differentiation. The goblet cells and mucinous areas stained with mucicarmine and PASD. The patient was diagnosed with hidradenocarcinoma with mucinous differentiation. Associated Paget's disease has only rarely been reported, and mucinous metaplasia is a previously unreported feature in hidradenocarcinoma.

Biodegradable biliary stent implantation in the treatment of benign bilioplastic-refractory biliary strictures: preliminary experience.

PubMed

Mauri, Giovanni; Michelozzi, Caterina; Melchiorre, Fabio; Poretti, Dario; Tramarin, Marco; Pedicini, Vittorio; Solbiati, Luigi; Cornalba, Gianpaolo; Sconfienza, Luca Maria

2013-12-01

To evaluate feasibility, safety, and outcome of patients treated with biodegradable biliary stents for benign biliary stenosis refractory to other treatments. Between March 2011 and September 2012, ten patients (seven men, three women; age 59 ± 7 years) with recurrent cholangitis due to postsurgical biliary stricture, previous multiple unsuccessful (two to five) bilioplasties, and unsuitability for surgical/endoscopic repair underwent percutaneous implantation of a biodegradable biliary stent. Patients were followed-up clinically and with ultrasound at 1, 3 and 6 months, and then at 6-month intervals. Stent implantation was always feasible. No immediate major or minor complications occurred. In all patients, 48-h cholangiographic control demonstrated optimal stent positioning and stenosis resolution. In a median follow-up time of 16.5 months (25th-75th percentiles = 11-20.25 months) no further invasive treatment was needed. Three patients experienced transient episodes of cholangitis. Neither re-stenosis nor dilatation of the biliary tree was documented during follow-up. No stent was visible at the 6-month follow-up. Percutaneous placement of biodegradable biliary stents represents a new option in treating benign biliary stenoses refractory to treatment with bilioplasty. This technique seems to be feasible, effective and free from major complications. Further investigations are warranted to confirm our preliminary results.

A procedure for Alcian blue staining of mucins on polyvinylidene difluoride membranes.

PubMed

Dong, Weijie; Matsuno, Yu-ki; Kameyama, Akihiko

2012-10-16

The isolation and characterization of mucins are critically important for obtaining insight into the molecular pathology of various diseases, including cancers and cystic fibrosis. Recently, we developed a novel membrane electrophoretic method, supported molecular matrix electrophoresis (SMME), which separates mucins on a polyvinylidene difluoride (PVDF) membrane impregnated with a hydrophilic polymer. Alcian blue staining is widely used to visualize mucopolysaccharides and acidic mucins on both blotted membranes and SMME membranes; however, this method cannot be used to stain mucins with a low acidic glycan content. Meanwhile, periodic acid-Schiff staining can selectively visualize glycoproteins, including mucins, but is incompatible with glycan analysis, which is indispensable for mucin characterizations. Here we describe a novel staining method, designated succinylation-Alcian blue staining, for visualizing mucins on a PVDF membrane. This method can visualize mucins regardless of the acidic residue content and shows a sensitivity 2-fold higher than that of Pro-Q Emerald 488, a fluorescent periodate Schiff-base stain. Furthermore, we demonstrate the compatibility of this novel staining procedure with glycan analysis using porcine gastric mucin as a model mucin.

Risk Factors for Dysplasia in Recurrent Respiratory Papillomatosis in an Adult and Pediatric Population.

PubMed

Karatayli-Ozgursoy, Selmin; Bishop, Justin Avery; Hillel, Alexander; Akst, Lee; Best, Simon R A

2016-03-01

Recurrent respiratory papillomatosis (RRP) is classically described as a benign neoplasm of the larynx caused by the low-risk human papillomavirus (HPV) viral subtypes. Nevertheless, transformation to dysplasia and invasive carcinoma can occur. We aimed to assess the prevalence of dysplasia and carcinoma-ex-papilloma in both adult-onset and juvenile-onset RRP and identify patient risk factors for this dysplastic transformation. Ten-year retrospective chart review of a tertiary otolaryngology referral center. Patients with papilloma were identified from a review of a pathology database and clinical records. Patient demographics, pathologic data, and treatment history, including use of cidofovir as an adjunctive therapy for papilloma, were extracted from electronic medical records. One hundred fifty-nine RRP patients were identified, 96 adult-onset (AORRP) and 63 juvenile-onset (JORRP) cases. Of this cohort, 139 (87%) had only benign papilloma as a pathologic diagnosis. In the AORRP cohort, 10 patients (10%) were diagnosed with dysplasia or carcinoma in situ in addition to papilloma, and 5 patients (5%) had malignant transformation to invasive carcinoma-ex-papilloma. There was a significantly higher age of disease onset for those with dysplasia or carcinoma versus those without dysplasia or carcinoma (56 vs 45 years old; P = .0005). Of the 63 JORRP patients, there were no cases of dysplasia but 3 (5%) cases of invasive carcinoma-ex-papilloma, all involving pulmonary disease. The JORRP patients with carcinoma-ex-papilloma had a younger average disease onset (2 vs 6 years old; P = .009) and a higher rate of tracheal involvement than those without carcinoma. Gender, smoking history, number of operations, or use of cidofovir showed no association with the development of dysplasia or carcinoma-ex-papillomatosis in either the AORRP or JORRP population. In a large series of RRP, age of disease onset is the strongest predictor of dysplastic transformation in the adult and

Pancreaticobiliary maljunction and biliary cancer.

PubMed

Kamisawa, Terumi; Kuruma, Sawako; Tabata, Taku; Chiba, Kazuro; Iwasaki, Susumu; Koizumi, Satomi; Kurata, Masanao; Honda, Goro; Itoi, Takao

2015-03-01

Pancreaticobiliary maljunction (PBM) is a congenital malformation in which the pancreatic and bile ducts join anatomically outside the duodenal wall. Japanese clinical practice guidelines on how to deal with PBM were made in 2012, representing a world first. According to the 2013 revision to the diagnostic criteria for PBM, in addition to direct cholangiography, diagnosis can be made by magnetic resonance cholangiopancreatography (MRCP), 3-dimensional drip infusion cholangiography computed tomography, endoscopic ultrasonography (US), or multiplanar reconstruction images by multidetector row computed tomography. In PBM, the common channel is so long that sphincter action does not affect the pancreaticobiliary junction, and pancreatic juice frequently refluxes into the biliary tract. Persistence of refluxed pancreatic juice injures epithelium of the biliary tract and promotes cancer development, resulting in higher rates of carcinogenesis in the biliary tract. In a nationwide survey, biliary cancer was detected in 21.6% of adult patients with congenital biliary dilatation (bile duct cancer, 32.1% vs. gallbladder cancer, 62.3%) and in 42.4% of PBM patients without biliary dilatation (bile duct cancer, 7.3% vs. gallbladder cancer, 88.1%). Pathophysiological conditions due to pancreatobiliary reflux occur in patients with high confluence of pancreaticobiliary ducts, a common channel ≥6 mm long, and occlusion of communication during contraction of the sphincter. Once the diagnosis of PBM is established, immediate prophylactic surgery is recommended. However, the surgical strategy for PBM without biliary dilatation remains controversial. To detect PBM without biliary dilatation early, MRCP is recommended for patients showing gallbladder wall thickening on screening US under suspicion of PBM.

Ovarian Epithelial Inclusions With Mucinous Differentiation: A Clinicopathologic Study of 42 Cases.

PubMed

Seidman, Jeffrey D; Krishnan, Jayashree

2017-07-01

Ovarian epithelial inclusions lined by mucinous epithelium are rare and of uncertain origin. Ovaries containing such inclusions were studied in 42 women. The inclusions were divided into 3 groups: serous epithelial lined with typical ciliated morphology but with distinct basophilic cytoplasmic mucin in some or all of the lining cells, those lined by typical mucinous epithelium, and those lined by a combination of typical mucinous epithelium and serous epithelium. The mean patient age was 61.5 years. Pure mucinous inclusions were found in 27 patients, serous-type inclusions with cytoplasmic mucin in 20, and mixed type in 10. All 3 types of inclusions were found in 1 patient. Two types of inclusions were found in 13. Four patients had associated mucinous neoplasms (1 mucinous cystadenoma, 1 atypical proliferative seromucinous tumor, and 2 seromucinous cystadenomas), and 11 patients (26%) had endometriosis. The fallopian tubes in 4 patients (9.5%) also displayed mucinous metaplasia; this was not significantly different from the 3.1% we found in our previously reported series of unselected tubes from the same population. These findings suggest that mucinous inclusions may arise as a direct metaplastic change in serous-type inclusions. Other possible origins of mucinous inclusions in the ovarian cortex include endometriosis and Brenner (transitional cell) nests. Whether such inclusions can be a source of mucinous ovarian neoplasms as are Brenner tumors and mature cystic teratomas is unknown and may warrant further investigation.

Mucinous tumours of appendix and ovary: an overview and evaluation of current practice.

PubMed

Rouzbahman, Marjan; Chetty, Runjan

2014-03-01

Mucinous lesions of the appendix and ovary are commonly encountered in routine practice. There are several published classification schemes for appendiceal mucinous neoplasms with resultant inconsistent use of terms and clinical doubt. While nomenclature is more settled with regards to ovarian mucinous neoplasms, the difficulty here lies with distinguishing primary from secondary mucinous tumours. This review highlights the terminology and nomenclature for appendiceal mucinous tumours, the relationship with ovarian mucinous neoplasms and pseudomyxoma peritonei, and the features that assist in separating primary from secondary ovarian mucinous tumours.

Management of occluded self-expanding biliary metal stents in malignant biliary disease.

PubMed

Nennstiel, Simon; Tschurtschenthaler, Isolde; Neu, Bruno; Algül, Hana; Bajbouj, Monther; Schmid, Roland M; von Delius, Stefan; Weber, Andreas

2018-02-01

Occlusion of self-expanding metal stents (SEMS) in malignant biliary obstruction occurs in up to 40% of patients. This study aimed to compare the different techniques to resolve stent occlusion in our collective of patients. Patients with malignant biliary obstruction and occlusion of biliary metal stent at a tertiary referral endoscopic center were retrospectively identified between April 1, 1994 and May 31, 2014. The clinical records were further analyzed regarding the characteristics of patients, malignant strictures, SEMS, management strategies, stent patency, subsequent interventions, survival time and case charges. A total of 108 patients with biliary metal stent occlusion were identified. Seventy-nine of these patients were eligible for further analysis. Favored management was plastic stent insertion in 73.4% patients. Second SEMS were inserted in 12.7% patients. Percutaneous transhepatic biliary drainage and mechanical cleansing were conducted in a minority of patients. Further analysis showed no statistically significant difference in median overall secondary stent patency (88 vs. 143 days, P = 0.069), median survival time (95 vs. 192 days, P = 0.116), median subsequent intervention rate (53.4% vs. 40.0%, P = 0.501) and median case charge (€5145 vs. €3473, P = 0.803) for the treatment with a second metal stent insertion compared to plastic stent insertion. In patients with survival time of more than three months, significantly more patients treated with plastic stents needed re-interventions than patients treated with second SEMS (93.3% vs. 57.1%, P = 0.037). In malignant biliary strictures, both plastic and metal stent insertions are feasible strategies for the treatment of occluded SEMS. Our data suggest that in palliative biliary stenting, patients especially those with longer expected survival might benefit from second SEMS insertion. Careful patient selection is important to ensure a proper decision for either management

Human Milk Mucin 1 and Mucin 4 Inhibit Salmonella enterica Serovar Typhimurium Invasion of Human Intestinal Epithelial Cells In Vitro123

PubMed Central

Liu, Bo; Yu, Zhuoteng; Chen, Ceng; Kling, David E.; Newburg, David S.

2012-01-01

Many human milk glycans inhibit pathogen binding to host receptors and their consumption by infants is associated with reduced risk of disease. Salmonella infection is more frequent among infants than among the general population, but the incidence is lower in breast-fed babies, suggesting that human milk could contain components that inhibit Salmonella. This study aimed to test whether human milk per se inhibits Salmonella invasion of human intestinal epithelial cells in vitro and, if so, to identify the milk components responsible for inhibition. Salmonella enterica serovar Typhimurium SL1344 (SL1344) invasion of FHs 74 Int and Caco-2 cells were the models of human intestinal epithelium infection. Internalization of fluorescein-5-isothiocyanate–labeled SL1344 into intestinal cells was measured by flow cytometry to quantify infection. Human milk and its fractions inhibited infection; the inhibitory activity localized to the high molecular weight glycans. Mucin 1 and mucin 4 were isolated to homogeneity. At 150 μg/L, a typical concentration in milk, human milk mucin 1 and mucin 4 inhibited SL1344 invasion of both target cell types. These mucins inhibited SL1344 invasion of epithelial cells in a dose-dependent manner. Thus, mucins may prove useful as a basis for developing novel oral prophylactic and therapeutic agents that inhibit infant diseases caused by Salmonella and related pathogens. PMID:22718031

Daily use of guaifenesin (Mucinex) in a patient with chronic bronchitis and pathologic mucus hypersecretion: A case report.

PubMed

Storms, William W; Miller, Judi E

2018-01-01

We report an improvement in symptoms and quality of life with long-term use of guaifenesin for the treatment of mucus-related symptoms in a patient with chronic bronchitis, who presented with mucus hypersecretion, cough and dyspnea.

[A case of mucinous noncystic carcinoma of the pancreas].

PubMed

Jung, Jun Young; Song, Moon Hee; Park, Young Sook; Jo, Yun Ju; Kim, Seong Hwan; Jun, Dae-Won; Kim, Dong Hee; Lee, Won Mi

2008-03-01

Mucinous (colloid) carcinoma is defined as pools of stromal extracellular mucin containing scanty, floating carcinoma cells. It is a well-defined entity in breast or large bowel. However, mucinous noncystic carcinoma of the pancreas (MNCC) is uncommon, comprising between 1% and 3% of all carcinomas of the pancreas. In the past, MNCC generally had been categorized together with ordinary ductal adenocarcinoma or misdiagnosed as mucinous cystadenocarcinoma or signet-ring cell carcinoma. The new WHO classification lists MNCC as a variant of ductal adenocarcinoma. Herein, we report a 32-year-old woman with incidentally found pancreatic body mass who underwent subtotal pancreatectomy. She was diagnosed as MNCC histologically.

Clinicopathological Characteristics and KRAS Mutation Status of Endometrial Mucinous Metaplasia and Carcinoma.

PubMed

Sung, Ji-Youn; Jung, Yoon Yang; Kim, Hyun-Soo

2018-05-01

Mucinous metaplasia of the endometrium occurs as a spectrum of epithelial alterations ranging from the formation of simple, tubular glands to architecturally complex glandular proliferation with intraglandular papillary projection and cellular tufts. Endometrial mucinous metaplasia often presents a diagnostic challenge in endometrial curettage. We analyzed the clinicopathological characteristics and the mutation status for V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) of 11 cases of endometrial mucinous metaplasia. Electronic medical record review and histopathological examination were performed. KRAS mutation status was analyzed using a pyrosequencing technique. Cases were classified histopathologically into simple (5/11) or papillary (6/11) mucinous metaplasias. All (6/6) papillary mucinous metaplasias were associated with atypical hyperplasia/endometrioid intraepithelial neoplasia (AH/EIN; 1/6) or carcinoma (5/6), whereas in a single patient with simple mucinous metaplasia, grade 1 endometrioid carcinoma was incidentally detected. The difference in frequency of association of the metaplasia with AH/EIN or carcinoma was significant (p=0.015). KRAS mutations were identified in five out of six cases of papillary mucinous metaplasias, comprising three cases with G12D and two with G12V mutations; the frequency of KRAS mutation was significantly higher (p=0.015) than in cases of simple mucinous metaplasia (0/5). Papillary mucinous metaplasia is frequently associated with endometrial neoplastic lesions. The high incidence of KRAS mutations in papillary mucinous metaplasia suggests that papillary mucinous metaplasia may be a precancerous lesion of a certain subset of mucinous carcinomas of the endometrium. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Current Status of Biliary Metal Stents

PubMed Central

Nam, Hyeong Seok; Kang, Dae Hwan

2016-01-01

Many advances have been achieved in biliary stenting over the past 30 years. Endoscopic stent placement has become the primary management therapy to relieve obstruction in patients with benign or malignant biliary tract diseases. Compared with plastic stents, a self-expandable metallic stent (SEMS) has been used for management in patients with malignant strictures because of a larger lumen and longer stent patency. Recently, SEMS has been used for various benign biliary strictures and leaks. In this article, we briefly review the characteristics of SEMS as well as complications of stent placement. We review the current guidelines for managing malignant and benign biliary obstructions. Recent developments in biliary stenting are also discussed. PMID:26911896

Mechanophysical Stimulations of Mucin Secretion in Cultures of Nasal Epithelial Cells

PubMed Central

Even-Tzur Davidovich, Nurit; Kloog, Yoel; Wolf, Michael; Elad, David

2011-01-01

Nasal epithelial cells secret mucins and are exposed in vivo to airflow-induced mechanophysical stresses, including wall shear stress (WSS), temperature, and humidity. In this work, human nasal epithelial cells cultured under air-liquid interface conditions were subjected to fields of airflow-induced oscillatory WSS at different temperature and humidity conditions. Changes in mucin secretion due to WSS were measured and the role of the cytoskeleton in mucin secretion was explored. Mucin secretion significantly increased in response to WSS in a magnitude-dependent manner with respect to static cultures and independently of the airflow temperature and humidity. In static cultures, mucin secretion decreased at high humidity with or without elevation of the temperature with respect to cultures at a comfortable climate. In cultures exposed to WSS, mucin secretion increased at high temperature with respect to cultures at comfortable climate conditions. The polymerization of actin microfilaments was shown to increase mucin secretion under WSS, whereas the dynamics of microtubule polymerization did not affect secretion. In conclusion, the data in this study show that mucin secretion is sensitive to oscillatory WSS as well as high temperature and humidity conditions. PMID:21689518

Characterization of Particle Translocation through Mucin Hydrogels

PubMed Central

Lieleg, Oliver; Vladescu, Ioana; Ribbeck, Katharina

2010-01-01

Abstract Biological functional entities surround themselves with selective barriers that control the passage of certain classes of macromolecules while rejecting others. A prominent example of such a selective permeability barrier is given by mucus. Mucus is a biopolymer-based hydrogel that lines all wet epithelial surfaces of the human body. It regulates the uptake of nutrients from our gastrointestinal system, adjusts itself with the menstrual cycle to control the passage of sperm, and shields the underlying cells from pathogens such as bacteria and viruses. In the case of drug delivery, the mucus barrier needs to be overcome for successful medical treatment. Despite its importance for both physiology and medical applications, the underlying principles which regulate the permeability of mucus remain enigmatic. Here, we analyze the mobility of microscopic particles in reconstituted mucin hydrogels. We show that electrostatic interactions between diffusing particles and mucin polymers regulate the permeability properties of reconstituted mucin hydrogels. As a consequence, various parameters such as particle surface charge and mucin density, and buffer conditions such as pH and ionic strength, can modulate the microscopic barrier function of the mucin hydrogel. Our findings suggest that the permeability of a biopolymer-based hydrogel such as native mucus can be tuned to a wide range of settings in different compartments of our bodies. PMID:20441741

Salivary Mucin 19 Glycoproteins

PubMed Central

Culp, David J.; Robinson, Bently; Cash, Melanie N.; Bhattacharyya, Indraneel; Stewart, Carol; Cuadra-Saenz, Giancarlo

2015-01-01

Saliva functions in innate immunity of the oral cavity, protecting against demineralization of teeth (i.e. dental caries), a highly prevalent infectious disease associated with Streptococcus mutans, a pathogen also linked to endocarditis and atheromatous plaques. Gel-forming mucins are a major constituent of saliva. Because Muc19 is the dominant salivary gel-forming mucin in mice, we studied Muc19−/− mice for changes in innate immune functions of saliva in interactions with S. mutans. When challenged with S. mutans and a cariogenic diet, total smooth and sulcal surface lesions are more than 2- and 1.6-fold higher in Muc19−/− mice compared with wild type, whereas the severity of lesions are up to 6- and 10-fold higher, respectively. Furthermore, the oral microbiota of Muc19−/− mice display higher levels of indigenous streptococci. Results emphasize the importance of a single salivary constituent in the innate immune functions of saliva. In vitro studies of S. mutans and Muc19 interactions (i.e. adherence, aggregation, and biofilm formation) demonstrate Muc19 poorly aggregates S. mutans. Nonetheless, aggregation is enhanced upon adding Muc19 to saliva from Muc19−/− mice, indicating Muc19 assists in bacterial clearance through formation of heterotypic complexes with salivary constituents that bind S. mutans, thus representing a novel innate immune function for salivary gel-forming mucins. In humans, expression of salivary MUC19 is unclear. We find MUC19 transcripts in salivary glands of seven subjects and demonstrate MUC19 glycoproteins in glandular mucous cells and saliva. Similarities and differences between mice and humans in the expression and functions of salivary gel-forming mucins are discussed. PMID:25512380

"Pseudomyxoma Endometrii": Endometrial Deposition of Acellular Mucin from a Low-Grade Appendiceal Mucinous Neoplasm as a Rare Mimic of Myxoid Uterine Tumors.

PubMed

Shaw, Kristin C; Kokh, Dina; Ioffe, Olga B; Staats, Paul N

2015-07-01

Low-grade appendiceal mucinous neoplasms (LAMNs) are commonly associated with deposition of mucin, with or without admixed low-grade epithelium, on peritoneal surfaces (pseudomyxoma peritonei). We describe a very rare presentation of LAMN as extensive mucin deposition in the endometrium of a 43-yr-old woman initially mistaken for a primary uterine myxoid neoplasm. The patient underwent endometrial curettage that demonstrated abundant myxoid/mucoid material interspersed with small vessels, bland eosinophilic spindled cells, scattered foci of typical endometrial stroma, and occasional endometrioid glands. The endometrial stroma was positive for CD10, and the eosinophilic spindled cells were positive for actin. The lesion was interpreted as "myxoid/mucinous neoplasm, most likely of smooth muscle/endometrial stromal origin." Subsequent laparotomy revealed peritoneal mucin in the anterior cul-de-sac and a dilated appendix. Pathologic review confirmed appendiceal LAMN and multifocal peritoneal mucinosis. The uterus contained scant residual mucoid material. On review of all pathologic material at our institution, the endometrial lesion was consistent with organizing mucin derived from the LAMN with entrapped benign endometrium. "Pseudomyxoma endometrii" is readily mistaken for a primary uterine myxoid neoplasm, particularly myxoid endometrial stromal tumor. A key to diagnosis is recognition that the material is mucin rather than myxoid stroma. This is evidenced by the absence of embedded stromal cells and presence of myofibroblastic, vascular, and macrophage infiltration associated with organization. Epithelium containing goblet cells is an important clue if present. The presence of rare endometrial glands within the endometrial stroma suggests that the latter is entrapped rather than neoplastic.

Advanced Mucinous Colorectal Cancer: Epidemiology, Prognosis and Efficacy of Chemotherapeutic Treatment.

PubMed

Ott, Claudia; Gerken, Michael; Hirsch, Daniela; Fest, Petra; Fichtner-Feigl, Stefan; Munker, Stefan; Schnoy, Elisabeth; Stroszczynski, Christian; Vogelhuber, Martin; Herr, Wolfgang; Evert, Matthias; Reng, Michael; Schlitt, Hans Jürgen; Klinkhammer-Schalke, Monika; Teufel, Andreas

2018-06-05

The clinicopathological significance of the mucinous subtype of colorectal cancer (CRC) remains controversial. As of today, none of the current guidelines differentiate treatment with respect to mucinous or nonmucinous cancer. Due to the lack of substantiated data, best treatment remains unclear and the mucinous subtype of CRC is usually treated along the lines of recommendations for adenocarcinoma of the colon. We investigated an East-Bavarian cohort of 8,758 patients with CRC. These included 613 (7.0%) patients with a mucinous subtype, who were analyzed for assessing their characteristics in clinical course and for evaluating the efficacy of common chemotherapy protocols. Mucinous CRC was predominantly located in the right hemicolon; it was diagnosed at more advanced stages and occurred with preponderance in women. A higher rate of G3/4 grading was observed at diagnosis (all p < 0.001). An association of mucinous CRC with younger age at initial diagnosis, previously reported by other groups, could not be confirmed. Patients with mucinous stage IV colon cancer demonstrated poorer survival (p = 0.006). In contrast, no differences in survival were observed for specific stages I-III colon cancer. Stage-dependent analysis of rectal cancer stages I-IV also showed no differences in survival. However, univariable overall analysis resulted in significant poorer survival of mucinous compared to nonmucinous rectal cancer (p = 0.029). Also, combined analysis of all patients with mucinous CRC revealed poorer overall survival (OS) of these patients compared to nonmucinous CRC patients (median 48.4 vs. 60.2 months, p = 0.049) but not in multivariable analysis (p = 0.089). Chemotherapeutic treatment showed comparable efficacy regarding OS for mucinous and nonmucinous cancers in both an adjuvant and palliative setting for colon cancer patients (p values comparing mucinous and nonmucinous cancers < 0.001-0.005). © 2018 S. Karger AG, Basel.

Mucinous breast carcinoma with myoepithelial-like spindle cells.

PubMed

Miyake, Yasuyuki; Hirokawa, Mitsuyoshi; Norimatsu, Yoshiaki; Kanahara, Takuo; Monobe, Yasumasa; Ohno, Setsuyo; Miyamoto, Tomoyuki; Yakushiji, Hiromasa; Sakaguchi, Takuya; Aratake, Yatsuki; Ohno, Eiji

2009-06-01

Appearance of spindle cells has been believed as a benign index of breast cytology. But, we have frequently observed the spindle cells in smears from mucinous carcinoma of the breast. Here, we characterized the biochemical nature of the spindle cells, so as to clarify their identity in cytology. Nineteen cases of breast mucinous carcinoma were used for cytological examination. The spindle cells were located at edges of tumor cell nests and in the backgrounds of cytological specimens. Immunohistological examination revealed that the spindle cells exhibited both immunoreactivity against carcinoembryonic antigen (CEA) and epithelial membrane antigen (EMA). Immunoreactivity against vimentin, cytokeratin, or alpha-smooth muscle actin was, however, not observed. The mode of distribution of biochemical markers suggests that the positive cells for anti-CEA antibody and anti-EMA antibody are tumor cells compressed by mucin, while the vimentin-positive cells are fibroblasts. We assert that the presence of spindle cells can be a characteristic feature of mucinous carcinoma of the breast. Discrimination of the spindle cells in mucinous carcinoma from myoepithelial cells and naked bipolar nuclei in benign lesions was established here. It should facilitate precise diagnosis of breast cancer. (c) 2009 Wiley-Liss, Inc.

H. pylori/NSAID--negative peptic ulcer--the mucin theory.

PubMed

Niv, Yaron

2010-11-01

The incidence of Helicobacter pylori (H. pylori) and non-steroidal anti inflammatory drug (NSAID)--negative peptic ulcer disease increases, especially in the Western world and in countries where H. pylori infection rate is low. For the diagnosis of "idiopathic ulcer" one should rule out, in addition to H. pylori infection and NSAID or aspirin therapy, also other drugs, other infectious agents, as well as malignant and benign rare diseases. The mucin unstirred layer keeps the pH above the mucosa stable, and prevents the enzymatic attack by pepsin. Inhibition of cyclo-oxygenase by NSAID and aspirin prevents mucin secretion and exposes the mucosa for toxic effect of acid and enzymes. There is also relationship between H. pylori and mucin that from one hand enables mucin invasion but on the other hand protects the gastric mucosa. Mucin genetic or epigenetic changes may be blamed for idiopathic peptic ulcer disease, but this hypothesis should be further investigated. Copyright © 2010 Elsevier Ltd. All rights reserved.

Percutaneous transhepatic cholangiography and intraductal radiofrequency ablation combined with biliary stent placement for malignant biliary obstruction.

PubMed

Li, Teng-Fei; Huang, Guo-Hao; Li, Zhen; Hao, Chang-Fu; Ren, Jian-Zhuang; Duan, Xu-Hua; Zhang, Kai; Chen, Chen; Han, Xin-Wei; Jiao, De-Chao; Zhang, Meng-Fan; Wang, Yan-Li

2015-05-01

To determine the safety and feasibility of percutaneous transhepatic cholangiography (PTC) and intraductal radiofrequency (RF) ablation combined with biliary stent placement for malignant biliary obstruction. Data from patients with unresectable malignant biliary obstruction who underwent PTC, intraductal RF ablation, and biliary stent placement (n = 12) or PTC and biliary stent placement only (control group; n = 14) were reviewed. Postoperative complications, jaundice remission, and stent patency were assessed. All procedures were successful. No severe complications (eg, biliary bleeding, perforation) occurred. Two experimental group patients developed cholangitis, which resolved with conservative treatment. The 1-week jaundice remission and 3-month stent patency rates were similar in both groups, but the 6-month stent patency rate was higher in the experimental group (P < .05). In the experimental group, one death occurred as a result of gastrointestinal hemorrhage (unrelated to stent placement) by 3 months, and there were two cases of recurrent jaundice by 6 months. The latter two patients underwent repeat PTC, ablation, and stent placement. In the control group, one death occurred as a result of hepatic failure caused by progressive jaundice at 3 months, and another death resulted from disseminated intravascular coagulation caused by jaundice recurrence at 138 days after stent placement. In addition, seven patients developed jaundice recurrence (50-151 d after stent placement). PTC and repeat stent placement were performed in these patients. Percutaneous transhepatic cholangiography and intraductal RF ablation combined with biliary stent placement for malignant biliary obstruction is safe and feasible and effectively prolongs stent patency time. Copyright © 2015 SIR. Published by Elsevier Inc. All rights reserved.

A Novel Mechanism for Desulfation of Mucin: Identification and Cloning of a Mucin-Desulfating Glycosidase (Sulfoglycosidase) from Prevotella Strain RS2

PubMed Central

Rho, Jung-hyun; Wright, Damian P.; Christie, David L.; Clinch, Keith; Furneaux, Richard H.; Roberton, Anthony M.

2005-01-01

A novel enzyme which may be important in mucin degradation has been discovered in the mucin-utilizing anaerobe Prevotella strain RS2. This enzyme cleaves terminal 2-acetamido-2-deoxy-β-d-glucopyranoside 6-sulfate (6-SO3-GlcNAc) residues from sulfomucin and from the model substrate 4-nitrophenyl 2-acetamido-2-deoxy-β-d-glucopyranoside 6-sodium sulfate. The existence of this mucin-desulfating glycosidase (sulfoglycosidase) suggests an alternative mechanism by which this bacterium may desulfate sulfomucins, by glycosidic removal of a sulfated sugar from mucin oligosaccharide chains. Previously, mucin desulfation was thought to take place by the action of a specific desulfating enzyme, which then allowed glycosidases to remove desulfated sugar. Sulfate removal from sulfomucins is thought to be a rate-limiting step in mucin degradation by bacteria in the regions of the digestive tract with a significant bacterial flora. The sulfoglycosidase was induced by growth of the Prevotella strain on mucin and was purified 284-fold from periplasmic extracts. Tryptic digestion and sequencing of peptides from the 100-kDa protein enabled the sulfoglycosidase gene to be cloned and sequenced. Active recombinant enzyme was made in an Escherichia coli expression system. The sulfoglycosidase shows sequence similarity to hexosaminidases. The only other enzyme that has been shown to remove 6-SO3-GlcNAc from glycoside substrates is the human lysosomal enzyme β-N-acetylhexosaminidase A, point mutations in which cause the inheritable, lysosomal storage disorder Tay-Sachs disease. The human enzyme removes GlcNAc from glycoside substrates also, in contrast to the Prevotella enzyme, which acts on a nonsulfated substrate at a rate that is only 1% of the rate observed with a sulfated substrate. PMID:15716424

CT biliary cystoscopy of gallbladder polyps

PubMed Central

Lou, Ming-Wu; Hu, Wei-Dong; Fan, Yi; Chen, Jin-Hua; E, Zhan-Sen; Yang, Guang-Fu

2004-01-01

AIM: CT virtual endoscopy has been used in the study of various organs of body including the biliary tract, however, CT virtual endoseopy in diagnosis of gallbladder polyps has not yet been reported. This study was to evaluate the diagnostic value of CT virtual endoscopy in polyps of the gallbladder. METHODS: Thirty-two cases of gallbladder polyps were examined by CT virtual endoscopy, ultrasound, CT scan with oral biliary contrast separately and confirmed by operation and pathology. CT biliary cystoscopic findings were analyzed and compared with those of ultrasound and CT scan with oral biliary contrast, and evaluated in comparison with operative and pathologic findings in all cases. RESULTS: The detection rate of gallbladder polyps was 93.8%(90/96), 96.9%(93/96) and 79.2%(76/96) for CT cystoscopy, ultrasound and CT scan with oral contrast, respectively. CT biliary cystoscopy corresponded well with ultrasound as well as pathology in demonstrating the location, size and configuration of polyps. CT endoscopy was superior to ultrasound in viewing the polyps in a more precise way, 3 dimensionally from any angle in space, and showing the surface in details. CT biliary cystoscopy was also superior to CT scan with oral biliary contrast in terms of observation of the base of polyps for the presence of a pedicle, detection rates as well as image quality. The smallest polyp detected by CT biliary cystoscopy was measured 1.5 mm×2.2 mm×2.5 mm. CONCLUSION: CT biliary cystoscopy is a non-invasive and accurate technique for diagnosis and management of gallbladder polyps. PMID:15069726

Multicenter study of endoscopic preoperative biliary drainage for malignant distal biliary obstruction

PubMed Central

Sasahira, Naoki; Hamada, Tsuyoshi; Togawa, Osamu; Yamamoto, Ryuichi; Iwai, Tomohisa; Tamada, Kiichi; Kawaguchi, Yoshiaki; Shimura, Kenji; Koike, Takero; Yoshida, Yu; Sugimori, Kazuya; Ryozawa, Shomei; Kakimoto, Toshiharu; Nishikawa, Ko; Kitamura, Katsuya; Imamura, Tsunao; Mizuide, Masafumi; Toda, Nobuo; Maetani, Iruru; Sakai, Yuji; Itoi, Takao; Nagahama, Masatsugu; Nakai, Yousuke; Isayama, Hiroyuki

2016-01-01

AIM: To determine the optimal method of endoscopic preoperative biliary drainage for malignant distal biliary obstruction. METHODS: Multicenter retrospective study was conducted in patients who underwent plastic stent (PS) or nasobiliary catheter (NBC) placement for resectable malignant distal biliary obstruction followed by surgery between January 2010 and March 2012. Procedure-related adverse events, stent/catheter dysfunction (occlusion or migration of PS/NBC, development of cholangitis, or other conditions that required repeat endoscopic biliary intervention), and jaundice resolution (bilirubin level < 3.0 mg/dL) were evaluated. Cumulative incidence of jaundice resolution and dysfunction of PS/NBC were estimated using competing risk analysis. Patient characteristics and preoperative biliary drainage were also evaluated for association with the time to jaundice resolution and PS/NBC dysfunction using competing risk regression analysis. RESULTS: In total, 419 patients were included in the study (PS, 253 and NBC, 166). Primary cancers included pancreatic cancer in 194 patients (46%), bile duct cancer in 172 (41%), gallbladder cancer in three (1%), and ampullary cancer in 50 (12%). The median serum total bilirubin was 7.8 mg/dL and 324 patients (77%) had ≥ 3.0 mg/dL. During the median time to surgery of 29 d [interquartile range (IQR), 30-39 d]. PS/NBC dysfunction rate was 35% for PS and 18% for NBC [Subdistribution hazard ratio (SHR) = 4.76; 95%CI: 2.44-10.0, P < 0.001]; the pig-tailed tip was a risk factor for PS dysfunction. Jaundice resolution was achieved in 85% of patients and did not depend on the drainage method (PS or NBC). CONCLUSION: PS has insufficient patency for preoperative biliary drainage. Given the drawbacks of external drainage via NBC, an alternative method of internal drainage should be explored. PMID:27076764

Transmembrane Mucins: Signaling Receptors at the Intersection of Inflammation and Cancer

PubMed Central

van Putten, Jos P.M.; Strijbis, Karin

2017-01-01

Mucosal surfaces line our body cavities and provide the interaction surface between commensal and pathogenic microbiota and the host. The barrier function of the mucosal layer is largely maintained by gel-forming mucin proteins that are secreted by goblet cells. In addition, mucosal epithelial cells express cell-bound mucins that have both barrier and signaling functions. The family of transmembrane mucins consists of diverse members that share a few characteristics. The highly glycosylated extracellular mucin domains inhibit invasion by pathogenic bacteria and can form a tight mesh structure that protects cells in harmful conditions. The intracellular tails of transmembrane mucins can be phosphorylated and connect to signaling pathways that regulate inflammation, cell-cell interactions, differentiation, and apoptosis. Transmembrane mucins play important roles in preventing infection at mucosal surfaces, but are also renowned for their contributions to the development, progression, and metastasis of adenocarcinomas. In general, transmembrane mucins seem to have evolved to monitor and repair damaged epithelia, but these functions can be highjacked by cancer cells to yield a survival advantage. This review presents an overview of the current knowledge of the functions of transmembrane mucins in inflammatory processes and carcinogenesis in order to better understand the diverse functions of these multifunctional proteins. PMID:28052300

Percutaneous transhepatic biliary stenting vs. surgical bypass in advanced malignant biliary obstruction: cost- effectiveness analysis.

PubMed

Yao, Li Qin; Tang, Cheng Wu; Zheng, Yin Yuan; Feng, Wen Ming; Huang, San Xiong; Bao, Ying

2013-01-01

This study aims to compare the clinical outcomes and costs between percutaneous transhepatic biliary stenting (PTBS) and surgical bypass. We randomly assigned 142 patients with unresectable malignant biliary obstruction between 2005 and 2010 to receive PTBS or surgical bypass as palliative treatment. PTBS was successfully performed in 70 patients who formed the PTBS group (failed in 7 patients). Sixty five patients underwent surgical bypass treatment. Additional gastrojejunostomy was performed in five patients. The effectiveness of biliary drainage, hospital stay, complications, cost, survival time and mortality were compared. Patients in PTBS group had shorter hospital stay and lower initial and overall expense than the surgical group (p<0.05). There was no significant difference in effectiveness of biliary drainage (p=0.9307) or survival time between two groups (p=0.4826). Early complications of PTBS group was significantly lower than surgical group (3/75 vs. 11/65, p=0.0342). Late complication in PTBS group did not differ significantly from surgical group (9/70 vs. 6/65, p=0.6823). The survival curves in the two groups showed no significant difference (p=0.1032). PTBD is a better palliative treatment than surgical bypass for unresectable malignant biliary obstruction for its high effectiveness of biliary drainage and acceptable expense and complication.

Pulmonary Mucinous Cystadenocarcinoma: Report a Case and Review of CT Findings

PubMed Central

Choi, Youn Ah; Han, Joungho; Choi, Joon Young; Kim, Jhingook; Kwon, O Jung; Lee, Kyung Soo

2013-01-01

A pulmonary mucinous cystadenocarcinoma is an extremely rare tumor that is considered to be a cystic variant of mucin-producing lung adenocarcinoma. We present a case of pulmonary mucinous cystadenocarcinoma in a 54-year-old woman. Chest CT scans showed a 4.3-cm-sized, lobulated, well-defined, and homogeneous mass in the right middle lobe with peripheral stippled calcifications that demonstrated low-attenuation with no enhancement after contrast administration; 18F-fluorodeoxyglucose (FDG) PET/CT demonstrated mild heterogeneous FDG uptake. The mass was diagnosed as adenocarcinoma with mucin production by transbronchial lung biopsy. Right middle lobectomy was performed, and the pathologic examination disclosed a pulmonary mucinous cystadenocarcinoma. PMID:23483761

Gallbladder mucin production and calcium carbonate gallstones in children.

PubMed

Sayers, Craig; Wyatt, Judy; Soloway, Roger D; Taylor, Donald R; Stringer, Mark D

2007-03-01

In contrast to adults, calcium carbonate gallstones are relatively common in children. Their pathogenesis is poorly understood. Cystic duct obstruction promotes calcium carbonate formation in bile and increases gallbladder mucin production. We tested the hypothesis that mucin producing epithelial cells would be increased in gallbladders of children with calcium carbonate gallstones. Archival gallbladder specimens from 20 consecutive children who had undergone elective cholecystectomy for cholelithiasis were examined. In each case, gallstone composition was determined by Fourier transform infrared microspectroscopy. Gallbladder specimens from six children who had undergone cholecystectomy for conditions other than cholelithiasis during the same period were used as controls. Multiple sections were examined in a blinded fashion and scored semiquantitatively for mucin production using two stains (alcian blue and periodic acid-Schiff). Increased mucin staining was observed in 50% or more epithelial cells in five gallbladder specimens from seven children with calcium carbonate stones, compared to 5 of 13 with other stone types (P = 0.17) and none of the control gallbladders (P = 0.02). Gallbladders containing calcium carbonate stones were significantly more likely than those containing other stone types or controls to contain epithelial cells with the greatest mucin content (P = 0.03). Gallbladders containing calcium carbonate stones were also more likely to show the ulcer-associated cell lineage. These results demonstrate an increase in mucin producing epithelial cells in gallbladders from children containing calcium carbonate stones. This supports the hypothesis that cystic duct obstruction leading to increased gallbladder mucin production may play a role in the development of calcium carbonate gallstones in children.

Developmental Programming: Insulin Sensitizer Prevents the GnRH-Stimulated LH Hypersecretion in a Sheep Model of PCOS

PubMed Central

Cardoso, Rodolfo C.; Burns, Ashleigh; Moeller, Jacob; Skinner, Donal C.

2016-01-01

Prenatal testosterone (T) treatment recapitulates the reproductive and metabolic phenotypes of polycystic ovary syndrome in female sheep. At the neuroendocrine level, prenatal T treatment results in disrupted steroid feedback on gonadotropin release, increased pituitary sensitivity to GnRH, and subsequent LH hypersecretion. Because prenatal T-treated sheep manifest functional hyperandrogenism and hyperinsulinemia, gonadal steroids and/or insulin may play a role in programming and/or maintaining these neuroendocrine defects. Here, we investigated the effects of prenatal and postnatal treatments with an androgen antagonist (flutamide [F]) or an insulin sensitizer (rosiglitazone [R]) on GnRH-stimulated LH secretion in prenatal T-treated sheep. As expected, prenatal T treatment increased the pituitary responsiveness to GnRH leading to LH hypersecretion. Neither prenatal interventions nor postnatal F treatment normalized the GnRH-stimulated LH secretion. Conversely, postnatal R treatment completely normalized the GnRH-stimulated LH secretion. At the tissue level, gestational T increased pituitary LHβ, androgen receptor, and insulin receptor-β, whereas it reduced estrogen receptor (ER)α protein levels. Although postnatal F normalized pituitary androgen receptor and insulin receptor-β, it failed to prevent an increase in LHβ expression. Contrarily, postnatal R treatment restored ERα and partially normalized LHβ pituitary levels. Immunohistochemical findings confirmed changes in pituitary ERα expression to be specific to gonadotropes. In conclusion, these findings indicate that increased pituitary responsiveness to GnRH in prenatal T-treated sheep is likely a function of reduced peripheral insulin sensitivity. Moreover, results suggest that restoration of ERα levels in the pituitary may be one mechanism by which R prevents GnRH-stimulated LH hypersecretion in this sheep model of polycystic ovary syndrome-like phenotype. PMID:27792406

Developmental Programming: Insulin Sensitizer Prevents the GnRH-Stimulated LH Hypersecretion in a Sheep Model of PCOS.

PubMed

Cardoso, Rodolfo C; Burns, Ashleigh; Moeller, Jacob; Skinner, Donal C; Padmanabhan, Vasantha

2016-12-01

Prenatal testosterone (T) treatment recapitulates the reproductive and metabolic phenotypes of polycystic ovary syndrome in female sheep. At the neuroendocrine level, prenatal T treatment results in disrupted steroid feedback on gonadotropin release, increased pituitary sensitivity to GnRH, and subsequent LH hypersecretion. Because prenatal T-treated sheep manifest functional hyperandrogenism and hyperinsulinemia, gonadal steroids and/or insulin may play a role in programming and/or maintaining these neuroendocrine defects. Here, we investigated the effects of prenatal and postnatal treatments with an androgen antagonist (flutamide [F]) or an insulin sensitizer (rosiglitazone [R]) on GnRH-stimulated LH secretion in prenatal T-treated sheep. As expected, prenatal T treatment increased the pituitary responsiveness to GnRH leading to LH hypersecretion. Neither prenatal interventions nor postnatal F treatment normalized the GnRH-stimulated LH secretion. Conversely, postnatal R treatment completely normalized the GnRH-stimulated LH secretion. At the tissue level, gestational T increased pituitary LHβ, androgen receptor, and insulin receptor-β, whereas it reduced estrogen receptor (ER)α protein levels. Although postnatal F normalized pituitary androgen receptor and insulin receptor-β, it failed to prevent an increase in LHβ expression. Contrarily, postnatal R treatment restored ERα and partially normalized LHβ pituitary levels. Immunohistochemical findings confirmed changes in pituitary ERα expression to be specific to gonadotropes. In conclusion, these findings indicate that increased pituitary responsiveness to GnRH in prenatal T-treated sheep is likely a function of reduced peripheral insulin sensitivity. Moreover, results suggest that restoration of ERα levels in the pituitary may be one mechanism by which R prevents GnRH-stimulated LH hypersecretion in this sheep model of polycystic ovary syndrome-like phenotype.

Percutaneous biliary drainage using open cell stents for malignant biliary hilar obstruction.

PubMed

Ahn, Sun Jun; Bae, Jae Ik; Han, Tae Sun; Won, Je Hwan; Kim, Ji Dae; Kwack, Kyu-Sung; Lee, Jae Hee; Kim, Young Chul

2012-01-01

To evaluate the feasibility, safety and the effectiveness of the complex assembly of open cell nitinol stents for biliary hilar malignancy. During the 10 month period between January and October 2007, 26 consecutive patients with malignant biliary hilar obstruction underwent percutaneous insertion of open cell design nitinol stents. Four types of stent placement methods were used according to the patients' ductal anatomy of the hilum. We evaluated the technical feasibility of stent placement, complications, patient survival, and the duration of stent patency. Bilobar biliary stent placement was conducted in 26 patients with malignant biliary obstruction-T (n = 9), Y (n = 7), crisscross (n = 6) and multiple intersecting types (n = 4). Primary technical success was obtained in 24 of 26 (93%) patients. The crushing of the 1st stent during insertion of the 2nd stent occurred in two cases. Major complications occurred in 2 of 26 patients (7.7%). One case of active bleeding from hepatic segmental artery and one case of sepsis after procedure occurred. Clinical success was achieved in 21 of 24 (87.5%) patients, who were followed for a mean of 141.5 days (range 25-354 days). The mean primary stent patency period was 191.8 days and the mean patient survival period was 299 days. Applying an open cell stent in the biliary system is feasible, and can be effective, especially in multiple intersecting stent insertions in the hepatic hilum.

Atomic force microscopy of gastric mucin

NASA Astrophysics Data System (ADS)

Chasan, Bernard; Hong, Zhenning; Bansil, Rama; Turner, Bradley; Ramakrishnan Bhaskar, K.; Afdhal, Nezam

2001-03-01

We report on the first results from an AFM study of porcine gastric mucin employing the tapping mode technique in aqueous solution. This glycoprotein is responsible for protecting the stomach epithelium from acid damage. Mucin was imaged on a mica substrate at pH7, and at pH2. At the higher pH we detected individual molecules in disordered configuration, with characteristic lengths of 20-40 nm. At the lower pH the mucin forms extended rod-like clusters that, at high concentrations, are aligned into planar arrays. Individual clusters are of order 50 nm long and 20 nm wide while the entire array is of order several hundred nm both in length and width. The clustering behavior at low pH is consistent with that previously detected in dynamic light scattering experiments by Cao et. al. (Biophysical J. 76:120-1258 1999).

Physical Properties of Human Whole Salivary Mucin:A Dynamic Light Scattering Study

NASA Astrophysics Data System (ADS)

Mahajan, Manish; Kumar, Vijay; Saraswat, Mayank; Yadav, Savita; Shukla, N. K.; Singh, T. P.

2008-04-01

Human salivary mucin, a primary mucous membrane coating glycoprotein forms the first line of defense against adverse environments, attributed to the complex formation between mucin subunits and non mucin species. Aim of the study was to emphasize the effect of pH, denaturants (guanidinum hydrochloride, urea) and detergents (CHAPS, TRITON X -100, SDS on human whole salivary mucin. Hydrodynamic size distribution was measured using DLS. It was observed that aggregation was due to increase in hydrophobic interactions, believed to be accomplished by unfolding of the protein core. Whereas, the detergents which solubilize the proteins by decreasing hydrophobicity lead to disaggregation of mucin into smaller fragments. Mucin subjected to tobacco extract and upon subsequent addition of nicotine was found to have a disaggregating effect on it, suggesting nicotine may be one of the factors responsible for the disaggregating effect of tobacco on mucin, an important carcinogenetic mechanism.

Pre-operative biliary drainage for obstructive jaundice

PubMed Central

Fang, Yuan; Gurusamy, Kurinchi Selvan; Wang, Qin; Davidson, Brian R; Lin, He; Xie, Xiaodong; Wang, Chaohua

2014-01-01

Background Patients with obstructive jaundice have various pathophysiological changes that affect the liver, kidney, heart, and the immune system. There is considerable controversy as to whether temporary relief of biliary obstruction prior to major definitive surgery (pre-operative biliary drainage) is of any benefit to the patient. Objectives To assess the benefits and harms of pre-operative biliary drainage versus no pre-operative biliary drainage (direct surgery) in patients with obstructive jaundice (irrespective of a benign or malignant cause). Search methods We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, Cochrane Central Register of Controlled Clinical Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and Science Citation Index Expanded until February 2012. Selection criteria We included all randomised clinical trials comparing biliary drainage followed by surgery versus direct surgery, performed for obstructive jaundice, irrespective of the sample size, language, and publication status. Data collection and analysis Two authors independently assessed trials for inclusion and extracted data. We calculated the risk ratio (RR), rate ratio (RaR), or mean difference (MD) with 95% confidence intervals (CI) based on the available patient analyses. We assessed the risk of bias (systematic overestimation of benefit or systematic underestimation of harm) with components of the Cochrane risk of bias tool. We assessed the risk of play of chance (random errors) with trial sequential analysis. Main results We included six trials with 520 patients comparing pre-operative biliary drainage (265 patients) versus no pre-operative biliary drainage (255 patients). Four trials used percutaneous transhepatic biliary drainage and two trials used endoscopic sphincterotomy and stenting as the method of pre-operative biliary drainage. The risk of bias was high in all trials. The proportion of patients with malignant obstruction varied between 60

Management of adult recurrent respiratory papillomatosis with oral acyclovir following micro laryngeal surgery: a case series.

PubMed

Chaturvedi, Jagdish; Sreenivas, V; Hemanth, V; Nandakumar, R

2014-01-01

To demonstrate the role of oral acyclovir in monthly regimes after microdebrider assisted excision in 3 patients with adult recurrent respiratory papillomatosis (ARRP). Three patients with ARRP who presented to a tertiary referral hospital in stridor were initially treated with a tracheostomy in order to secure airway. On further evaluation by videolaryngoscopy extensive bilateral laryngeal papillomatosis was noted with history of similar conditions in the past for which they were repeatedly operated. They were admitted and underwent Microlaryngeal surgery and laryngeal microdebrider assisted surgery under general anesthesia. Post operatively a course of oral acyclovir at 800 mg/5 times/day for 5 days was administered. On repeat assessment with videolaryngoscopy at monthly intervals a complete remission of the disease was noted with no residual disease at the end of 1 year in 2 cases. One case had a recurrence. Renal parameters were monitored periodically. It may be concluded that the action of anti viral drugs at regular intervals in addition to a short course of oral steroids lead to rapid recovery and prevented latent virus activation within the laryngo tracheal system hence maintaining long term improvement. This can avoid multiple laryngeal surgeries, repeated respiratory emergencies and risk for malignant transformation in the future thereby reducing morbidity and effect on quality of life.

Characterization of human ocular mucin secretion mediated by 15(S)-HETE.

PubMed

Jumblatt, James E; Cunningham, Lauren T; Li, Yang; Jumblatt, Marcia M

2002-11-01

The eicosanoid 15-(S)-hydroxy-5,8,11,13-eicosatetraenoic acid [15(S)-HETE] is reported to stimulate mucin production in both airway and ocular surface epithelia. The current study was undertaken to evaluate the effects of 15(S)-HETE on secretion of specific ocular mucins by human conjunctiva. Segments of human bulbar conjunctival tissue were incubated with 15(S)-HETE (1-1000 nM) for 30 minutes at 37 degrees C. Secretion of human ocular mucins MUC1, MUC2, MUC4, and MUC5AC into the incubation media was measured by dot-blot immunoassay using antibodies directed to unique mucin polypeptide epitopes. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting were used to verify the specificity of anti-mucin antibody binding and to investigate the presence of MUC1 mucin in human tears. 15(S)-HETE (10(-8)-10(-6) M) stimulated secretion of conjunctival mucins in a concentration-dependent manner. Significant increases in total mucin secretion were observed at 10(-7) M 15(S)-HETE with a maximum response (>50% increase above controls) at 10(-6) M. Results of immunoassays showed that 15(S)-HETE differentially stimulates secretion of MUC1 mucin with no detectable effects on MUC2, MUC4, or MUC5AC release. Western analysis of tear samples from human volunteers indicated that MUC1 is a component of the preocular tear film. The results demonstrate that 15(S)-HETE is a selective secretogogue for MUC1 in isolated human conjunctival tissue. Although the biochemical mechanism(s) and cellular origins of MUC1 secretion remain to be established, the ubiquitous expression of MUC1 in corneal and conjunctival epithelia and its presence in human tears suggest that secreted MUC1 may contribute to the mucin layer that coats and protects the ocular surface.

Hidradenocarcinoma showing prominent mucinous and squamous differentiation and associated pagetoid cells.

PubMed

Honda, Yumi; Tanigawa, Hiroki; Harada, Miho; Fukushima, Satoshi; Masuguchi, Shinichi; Ishihara, Tsuyoshi; Ihn, Hironobu; Iyama, Ken-ichi

2013-05-01

Herein, we report a 63-year-old man presenting with hidradenocarcinoma showing prominent mucinous and squamous differentiation on his back. The tumor was dermal-based, solid and cystic. Tumor cells with squamous differentiation and with keratin pearl formation were identified predominantly in the superficial dermis, and mucinous cells were identified principally in the cystic lesion in the deep dermis. Interestingly, the additional feature of pagetoid cells was identified in the overlying epidermis. Both the mucinous cells in hidradenocarcinoma and pagetoid cells had intracytoplasmic mucin; however, they had different histopathologic findings and immunophenotypes. Mucinous cells in hidradenocarcinoma had small nuclei and abundant intracytoplasmic mucin presenting goblet cells with low rate of positive immunostaining for p53 and Ki67. In contrast, pagetoid cells had larger nuclei with less intracytoplasmic mucin. Both p53- and Ki67-positive cells were increased in pagetoid cells. Additionally, mucinous cells in hidradenocarcinoma were MUC1(+)/MUC2(-)/MUC5AC(+)/MUC6(+), but pagetoid cells were MUC1(+; focal)/MUC2(-)/MUC5AC(-)/MUC6(+; focal). The derivation of pagetoid cells is unclear; however, the localized small region of pagetoid cells over the hidradenocarcinoma in the present case may suggest a common histogenesis of these two malignant neoplasms. Copyright © 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.

Contact lens materials, mucin fragmentation and relation to symptoms.

PubMed

Berry, Monica; Purslow, Chris; Murphy, Paul J; Pult, Heiko

2012-07-01

Mucins adhere to contact lenses (CLs), reflecting the renewal of the preocular fluid and enzymatic activity at the ocular surface. In this study, we aimed to analyze mucin fragmentation on materials new to the ocular surface and investigate whether this correlates with wearing comfort. Lenses were obtained from new CL wearers after 2 weeks each of wearing vifilcon A, followed by senofilcon A, and then by vifilcon A lenses. Symptoms were evaluated using the Ocular Surface Disease Index (OSDI). CLs were extracted in a mixture of guanidinium hydrochloride and radioimmunoprecipitation assay buffer. Mucin mobility was analyzed after electrophoresis, Western blotting, and visualization with antibodies against mucin peptide core. Mobilities, normalized to total reactivity in the lane, were compared between visits for each subject and were expressed as shifts. Mucin (MUC)5AC polymers exceeding 260 kDa were observed in agarose gels; NuPAGE resolved polymers from 260 to 3.5 kDa: when large mucins were detected, the smallest fragments were missing. Fragmentation patterns were significantly different between lens types for MUC1 (analysis of variance, P = 0.006) and MUC4 (P < 0.001) but not for MUC5AC or MUC16 (P > 0.293). Mobility shifts of MUC1 and MUC4 were significantly negatively correlated (Pearson, r = -0.908; P = 0.002). For OSDI scores >15, mucin fragmentation was unchanged, whereas for OSDI scores <15, MUC4 and MUC5AC fragments were longer on vifilcon A than on senofilcon lenses (unpaired t test, P = 0.046), irrespective of the direction of change (analysis of variance, P > 0.366). Changes in MUC1 breakdown were significantly negatively correlated to the overall OSDI score (r = -0.891, P = 0.001). In asymptomatic CL wearers, only changes in mucin fragmentation in response to a new material were consistent and fast, irrespective of CL order. Lack of change seems, therefore, to be connected with discomfort during CL wear.

HRCT features of surgically resected invasive mucinous adenocarcinoma associated with interstitial pneumonia.

PubMed

Miyamoto, Atsushi; Kurosaki, Atsuko; Fujii, Takeshi; Kishi, Kazuma; Homma, Sakae

2017-05-01

Lung cancer is prevalent among patients with interstitial pneumonia (IP). HRCT findings mucinous adenocarcinoma in patients with IP have not been described. In 112 consecutive patients with 120 surgically resected IP-associated lung cancers, 42 patients had pathologically proven invasive adenocarcinoma (IA). A total of 14 out of 42 patients (10 men, 4 women, mean age, 68.4 years) had invasive mucinous adenocarcinoma. We reviewed the patients' medical records and HRCT scans. Invasive mucinous adenocarcinoma were most commonly associated with idiopathic IP (n = 13) affecting the lower lobe adjacent to a fibrocystic changes. In 11 patients with invasive mucinous adenocarcinoma or other types of IA, the tumour was adjacent to a fibrocystic lesion. In invasive mucinous adenocarcinoma, malignant signs included lobulation (n = 11), spiculation (n = 9), vascular convergence (n = 10) and pleural indentation (n = 2). Characteristic findings of mucinous adenocarcinoma (i.e. vague margins (n = 10), lobular-bounded margins (n = 11), air bronchogram (n = 11) and bubble-like low attenuation (n = 8)) were more common in invasive mucinous adenocarcinoma than in other IA types. All invasive mucinous adenocarcinoma tumours (n = 11) were closely associated with fibrosis. Mixed ground-glass opacity and consolidation adjacent to a fibrocystic lesion with malignant signs and characteristic features of mucinous adenocarcinoma indicate malignancy. © 2016 Asian Pacific Society of Respirology.

Methods to Assess the Direct Interaction of C. jejuni with Mucins.

PubMed

Clyne, Marguerite; Duggan, Gina; Naughton, Julie; Bourke, Billy

2017-01-01

Studies of the interaction of bacteria with mucus-secreting cells can be complemented at a more mechanistic level by exploring the interaction of bacteria with purified mucins. Here we describe a far Western blotting approach to show how C. jejuni proteins separated by SDS PAGE and transferred to a membrane or slot blotted directly onto a membrane can be probed using biotinylated mucin. In addition we describe the use of novel mucin microarrays to assess bacterial interactions with mucins in a high-throughput manner.

Structural investigation of porcine stomach mucin by X-ray fiber diffraction and homology modeling

DOE Office of Scientific and Technical Information (OSTI.GOV)

Veluraja, K., E-mail: veluraja@msuniv.ac.in; Vennila, K.N.; Umamakeshvari, K.

Research highlights: {yields} Techniques to get oriented mucin fibre. {yields} X-ray fibre diffraction pattern for mucin. {yields} Molecular modeling of mucin based on X-ray fibre diffraction pattern. -- Abstract: The basic understanding of the three dimensional structure of mucin is essential to understand its physiological function. Technology has been developed to achieve orientated porcine stomach mucin molecules. X-ray fiber diffraction of partially orientated porcine stomach mucin molecules show d-spacing signals at 2.99, 4.06, 4.22, 4.7, 5.37 and 6.5 A. The high intense d-spacing signal at 4.22 A is attributed to the antiparallel {beta}-sheet structure identified in the fraction of themore » homology modeled mucin molecule (amino acid residues 800-980) using Nidogen-Laminin complex structure as a template. The X-ray fiber diffraction signal at 6.5 A reveals partial organization of oligosaccharides in porcine stomach mucin. This partial structure of mucin will be helpful in establishing a three dimensional structure for the whole mucin molecule.« less

WT1 immunoreactivity in breast carcinoma: selective expression in pure and mixed mucinous subtypes.

PubMed

Domfeh, Akosua B; Carley, AnnaMarie L; Striebel, Joan M; Karabakhtsian, Rouzan G; Florea, Anca V; McManus, Kim; Beriwal, Sushil; Bhargava, Rohit

2008-10-01

Current literature suggests that strong WT1 expression in a carcinoma of unknown origin virtually excludes a breast primary. Our previous pilot study on WT1 expression in breast carcinomas has shown WT1 expression in approximately 10% of carcinomas that show mixed micropapillary and mucinous morphology (Mod Pathol 2007;20(Suppl 2):38A). To definitively assess as to what subtype of breast carcinoma might express WT1 protein, we examined 153 cases of invasive breast carcinomas. These consisted of 63 consecutive carcinomas (contained 1 mucinous tumor), 20 cases with micropapillary morphology (12 pure and 8 mixed), 6 micropapillary 'mimics' (ductal no special type carcinomas with retraction artifacts), 33 pure mucinous carcinomas and 31 mixed mucinous carcinomas (mucinous mixed with other morphologic types). Overall, WT1 expression was identified in 33 carcinomas, that is, 22 of 34 (65%) pure mucinous carcinomas and in 11 of 33 (33%) mixed mucinous carcinomas. The non-mucinous component in these 11 mixed mucinous carcinomas was either a ductal no special type carcinoma (8 cases) or a micropapillary component (3 cases). WT1 expression level was similar in both the mucinous and the non-mucinous components. The degree of WT1 expression was generally weak to moderate (>90% cases) and rarely strong (<10% cases). None of the breast carcinoma subtype unassociated with mucinous component showed WT1 expression.

Mucin expression in reactive gastropathy: an immunohistochemical analysis.

PubMed

Mino-Kenudson, Mari; Tomita, Shigeki; Lauwers, Gregory Y

2007-01-01

Reactive gastropathy is the second most common diagnosis made on gastric biopsies. Increased epithelial proliferation and modifications of epithelial cytokeratin profile, distinct from those of Helicobacter pylori gastritis, have been previously reported. However, the evaluation of mucins, important components of the protective mucosal mucous layer, has not been reported. To investigate alterations of membrane and secreted mucins in reactive gastropathy of various etiologies using antibodies against mucin glycoproteins. Thirty-eight gastric biopsies diagnosed as reactive gastropathy, related to nonsteroidal anti-inflammatory drugs (n = 18) or bile reflux (n = 6) or of indeterminate etiology (n = 14), were evaluated using antibodies to MUC1, MUC5AC, MUC6, and MUC2. All cases were confirmed to be negative for H. pylori. The biopsies were classified in 3 groups based on the severity of cytoarchitectural changes (mild, moderate, and severe). Mucin expression and its distribution were recorded and the results correlated with the cytoarchitectural alterations and etiologies. Loss of MUC1, either patchy or complete, was noted in 67% of the cases. Aberrant expression of MUC5AC in pyloric glands was observed in 81% of the cases, and aberrant expression of MUC6 in the upper foveolar epithelium was diffusely seen in 14% of the cases. Aberrant expression of MUC2 in non-goblet cells was observed in a single case. Aberrant expression of MUC6 was less extensive in the nonsteroidal anti-inflammatory drugs group than in other 2 groups (P = .03). Concurrently, the diffuse distribution of aberrant MUC6 expression was seen only in the cases of severe gastropathy (P = .09). There was no correlation between modifications in expression of other mucins and either the etiologies or the severity of cytoarchitectural changes. Expressions of membrane (MUC1) and secreted (MUC5AC, MUC6) mucins are frequently modified in reactive gastropathy. The alteration of MUC1, which is involved in cell

Management of blunt and penetrating biliary tract trauma.

PubMed

Thomson, Benjamin N J; Nardino, Benson; Gumm, Kellie; Robertson, Amanda J; Knowles, Brett P; Collier, Neil A; Judson, Rodney

2012-06-01

Penetrating or blunt injury to the biliary tree remains a rare complication of trauma occurring in 0.1% of trauma admissions. Because of the different presentations, sites of biliary tract injury, and associated organ injury, there are many possible management pathways to be considered. A retrospective analysis of prospectively gathered data was performed for all gallbladder and biliary tract injuries presenting to the trauma service or hepatobiliary unit of the Royal Melbourne Hospital between January 1, 1999, and March 30, 2011. There were 33 biliary injuries in 30 patients (0.1%) among 26,014 trauma admissions. Three of the 30 patients (10%) died. Of 10 gallbladder injuries, 8 were managed with cholecystectomy. There were 23 injuries to the biliary tree. Fourteen patients had injuries to the intrahepatic biliary tree of which seven involved segmental ducts. Of these, four segmental duct injuries required hepatic resection or debridement. Nine patients had injury to the extrahepatic biliary tree of which five required T-tube placement ± bilioenteric anastomosis and one a pancreaticoduodenectomy. Biliary injury is a rare but important consequence of abdominal trauma, and good outcomes are possible when a major trauma center and hepatopancreaticobiliary service coexist. Cholecystectomy remains the gold standard for gallbladder injury. Drainage with or without endoscopic stenting will resolve the majority of intrahepatic and partial biliary injuries. Hepaticojejunostomy remains the gold standard for complete extrahepatic biliary disruption. Hepatic and pancreatic resection are only required in the circumstances of unreconstructable biliary injury. Therapeutic study, level V. Copyright © 2012 by Lippincott Williams & Wilkins.

Baseline Goblet Cell Mucin Secretion in the Airways Exceeds Stimulated Secretion over Extended Time Periods, and Is Sensitive to Shear Stress and Intracellular Mucin Stores

PubMed Central

Doyle, Sean P.; Nguyen, Kristine; Ribeiro, Carla M. P.; Vasquez, Paula A.; Forest, M. Gregory; Lethem, Michael I.; Dickey, Burton F.; Davis, C. William

2015-01-01

Airway mucin secretion studies have focused on goblet cell responses to exogenous agonists almost to the exclusion of baseline mucin secretion (BLMS). In human bronchial epithelial cell cultures (HBECCs), maximal agonist-stimulated secretion exceeds baseline by ~3-fold as measured over hour-long periods, but mucin stores are discharged completely and require 24 h for full restoration. Hence, over 24 h, total baseline exceeds agonist-induced secretion by several-fold. Studies with HBECCs and mouse tracheas showed that BLMS is highly sensitive to mechanical stresses. Harvesting three consecutive 1 h baseline luminal incubations with HBECCs yielded equal rates of BLMS; however, lengthening the middle period to 72 h decreased the respective rate significantly, suggesting a stimulation of BLMS by the gentle washes of HBECC luminal surfaces. BLMS declined exponentially after washing HBECCs (t1/2 = 2.75 h), to rates approaching zero. HBECCs exposed to low perfusion rates exhibited spike-like increases in BLMS when flow was jumped 5-fold: BLMS increased >4 fold, then decreased within 5 min to a stable plateau at 1.5–2-fold over control. Higher flow jumps induced proportionally higher BLMS increases. Inducing mucous hyperplasia in HBECCs increased mucin production, BLMS and agonist-induced secretion. Mouse tracheal BLMS was ~6-fold higher during perfusion, than when flow was stopped. Munc13-2 null mouse tracheas, with their defect of accumulated cellular mucins, exhibited similar BLMS as WT, contrary to predictions of lower values. Graded mucous metaplasia induced in WT and Munc13-2 null tracheas with IL-13, caused proportional increases in BLMS, suggesting that naïve Munc13-2 mouse BLMS is elevated by increased mucin stores. We conclude that BLMS is, [i] a major component of mucin secretion in the lung, [ii] sustained by the mechanical activity of a dynamic lung, [iii] proportional to levels of mucin stores, and [iv] regulated differentially from agonist-induced mucin

Problems related to CMV infection and biliary atresia.

PubMed

Moore, Samuel W; Zabiegaj-Zwick, Caroline; Nel, Etienne

2012-09-11

Human cytomegalovirus (CMV) infection is related to biliary disease, being cholestatic in its own right. It has also been associated with intrahepatic bile duct destruction and duct paucity, indicating a possible role in extrahepatic biliary atresia pathogenesis and progression. When related to biliary atresia CMV IGM positive patients appear to have more liver damage thus affecting outcome. Methods We carried out a retrospective chart review on 74 patients diagnosed with hepatobiliary disease (2000-2011). included clinical and outcome review as well as evaluation of potential risk factors. Patients were divided into 2 groups those with biliary atresia and those without Biliary atresia (BA). The 2 groups were compared in terms of CMV infection. Of the 74 patients with hepatobiliary disease investigated, 39 (52%) were shown to have Biliary atresia and 35 other cases. 12 of the BA group and 4 of the non-BA were excluded due to lack of data Twenty-seven (69%) of the biliary atresia group had sufficient available data for review. Of these, 21 (78% of the 27) had CMV positivity (IgM/IgG) on testing, with 20 of these being IgM positive versus 8 in the non-biliary atresia group. (p<0.01) Two (7.5%) of 27 BA infants were HIV exposed being born to HIV positive mothers whereas HIV positivity was observed in 7 (35%) of the non-biliary atresia group (p<0.01). Both of these biliary atresia infants were CMV IgM positive. Long- term outcome of the 21 with CMV positivity showed 3 deaths (non-HIV exposed) and a higher rate of severe early liver damage suggesting a poorer outcome in CMV affected patients. This study suggests a correlation between CMV exposure, infection and surgical hepatobiliary disease including biliary atresia affecting outcome.HIV positivity does not preclude Biliary atresia and should be further investigated.

Cystic mucinous adenocarcinoma of the lung: a case report

PubMed Central

2011-01-01

Mucinous cystic tumors of the lung are uncommon, the preoperative pathologic diagnosis is difficult and their biological behavior is still controversial. We report the case of a patient with a clinically benign cystic lesion that post-operatively showed to be consistent with an invasive adenocarcinoma arising in a mucinous cystadenoma of the lung, We underline the difficulty of the clinical pre-operative diagnosis of this cystic neoplasia radiologically mimicking a hydatid cyst, and we report the negative TTF1 immunostaining potentially misleading in the differential diagnosis with metastatic mucinous carcinomas. Finallly, we evidence the presence of a pre-existing mucinous benign lesion suggesting early and complete resection of benign appearing lung cysts because they can undergo malignant transformation if left untreated or they can already harbor foci of invasive carcinoma at the time of the presentation. Even if a good prognosis, better than in other lung carcinomas, with no recurrrence or metastasis after complete surgical exicision, has been reported for cystic mucinous cystoadenocarcinomas, the follow-up showed an aggressive biological behaviour, with the early onset of metastasis, in keeping with P53 positive immunostaining and high Ki-67 proliferation index. PMID:21970610

Secreted mucins in pseudomyxoma peritonei: pathophysiological significance and potential therapeutic prospects

PubMed Central

2014-01-01

Pseudomyxoma peritonei (PMP, ORPHA26790) is a clinical syndrome characterized by progressive dissemination of mucinous tumors and mucinous ascites in the abdomen and pelvis. PMP is a rare disease with an estimated incidence of 1–2 out of a million. Clinically, PMP usually presents with a variety of unspecific signs and symptoms, including abdominal pain and distention, ascites or even bowel obstruction. It is also diagnosed incidentally at surgical or non-surgical investigations of the abdominopelvic viscera. PMP is a neoplastic disease originating from a primary mucinous tumor of the appendix with a distinctive pattern of the peritoneal spread. Computed tomography and histopathology are the most reliable diagnostic modalities. The differential diagnosis of the disease includes secondary peritoneal carcinomatoses and some rare peritoneal conditions. Optimal elimination of mucin and the mucin-secreting tumor comprises the current standard of care for PMP offered in specialized centers as visceral resections and peritonectomy combined with intraperitoneal chemotherapy. This multidisciplinary approach has reportedly provided a median survival rate of 16.3 years, a median progression-free survival rate of 8.2 years and 10- and 15-year survival rates of 63% and 59%, respectively. Despite its indolent, bland nature as a neoplasm, PMP is a debilitating condition that severely impacts quality of life. It tends to be diagnosed at advanced stages and frequently recurs after treatment. Being ignored in research, however, PMP remains a challenging, enigmatic entity. Clinicopathological features of the PMP syndrome and its morbid complications closely correspond with the multifocal distribution of the secreted mucin collections and mucin-secreting implants. Novel strategies are thus required to facilitate macroscopic, as well as microscopic, elimination of mucin and its source as the key components of the disease. In this regard, MUC2, MUC5AC and MUC5B have been found as

TOKYO criteria 2014 for transpapillary biliary stenting.

PubMed

Isayama, Hiroyuki; Hamada, Tsuyoshi; Yasuda, Ichiro; Itoi, Takao; Ryozawa, Shomei; Nakai, Yousuke; Kogure, Hirofumi; Koike, Kazuhiko

2015-01-01

It is difficult to carry out meta-analyses or to compare the results of different studies of biliary stents because there is no uniform evaluation method. Therefore, a standardized reporting system is required. We propose a new standardized system for reporting on biliary stents, the 'TOKYO criteria 2014', based on a consensus among Japanese pancreatobiliary endoscopists. Instead of stent occlusion, we use recurrent biliary obstruction, which includes occlusion and migration. The time to recurrent biliary obstruction was estimated using Kaplan-Meier analysis with the log-rank test. We can evaluate both plastic and self-expandable metallic stents (uncovered and covered). We also propose specification of the cause of recurrent biliary obstruction, identification of complications other than recurrent biliary obstruction, indication of severity, measures of technical and clinical success, and a standard for clinical care. Most importantly, the TOKYO criteria 2014 allow comparison of biliary stent quality across studies. Because blocked stents can be drained not only using transpapillary techniques but also by an endoscopic ultrasonography-guided transmural procedure, we should devise an evaluation method that includes transmural stenting in the near future. © 2014 The Authors. Digestive Endoscopy © 2014 Japan Gastroenterological Endoscopy Society.

Low Grade Peritoneal Mucinous Carcinomatosis Associated with Human Papilloma Virus Infection: Case Report

PubMed Central

Gatalica, Zoran; Foster, Jason M.; Loggie, Brian W.

2008-01-01

Pseudomyxoma peritonei is a clinical syndrome characterized by peritoneal dissemination of a mucinous tumor with mucinous ascites. The vast majority of the pseudomyxoma peritoneis are associated with mucinous neoplasms of the appendix. We describe a case of pseudomyxoma peritonei associated with mucinous adenocarcinoma of the cervix in a 60-year-old woman. The patient developed low grade mucinous peritoneal carcinomatosis 8 years after hysterectomy for cervical adenocarcinoma. No other primary mucinous tumor was identified and peritoneal carcinomatosis tested positive for high-risk human papilloma virus (HPV), showing both integrated and episomal pattern. HPV has been previously associated with development of cervical carcinomas (both squamous and mucinous) but neither has cervical adenocarcinoma nor HPV been implicated in development of pseudomyxoma peritonei. To the best of our knowledge, this is the first description of HPV-associated malignancy presenting as pseudomyxoma peritonei. PMID:18925701

Influences of animal mucins on lysozyme activity in solution and on hydroxyapatite surfaces.

PubMed

Park, Won-Kyu; Chung, Jin-Woo; Kim, Young-Ku; Chung, Sung-Chang; Kho, Hong-Seop

2006-10-01

The purpose of this study was to investigate the influence of animal mucins on lysozyme activity in solution and on the surface of hydroxyapatite (HA) beads. The effects of animal mucins on lysozyme activity in solution were examined by incubating porcine gastric mucin (PGM) or bovine submaxillary mucin (BSM) with hen egg-white lysozyme (HEWL) or salivary samples. HA-immobilised animal mucins or lysozyme were used to determine the influence of animal mucins on lysozyme activity on HA surfaces. Lysozyme activity was determined by turbidity measurement of a Micrococcus lysodeikticus substrate suspension. Protein concentration was determined by ninhydrin assay. PGM inhibited the activity of HEWL and salivary lysozyme in solution. The amount of inhibition was dependent on mucin concentration, incubation time and temperature, and the structural integrity of the mucin. The inhibition of salivary lysozyme activity by PGM was greater in submandibular/sublingual saliva than in parotid saliva. The inhibition of lysozyme activity by PGM was markedly dependent on pH. However, BSM did not inhibit the in-solution lysozyme activities of HEWL and clarified saliva. Both PGM and BSM bound to HA surfaces, and HA-adsorbed animal mucins increased the subsequent adsorption of lysozyme. When HA beads were exposed to a mixture of HEWL and PGM or BSM, lysozyme activity on the HA surfaces was significantly increased. The results suggest that animal mucins affect lysozyme activity, and the effects are different on HA surfaces compared with in solution. Further research is needed to determine the effect of animal mucins on lysozyme activity in vivo.

Differential expression of matrix metalloproteinase-13 in mucinous and nonmucinous colorectal carcinomas.

PubMed

Foda, Abd Al-Rahman Mohammad; El-Hawary, Amira K; Abdel-Aziz, Azza

2013-08-01

Colorectal carcinoma (CRC) is a major health problem all over the world. Mucinous CRCs are known to have a peculiar behavior and genetic derangements. This study aimed to investigate matrix metalloproteinase (MMP)-13 expression in mucinous and nonmucinous CRCs. We studied tumor tissue specimens from 150 patients with mucinous and nonmucinous CRC who underwent radical surgery from January 2007 to January 2012. High-density manual tissue microarrays were constructed using a modified mechanical pencil tip technique, and paraffin sections were submitted for immunohistochemistry using MMP-13. Statistical analysis was performed for clinical and pathological data of all studied cases together with MMP-13 expression in mucinous and nonmucinous groups. Mucinous carcinoma was significantly associated with young age, more depth of invasion, lymph node metastasis, and less peritumoral and intratumoral neutrophils. Nonmucinous carcinomas showed higher MMP-13 expression compared with mucinous carcinomas. Despite the negative or low expression of MMP-13, mucinous carcinomas had more depth of invasion and more frequency of lymph node metastasis than did nonmucinous carcinomas. Copyright © 2013 Elsevier Inc. All rights reserved.

Mucinous cystadenocarcinoma of the breast coexisting with infiltrating ductal carcinoma.

PubMed

Chen, Wei-Yu; Chen, Ching-Shyang; Chen, Hsin-Chi; Hung, Yi-Ju; Chu, Jan-Show

2004-10-01

A recently described and rare variant of breast carcinoma, mucinous cystadenocarcinoma (MCA), is reported in a 65-year-old post-menopausal woman. She presented with a gradually enlarged breast tumor. A well-circumscribed tumor measuring about 3 cm in diameter was noted in the mammographic and ultrasonographic examinations. The mammographic and ultrasonographic findings were indistinguishable from more common mucinous carcinoma (colloid carcinoma) of the breast. The gross appearance of the tumor was well-defined and cystic, consisting of abundant transparent to bloody mucin, as well as whitish solid parts. Microscopically, the tumor was characterized by abundant extracellular and intracellular mucin. It looked like a mucinous cystic neoplasm of the ovary and pancreas. Particularly, few microscopic foci of ordinary intermediate-grade infiltrating ductal carcinoma (IDC) and ductal carcinoma in situ (DCIS) were observed around the main lesion in this case. A transition from ordinary DCIS to MCA in situ was found. It might indicate MCA derives from a metaplasia process of ordinary DCIS. MCA can be easily differentiated from mucinous carcinoma by quite different histologic and immunohistochemical findings. According to the previously reported and present cases, MCA of the breast more commonly affects elderly women and has a relatively favorable prognosis.

Mucin gel assembly is controlled by a collective action of non-mucin proteins, disulfide bridges, Ca2+-mediated links, and hydrogen bonding.

PubMed

Meldrum, Oliver W; Yakubov, Gleb E; Bonilla, Mauricio R; Deshmukh, Omkar; McGuckin, Michael A; Gidley, Michael J

2018-04-11

Mucus is characterized by multiple levels of assembly at different length scales which result in a unique set of rheological (flow) and mechanical properties. These physical properties determine its biological function as a highly selective barrier for transport of water and nutrients, while blocking penetration of pathogens and foreign particles. Altered integrity of the mucus layer in the small intestine has been associated with a number of gastrointestinal tract pathologies such as Crohn's disease and cystic fibrosis. In this work, we uncover an intricate hierarchy of intestinal mucin (Muc2) assembly and show how complex rheological properties emerge from synergistic interactions between mucin glycoproteins, non-mucin proteins, and Ca 2+ . Using a novel method of mucus purification, we demonstrate the mechanism of assembly of Muc2 oligomers into viscoelastic microscale domains formed via hydrogen bonding and Ca 2+ -mediated links, which require the joint presence of Ca 2+ ions and non-mucin proteins. These microscale domains aggregate to form a heterogeneous yield stress gel-like fluid, the macroscopic rheological properties of which are virtually identical to that of native intestinal mucus. Through proteomic analysis, we short-list potential protein candidates implicated in mucin assembly, thus paving the way for identifying the molecules responsible for the physiologically critical biophysical properties of mucus.

Spectrum of mucin-producing neoplastic conditions of the abdomen and pelvis: Cross-sectional imaging evaluation

PubMed Central

Lee, Nam Kyung; Kim, Suk; Kim, Hyun Sung; Jeon, Tae Yong; Kim, Gwang Ha; Kim, Dong Uk; Park, Do Youn; Kim, Tae Un; Kang, Dae Hwan

2011-01-01

Various mucin-producing neoplasms originate in different abdominal and pelvic organs. Mucinous neoplasms differ from non-mucinous neoplasms because of the differences in clinical outcome and imaging appearance. Mucinous carcinoma, in which at least 50% of the tumor is composed of large pools of extracellular mucin and columns of malignant cells, is associated with a worse prognosis. Signet ring cell carcinoma is characterized by large intracytoplasmic mucin vacuoles that expand in the malignant cells with the nucleus displaced to the periphery. Its prognosis is also generally poor. In contrast, intraductal papillary mucinous neoplasm of the bile duct and pancreas, which is characterized by proliferation of ductal epithelium and variable mucin production, has a better prognosis than other malignancies in the pancreaticobiliary tree. Imaging modalities play a critical role in differentiating mucinous from non-mucinous neoplasms. Due to high water content, mucin has a similar appearance to water on ultrasound (US), computed tomography (CT), and magnetic resonance imaging, except when thick and proteinaceous, and then it tends to be hypoechoic with fine internal echoes or have complex echogenicity on US, hyperdense on CT, and hyperintense on T1- and hypointense on T2-weighted images, compared to water. Therefore, knowledge of characteristic mucin imaging features is helpful to diagnose various mucin-producing neoplastic conditions and to facilitate appropriate treatment. PMID:22147976

Human Gastric Mucins Differently Regulate Helicobacter pylori Proliferation, Gene Expression and Interactions with Host Cells

PubMed Central

Skoog, Emma C.; Sjöling, Åsa; Navabi, Nazanin; Holgersson, Jan; Lundin, Samuel B.; Lindén, Sara K.

2012-01-01

Helicobacter pylori colonizes the mucus niche of the gastric mucosa and is a risk factor for gastritis, ulcers and cancer. The main components of the mucus layer are heavily glycosylated mucins, to which H. pylori can adhere. Mucin glycosylation differs between individuals and changes during disease. Here we have examined the H. pylori response to purified mucins from a range of tumor and normal human gastric tissue samples. Our results demonstrate that mucins from different individuals differ in how they modulate both proliferation and gene expression of H. pylori. The mucin effect on proliferation varied significantly between samples, and ranged from stimulatory to inhibitory, depending on the type of mucins and the ability of the mucins to bind to H. pylori. Tumor-derived mucins and mucins from the surface mucosa had potential to stimulate proliferation, while gland-derived mucins tended to inhibit proliferation and mucins from healthy uninfected individuals showed little effect. Artificial glycoconjugates containing H. pylori ligands also modulated H. pylori proliferation, albeit to a lesser degree than human mucins. Expression of genes important for the pathogenicity of H. pylori (babA, sabA, cagA, flaA and ureA) appeared co-regulated in response to mucins. The addition of mucins to co-cultures of H. pylori and gastric epithelial cells protected the viability of the cells and modulated the cytokine production in a manner that differed between individuals, was partially dependent of adhesion of H. pylori to the gastric cells, but also revealed that other mucin factors in addition to adhesion are important for H. pylori-induced host signaling. The combined data reveal host-specific effects on proliferation, gene expression and virulence of H. pylori due to the gastric mucin environment, demonstrating a dynamic interplay between the bacterium and its host. PMID:22563496

Simultaneous liver mucinous cystic and intraductal papillary mucinous neoplasms of the bile duct: a case report.

PubMed

Budzynska, Agnieszka; Hartleb, Marek; Nowakowska-Dulawa, Ewa; Krol, Robert; Remiszewski, Piotr; Mazurkiewicz, Michal

2014-04-14

Cystic hepatic neoplasms are rare tumors, and are classified into two separate entities: mucinous cystic neoplasms (MCNs) and intraductal papillary mucinous neoplasms of the bile duct (IPMN-B). We report the case of a 56-year-old woman who presented with abdominal pain and jaundice due to the presence of a large hepatic multilocular cystic tumor associated with an intraductal tumor. Partial hepatectomy with resection of extrahepatic bile ducts demonstrated an intrahepatic MCN and an intraductal IPMN-B. This is the first report of the simultaneous occurrence of these two histologically distinct entities in the liver.

Allergen-induced IL-9 directly stimulates mucin transcription in respiratory epithelial cells

PubMed Central

Longphre, M.; Li, D.; Gallup, M.; Drori, E.; Ordoñez, C.L.; Redman, T.; Wenzel, S.; Bice, D. E.; Fahy, J.V.; Basbaum, C.

1999-01-01

A hallmark of asthma is mucin overproduction, a condition that contributes to airway obstruction. The events responsible for mucin overproduction are not known but are thought to be associated with mediators of chronic inflammation. Others have shown that T-helper 2 (Th2) lymphocytes are required for mucous cell metaplasia, which then leads to mucin overproduction in animal models of allergy. We hypothesized that Th2 cell mediators are present in asthmatic airway fluid and directly stimulate mucin synthesis in airway epithelial cells. Results in cultured airway epithelial cells showed that samples of asthmatic fluid stimulated mucin (MUC5AC) synthesis severalfold more potently than non-asthmatic fluid. Consistent with this, lavage fluid from the airways of allergen-challenged dogs stimulated mucin synthesis severalfold more potently than that from non–allergen-challenged dogs. Fractionation of dog samples revealed 2 active fractions at <10 kDa and 30–100 kDa. Th2 cytokines in these molecular weight ranges are IL-9 (36 kDa), IL-5 (56 kDa), and IL-13 (10 kDa). Antibody blockade of ligand-receptor interaction for IL-9 (but not IL-5 or IL-13) inhibited mucin stimulation by dog airway fluid. Furthermore, recombinant IL-9, but not IL-5 or IL-13, stimulated mucin synthesis. These results indicate that IL-9 may account for as much as 50–60% of the mucin-stimulating activity of lung fluids in allergic airway disease. J. Clin. Invest. 104:1375–1382 (1999). PMID:10562299

Evidence and Role for Bacterial Mucin Degradation in Cystic Fibrosis Airway Disease

PubMed Central

Flynn, Jeffrey M.; Niccum, David; Dunitz, Jordan M.

2016-01-01

Chronic lung infections in cystic fibrosis (CF) patients are composed of complex microbial communities that incite persistent inflammation and airway damage. Despite the high density of bacteria that colonize the lower airways, nutrient sources that sustain bacterial growth in vivo, and how those nutrients are derived, are not well characterized. In this study, we examined the possibility that mucins serve as an important carbon reservoir for the CF lung microbiota. While Pseudomonas aeruginosa was unable to efficiently utilize mucins in isolation, we found that anaerobic, mucin-fermenting bacteria could stimulate the robust growth of CF pathogens when provided intact mucins as a sole carbon source. 16S rRNA sequencing and enrichment culturing of sputum also identified that mucin-degrading anaerobes are ubiquitous in the airways of CF patients. The collective fermentative metabolism of these mucin-degrading communities in vitro generated amino acids and short chain fatty acids (propionate and acetate) during growth on mucin, and the same metabolites were also found in abundance within expectorated sputum. The significance of these findings was supported by in vivo P. aeruginosa gene expression, which revealed a heightened expression of genes required for the catabolism of propionate. Given that propionate is exclusively derived from bacterial fermentation, these data provide evidence for an important role of mucin fermenting bacteria in the carbon flux of the lower airways. More specifically, microorganisms typically defined as commensals may contribute to airway disease by degrading mucins, in turn providing nutrients for pathogens otherwise unable to efficiently obtain carbon in the lung. PMID:27548479

[Correction of indigestion in chronic biliary pancreatitis].

PubMed

Trukhan, D I; Tarasova, L V

2013-01-01

Chronic pancreatitis (CP) is one of the most urgent and investigated problems in gastroenterology. Despite the variety of the spectrum of etiologic, pathogenetic and provoking factors for CP, one of the leading causes of disease pathology is pathology of biliary tract. A key element in the treatment of CP is a correction of the digestive system, with biliary pancreatitis feature that distinguishes it from other forms of pancreatitis, is a combination of exocrine pancreatic insufficiency with chronic biliary insufficiency. The variety of biochemical and immunological effects of ursodeoxycholic acid (UDCA) can treat it with biliary pancreatitis as the drug of etiological, pathogenetic and substitution therapy. UDCA (Ursosan) in combination with modern mini-microspheroidal polyfermental drugs significantly improves the clinical efficacy of the correction of the digestive system in biliary pancreatitis.

A prospective study of radionuclide biliary scanning in acute pancreatitis.

PubMed Central

Neoptolemos, J. P.; Fossard, D. P.; Berry, J. M.

1983-01-01

Early surgery for biliary pancreatitis has resulted in a need for an accurate method of gallstone detection in acute pancreatitis. Fifty patients with acute pancreatitis were studied prospectively to assess the diagnostic value of Radionuclide Biliary Scanning (RBS) performed within 72 hours of an attack. To assess the general accuracy of RBS a further 154 patients with suspected acute cholecystitis or biliary colic were similarly studied. There were 34 patients with biliary pancreatitis and 18 (53%) had a positive scan (no gallbladder seen). There were 16 patients with non-biliary pancreatitis and 5 (31%) had a positive scan. All 51 patients with acute cholecystitis had a positive scan, as did 82% of the 51 patients with biliary colic. There were 52 patients with no biliary or pancreatic disease and none of these had a positive scan. RBS is highly accurate in confirming a diagnosis of acute cholecystitis or biliary colic. However, it cannot be relied on to differentiate between biliary and non-biliary pancreatitis and should certainly not be used as the basis for biliary surgery in these patients. PMID:6859781

Percutaneous Transhepatic Biliary Drainage in the Management of Postsurgical Biliary Leaks in Patients with Nondilated Intrahepatic Bile Ducts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cozzi, Guido, E-mail: guido.cozzi@istitutotumori.mi.it; Severini, Aldo; Civelli, Enrico

2006-06-15

Purpose. To assess the feasibility of percutaneous transhepatic biliary drainage (PTBD) for the treatment of postsurgical biliary leaks in patients with nondilated intrahepatic bile ducts, its efficacy in restoring the integrity of bile ducts, and technical procedures to reduce morbidity. Methods. Seventeen patients out of 936 undergoing PTBD over a 20-year period had a noncholestatic liver and were retrospectively reviewed. All patients underwent surgery for cancer and suffered a postsurgical biliary leak of 345 ml/day on average; 71% were in poor condition and required permanent nutritional support. An endoscopic approach failed or was excluded due to inaccessibility of the bilemore » ducts. Results. Established biliary leaks and site of origin were diagnosed an average of 21 days (range 1-90 days) after surgery. In all cases percutaneous access to the biliary tree was achieved. An external (preleakage) drain was applied in 7 cases, 9 patients had an external-internal fistula bridging catheter, and 1 patient had a percutaneous hepatogastrostomy. Fistulas healed in an average of 31 days (range 3-118 days ) in 15 of 17 patients (88%) following PTBD. No major complications occurred after drainage. Post-PTBD cholangitis was observed in 6 of 17 patients (35%) and was related to biliary sludge formation occurring mostly when drainage lasted >30 days and was of the external-internal type. Median patient survival was 17.7 months and in all cases the repaired biliary leaks remained healed. Conclusions. PTBD is a feasible, effective, and safe procedure for the treatment of postsurgical biliary leaks. It is therefore a reliable alternative to surgical repair, which entails longer hospitalization and higher costs.« less

Radiological interventions in malignant biliary obstruction

PubMed Central

Madhusudhan, Kumble Seetharama; Gamanagatti, Shivanand; Srivastava, Deep Narayan; Gupta, Arun Kumar

2016-01-01

Malignant biliary obstruction is commonly caused by gall bladder carcinoma, cholangiocarcinoma and metastatic nodes. Percutaneous interventions play an important role in managing these patients. Biliary drainage, which forms the major bulk of radiological interventions, can be palliative in inoperable patients or pre-operative to improve liver function prior to surgery. Other interventions include cholecystostomy and radiofrequency ablation. We present here the indications, contraindications, technique and complications of the radiological interventions performed in patients with malignant biliary obstruction. PMID:27247718

Mucinous cystadenocarcinoma of the breast with a basal-like immunophenotype.

PubMed

Deng, Yunte; Xue, Debin; Wang, Xiaoyan; Xu, Sanpeng; Ao, Qilin; Hu, Zhiyong; Wang, Guoping

2012-06-01

Mucinous cystadenocarcinoma (MCA) of the breast is extremely rare and was only recently described as a distinct variant of invasive ductal carcinoma of the breast. A case of MCA is reported in a 41-year-old woman. Mammographic and ultrasonographic examinations showed an irregularly shaped 10.0 × 8.0 × 5.5 cm lesion with patching calcification in the upper outer quadrant of the left breast. The gross examination revealed that the tumor has a well-circumscribed edge with a gelatinous cut surface and hemorrhage and necrosis were also noticed in the mass. Microscopically, the mass resembled mucinous cystic neoplasm of the ovary and pancreas closely, with cystic areas lined by columnar mucinous cells and associated with abundant extracellular and intracellular mucin, which is distinctively different from mucinous carcinoma with typically nests of low grade neoplastic cells floating in the mucin pool. The tumor cells were positive for CK7, CK20 and CDX2 were negative and displayed a typical immunophenotype of basal-like breast cancer (ER, PR, HER2 were negative, CK5/6 and EGFR were positive). Metastatic carcinoma was identified in three of 14 axillary lymph nodes. We describe here a very unusual case of breast MCA with basal-like immunophenotype. © 2012 The Authors. Pathology International © 2012 Japanese Society of Pathology and Blackwell Publishing Asia Pty Ltd.

Long-term outcomes and risk factors of biliary stent dysfunction after endoscopic double stenting for malignant biliary and duodenal obstructions.

PubMed

Matsumoto, Kazuyuki; Kato, Hironari; Tsutsumi, Koichiro; Mizukawa, Sho; Yabe, Syuntaro; Seki, Hiroyuki; Akimoto, Yutaka; Uchida, Daisuke; Tomoda, Takeshi; Yamamoto, Naoki; Horiguchi, Shigeru; Kuwaki, Kenji; Okada, Hiroyuki

2017-07-01

Few reports describe the endoscopic double-stenting procedure for malignant biliary and duodenal obstructions. We evaluated the clinical outcomes from double stenting, and analyzed the risk factors for biliary stent dysfunction following double stenting. Eighty-one patients who underwent endoscopic double stenting for malignant biliary and duodenal obstructions were retrospectively analyzed. We determined the stent dysfunction rate and the biliary stent dysfunction risk factors, and analyzed the endoscopic reintervention results. Overall survival time and survival time following double stenting were 365 (38-1673) days and 73 (20-954) days, respectively. After double stenting, the 3-month and 6-month duodenal stent dysfunction rates were 14% and 41%, respectively. Reintervention technical success rate was 100% (10/10), and mean gastric outlet obstruction scoring system scores improved from 0.7 to 2.4 points (P < 0.001). The 3-month and 6-month biliary stent dysfunction rates were 26% and 41%, respectively. The reintervention technical and clinical success rates were 95% (20/21) and 81% (17/21), respectively. Risk factors for biliary stent dysfunction following double stenting were events associated with duodenal stent dysfunction (odds ratio [OR], 11.1; 95% confidence interval [CI], 2.09-87.4; P = 0.0044) and the biliary stent end's location (OR, 6.93; 95% CI, 1.37-40.2; P = 0.0019). Some patients had stent dysfunction irrespective of the survival period after double stenting. Endoscopic reintervention was technically feasible and clinically effective even after double stenting. Duodenal stent dysfunction and biliary stent end's location were risk factors for biliary stent dysfunction. © 2017 Japan Gastroenterological Endoscopy Society.

Gelation of mucin: Protecting the stomach from autodigestion

NASA Astrophysics Data System (ADS)

Bansil, Rama

2011-03-01

In this talk I will describe the molecular mechanisms involved in the remarkable ability of the mucus lining of the stomach for protecting the stomach from being digested by the acidic gastric juices that it secretes. These physical properties can be attributed to the presence of a high molecular weight glycoprotein found in mucus, called mucin. Rheology and other measurements show that gastric mucin forms a gel under acidic pH. A model of gelation based on the interplay of hydrophobic and electrostatic interactions will be discussed. Molecular Dynamics simulation studies of folding and aggregation of mucin domains provide further support for this model. The relevance of gelation to the motion of the ulcer causing bacterium H. pylori will be discussed.

Proteolytic fragmentation and peptide mapping of human carboxyamidomethylated tracheobronchial mucin.

PubMed

Rose, M C; Kaufman, B; Martin, B M

1989-05-15

Human tracheobronchial mucin was isolated from lung mucosal gel by chromatography on Sepharose 4B in the presence of dissociating and reducing agents, and its thiol residues were carboxyamidomethylated with iodo[1(-14)C]acetamide. The 14C-carboxyamido-methylated mucin was purified by chromatography on Sepharose 2B. No low molecular weight components were detected by molecular sieve chromatography or polyacrylamide gel electrophoresis in the presence of dissociating and reducing agents or by analytical density centrifugation in CsCl/guanidinium chloride. After digestion of the purified 14C-mucin with trypsin-L-1-tosylamido-2-phenylethyl chloromethyl ketone, three fractions (TR-1, TR-2, and TR-3) were observed by chromatography on Sepharose 4B. TR-1, a 260-kDa mucin glycopeptide fragment, contained all of the neutral hexose and blood group activity and 20% of the radioactivity in the undigested mucin. TR-1 was refractory to a second incubation with trypsin but could be digested by papain or Pronase to a smaller mucin glycopeptide fraction, as judged by the slight decrease in apparent molecular weight on Sepharose CL-4B. These mucin glycopeptides contained approximately 50% of the radioactivity in the TR-1 fraction, indicating that the glycosylated domains of carboxyamidomethylated tracheobronchial mucin contained thiol residues. The remainder of the radioactivity from papain or Pronase digests of TR-1 eluted, like the TR-3 fractions, in the salt fraction on Sepharose CL-4B. Peptide mapping of the nonglycosylated TR-3 fraction by TLC and high voltage electrophoresis yielded six principal and several less intensely stained ninhydrin reactive components, with the radiolabel concentrated in one of the latter peptides. Peptide purification of the TR-3 fraction by high pressure liquid chromatography on a C18 reverse phase column demonstrated the presence of four major peptides, with TR-3A being the dominant component. The TR-3D peptide contained S

Rebamipide increases the mucin-like glycoprotein production in corneal epithelial cells.

PubMed

Takeji, Yasuhiro; Urashima, Hiroki; Aoki, Akihiro; Shinohara, Hisashi

2012-06-01

Dry eye is a multifactorial disease of tears and the ocular surface due to tear deficiency or excessive tear evaporation. Tear film instability is due to a disturbance in ocular surface mucin leading to a dysfunction of mucin, resulting in dry eye. In this study, we examined the effect of rebamipide, an anti-ulcer agent, on glycoconjugate production, as an indicator of mucin-like glycoprotein in cultured corneal epithelial cells. Further, we investigated the effect of rebamipide on the gene expression of membrane-associated mucins. Confluent cultured human corneal epithelial cells were incubated with rebamipide for 24 h. The glycoconjugate content in the supernatant and the cell extracts was measured by wheat germ agglutinin-enzyme-linked lectin assay combined gel-filtration method. In the experiment on mucin gene expression, cultured human corneal epithelial cells were collected at 0, 3, 6, and 12 h after administration of rebamipide. Real-time quantitative polymerase chain reaction was used to analyze the quantity of MUC1, MUC 4, and MUC16 gene expression. Rebamipide significantly increased the glycoconjugate contents in the supernatant and cell extract. In the mucin gene expression in the cells, rebamipide increased MUC1 and MUC4 gene expression, but did not increase MUC16 gene expression. Rebamipide promoted glycoconjugate, which has a property as a mucin-like glycoprotein, in human corneal epithelial cells. The increased production was mediated by MUC1 and MUC4 gene expression.

Helicobacter pylori and gastric mucin expression: A systematic review and meta-analysis.

PubMed

Niv, Yaron

2015-08-21

To investigate the relationship between Helicobacter pylori (H. pylori) and mucin expression in gastric mucosa. English Medical literature searches were conducted for gastric mucin expression in H. pylori infected people vs uninfected people. Searches were performed up to December 31(th) 2014, using MEDLINE, PubMed, EMBASE, Scopus, and CENTRAL. Studies comparing mucin expression in the gastric mucosa in patients positive and negative for H. pylori infection, were included. Meta-analysis was performed by using Comprehensive meta-analysis software (Version 3, Biostat Inc., Englewood, NJ, United States). Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated compared mucin expression in individual studies by using the random effects model. Heterogeneity between studies was evaluated using the Cochran Q-test, and it was considered to be present if the Q-test P value was less than 0.10. I(2) statistic was used to measure the proportion of inconsistency in individual studies, with I(2) > 50% representing substantial heterogeneity. We also calculated a potential publication bias. Eleven studies, which represent 53 sub-studies of 15 different kinds of mucin expression, were selected according to the inclusion criteria. Every kind of mucin has been considered as one study. When a specific mucin has been studied in more than one paper, we combined the results in a nested meta-analysis of this particular mucin: MUC2, MUC6, STn, Paradoxical con A, Tn, T, Type 1 chain mucin, LeA, SLeA, LeB, AB-PAS, MUC1, and MUC5AC. The odds ratio of mucin expression in random analysis was 2.33, 95%CI: 1.230-4.411, P = 0.009, higher expression in H. pylori infected patients. Odds ratio for mucin expression in H. pylori positive patients was higher for MUC6 (9.244, 95%CI: 1.567-54.515, P = 0.014), and significantly lower for MUC5AC (0.447, 95%CI: 0.211-0.949, P = 0.036). Thus, H. pylori infection may increase MUC6 expression and decrease MUC5AC expression by 924% and 52

Mucin levels in saliva of adolescents with dental caries

PubMed Central

Gabryel-Porowska, Halina; Gornowicz, Agnieszka; Bielawska, Anna; Wójcicka, Anna; Maciorkowska, Elżbieta; Grabowska, Stanisława Zyta; Bielawski, Krzysztof

2014-01-01

Background Human saliva, a complex secretion that contains a mixture of inorganic and organic molecules, plays an essential role in the maintenance of oral health. Mucins are the major macromolecular component of the secretion and are considered the first line of defense for epithelial tissues. The aim of this study was to compare levels of mucins (MUC5B, MUC7, and MUC1) in saliva of young subjects with dental caries. Material/Methods All patients had DMF (decay/missing/filled) higher than value 0. Eight subjects with DMF=3 (control group) and 27 adolescents with DMF >11 (research group) were recruited for this study. Clinical evaluation procedures were oral examination, including tooth, periodontal, oral mucosal status, and collection of saliva samples. Saliva was collected for mucin assay. Enzyme-linked immunosorbent assay was used to quantitate MUC5B, MUC7, and MUC1. Results Our results indicate that adolescents with very high intensity of dental caries disease had increased levels of MUC1 and MUC5B. The membrane mucin MUC1 protein levels in the group with DMF>11 (research group) were higher compared to the group with DMF=3 (control group), and the increase was statistically significant (p=0.011). Similarly, secreted mucin MUC5B protein levels were higher (p=0.06) in the group with DMF>11 (research group). Although MUC7 protein levels were slightly reduced in symptomatic subjects, the decrease was statistically insignificant (p=0.918). Conclusions Our data suggest links between the production of mucins, especially MUC1 and MUC5B in saliva, and dental caries disease. PMID:24441930

Broncho-biliary fistula secondary to biliary obstruction and lung abscess in a patient with pancreatic neuro-endocrine tumor.

PubMed

Panda, Dipanjan; Aggarwal, Mayank; Yadav, Vikas; Kumar, Sachin; Mukund, Amar; Baghmar, Saphalta

2016-06-01

We present a case report of broncho-biliary fistula that developed due to the blockage of biliary stent placed during the management of pancreatic neuroendocrine tumor (pNET); diagnosed on high clinical suspicion, percutaneous cholangiogram and contrast enhanced computed tomography (CECT); and successfully treated with percutaneous transhepatic biliary drainage (PTBD). Copyright © 2016 National Cancer Institute, Cairo University. Production and hosting by Elsevier B.V. All rights reserved.

Mucin can enhance growth, biofilm formation, and survival of Streptococcus mutans.

PubMed

Mothey, Deepa; Buttaro, Bettina A; Piggot, Patrick J

2014-01-01

Streptococcus mutans is a member of the dental plaque and is the primary causative agent of dental caries. It can survive extended periods of starvation, which may occur in different niches within the oral cavity. We have found that mucin compensated for the absence of amino acids to promote exponential growth and biofilm formation of S. mutans in minimal medium supplemented with glucose and sucrose, respectively. Mucin extended survival in conditions where there was no net growth provided the operon encoding the pyruvate dehydrogenase complex was intact. Mucin extended survival in conditions of amino acid sufficiency provided the tagatose pathway for galactose utilization was intact, suggesting that S. mutans can scavenge sufficient galactose from mucin to enhance survival, although not to serve as a primary carbon and energy source. The results suggest that mucin has a metabolic role in promoting survival of S. mutans. © 2013 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

Efficacy of a novel mucolytic agent on pseudomyxoma peritonei mucin, with potential for treatment through peritoneal catheters

PubMed Central

Akhter, Javed; Pillai, Krishna; Chua, Terence C; Alzarin, Naeef; Morris, David Lawson

2014-01-01

Compared to current treatment for pseudomyxoma peritonei (PMP), the extraction of solubilised mucin through peritoneal catheter can be minimally invasive. However, mucin has variable appearance that may influence mucolysis. Hence, we investigated the mucolysis of 36 mucin samples with a novel agent. Using visual inspection and hardness index, PMP mucin was classified into three grades. The mucin pathological category was identified from patient record. Subsequently, the dissolution of the samples was tested. For in vitro, 1 g of mucin was treated to the mucolytic agent in 10 ml TRIS buffer at 37 deg. Celsius for 3 hours, with weighing of residual mucin. Control treatment was similar but received TRIS buffer. For in vivo, 2 g of implanted intra-peritoneal mucin in nude rats was treated to mucolytic (2 X 500 ul/24 hr, over 48 hours, plus another treatment before sacrifice at 56 hours, with weighing of residual mucin. Controls were treated but only with TRIS buffer. Six animals were used for each mucin grade (3 mucolytic treated & and 3 controls). Grades of mucin were soft mucin (62%), semi hard (20%) and hard mucin (18%). Diffuse peritoneal adenomucinosis had 50% of soft mucin and peritoneal mucinous carcinoma had 11% (P = 0.0382). In vitro and in vivo absolute disintegration was 100% for soft, 57.38% and 48.67% for semi hard, 50% and 28.67% for hard mucin. Majority of mucin were soft with complete disintegration, the rest showed variable disintegration, suggesting that the mucolytic has potential for treating PMP. PMID:25232491

Viral papillomatosis in Florida manatees (Trichechus manatus latirostris).

PubMed

Bossart, Gregory D; Ewing, Ruth Y; Lowe, Mark; Sweat, Mark; Decker, Susan J; Walsh, Catherine J; Ghim, Shin-je; Jenson, A Bennett

2002-02-01

The Florida manatee (Trichechus manatus latirostris) is one of the most endangered marine mammals in American coastal waters. Naturally resistant to infectious disease, the manatee immune system appears highly developed to protect it against the harsh marine environment and the effects of human-related injury. In 1997, seven captive Florida manatees developed multiple, cutaneous, pedunculated papillomas over a period of 6 months. Approximately 3 years later, four of the seven manatees developed multiple, cutaneous, sessile papillomas topically and clinically distinct from the initial lesions, some of which are still present. Histologic, ultrastructural, and immunohistochemical features indicated that the two distinct phenotypic lesions were caused by papillomaviruses (PVs). Preliminary immunologic data correlated with daily clinical observations suggested that the manatees were immunologically suppressed and that the papillomas were caused by activation of latent PV infections and reinoculation from active infections. The emergence of PV-induced papillomas in captive manatees, the possibility of activation of latent infection or transmission of active infection to free-ranging manatees, and the underlying cause of immune suppression predisposing manatees to develop viral papillomatosis are serious concerns for the future management of this highly endangered species. Copyright 2002 Elsevier Science.

Emerging potential of natural products for targeting mucins for therapy against inflammation and cancer.

PubMed

Macha, Muzafar A; Krishn, Shiv Ram; Jahan, Rahat; Banerjee, Kasturi; Batra, Surinder K; Jain, Maneesh

2015-03-01

Deregulated mucin expression is a hallmark of several inflammatory and malignant pathologies. Emerging evidence suggests that, apart from biomarkers, these deregulated mucins are functional contributors to the pathogenesis in inflammation and cancer. Both overexpression and downregulation of mucins in various organ systems is associated with pathobiology of inflammation and cancer. Restoration of mucin homeostasis has become an important goal for therapy and management of such disorders has fueled the quest for selective mucomodulators. With improved understanding of mucin regulation and mechanistic insights into their pathobiological roles, there is optimism to find selective non-toxic agents capable of modulating mucin expression and function. Recently, natural compounds derived from dietary sources have drawn attention due to their anti-inflammatory and anti-oxidant properties and low toxicity. Considerable efforts have been directed towards evaluating dietary natural products as chemopreventive and therapeutic agents; identification, characterization and synthesis of their active compounds; and improving their delivery and bioavailability. We describe the current understanding of mucin regulation, rationale for targeting mucins with natural products and discuss some natural products that modulate mucin expression and functions. We further discuss the approaches and parameters that should guide future research to identify and evaluate selective natural mucomodulators for therapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

Emerging Potential of Natural Products for Targeting Mucins for Therapy Against Inflammation and Cancer

PubMed Central

Macha, Muzafar A.; Krishn, Shiv Ram; Jahan, Rahat; Banerjee, Kasturi; Batra, Surinder K.; Jain, Maneesh

2015-01-01

Deregulated mucin expression is a hallmark of several inflammatory and malignant pathologies. Emerging evidence suggests that, apart from biomarkers, these deregulated mucins are functional contributors to pathogenesis in inflammation and cancer. Both overexpression and downregulation of mucins in various organ systems is associated with pathobiology of inflammation and cancer. Restoration of mucin homeostasis has become an important goal for therapy and management of such disorders and has fueled the quest for selective mucomodulators. With improved understanding of mucin regulation and mechanistic insights into their pathobiological roles, there is optimism to find selective non-toxic agents capable of modulating mucin expression and function. Recently, natural compounds derived from dietary sources have drawn attention due to their anti-inflammatory and anti-oxidant properties and low toxicity. Considerable efforts have been directed towards evaluating dietary natural products as chemopreventive and therapeutic agents; identification, characterization and synthesis of their active compounds; and improving their delivery and bioavailability. We describe the current understanding of mucin regulation, rationale for targeting mucins with natural products and discuss some natural products that modulate mucin expression and functions. We further discuss the approaches and parameters that should guide future research to identify and evaluate selective natural mucomodulators for therapy. PMID:25624117

Long-term follow-up and outcome in patients with recurrent respiratory laryngeal papillomatosis.

PubMed

Rasmussen, Eva Rye; Schnack, Didde T; Jørkov, Andreas Schjellerup; Raja, Anna Axelsson; Olsen, Caroline Holkmann; Homøe, Preben

2017-12-01

Recurrent respiratory papillomatosis is characterized by wart-like lesions of the upper airway and is most frequently caused by human papillomavirus (HPV). The disease has significant impact on quality of life due to potential airway obstruction, dysphonia and the need for serial surgeries. The main objective of this study was to describe patient characteristics and long-term follow-up data in a Danish cohort with the disease. The study was a longitudinal retrospective cohort-study using data from electronic medical records and a pathology database. A total of 61 adult and four juvenile patients were identified. The male-to-female ratio was 2.4. In the adult population, the mean age at onset was 45 years. The median number of surgeries was four (interquartile range: 2.8). The mean follow-up time was 8.7 years (range: 7 days-30 years). Three cases of malignant transformation were observed. In the juvenile population, the mean age of onset was 8.5 years (range: 3-12 years). The mean follow-up time was 11.5 years (range: 2-23 years), and the number of surgeries per year at risk was one/year. CO2-laser and microdebrider were the surgical techniques usually employed. 43% of histopathologic analyses could detect HPV infection (subtype 6 or 11). More males than females suffer from respiratory papillomatosis; age of onset was either in childhood or in mid-life. Use of CO2-laser or microdebrider was the preferred surgical approach in this cohort. none. not relevant. Articles published in the DMJ are “open access”. This means that the articles are distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits any non-commercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.

Benign Biliary Strictures: Diagnostic Evaluation and Approaches to Percutaneous Treatment.

PubMed

Fidelman, Nicholas

2015-12-01

Interventional radiologists are often consulted to help identify and treat biliary strictures that can result from a variety of benign etiologies. Mainstays of noninvasive imaging for benign biliary strictures include ultrasound, contrast-enhanced computed tomography and magnetic resonance imaging, magnetic resonance cholangiopancreatography, and computed tomography cholangiography. Endoscopic retrograde cholangiography is the invasive diagnostic procedure of choice, allowing both localization of a stricture and treatment. Percutaneous biliary interventions are reserved for patients who are not candidates for endoscopic retrograde cholangiography (eg, history of distal gastrectomy and biliary-enteric anastomosis to a jejunal roux limb). This review discusses the roles of percutaneous transhepatic cholangiography and biliary drainage in the diagnosis of benign biliary strictures. The methodology for crossing benign biliary strictures, approaches to balloon dilation, management of recalcitrant strictures (ie, large-bore biliary catheters and retrievable covered stents), and the expected outcomes and complications of percutaneous treatment of benign biliary strictures are also addressed. Copyright © 2015 Elsevier Inc. All rights reserved.

Extrahepatic biliary atresia: current concepts and future directions.

PubMed

de Carvalho, Elisa; Ivantes, Cláudia Alexandra Pontes; Bezerra, Jorge A

2007-01-01

To provide an updated review on extrahepatic biliary atresia, focusing mainly on its etiopathogenesis, diagnosis, treatment and prognosis. MEDLINE and PubMed databases were searched using the following keywords: biliary atresia, etiopathogenesis, diagnosis, treatment, prognosis, children. Extrahepatic biliary atresia is the main indication for liver transplantation among pediatric patients. As to its etiology, cytomegalovirus, reovirus and rotavirus have been widely investigated as possible triggers of the immunomediated obstruction of the biliary tree. The immune response, especially the predominant TH1 and interferon-gamma responses, genetic susceptibility and disorders related to the embryonic development of the biliary tree can play a role in the etiopathogenesis of extrahepatic biliary atresia. Yet today, portoenterostomy is the only available treatment, with better results when performed in the first 2 months of life. As to prognosis, all untreated children eventually die due to complications resulting from portal hypertension and liver cirrhosis, and most treated children have to undergo liver transplantation. Extrahepatic biliary atresia is still the major indication for pediatric liver transplantation, and to change this scenario some more light should be shed upon the etiopathogenesis of biliary atresia in different disease phenotypes. Future research into the role of interferon-gamma and of other cytokines is necessary in order to assess whether these aspects should be potential targets for therapeutic intervention.

Failed CTL/NK cell killing and cytokine hypersecretion are directly linked through prolonged synapse time

PubMed Central

Rudd-Schmidt, Jesse A.; Lopez, Jamie A.; Ramsbottom, Kelly M.; Mannering, Stuart I.; Andrews, Daniel M.; Voskoboinik, Ilia

2015-01-01

Failure of cytotoxic T lymphocytes (CTLs) or natural killer (NK) cells to kill target cells by perforin (Prf)/granzyme (Gzm)-induced apoptosis causes severe immune dysregulation. In familial hemophagocytic lymphohistiocytosis, Prf-deficient infants suffer a fatal “cytokine storm” resulting from macrophage overactivation, but the link to failed target cell death is not understood. We show that prolonged target cell survival greatly amplifies the quanta of inflammatory cytokines secreted by CTLs/NK cells and that interferon-γ (IFN-γ) directly invokes the activation and secondary overproduction of proinflammatory IL-6 from naive macrophages. Furthermore, using live cell microscopy to visualize hundreds of synapses formed between wild-type, Prf-null, or GzmA/B-null CTLs/NK cells and their targets in real time, we show that hypersecretion of IL-2, TNF, IFN-γ, and various chemokines is linked to failed disengagement of Prf- or Gzm-deficient lymphocytes from their targets, with mean synapse time increased fivefold, from ∼8 to >40 min. Surprisingly, the signal for detachment arose from the dying target cell and was caspase dependent, as delaying target cell death with various forms of caspase blockade also prevented their disengagement from fully competent CTLs/NK cells and caused cytokine hypersecretion. Our findings provide the cellular mechanism through which failed killing by lymphocytes causes systemic inflammation involving recruitment and activation of myeloid cells. PMID:25732304

Biliary bypass surgery - Analysis of indications & outcome of different procedures.

PubMed

Hussain Talpur, K Altaf; Mahmood Malik, Arshad; Iqbal Memon, Amir; Naeem Qureshi, Jawed; Khan Sangrasi, Ahmed; Laghari, Abdul Aziz

2013-05-01

This study reports the indications and outcome of various biliary bypass surgical procedures from a single centre over a period of 10 years. This is a prospective observational study conducted over a period of 10 years (January 2001-december 2010). A total of 1500 patients were included, who underwent pancreatico-biliary surgery due to common bile duct (CBD) stones, congenital anomalies of biliary tree, unoperable pancreatico-biliary malignancies, CBD strictures and cases who developed iatrogenic biliary injuries during cholecystectomy (both open & laproscopic) during this period of time. The patients who required biliary bypass surgery were further analysed for indications and outcome. Out of 1500 patients 83(5.53%) required biliary bypass surgical procedures. The CBD stones were observed as the most common indication (25.3%), followed by CBD injuries after open(10.84%) or laproscopic-cholecystectomy (14.46%), carcinoma head of pancreas (12.05%) and CBD obstruction(14.46%) either due to CBD strictures or unknown distal obstruction. Roux-en-Y-hepatico-jejunostomy (26.51%) was the most frequently performed procedure, followed by choledochoduodenostomy and Roux-en-Y choledocho-jejunostomy (i.e. 25.3% and 12.05% respectively). Roux-en-Y biliary bypass procedure was observed to be associated with better outcome in terms of rate of complications as well duration of hospital stay. Biliary bypass surgical procedures are the better options to restore the continuity of biliary system in patients with iatrogenic biliary tree injuries and un-operable pancreatico-biliary malignancy. Roux-en-Y biliary bypass procedure is safe and problem solving method in these cases.

Endoscopic biliary stent insertion through specialized duodenal stent for combined malignant biliary and duodenal obstruction facilitated by stent or PTBD guidance.

PubMed

Lee, Jong Jin; Hyun, Jong Jin; Choe, Jung Wan; Lee, Dong-Won; Kim, Seung Young; Jung, Sung Woo; Jung, Young Kul; Koo, Ja Seol; Yim, Hyung Joon; Lee, Sang Woo

2017-11-01

Endoscopic stenting for combined malignant biliary and duodenal obstruction is technically demanding. However, this procedure can be facilitated when there is guidance from previously inserted stent or PTBD tube. This study aimed to evaluate the feasibility and clinical success rate of endoscopic placement of biliary self-expandable metal stent (SEMS) through duodenal SEMS in patients with combined biliary and duodenal obstruction due to inoperable or metastatic periampullary malignancy. A total of 12 patients with combined malignant biliary and duodenal stricture underwent insertion of biliary SEMS through the mesh of specialized duodenal SEMS from July 2012 to October 2016. Technical and clinical success rate, adverse events and survival after completion of SEMS insertion were evaluated. The duodenal strictures were located in the first portion of the duodenum in four patients (Type I), in the second portion in three patients (Type II), and in the third portion in five patients (Type III). Technical success rate of combined metallic stenting was 91.7%. Insertion of biliary SEMS was guided by previously inserted biliary SEMS in nine patients, plastic stent in one patient, and PTBD in two patients. Clinical success rate was 90.9%. There were no early adverse events after the procedure. Mean survival period after combined metallic stenting was 91.9 days (range: 15-245 days). Endoscopic placement of biliary SEMS through duodenal SEMS is feasible with high success rates and relatively easy when there is guidance. This method can be a good alternative for palliation in patients with combined biliary and duodenal obstruction.

Folding and Aggregation of Mucin Domains.

NASA Astrophysics Data System (ADS)

Urbanc, Brigita; Bansil, Rama; Turner, Bradley

2007-03-01

Mucin glycoproteins consist of tandem repeating glycosylated regions flanked by non-repetitive protein domains with little glycosylation. These non-repetitive domains are involved in polymerization of mucin via disulfide bonds and play an important role in the pH dependent gelation of gastric mucin, which is essential to protecting the stomach from autodigestion. We have examined the folding and aggregation of the non-repetitive sequence of von Willebrand factor vWF-C1 domain (67 amino acids) and PGM 2X (242 amino acids) using Discrete Molecular Dynamics (four-bead protein model with hydrogen bonding and amino acid-specific hydrophobic/hydrophilic and electrostatic interactions of side chains). Simulations of vWF C1 show 4-6 β-strands separated by turns/loops with more loops at lower pH. A simulation of several vWF C1 proteins at low pH shows aggregates still with a high content of β-strands and enhanced turn/loop regions. For the PGM 2X simulation the contact map shows several salt bridges enclosing hairpin turns. The implications of these simulations for describing the aggregation/gelation of PGM will be discussed.

Pharmacokinetics and Biliary Excretion of Fisetin in Rats.

PubMed

Huang, Miao-Chan; Hsueh, Thomas Y; Cheng, Yung-Yi; Lin, Lie-Chwen; Tsai, Tung-Hu

2018-06-14

The hypothesis of this study is that fisetin and phase II conjugated forms of fisetin may partly undergo biliary excretion. To investigate this hypothesis, male Sprague-Dawley rats were used for the experiment, and their bile ducts were cannulated with polyethylene tubes for bile sampling. The pharmacokinetic results demonstrated that the average area-under-the-curve (AUC) ratios ( k (%) = AUC conjugate /AUC free-form ) of fisetin, its glucuronides, and its sulfates were 1:6:21 in plasma and 1:4:75 in bile, respectively. Particularly, the sulfated metabolites were the main forms that underwent biliary excretion. The biliary excretion rate ( k BE (%) = AUC bile /AUC plasma ) indicates the amount of fisetin eliminated by biliary excretion. The biliary excretion rates of fisetin, its glucuronide conjugates, and its sulfate conjugates were approximately 144, 109, and 823%, respectively, after fisetin administration (30 mg/kg, iv). Furthermore, biliary excretion of fisetin is mediated by P-glycoprotein.

Mucinous cystadenocarcinoma of the breast: the challenge of diagnosing a rare entity.

PubMed

Koufopoulos, Nektarios; Goudeli, Christina; Syrios, John; Filopoulos, Evangelos; Khaldi, Lubna

2017-10-03

Mucinous cystadenocarcinoma is an extremely rare variant of primary breast tumor which is histologically similar to mucinous cystadenocarcinoma of the ovary and pancreas. Herein we report a case of a 63 years old woman diagnosed with diverse histological types of non-synchronous rare primary breast tumors, a medullary carcinoma of the right breast and a mucinous cystadenocarcinoma of the left breast. Macroscopically the neoplasm appeared multilocular filled with mucoid material. Under light microscopy the cystic areas were lined by columnar cells with abundant intracellular and extracellular mucin. Solid areas were composed of tall columnar cells with intracellular mucin. Moderate to marked atypia was noticed and tumor cells stained positive for cytokeratin 7 and negative for cytokeratin 20. Moreover tumor cells displayed a basal like immunophenotype expressed as followed: ER negative, PR negative, HER-2 negative, cytokeratin (CK5/6) positive and EGFR positive.

Aspergillosis and the role of mucins in cystic fibrosis.

PubMed

Cowley, Abigail C; Thornton, David J; Denning, David W; Horsley, Alexander

2017-04-01

The prevalence of aspergillosis in CF patients has until recently been underestimated, but increasing evidence suggests that it may play an important role in the progression of CF lung disease. In healthy airways, Aspergillus fumigatus can be efficiently removed from the lung by mechanisms such as mucociliary clearance and cough. However, these mechanisms are defective in CF, allowing pathogens such as A. fumigatus to germinate and establish chronic infections within the airways. The precise means by which A. fumigatus contributes to CF lung disease remain largely unclear. As the first point of contact within the lung, and an important component of the innate immune system, it is likely that the mucus barrier plays an important role in this process. Study of the functional interplay between this vital protective barrier, and in particular its principal structural components, the polymeric gel-forming mucins, and CF pathogens such as A. fumigatus, is at an early stage. A. fumigatus protease activity has been shown to upregulate mucus production by inducing mucin mRNA and protein expression, and A. fumigatus proteases and glycosidases are able to degrade mucins. This may allow A. fumigatus to alter mucus barrier properties to promote fungal colonization of the airways and/or utilize mucins as a nutrient source. Moreover, conidial surface lectin binding to mucin glycans is a key aspect of clearance of Aspergillus from the lung in health but may be an important aspect of colonization, where mucociliary clearance is compromised, as in the CF lung. Here we discuss the nature of the mucus barrier and its mucin components in CF, and how they may be implicated in A. fumigatus infection. Pediatr Pulmonol 2017;52:548-555. © 2016 The Authors. Pediatric Pulmonology. Published by Wiley Periodicals, Inc. © 2016 The Authors. Pediatric Pulmonology Published by Wiley Periodicals, Inc.

Aspergillosis and the role of mucins in cystic fibrosis

PubMed Central

Cowley, Abigail C.; Thornton, David J.; Denning, David W.

2016-01-01

Summary The prevalence of aspergillosis in CF patients has until recently been underestimated, but increasing evidence suggests that it may play an important role in the progression of CF lung disease. In healthy airways, Aspergillus fumigatus can be efficiently removed from the lung by mechanisms such as mucociliary clearance and cough. However, these mechanisms are defective in CF, allowing pathogens such as A. fumigatus to germinate and establish chronic infections within the airways. The precise means by which A. fumigatus contributes to CF lung disease remain largely unclear. As the first point of contact within the lung, and an important component of the innate immune system, it is likely that the mucus barrier plays an important role in this process. Study of the functional interplay between this vital protective barrier, and in particular its principal structural components, the polymeric gel‐forming mucins, and CF pathogens such as A. fumigatus, is at an early stage. A. fumigatus protease activity has been shown to upregulate mucus production by inducing mucin mRNA and protein expression, and A. fumigatus proteases and glycosidases are able to degrade mucins. This may allow A. fumigatus to alter mucus barrier properties to promote fungal colonization of the airways and/or utilize mucins as a nutrient source. Moreover, conidial surface lectin binding to mucin glycans is a key aspect of clearance of Aspergillus from the lung in health but may be an important aspect of colonization, where mucociliary clearance is compromised, as in the CF lung. Here we discuss the nature of the mucus barrier and its mucin components in CF, and how they may be implicated in A. fumigatus infection. Pediatr Pulmonol 2017;52:548–555. © 2016 The Authors. Pediatric Pulmonology. Published by Wiley Periodicals, Inc. PMID:27870227

Mupirocin-mucin agar for selective enumeration of Bifidobacterium bifidum.

PubMed

Pechar, Radko; Rada, Vojtech; Parafati, Lucia; Musilova, Sarka; Bunesova, Vera; Vlkova, Eva; Killer, Jiri; Mrazek, Jakub; Kmet, Vladimir; Svejstil, Roman

2014-11-17

Bifidobacterium bifidum is a bacterial species exclusively found in the human intestinal tract. This species is becoming increasingly popular as a probiotic organism added to lyophilized products. In this study, porcine mucin was used as the sole carbon source for the selective enumeration of B. bifidum in probiotic food additives. Thirty-six bifidobacterial strains were cultivated in broth with mucin. Only 13 strains of B. bifidum utilized the mucin to produce acids. B. bifidum was selectively enumerated in eight probiotic food supplements using agar (MM agar) containing mupirocin (100 mg/L) and mucin (20 g/L) as the sole carbon source. MM agar was fully selective if the B. bifidum species was presented together with Bifidobacterium animalis subsp. lactis, Bifidobacterium breve, and Bifidobacterium longum subsp. longum species and with lactic acid bacteria (lactobacilli, streptococci). Isolated strains of B. bifidum were identified using biochemical, PCR, MALDI-TOF procedures and 16S rRNA gene sequencing. The novel selective medium was also suitable for the isolation of B. bifidum strains from human fecal samples. Copyright © 2014 Elsevier B.V. All rights reserved.

Oncocytic Type Intraductal Papillary Mucinous Neoplasm of the Pancreas with Unusually Low Mucin Production Mimicking Intraductal Tubulopapillary Neoplasm: A Report of a Case Diagnosed by a Preoperative Endoscopic Biopsy

PubMed Central

Yoshida, Yukinari; Endo, Takao; Tanaka, Eiichi; Kikuchi, Takefumi; Akino, Kimishige; Mita, Hiroaki; Adachi, Yasuyo; Nakamura, Masahiro; Adachi, Yasushi; Ishii, Yoshifumi; Matsumoto, Joe; Hirano, Satoshi; Nitta, Takeo; Mitsuhashi, Tomoko; Kato, Yasuo

2017-01-01

We herein report the case of a 78-year-old woman with an intraductal tumor with scant mucin production in a moderately dilated main pancreatic duct that resembled an intraductal tubulopapillary neoplasm (ITPN) on imaging. An endoscopic transpapillary forceps biopsy enabled an accurate preoperative diagnosis of the tumor as an oncocytic type intraductal papillary mucinous neoplasm (IPMN) of the pancreas microscopically showing papillary growth consisting of oncocytic cells with a typical mucin expression profile, although with few intraepithelial lumina containing mucin. This is the first case of an oncocytic type IPMN mimicking an ITPN that was able to be diagnosed preoperatively. PMID:29021473

Mucin Production and Mucous Cell Metaplasia in Otitis Media

PubMed Central

Lin, Jizhen; Caye-Thomasen, Per; Tono, Tetsuya; Zhang, Quan-An; Nakamura, Yoshihisa; Feng, Ling; Huang, Jianmin; Ye, Shengnan; Hu, Xiaohua; Kerschner, Joseph E.

2012-01-01

Otitis media (OM) with mucoid effusion, characterized by mucous cell metaplasia/hyperplasia in the middle ear cleft and thick fluid accumulation in the middle ear cavity, is a subtype of OM which frequently leads to chronic OM in young children. Multiple factors are involved in the developmental process of OM with mucoid effusion, especially disorders of mucin production resulting from middle ear bacterial infection and Eustachian tube dysfunction. In this review, we will focus on several aspects of this disorder by analyzing the cellular and molecular events such as mucin production and mucous cell differentiation in the middle ear mucosa with OM. In addition, infectious agents, mucin production triggers, and relevant signaling pathways will be discussed. PMID:22685463

Helicobacter pylori and gastric mucin expression: A systematic review and meta-analysis

PubMed Central

Niv, Yaron

2015-01-01

AIM: To investigate the relationship between Helicobacter pylori (H. pylori) and mucin expression in gastric mucosa. METHODS: English Medical literature searches were conducted for gastric mucin expression in H. pylori infected people vs uninfected people. Searches were performed up to December 31th 2014, using MEDLINE, PubMed, EMBASE, Scopus, and CENTRAL. Studies comparing mucin expression in the gastric mucosa in patients positive and negative for H. pylori infection, were included. Meta-analysis was performed by using Comprehensive meta-analysis software (Version 3, Biostat Inc., Englewood, NJ, United States). Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated compared mucin expression in individual studies by using the random effects model. Heterogeneity between studies was evaluated using the Cochran Q-test, and it was considered to be present if the Q-test P value was less than 0.10. I2 statistic was used to measure the proportion of inconsistency in individual studies, with I2 > 50% representing substantial heterogeneity. We also calculated a potential publication bias. RESULTS: Eleven studies, which represent 53 sub-studies of 15 different kinds of mucin expression, were selected according to the inclusion criteria. Every kind of mucin has been considered as one study. When a specific mucin has been studied in more than one paper, we combined the results in a nested meta-analysis of this particular mucin: MUC2, MUC6, STn, Paradoxical con A, Tn, T, Type 1 chain mucin, LeA, SLeA, LeB, AB-PAS, MUC1, and MUC5AC. The odds ratio of mucin expression in random analysis was 2.33, 95%CI: 1.230-4.411, P = 0.009, higher expression in H. pylori infected patients. Odds ratio for mucin expression in H. pylori positive patients was higher for MUC6 (9.244, 95%CI: 1.567-54.515, P = 0.014), and significantly lower for MUC5AC (0.447, 95%CI: 0.211-0.949, P = 0.036). Thus, H. pylori infection may increase MUC6 expression and decrease MUC5AC expression by

Giant Appendicular Mucocele Due to Mucinous Cystadenoma.

PubMed

Sertkaya, Mehmet; Emre, Arif; Pircanoglu, Eyüp Mehmet; Peker, Onur; Cengiz, Emrah; Karaagaç, Mustafa

2016-01-01

Mucocele of the appendix is a rare clinicopathological entity simulating acute appendicitis. The most common form of the mucocele is cystadenoma, which is characterized by luminal dilatation producing large amounts of mucin. We present a new case of a giant mucocele of appendix with mucinous cystadenoma. A 61-year-old female was admitted with complaints of severe lower right quadrant pain. Ultrasonography and computed tomography (CT) suggested that it was a mucocele, but due to severity of pain, she underwent an emergency operation. Fortunately, without a perforation, it was a giant mucocele and the operation was terminated with an uneventful appendectomy with segmental cecal resection. The histopathological evaluation of the specimen reported to be a mucocele with mucinous cystadenoma with negative surgical margins. The patient was discharged postoperative 6th day, and a control colonoscopy and abdominal CT was planned for 6 months following surgery. Appendicular mucocele is rare and difficult to diagnose preoperatively, and sometimes it may be of large size which increases the risk of perforation. Pseudomyxoma peritonei (PP) is the most feared complication of mucocele perforation. Appendectomy with negative margins is a requirement for adequate treatment for most cases. Utmost care should be taken during surgery to avoid perforation of mucocele. Sertkaya M, Emre A, Pircanoglu EM, Peker O, Cengiz E, Karaagaç M. Giant Appendicular Mucocele Due to Mucinous Cystadenoma. Euroasian J Hepato-Gastroenterol 2016;6(2):186-189.

Molecular genetics and targeted therapeutics in biliary tract carcinoma

PubMed Central

Marks, Eric I; Yee, Nelson S

2016-01-01

The primary malignancies of the biliary tract, cholangiocarcinoma and gallbladder cancer, often present at an advanced stage and are marginally sensitive to radiation and chemotherapy. Accumulating evidence indicates that molecularly targeted agents may provide new hope for improving treatment response in biliary tract carcinoma (BTC). In this article, we provide a critical review of the pathogenesis and genetic abnormalities of biliary tract neoplasms, in addition to discussing the current and emerging targeted therapeutics in BTC. Genetic studies of biliary tumors have identified the growth factors and receptors as well as their downstream signaling pathways that control the growth and survival of biliary epithelia. Target-specific monoclonal antibodies and small molecules inhibitors directed against the signaling pathways that drive BTC growth and invasion have been developed. Numerous clinical trials designed to test these agents as either monotherapy or in combination with conventional chemotherapy have been completed or are currently underway. Research focusing on understanding the molecular basis of biliary tumorigenesis will continue to identify for targeted therapy the key mutations that drive growth and invasion of biliary neoplasms. Additional strategies that have emerged for treating this malignant disease include targeting the epigenetic alterations of BTC and immunotherapy. By integrating targeted therapy with molecular profiles of biliary tumor, we hope to provide precision treatment for patients with malignant diseases of the biliary tract. PMID:26819503

Molecular genetics and targeted therapeutics in biliary tract carcinoma.

PubMed

Marks, Eric I; Yee, Nelson S

2016-01-28

The primary malignancies of the biliary tract, cholangiocarcinoma and gallbladder cancer, often present at an advanced stage and are marginally sensitive to radiation and chemotherapy. Accumulating evidence indicates that molecularly targeted agents may provide new hope for improving treatment response in biliary tract carcinoma (BTC). In this article, we provide a critical review of the pathogenesis and genetic abnormalities of biliary tract neoplasms, in addition to discussing the current and emerging targeted therapeutics in BTC. Genetic studies of biliary tumors have identified the growth factors and receptors as well as their downstream signaling pathways that control the growth and survival of biliary epithelia. Target-specific monoclonal antibodies and small molecules inhibitors directed against the signaling pathways that drive BTC growth and invasion have been developed. Numerous clinical trials designed to test these agents as either monotherapy or in combination with conventional chemotherapy have been completed or are currently underway. Research focusing on understanding the molecular basis of biliary tumorigenesis will continue to identify for targeted therapy the key mutations that drive growth and invasion of biliary neoplasms. Additional strategies that have emerged for treating this malignant disease include targeting the epigenetic alterations of BTC and immunotherapy. By integrating targeted therapy with molecular profiles of biliary tumor, we hope to provide precision treatment for patients with malignant diseases of the biliary tract.

Pulmonary mucinous cystadenocarcinoma presenting as a pleural mesothelioma☆

PubMed Central

Kassir, Radwan; Forest, Fabien; Kaczmarek, David

2013-01-01

INTRODUCTION Primary Pulmonary Mucinous Cystadenocarcinoma PPMC is an extremely rare subtype of pulmonary adenocarcinoma, with only a few dozen cases reported in the literature to date. PRESENTATION OF CASE We report a extremely rare case of pulmonary mucinous cystadenocarcinoma presenting as a pleural mesothelioma. 53-year-old man exposed to asbestos, he is admitted in hospital with a 5 cm mass in right pleura. He was treated by wedge resection. Sparse groups of malignant cells were microscopically observed in pools of mucin. The postoperative histopathological findings were in accordance with the diagnosis of pulmonary mucinous cystadenocarcinoma on cystic adenoid malformation of lung. 5 years later, the patient has no recurrence. DISCUSSION PPMC is usually asymptomatic; hemoptysis is seen occasionally. Preoperative diagnosis is very difficult to establish. Both FNA cytology and transbronchial lung biopsy seem inadequate. Our patient went on to undergo open lung biopsy and histopathological testing that confirmed the diagnosis of PMC. CONCLUSION It is important to differentiate this rare pathological feature of the lung from other lung tumors as the treatment is surgical rather than medical. Thoracic surgeons should bear in mind this rare tumor for the differential diagnosis of a pleural mesothelioma because this tumor has a favorable prognosis. PMID:24055913

Mucin-1 and its relation to grade, stage and survival in ovarian carcinoma patients

PubMed Central

2012-01-01

Background Mucin-1 is known to be over-expressed by various human carcinomas and is shed into the circulation where it can be detected in patient’s serum by specific anti-Mucin-1 antibodies, such as the tumour marker assays CA 15–3 and CA 27.29. The prognostic value of Mucin-1 expression in ovarian carcinoma remains uncertain. One aim of this study was to compare the concentrations of Mucin-1 in a cohort of patients with either benign or malignant ovarian tumours detected by CA 15–3 and CA 27.29. Another aim of this study was to evaluate Mucin-1 expression by immunohistochemistry in a different cohort of ovarian carcinoma patients with respect to grade, stage and survival. Methods Patients diagnosed with and treated for ovarian tumours were included in the study. Patient characteristics, histology including histological subtype, tumour stage, grading and follow-up data were available from patient records. Serum Mucin-1 concentrations were measured with ELISA technology detecting CA 15–3 and CA 27.29, Mucin-1 tissue expression was determined by immunohistochemistry using the VU4H5 and VU3C6 anti-Mucin-1 antibodies. Statistical analysis was performed by using SPSS 18.0. Results Serum samples of 118 patients with ovarian tumours were obtained to determine levels of Mucin-1. Median CA 15–3 and CA 27.29 concentrations were significantly higher in patients with malignant disease (p< 0.001) than in patients with benign disease. Paraffin-embedded tissue of 154 patients with ovarian carcinoma was available to determine Mucin-1 expression. The majority of patients presented with advanced stage disease at primary diagnosis. Median follow-up time was 11.39 years. Immunohistochemistry results for VU4H5 showed significant differences with respect to tumour grade, FIGO stage and overall survival. Patients with negative expression had a mean overall survival of 9.33 years compared to 6.27 years for patients with positive Mucin-1 expression. Conclusions This study found

Diurnal variation in the biliary excretion of flomoxef in patients with percutaneous transhepatic biliary drainage

PubMed Central

Hishikawa, Shuji; Kobayashi, Eiji; Sugimoto, Koh-ichi; Miyata, Michio; Fujimura, Akio

2001-01-01

Aims To examine diurnal variation in biliary excretion of flomoxef. Methods Flomoxef (1 g) was injected intravenously in eight patients with percutaneous transhepatic cholangiography with drainage at 09.00 h and 21.00 h by a cross-over design with a 36 h washout period. Drained biliary fluid was collected for 6 h after each dosing. These patients still had mild to moderate hepatic dysfunction. Results Bile flow and bile acid excretion for 6 h after dosing did not differ significantly between the 09.00 h and 21.00 h treatments. The maximum concentration of biliary flomoxef was significantly greater and its total excretion for 6 h tended to be greater after the 21.00 h dose [maximum concentration (µg ml−1): 34.2 ± 29.9 (09.00 h dose) vs 43.5 ± 28.3 (21.00 h dose) (95% confidence interval for difference: 2.6∼15.9, P = 0.013); total excretion (mg 6 h−1): 1.4 ± 1.3 (09.00 h dose) vs 1.6 ± 1.2 (21.00 h dose) (95% confidence interval for difference: −26.8, 313.7, P = 0.087)]. The period that biliary flomoxef remained above the minimal inhibitory concentration did not differ significantly between the two treatment times. Conclusions These results suggest that biliary excretion of flomoxef shows diurnal variation. However, as the difference was relatively small, flomoxef could be given at any time of day without any dosage adjustments. PMID:11453891

Diurnal variation in the biliary excretion of flomoxef in patients with percutaneous transhepatic biliary drainage.

PubMed

Hishikawa, S; Kobayashi, E; Sugimoto , K; Miyata, M; Fujimura, A

2001-07-01

To examine diurnal variation in biliary excretion of flomoxef. Flomoxef (1 g) was injected intravenously in eight patients with percutaneous transhepatic cholangiography with drainage at 09.00 h and 21.00 h by a cross-over design with a 36 h washout period. Drained biliary fluid was collected for 6 h after each dosing. These patients still had mild to moderate hepatic dysfunction. Bile flow and bile acid excretion for 6 h after dosing did not differ significantly between the 09.00 h and 21.00 h treatments. The maximum concentration of biliary flomoxef was significantly greater and its total excretion for 6 h tended to be greater after the 21.00 h dose [maximum concentration (microg ml(-1)): 34.2 +/- 29.9 (09.00 h dose) vs 43.5 +/- 28.3 (21.00 h dose) (95% confidence interval for difference: 2.6 approximately 15.9, P = 0.013); total excretion (mg 6 h(-1)): 1.4 +/- 1.3 (09.00 h dose) vs 1.6 +/- 1.2 (21.00 h dose) (95% confidence interval for difference: -26.8, 313.7, P = 0.087)]. The period that biliary flomoxef remained above the minimal inhibitory concentration did not differ significantly between the two treatment times. These results suggest that biliary excretion of flomoxef shows diurnal variation. However, as the difference was relatively small, flomoxef could be given at any time of day without any dosage adjustments.

Functional Self-Expandable Metal Stents in Biliary Obstruction

PubMed Central

Kwon, Chang-Il; Ko, Kwang Hyun; Hahm, Ki Baik

2013-01-01

Biliary stents are widely used not only for palliative treatment of malignant biliary obstruction but also for benign biliary diseases. Each plastic stent or self-expandable metal stent (SEMS) has its own advantages, and a proper stent should be selected carefully for individual condition. To compensate and overcome several drawbacks of SEMS, functional self-expandable metal stent (FSEMS) has been developed with much progress so far. This article looks into the outcomes and defects of each stent type for benign biliary stricture and describes newly introduced FSEMSs according to their functional categories. PMID:24143314

Radiopaque biodegradable stent for duct-to-duct biliary reconstruction in pigs.

PubMed

Tanimoto, Yoshisato; Tashiro, Hirotaka; Mikuriya, Yoshihiro; Kuroda, Shintaro; Hashimoto, Masakazu; Kobayashi, Tsuyoshi; Taniura, Tokunori; Ohdan, Hideki

2016-06-01

Biliary stricture is a common cause of morbidity after liver transplantation. We previously developed a duct-to-duct biliary anastomosis technique using a biodegradable stent tube and confirmed the feasibility and safety of biliary stent use. However, the duration and mechanism of biliary stent absorption in the common bile duct remain unclear. Radiopaque biodegradable biliary stents were created using a copolymer of L-lactide and ε-caprolactone (70: 30) and coated with barium sulfate. Stents were surgically implanted in the common bile duct of 11 pigs. Liver function tests and computed tomography (CT) scans were performed postoperatively, and autopsies were conducted 6 months after biliary stent implantation. After the surgery, all 11 pigs had normal liver function and survived without any significant complications such as biliary leakage. A CT scan at 2 months post-procedure showed that the biliary stents were located in the hilum of the liver. The stents were not visible by CT scan at the 6-month follow-up examination. The surgical implantation of radiopaque biodegradable biliary stents in biliary surgery represents a new option for duct-to-duct biliary reconstruction. This technique appears to be feasible and safe and is not associated with any significant biliary complications. The advantage of coated biliary stent use is that it may be visualized using abdominal radiography such as CT.

Breast Mucin Tumor-Specific Epitopes for Cancer Immunotherapy

DTIC Science & Technology

1998-09-01

reactivity with tumor-specific monoclonal antibodies show that antigenicity is maximized with the 40 amino acid MUC1-mtr2. By contrast, the MUC1-mtr3...associated mucins (7). The presence of tumor-specific epitopes is evidenced by the development of many monoclonal antibodies (mAb) that recognize...P1-P5 in the tandem repeat sequence (7). This epitope was identified by competition of antibody binding to tumor- specific mucin by synthetic

Mucinous cystadenocarcinoma of the breast: the challenge of diagnosing a rare entity

PubMed Central

Koufopoulos, Nektarios; Goudeli, Christina; Syrios, John; Filopoulos, Evangelos; Khaldi, Lubna

2017-01-01

Mucinous cystadenocarcinoma is an extremely rare variant of primary breast tumor which is histologically similar to mucinous cystadenocarcinoma of the ovary and pancreas. Herein we report a case of a 63 years old woman diagnosed with diverse histological types of non-synchronous rare primary breast tumors, a medullary carcinoma of the right breast and a mucinous cystadenocarcinoma of the left breast. Macroscopically the neoplasm appeared multilocular filled with mucoid material. Under light microscopy the cystic areas were lined by columnar cells with abundant intracellular and extracellular mucin. Solid areas were composed of tall columnar cells with intracellular mucin. Moderate to marked atypia was noticed and tumor cells stained positive for cytokeratin 7 and negative for cytokeratin 20. Moreover tumor cells displayed a basal like immunophenotype expressed as followed: ER negative, PR negative, HER-2 negative, cytokeratin (CK5/6) positive and EGFR positive. PMID:29081926

Eosinophilic Mucin Otomastoiditis and Otopolyposis: A Progressive Form of Eosinophilic Otitis Media.

PubMed

Azadarmaki, Roya; Westra, William; Prasad, Sanjay

2015-09-01

The purpose of this study is to introduce and define a disease entity on a continuum of eosinophilic otitis media: eosinophilic mucin otomastoiditis and otopolyposis. A case of a 66-year-old woman with complicated chronic otitis media is reported. A literature review of the National Library of Medicine's online database, with a focus on eosinophilic otitis media and eosinophilic mucin rhinosinusitis, was performed. The authors report the case of a 66-year-old woman with a history of asthma, chronic rhinosinusitis, nasal polyposis, and chronic otitis media who presented with allergic middle ear mucin and otic polyps. Treatment involved a tympanomastoidectomy with removal of otic polyps and steroid therapy. Eosinophilic mucin otomastoiditis with otopolyposis is a disease entity on a continuum of eosinophilic otitis media. This disease process shares similarities with eosinophilic mucin rhinosinusitis. Otic polypectomy and steroids are suggested therapeutic measures. © The Author(s) 2015.

Mucinous metaplasia of breast carcinoma with macrocystic transformation resembling ovarian mucinous cystadenocarcinoma in a case of synchronous bilateral infiltrating ductal carcinoma.

PubMed

Lee, Sheng-Huang; Chaung, Chen-Rong

2008-09-01

Mammary mucinous cystadenocarcinoma (MCA) is a rare, invasive ductal carcinoma (IDC) of the breast that is virtually identical morphologically to MCA of the ovary, pancreas or appendix. Synchronous bilateral breast tumors, not uncommonly encountered in fibroadenoma and lobular carcinoma, are unusual in IDC. Reported herein is a primary MCA of the right breast coexisting with a bilateral ordinary IDC in a 55-year-old Taiwanese woman who underwent modified radical mastectomy of both breasts with bilateral axillary level I and II lymph node dissection. In the right breast a 2.5 cm unilocular mucus-filled cyst was found. It had complex papillae, some of which were supported by delicate fibrovascular stroma, lined by simple to slightly stratified columnar neoplastic epithelial cells with intracellular mucin and an abundance of intracystic extracellular mucin, coexisting with a low-grade ordinary IDC. In the left breast a high-grade ordinary IDC was discovered. The patient had undergone simple abdominal total hysterectomy for myoma uteri along with bilateral salpingo-oophorectomy 10 years previously. Based on pathological studies and a literature review, it is suggested that mammary MCA arises from mucinous metaplasia and macrocystic transformation of ordinary breast carcinoma. A brief discussion of bilateral breast cancers is also given.

Primary pulmonary mucinous cystadenocarcinoma presenting as a complex bronchocele: a case report

PubMed Central

2009-01-01

Introduction Primary pulmonary mucinous cystadenocarcinoma is a rare variety of lung cancer. It is characterized pathologically by copious mucin production predominantly in the extracellular space. This tumour has a remarkably favorable prognosis. Case presentation We present imaging and histopathological findings of primary pulmonary mucinous cystadenocarcinoma presenting as a complex bronchocele in a 67-year-old Caucasian woman. Conclusion Diagnosis of pulmonary mucinous cystadenocarcinoma should be considered in patients presenting with bronchocele that has suspicious imaging features, because the results of fine needle aspiration cytology and bronchoscopy are frequently inconclusive in these tumours. Positive emission tomography has an important role in helping to identify these tumours. PMID:19830231

Mucinous metaplasia of the vulva in a case of lichen sclerosus. A case report

PubMed Central

Rakha, E; Mayne, C; Brown, L

2005-01-01

Mucinous metaplasia of the genital area is a rare condition characterised by the emergence of mucin containing cells in stratified squamous epithelium. This report describes a unique case of benign mucinous metaplasia of the vulva associated with lichen sclerosus in a 60 year old woman. Histopathology revealed cervical type metaplasia with otherwise typical lichen sclerosus. This report discusses the pathogenesis and differential diagnosis of mucinous epithelium. PMID:16254116

Molecular Structure and Equilibrium Forces of Bovine Submaxillary Mucin Adsorbed at a Solid-Liquid Interface.

PubMed

Zappone, Bruno; Patil, Navinkumar J; Madsen, Jan B; Pakkanen, Kirsi I; Lee, Seunghwan

2015-04-21

By combining dynamic light scattering, circular dichroism spectroscopy, atomic force microscopy, and surface force apparatus, the conformation of bovine submaxillary mucin in dilute solution and nanomechanical properties of mucin layers adsorbed on mica have been investigated. The samples were prepared by additional chromatographic purification of commercially available products. The mucin molecule was found to have a z-average hydrodynamic diameter of ca. 35 nm in phosphate buffered solution, without any particular secondary or tertiary structure. The contour length of the mucin is larger than, yet of the same order of magnitude as the diameter, indicating that the molecule can be modeled as a relatively rigid polymeric chain due to the large persistence length of the central glycosylated domain. Mucin molecules adsorbed abundantly onto mica from saline buffer, generating polymer-like, long-ranged, repulsive, and nonhysteretic forces upon compression of the adsorbed layers. Detailed analysis of such forces suggests that adsorbed mucins had an elongated conformation favored by the stiffness of the central domain. Acidification of aqueous media was chosen as means to reduce mucin-mucin and mucin-substrate electrostatic interactions. The hydrodynamic diameter in solution did not significantly change when the pH was lowered, showing that the large persistence length of the mucin molecule is due to steric hindrance between sugar chains, rather than electrostatic interactions. Remarkably, the force generated by an adsorbed layer with a fixed surface coverage also remained unaltered upon acidification. This observation can be linked to the surface-protective, pH-resistant role of bovine submaxillary mucin in the variable environmental conditions of the oral cavity.

Office-based treatment of glottal dysplasia and papillomatosis with the 585-nm pulsed dye laser and local anesthesia.

PubMed

Zeitels, Steven M; Franco, Ramon A; Dailey, Seth H; Burns, James A; Hillman, Robert E; Anderson, R Rox

2004-04-01

Treatment of glottal papillomatosis and dysplasia was mirror-guided and performed in surgeons' offices in the 19th century. It migrated to the operating room in the 20th century to accommodate direct laryngoscopic surgery, which required assistants to administer anesthesia and procedural support. Presently, the primary treatment goals, which are disease regression and voice restoration or maintenance, are tempered by the morbidity of general anesthesia and potential treatment-induced vocal deterioration. In fact, general anesthesia has been appropriately considered to be an acceptable source of morbidity for the promise of a precise procedure, which usually ensures airway safety and an optimal vocal outcome. However, patients with recurrent glottal papillomatosis and keratosis with dysplasia are typically monitored with various degrees of watchful waiting until there is a subjective judgment (on the part of the patient and surgeon) that the disease is more of a liability than is the procedure to treat it. Innovations in the 585-nm pulsed dye laser delivery system have allowed for its use in the clinic with local anesthesia through the working channel of a flexible fiberoptic laryngoscope. A prospective assessment was done on 51 patients in 82 cases of recurrent glottal papillomatosis (30) and dysplasia (52). All individuals had previously undergone microlaryngoscopic management with histopathologic evaluation. Five procedures could not be completed because of impaired exposure (2) or discomfort (3). Of those patients who could be treated, there was at least a 50% disease involution in 68 of 77 cases (88%) and 25% to 50% disease regression in the remaining 9 (12%). Patient self-assessment of the voice revealed that 34 of 77 were improved, 39 were unchanged, 4 were slightly worse, and none were substantially worse. These data confirm that diseased mucosa can be normalized without resection or substantial loss of vocal function. The putative mechanisms, which vary

Rectal Cancer: Mucinous Carcinoma on Magnetic Resonance Imaging Indicates Poor Response to Neoadjuvant Chemoradiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Oberholzer, Katja, E-mail: oberholz@radiologie.klinik.uni-mainz.de; Menig, Matthias; Kreft, Andreas

2012-02-01

Purpose: To assess response of locally advanced rectal carcinoma to chemoradiation with regard to mucinous status and local tumor invasion found at pretherapeutic magnetic resonance imaging (MRI). Methods and Materials: A total of 88 patients were included in this prospective study of patients with advanced mrT3 and mrT4 carcinomas. Carcinomas were categorized by MRI as mucinous (mucin proportion >50% within the tumor volume), and as nonmucinous. Patients received neoadjuvant chemoradiation consisting of 50.4 Gy (1.8 Gy/fraction) and 5-fluorouracil on Days 1 to 5 and Days 29 to 33. Therapy response was assessed by comparing pretherapeutic MRI with histopathology of surgicalmore » specimens (minimum distance between outer tumor edge and circumferential resection margin = CRM, T, and N category). Results: A mucinous carcinoma was found in 21 of 88 patients. Pretherapeutic mrCRM was 0 mm (median) in the mucinous and nonmucinous group. Of the 88 patients, 83 underwent surgery with tumor resection. The ypCRM (mm) at histopathology was significantly lower in mucinous carcinomas than in nonmucinous carcinomas (p {<=} 0.001). Positive resection margins (ypCRM {<=} 1 mm) were found more frequently in mucinous carcinomas than in nonmucinous ones (p {<=} 0.001). Treatment had less effect on local tumor stage in mucinous carcinomas than in nonmucinous carcinomas (for T downsizing, p = 0.012; for N downstaging, p = 0.007). Disease progression was observed only in patients with mucinous carcinomas (n = 5). Conclusion: Mucinous status at pretherapeutic MRI was associated with a noticeably worse response to chemoradiation and should be assessed by MRI in addition to local tumor staging to estimate response to treatment before it is initiated.« less

[BILIARY HYPERTENSION IN CHRONIC PANCREATITIS AND PECULIARITIES OF ITS DIAGNOSIS].

PubMed

Kopchak, V M; Pylypchuk, V I; Khomyak, I V; Pererva, L O; Shevkolenko, G G; Davydenko, N G

2016-02-01

Possibilities of various diagnostic methods for biliary hypertension detection in chronic pancreatitis were analyzed. Biliary hypertension was revealed in 163 (31%) patients, suffering chronic pancreatitis. The laboratory investigations data, ultrasonographic investigation, computer tomography, endoscopic retrograde cholangiopancreatography, magnet-resonance cholangiopancreatography, intraoperative measurement of the biliary ducts width, intraoperative measurement of biliary pressure were applied for diagnosis. Endoscopic retrograde cholangiopancreatography, magnet-resonance cholangiopancreatography and intraoperative measurement of biliary pressure are considered the most sensitive methods for chronic pancreatitis diagnosis.

Indocyanine-green-loaded microballoons for biliary imaging in cholecystectomy

NASA Astrophysics Data System (ADS)

Mitra, Kinshuk; Melvin, James; Chang, Shufang; Park, Kyoungjin; Yilmaz, Alper; Melvin, Scott; Xu, Ronald X.

2012-11-01

We encapsulate indocyanine green (ICG) in poly[(D,L-lactide-co-glycolide)-co-PEG] diblock (PLGA-PEG) microballoons for real-time fluorescence and hyperspectral imaging of biliary anatomy. ICG-loaded microballoons show superior fluorescence characteristics and slower degradation in comparison with pure ICG. The use of ICG-loaded microballoons in biliary imaging is demonstrated in both biliary-simulating phantoms and an ex vivo tissue model. The biliary-simulating phantoms are prepared by embedding ICG-loaded microballoons in agar gel and imaged by a fluorescence imaging module in a Da Vinci surgical robot. The ex vivo model consists of liver, gallbladder, common bile duct, and part of the duodenum freshly dissected from a domestic swine. After ICG-loaded microballoons are injected into the gallbladder, the biliary structure is imaged by both hyperspectral and fluorescence imaging modalities. Advanced spectral analysis and image processing algorithms are developed to classify the tissue types and identify the biliary anatomy. While fluorescence imaging provides dynamic information of movement and flow in the surgical region of interest, data from hyperspectral imaging allow for rapid identification of the bile duct and safe exclusion of any contaminant fluorescence from tissue not part of the biliary anatomy. Our experiments demonstrate the technical feasibility of using ICG-loaded microballoons for biliary imaging in cholecystectomy.

[Biliary dysfunction in obese children].

PubMed

Aleshina, E I; Gubonina, I V; Novikova, V P; Vigurskaia, M Iu

2014-01-01

To examine the state of the biliary system, a study of properties of bile "case-control") 100 children and adolescents aged 8 to 18 years, held checkup in consultative and diagnostic center for chronic gastroduodenitis. BMI children were divided into 2 groups: group 1-60 children with obesity (BMI of 30 to 40) and group 2-40 children with normal anthropometric indices. Survey methods included clinical examination pediatrician, endocrinologist, biochemical parameters (ALT, AST, alkaline phosphatase level, total protein, bilirubin, lipidogram, glucose, insulin, HOMA-index), ultrasound of the abdomen and retroperitoneum, EGD with aspiration of gallbladder bile. Crystallography bile produced by crystallization of biological substrates micromethods modification Prima AV, 1992. Obese children with chronic gastroduodenita more likely than children of normal weight, had complaints and objective laboratory and instrumental evidence of insulin resistance and motor disorders of the upper gastrointestinal and biliary tract, liver enlargement and biliary "sludge". Biochemical parameters of obese children indicate initial metabolic changes in carbohydrate and fat metabolism and cholestasis, as compared to control children. Colloidal properties of bile in obese children with chronic gastroduodenita reduced, as indicated by the nature of the crystallographic pattern. Conclusions: Obese children with chronic gastroduodenitis often identified enlarged liver, cholestasis and biliary dysfunction, including with the presence of sludge in the gallbladder; most often--hypertonic bile dysfunction. Biochemical features of carbohydrate and fat metabolism reflect the features of the metabolic profile of obese children. Crystallography bile in obese children reveals the instability of the colloidal structure of bile, predisposing children to biliary sludge, which is a risk factor for gallstones.

Expression of membrane-associated mucins MUC1 and MUC4 in major human salivary glands.

PubMed

Liu, Bing; Lague, Jessica R; Nunes, David P; Toselli, Paul; Oppenheim, Frank G; Soares, Rodrigo V; Troxler, Robert F; Offner, Gwynneth D

2002-06-01

Mucins are high molecular weight glycoproteins secreted by salivary glands and epithelial cells lining the digestive, respiratory, and reproductive tracts. These glycoproteins, encoded in at least 13 distinct human genes, can be subdivided into gel-forming and membrane-associated forms. The gel-forming mucin MUC5B is secreted by mucous acinar cells in major and minor salivary glands, but little is known about the expression pattern of membrane-associated mucins. In this study, RT-PCR and Northern blotting demonstrated the presence of transcripts for MUC1 and MUC4 in both parotid and submandibular glands, and in situ hybridization localized these transcripts to epithelial cells lining striated and excretory ducts and in some serous acinar cells. The same cellular distribution was observed by immunohistochemistry. Soluble forms of both mucins were detected in parotid secretion after immunoprecipitation with mucin-specific antibodies. These studies have shown that membrane-associated mucins are produced in both parotid and submandibular glands and that they are expressed in different cell types than gel-forming mucins. Although the function of these mucins in the oral cavity remains to be elucidated, it is possible that they both contribute to the epithelial protective mucin layer and act as receptors initiating one or more intracellular signal transduction pathways.

T-drain reduces the incidence of biliary leakage after liver resection.

PubMed

Eurich, Dennis; Henze, S; Boas-Knoop, S; Pratschke, J; Seehofer, D

2016-12-01

Biliary leakage is a serious complication after liver resection and represents the major cause of post-operative morbidity. In spite of already identified risk factors, little is known about the role of intra-biliary pressure following liver surgery in the development of biliary leakage. Biliary decompression may have a positive impact and reduce the incidence of biliary leakage at the parenchymal resection site. 397 patients undergoing liver resection without bilioenteric anastomosis were included in the retrospective analysis of the risk factors for the development of biliary leakage focusing on the intra-operative reduction of the biliary pressure by T-tube and liver histology. Among 397 analyzed patients after parenchymal resection, biliary leakage occurred in 39 cases (9.8 %). The extent of parenchymal resection was not associated with the total occurrence of biliary leak (p = 0.626). Lower incidence of biliary leakage from the resection surface was significantly associated with the use of T-tube (4.9 vs. 13.2 %; p = 0.006). In the subgroup analysis, insertion of a T-tube was not associated with a reduction of biliary leakage after anatomical hemihepatectomies (p = 0.103) and extraanatomical liver resection (p = 0.676). However, a high statistical significance could be detected in patients with extended hemihepatectomies (58.3 vs. 3.8 %; p < 0.001). Once biliary leak occurred without T-tube, median hospitalization duration significantly increased compared to patients with biliary decompression and without biliary leak (p < 0.001). The results of our retrospective data analysis suggest a significant beneficial impact of the T-tube on the development of biliary leakage in patients undergoing extended liver surgery.

Post-cholecystectomy biliary strictures: not always benign.

PubMed

Sharma, Ajay; Behari, Anu; Sikora, Sadiq S; Kumar, Ashok; Saxena, Rajan; Kapoor, Vinay K

2008-07-01

Post-cholecystectomy malignant biliary obstruction masquerading as benign biliary stricture (BBS) has not been reported in the literature; it presents a diagnostic and management challenge. Of the 349 post-cholecystectomy BBS managed at a tertiary care hospital in northern India between 1989 and 2004, 11 patients were found to have biliary malignancy. Records of these 11 patients were analyzed retrospectively for the purpose of this study. Mean age of patients with malignant biliary strictures was significantly higher (52 vs 38 years, P = 0.000); they were more likely to have jaundice (100% vs 78%, P = 0.008) and pruritus (82% vs 48%, P = 0.03). Unlike most patients with BBS referred from elsewhere to us, they had had a smooth postoperative course uncomplicated by bile leak, had a longer cholecystectomy-presentation interval, and were more likely to have high strictures ((Bismuth type III/IV) 91% vs 49%, P = 0.008). Post-cholecystectomy biliary obstruction is not always benign. High bilirubin levels and hilar strictures, especially after an uneventful cholecystectomy, in a middle-aged patient should raise a suspicion of underlying missed malignancy.

Guanylyl Cyclase C Is a Specific Marker for Differentiating Primary and Metastatic Ovarian Mucinous Neoplasms

PubMed Central

Ciocca, Vincenzo; Bombonati, Alessandro; Palazzo, Juan P.; Schulz, Stephanie; Waldman, Scott A.

2011-01-01

Distinguishing primary ovarian mucinous neoplasms from metastatic mucinous adenocarcinomas with ovarian involvement can be difficult, especially when characteristic gross and microscopic features are not present. CK7/CK20 expression appears to be more useful for distinguishing metastatic gastrointestinal adenocarcinomas from the lower tract. The addition of CDX2 for distinguishing metastatic upper gastrointestinal tract adenocarcinomas from primary ovarian mucinous neoplasms offers little advantage over CK7/CK20 coordinate expression. Guanylyl cyclase C (GCC) is a brush border membrane receptor for the endogenous peptides guanylin and uroguanylin, and the homologous diarrheagenic bacterial heat-stable enterotoxins that is selectively expressed by epithelial cells from the duodenum to the rectum, but not by normal epithelia of the stomach or esophagus, or normal extramucosal cells in humans. We studied 50 ovarian tumors: 27 primary ovarian mucinous neoplasms (7 cystadenomas, 10 borderline tumors, and 10 cystadenocarcinomas) and 23 metastatic mucinous adenocarcinomas with ovarian involvement (13 colorectal adenocarcinomas, 4 gastric adenocarcinomas, 6 appendiceal mucinous tumors (4 adenocarcinomas, 1 with neuroendocrine features, and 2 appendiceal mucinous cystadenomas). For primary ovarian mucinous neoplasms, 25 of 27 were negative for GCC. Twelve of thirteen cases of colorectal adenocarcinoma (except for 1 neuroendocrine adenocarcinoma) were positive for GCC. Three of four appendiceal mucinous adenocarcinomas were positive for GCC in both the primary and metastatic tumors (except for 1 neuroendocrine adenocarcinoma). Two of two appendiceal mucinous cystadenomas were positive for GCC. Of four cases of gastric adenocarcinoma with ovarian involvement, only one (primary tumor) exhibited focal GCC staining. These findings suggest GCC may be a useful marker for differentiating primary and secondary ovarian mucinous neoplasms. PMID:19694825

Mucinous cystadenoma of the appendix presenting as an umbilical hernia: A case report.

PubMed

Ren, Bingbing; Meng, Xiangchao; Cao, Z I; Guo, Chunli; Zhang, Zili

2016-06-01

Mucinous cystadenoma of the appendix is a rare condition that develops as a result of proliferation of mucin-secreting cells in an occluded appendix. Mucinous cystadenoma of the appendix presenting as an umbilical hernia is a rare clinical entity. The most common causes of this condition are known to be ascites, hepatitis and cirrhosis; however, the patient in the present study, was diagnosed as hepatitis- and cirrhosis-negative, with no history of chronic coughing or constipation. The aim of the present study was to report a rare case of mucinous cystadenoma of the appendix presenting as an umbilical hernia in a 66-year-old female patient. The patient had a 6-month history of a reducible mass in the umbilical region and was diagnosed with umbilical hernia. Computed tomography and ultrasonography were performed and revealed massive ascites. Ultimately, a laparoscopic appendectomy was performed and borderline mucinous appendiceal cystadenoma of low malignant potential was confirmed. In addition, the present study discussed the association between mucinous cystadenoma of the appendix and umbilical hernia, as well as the diagnostic process and treatment strategies.

Mucinous cystadenoma of the appendix presenting as an umbilical hernia: A case report

PubMed Central

REN, BINGBING; MENG, XIANGCHAO; CAO, ZI; GUO, CHUNLI; ZHANG, ZILI

2016-01-01

Mucinous cystadenoma of the appendix is a rare condition that develops as a result of proliferation of mucin-secreting cells in an occluded appendix. Mucinous cystadenoma of the appendix presenting as an umbilical hernia is a rare clinical entity. The most common causes of this condition are known to be ascites, hepatitis and cirrhosis; however, the patient in the present study, was diagnosed as hepatitis- and cirrhosis-negative, with no history of chronic coughing or constipation. The aim of the present study was to report a rare case of mucinous cystadenoma of the appendix presenting as an umbilical hernia in a 66-year-old female patient. The patient had a 6-month history of a reducible mass in the umbilical region and was diagnosed with umbilical hernia. Computed tomography and ultrasonography were performed and revealed massive ascites. Ultimately, a laparoscopic appendectomy was performed and borderline mucinous appendiceal cystadenoma of low malignant potential was confirmed. In addition, the present study discussed the association between mucinous cystadenoma of the appendix and umbilical hernia, as well as the diagnostic process and treatment strategies. PMID:27313766

Biliary bypass surgery – Analysis of indications & outcome of different procedures

PubMed Central

Hussain Talpur, K.Altaf; Mahmood Malik, Arshad; Iqbal Memon, Amir; Naeem Qureshi, Jawed; Khan Sangrasi, Ahmed; Laghari, Abdul Aziz

2013-01-01

Objectives: This study reports the indications and outcome of various biliary bypass surgical procedures from a single centre over a period of 10 years. Methods: This is a prospective observational study conducted over a period of 10 years (January 2001-december 2010). A total of 1500 patients were included, who underwent pancreatico-biliary surgery due to common bile duct (CBD) stones, congenital anomalies of biliary tree, unoperable pancreatico-biliary malignancies, CBD strictures and cases who developed iatrogenic biliary injuries during cholecystectomy (both open & laproscopic) during this period of time. The patients who required biliary bypass surgery were further analysed for indications and outcome. Results: Out of 1500 patients 83(5.53%) required biliary bypass surgical procedures. The CBD stones were observed as the most common indication (25.3%), followed by CBD injuries after open(10.84%) or laproscopic-cholecystectomy (14.46%), carcinoma head of pancreas (12.05%) and CBD obstruction(14.46%) either due to CBD strictures or unknown distal obstruction. Roux-en-Y-hepatico-jejunostomy (26.51%) was the most frequently performed procedure, followed by choledochoduodenostomy and Roux-en-Y choledocho-jejunostomy (i.e. 25.3% and 12.05% respectively). Roux-en-Y biliary bypass procedure was observed to be associated with better outcome in terms of rate of complications as well duration of hospital stay. Conclusion: Biliary bypass surgical procedures are the better options to restore the continuity of biliary system in patients with iatrogenic biliary tree injuries and un-operable pancreatico-biliary malignancy. Roux-en-Y biliary bypass procedure is safe and problem solving method in these cases. PMID:24353631

Expanding the histologic spectrum of mucinous tubular and spindle cell carcinoma of the kidney.

PubMed

Fine, Samson W; Argani, Pedram; DeMarzo, Angelo M; Delahunt, Brett; Sebo, Thomas J; Reuter, Victor E; Epstein, Jonathan I

2006-12-01

Mucinous tubular and spindle cell carcinomas (MTSCs) are polymorphic neoplasms characterized by small, elongated tubules lined by cuboidal cells and/or cords of spindled cells separated by pale mucinous stroma. Nonclassic morphologic variants and features of MTSC have not been well studied. We identified 17 previously unreported MTSCs from Surgical Pathology and consultative files of the authors and their respective institutions and studied their morphologic features. A total of 10/17 cases were considered "classic," as described above, with 5/10 showing at least focal (20% to 50%) tubular predominance without apparent mucinous matrix. Alcian blue staining revealed abundant (>50%) mucin in all classic cases. Seven of 17 MTSCs were classified as "mucin-poor," with little to no extracellular mucin appreciable by hematoxylin and eosin. Four of these cases showed equal tubular and spindled morphology, 2 cases showed spindle cell predominance (70%; 95%), and 1 case showed tubular predominance (90%). In 5/7 mucin-poor cases, staining for Alcian blue revealed scant (<10%) mucin in cellular areas with the other 2 cases having 30% mucin. Unusual histologic features identified in the 17 cases were: foamy macrophages (n=8), papillations/well formed papillae (n=6/n=1), focal clear cells in tubules (n=3), necrosis (n=3), oncocytic tubules (n=2; 40%, 5%), numerous small vacuoles (n=2), heterotopic bone (n=1), psammomatous calcification (n=1), and nodular growth with lymphocytic cuffing (n=1). An exceptional case contained a well-circumscribed, HMB45-positive angiomyolipoma within the MTSC. MTSCs may be "mucin-poor" and show a marked predominance of either of its principal morphologic components, which coupled with the presence of other unusual features such as clear cells, papillations, foamy macrophages, and necrosis, may mimic other forms of renal cell carcinoma. Pathologists must be aware of the spectrum of histologic findings within MTSCs to ensure their accurate diagnosis.

Targeting Src and tubulin in mucinous ovarian carcinoma

PubMed Central

Liu, Tao; Hu, Wei; Dalton, Heather J.; Choi, Hyun Jin; Huang, Jie; Kang, Yu; Pradeep, Sunila; Miyake, Takahito; Song, Jian H.; Wen, Yunfei; Lu, Chunhua; Pecot, Chad V.; Bottsford-Miller, Justin; Zand, Behrouz; Jennings, Nicholas B; Ivan, Cristina; Gallick, Gary E.; Baggerly, Keith A; Hangauer, David G.; Coleman, Robert L.; Frumovitz, Michael; Sood, Anil K.

2013-01-01

Purpose To investigate the antitumor effects of targeting Src and tubulin in mucinous ovarian carcinoma. Experimental design The in vitro and in vivo effects and molecular mechanisms of KX-01, which inhibits Src pathway and tubulin polymerization, were examined in mucinous ovarian cancer models. Results In vitro studies using RMUG-S and RMUG-L cell lines showed that KX-01 inhibited cell proliferation, induced apoptosis, arrested the cell cycle at the G2/M phase, and enhanced the cytotoxicity of oxaliplatin in the KX-01-sensitive cell line, RMUG-S. In vivo studies showed that KX-01 significantly decreased tumor burden in RMUG-S and RMUG-L mouse models relative to untreated controls, and the effects were greater when KX-01 was combined with oxaliplatin. KX-01 alone and in combination with oxaliplatin significantly inhibited tumor growth by reducing cell proliferation and inducing apoptosis in vivo. PTEN knock-in experiments in RMUG-L cells showed improved response to KX-01. Reverse phase protein array analysis showed that in addition to blocking downstream molecules of Src family kinases, KX-01 also activated acute stress-inducing molecules. Conclusion Our results showed that targeting both the Src pathway and tubulin with KX-01 significantly inhibited tumor growth in preclinical mucinous ovarian cancer models, suggesting that this may be a promising therapeutic approach for patients with mucinous ovarian carcinoma. PMID:24100628

Primary mucinous carcinoma with rhabdoid cells of the thyroid gland: a case report.

PubMed

Matsuo, Mioko; Tuneyoshi, Masazumi; Mine, Mari

2016-06-10

Primary mucinous carcinoma of the thyroid gland is a rare disease; only 6 cases of primary mucinous carcinoma of the thyroid have been previously reported. Primary mucinous carcinoma of the thyroid gland with incomplete tumor resection tends to be associated with a poor prognosis, resulting in death within a few months. An early and appropriate diagnosis may contribute to improvement in patient prognosis; however, it is extremely difficult to diagnose primary mucinous carcinoma of the thyroid. We present the seventh reported case of primary mucinous carcinoma in the thyroid gland; moreover, rhabdoid cells were detected, which, to our knowledge, is a novel finding. An 81-year-old Japanese woman was initially diagnosed with a poorly differentiated thyroid carcinoma, and she underwent a hemithyroidectomy. Pathological examination revealed the presence of abundant mucus and agglomeration of large atypical cells. Rhabdoid cells were also seen scattered among the tumor cells. Immunostaining was performed for various markers, and on the basis of these results, we diagnosed the lesion as primary mucinous carcinoma with rhabdoid cells in the thyroid gland. Ten months after surgery, recurrence was noted in the paratracheal lymph nodes; therefore, total resection of the residual thyroid gland and paratracheal lymphadenectomy with thyroid-stimulating hormone suppression were performed. The patient is currently alive and disease-free. The current case is of interest not only because of the rare histological findings, but also because the patient achieved long-term survival following diagnosis of a mucinous carcinoma. We believe this report will be helpful for diagnosing future cases of mucinous carcinoma of the thyroid.

The mucin expression profile of endometrial carcinoma and correlation with clinical-pathologic parameters.

PubMed

Morrison, Carl; Merati, Kambiz; Marsh, William L; De Lott, Lindsey; Cohn, David E; Young, Gregory; Frankel, Wendy L

2007-12-01

Mucin expression patterns have been studied in tumors from various sites. Previous studies have shown an association of MUC1 with poor prognosis and MUC2 and MUC5AC with a mucinous phenotype. The pattern of mucin expression in endometrial carcinomas has not been documented in a large series. We determined the mucin expression profile in endometrial carcinomas and evaluated the relationship between mucin expression and clinical-pathologic parameters. A tissue microarray of 310 cases of endometrial carcinoma with known clinical outcome was constructed from formalin-fixed, paraffin-embedded donor blocks using two 0.6 mm cores from each tumor. Sections were stained with monoclonal antibodies against MUC1, MUC2, MUC4, MUC5AC, and MUC6. Staining was considered positive if greater than or equal to 5% of cells stained positively in either core. Mucin expression was correlated with tumor type, histologic grade, International Federation Gynecology and Obstetrics stage, lymph node involvement, depth of myometrial invasion, patient age, ethnicity, and clinical outcome. MUC1 was expressed in 267/310 (86.1%) of endometrial carcinomas, MUC2 in 2/310 (0.6%), MUC4 in 73/310 (23.5%), MUC5AC in 1/310 (0.3%), and MUC6 in 4/310 (1.2%). Endometrioid endometrial carcinoma showed a higher rate of MUC1 expression than nonendometrioid endometrial carcinoma (227/258, 88.0% vs. 39/52, 75.0%, P=0.01). No significant differences in any of the mucins were noted among the other end points evaluated. Mucin expression did not correlate with tumor grade, stage, or patient outcome.

Excess Secretion of Gel-Forming Mucins and Associated Innate Defense Proteins with Defective Mucin Un-Packaging Underpin Gallbladder Mucocele Formation in Dogs

PubMed Central

Kesimer, Mehmet; Cullen, John; Cao, Rui; Radicioni, Giorgia; Mathews, Kyle G.; Seiler, Gabriela; Gookin, Jody L.

2015-01-01

Mucosal protection of the gallbladder is vital yet we know very little about the mechanisms involved. In domestic dogs, an emergent syndrome referred to as gallbladder mucocele formation is characterized by excessive secretion of abnormal mucus that results in obstruction and rupture of the gallbladder. The cause of gallbladder mucocele formation is unknown. In these first mechanistic studies of this disease, we investigated normal and mucocele-forming dog gallbladders to determine the source, identity, biophysical properties, and protein associates of the culprit mucins with aim to identify causes for abnormal mucus behavior. We established that mucocele formation involves an adoptive excess secretion of gel forming mucins with abnormal properties by the gallbladder epithelium. The mucus is characterized by a disproportionally significant increase in Muc5ac relative to Muc5b, defective mucin un-packaging, and mucin-interacting innate defense proteins that are capable of dramatically altering the physical and functional properties of mucus. These findings provide an explanation for abnormal mucus behavior and based on similarity to mucus observed in the airways of people with cystic fibrosis, suggest that abnormal mechanisms for maintenance of gallbladder epithelial hydration may be an instigating factor for mucocele formation in dogs. PMID:26414376

Proposed standards for reporting outcomes of treating biliary injuries.

PubMed

Cho, Jai Young; Baron, Todd H; Carr-Locke, David L; Chapman, William C; Costamagna, Guido; de Santibanes, Eduardo; Dominguez Rosado, Ismael; Garden, O James; Gouma, Dirk; Lillemoe, Keith D; Angel Mercado, Miguel; Mullady, Daniel K; Padbury, Robert; Picus, Daniel; Pitt, Henry A; Sherman, Stuart; Shlansky-Goldberg, Richard; Tornqvist, Bjorn; Strasberg, Steven M

2018-04-01

There is no standard nor widely accepted way of reporting outcomes of treatment of biliary injuries. This hinders comparison of results among approaches and among centers. This paper presents a proposal to standardize terminology and reporting of results of treating biliary injuries. The proposal was developed by an international group of surgeons, biliary endoscopists and interventional radiologists. The method is based on the concept of "patency" and is similar to the approach used to create reporting standards for arteriovenous hemodialysis access. The group considered definitions and gradings under the following headings: Definition of Patency, Definition of Index Treatment Periods, Grading of Severity of Biliary Injury, Grading of Patency, Metrics, Comparison of Surgical to Non Surgical Treatments and Presentation of Case Series. A standard procedure for reporting outcomes of treating biliary injuries has been produced. It is applicable to presenting results of treatment by surgery, endoscopy, and interventional radiology. Copyright © 2017 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.

Biliary complications of cholecystectomy.

PubMed

Joshi, Rajeev M; Shetty, Tilakdas S; Singh, Rajinder; Adhikari, Devbrata R; Patil, Bhushan P; Bhange, Snehal A

2008-01-01

Biliary complications occur because of causes such as obscure or variant anatomy, predisposing conditions such as fibrosis or severe inflammation, equipment failure, and surgeon factors. The aim of this study was to review the optimal surgical treatment. Analysis of 81 patients with bile duct injuries treated in a single referral unit over an 8.5-year period was done. Time of detection of biliary injury and its presentation were ascertained as well as the level of injury (Strasburg's). In 8 patients, injury was detected intraoperatively, and 41 were detected in the early postoperative period with bile leak (n = 25) or obstructive jaundice (n = 10). Those diagnosed in the delayed postoperative period (n = 32) presented with recurrent cholangitis (n = 9), obstructive jaundice (n = 16), and a cholestatic enzymatic profile (n = 1). Roux-en-Y hepatico-jejunostomy was the preferred option (n = 64). One patient died because of biliary peritonitis. Improper treatment is associated with disastrous results, but early recognition and correct management can lead to a successful outcome and good prognosis.

Mucinous Histology Signifies Poor Oncologic Outcome in Young Patients With Colorectal Cancer.

PubMed

Soliman, Basem G; Karagkounis, Georgios; Church, James M; Plesec, Thomas; Kalady, Matthew F

2018-05-01

The incidence of colorectal cancer in the young (under age 40) is increasing, and this population has worse oncologic outcomes. Mucinous histology is a potential prognostic factor in colorectal cancer, but has not been evaluated specifically in young patients. The objective of the study was to determine factors associated with poor outcome in young patients with colorectal cancer (≤40 years) and to determine relationships between mucinous histology and oncologic outcomes in this population. This is a retrospective study. Patients from a single-institution tertiary care center were studied. A total of 224 patients with colorectal cancer under 40 years of age diagnosed between 1990 and 2010 were included (mean age, 34.7 years; 51.3% female). 34 patients (15.2%) had mucinous histology. There were no interventions. Oncologic outcomes were analyzed according to the presence of mucinous histology. The mucinous and nonmucin colorectal cancer study populations were statistically similar in age, sex, tumor location, pathological stage, differentiation, and adjuvant chemotherapy use. Five-year disease-free survival was 29.1% versus 71.3% (p < 0.0001) and 5-year overall survival was 54.7% versus 80.3% (p < 0.0001) for mucinous and nonmucinous patients, respectively. Mucinous colorectal cancers recurred earlier at a median time of 36.4 months versus 94.2 months for nonmucin colorectal cancers (p < 0.001). On multivariate analysis, pathological stage (stage II HR, 3.61; 95% CI, 1.37-9.50; stage III HR, 5.27; 95% CI, 2.12-12.33), positive margins (HR, 1.95; 95% CI, 1.12-3.23), angiolymphatic invasion (HR, 2.15; 95% CI, 1.26-3.97), and mucinous histology (HR, 2.36; 95% CI, 1.44-3.96) were independently associated with worse disease-free and overall survival. This is a retrospective study without genetic information. Mucinous histology is a negative prognostic factor in young patients with colorectal cancer. This is associated with early and high recurrence rates, despite use of

Endoscopic Stent Placement in the Palliation of Malignant Biliary Obstruction

PubMed Central

2011-01-01

Biliary drainage with biliary stent placement is the treatment of choice for palliation in patients with malignant biliary obstruction caused by unresectable neoplasms. In such patients, the endoscopic approach can be initially used with percutaneous radiological intervention. In patients with unresectable malignant distal bile duct obstructions, endoscopic biliary drainage with biliary stent placement has now become the main and least invasive palliative modality, which has been proven to be more effective in >80% of cases with lower morbidity than surgery, and perhaps may provide a survival benefit. In patients with unresectable malignant hilar obstruction, the endoscopic approach for biliary drainage with biliary stent placement has also been considered as the treatment of choice. There is still a lack of clear consensus on the use of covered versus uncovered metal stents in malignant distal bile duct obstructions and plastic versus metal stents and unilateral versus bilateral drainage in malignant hilar obstructions. PMID:22741117

[Association of biliary calculosis and portal cavernomatosis].

PubMed

Crespi, C; De Giorgio, A M

1992-08-01

This paper reports the case of a woman, who underwent surgery because of cholelithiasis, with intraoperative finding of prehepatic portal hypertension from portal vein thrombosis ("portal cavernoma") with healthy liver, later confirmed by angiographic studies. This rare pathologic association carries a higher risk of major operative complications; therefore the Authors agree with the general belief that, for these cases, biliary tract surgery should be as simple and safe as possible. In the case of preoperative diagnosis of biliary disease associated with portal cavernoma, should a surgical approach on the biliary tract be required, we agree on the advisability of performing a shunting procedure before any kind of biliary surgery. In case of variceal bleeding endoscopic sclerotherapy will be the first choice; surgical procedures (shunting) should be seen as a second choice in case of rebleeding after sclerotherapy.

Ulcerative colitis associated with primary biliary cirrhosis.

PubMed

Koulentaki, M; Koutroubakis, I E; Petinaki, E; Tzardi, M; Oekonomaki, H; Mouzas, I; Kouroumalis, E A

1999-10-01

Primary biliary cirrhosis and ulcerative colitis are two diseases with many features of autoimmunity. Thirteen cases of coexistence of the two diseases have been reported in the literature so far. Patients are usually younger and more often males than the ordinary primary biliary cirrhosis patient, while the colitis is mild and easily controllable. In a homogeneous population of 550,000 inhabitants of the island of Crete, 412 cases of ulcerative colitis and 82 individuals with primary biliary cirrhosis or autoimmune cholangitis have been identified. In two cases, coexistence of the two diseases was found. Immunological screening for AMA positivity in 150 ulcerative colitis sera disclosed no further cases. Prevalence of primary biliary cirrhosis in ulcerative colitis patients seems at least 30 times higher than in the general population in our area. A possible immunological link between the two diseases is discussed.

Adult bile duct strictures: differentiating benign biliary stenosis from cholangiocarcinoma.

PubMed

Nguyen Canh, Hiep; Harada, Kenichi

2016-12-01

Biliary epithelial cells preferentially respond to various insults under chronic pathological conditions leading to reactively atypical changes, hyperplasia, or the development of biliary neoplasms (such as biliary intraepithelial neoplasia, intraductal papillary neoplasm of the bile duct, and cholangiocarcinoma). Moreover, benign biliary strictures can be caused by a variety of disorders (such as IgG4-related sclerosing cholangitis, eosinophilic cholangitis, and follicular cholangitis) and often mimic malignancies, despite their benign nature. In addition, primary sclerosing cholangitis is a well-characterized precursor lesion of cholangiocarcinoma and many other chronic inflammatory disorders increase the risk of malignancies. Because of these factors and the changes in biliary epithelial cells, biliary strictures frequently pose a diagnostic challenge. Although the ability to differentiate neoplastic from non-neoplastic biliary strictures has markedly progressed with the advance in radiological modalities, brush cytology and bile duct biopsy examination remains effective. However, no single modality is adequate to diagnose benign biliary strictures because of the low sensitivity. Therefore, understanding the underlying causes by compiling the entire clinical, laboratory, and imaging data; considering the under-recognized causes; and collaborating between experts in various fields including cytopathologists with multiple approaches is necessary to achieve an accurate diagnosis.

Mucins and Cytokeratins as Serum Tumor Markers in Breast Cancer.

PubMed

Nicolini, Andrea; Ferrari, Paola; Rossi, Giuseppe

2015-01-01

Structural and functional characteristics of mucins and cytokeratins are shortly described. Thereafter, those commonly used in breast cancer as serum tumor markers are considered. First CA15.3, MCA, CA549, CA27.29 mucins and CYFRA21.1, TPA, TPS cytokeratins alone or in association have been examined in different stages and conditions. Then their usefulness in monitoring disease-free breast cancer patients is evaluated. The central role of the established cut-off and critical change, the "early" treatment of recurrent disease and the potential benefit in survival are other issues that have been highlighted and discussed. The successive sections and subsections deal with the monitoring of advanced disease. In them, the current recommendations and the principal findings on using the above mentioned mucins and cytokeratins have been reported. A computer program for interpreting consecutive measurements of serum tumor markers also has been illustrated. The final part of the chapter is devoted to mucins and cytokeratins as markers of circulating and disseminated tumor cells and their usefulness for prognosis.

Simple Sugars to Complex Disease—Mucin-Type O-Glycans in Cancer

PubMed Central

Kudelka, Matthew R.; Ju, Tongzhong; Heimburg-Molinaro, Jamie; Cummings, Richard D.

2017-01-01

Mucin-type O-glycans are a class of glycans initiated with N-acetylgalactosamine (GalNAc) α-linked primarily to Ser/Thr residues within glycoproteins and often extended or branched by sugars or saccharides. Most secretory and membrane-bound proteins receive this modification, which is important in regulating many biological processes. Alterations in mucin-type O-glycans have been described across tumor types and include expression of relatively small-sized, truncated O-glycans and altered terminal structures, both of which are associated with patient prognosis. New discoveries in the identity and expression of tumor-associated O-glycans are providing new avenues for tumor detection and treatment. This chapter describes mucin-type O-glycan biosynthesis, altered mucin-type O-glycans in primary tumors, including mechanisms for structural changes and contributions to the tumor phenotype, and clinical approaches to detect and target altered O-glycans for cancer treatment and management. PMID:25727146

Congenital biliary tract malformation resembling biliary cystadenoma in a captive juvenile African lion (Panthera leo).

PubMed

Caliendo, Valentina; Bull, Andrew C J; Stidworthy, Mark F

2012-12-01

A captive 3-mo-old white African lion (Panthera leo) presented with clinical signs of acute pain and a distended abdomen. Despite emergency treatment, the lion died a few hours after presentation. Postmortem examination revealed gross changes in the liver, spleen, and lungs and an anomalous cystic structure in the bile duct. Histologic examination identified severe generalized multifocal to coalescent necrotizing and neutrophilic hepatitis, neutrophilic splenitis, and mild interstitial pneumonia, consistent with bacterial septicemia. The abnormal biliary structures resembled biliary cystadenoma. However, due to the age of the animal, they were presumed to be congenital in origin. Biliary tract anomalies and cystadenomas have been reported previously in adult lions, and this case suggests that at least some of these examples may have a congenital basis. It is unclear whether the lesion was an underlying factor in the development of hepatitis.

The oncocytic subtype is genetically distinct from other pancreatic intraductal papillary mucinous neoplasm subtypes

PubMed Central

Basturk, Olca; Tan, Marcus; Bhanot, Umesh; Allen, Peter; Adsay, Volkan; Scott, Sasinya N; Shah, Ronak; Berger, Michael F; Askan, Gokce; Dikoglu, Esra; Jobanputra, Vaidehi; Wrzeszczynski, Kazimierz O; Sigel, Carlie; Iacobuzio-Donahue, Christine; Klimstra, David S

2017-01-01

In 2010, the World Health Organization reclassified the entity originally described as intraductal oncocytic papillary neoplasm as the ‘oncocytic subtype’ of intraductal papillary mucinous neoplasm. Although several key molecular alterations of other intraductal papillary mucinous neoplasm subtypes have been discovered, including common mutations in KRAS, GNAS, and RNF3, those of oncocytic subtype have not been well characterized. We analyzed 11 pancreatic ‘oncocytic subtype’ of intraductal papillary mucinous neoplasms. Nine pancreatic ‘oncocytic subtype’ of intraductal papillary mucinous neoplasms uniformly exhibited typical entity-defining morphology of arborizing papillae lined by layers of cells with oncocytic cytoplasm, prominent, nucleoli, and intraepithelial lumina. The remaining two were atypical. One lacked the arborizing papilla and had flat oncocytic epithelium only; the other one had focal oncocytic epithelium in a background of predominantly intestinal subtype intraductal papillary mucinous neoplasm. Different components of this case were analyzed separately. Formalin-fixed, paraffin-embedded specimens of all cases were microdissected and subjected to high-depth-targeted next-generation sequencing for a panel of 300 key cancer-associated genes in a platform that enabled the identification of sequence mutations, copy number alterations, and select structural rearrangements involving all targeted genes. Fresh frozen specimens of two cases were also subjected to whole-genome sequencing. For the nine typical pancreatic ‘oncocytic subtype’ of intraductal papillary mucinous neoplasms, the number of mutations per case, identified by next-generation sequencing, ranged from 1 to 10 (median = 4). None of these cases had KRAS or GNAS mutations and only one had both RNF43 and PIK3R1 mutations. ARHGAP26, ASXL1, EPHA8, and ERBB4 genes were somatically altered in more than one of these typical ‘oncocytic subtype’ of intraductal papillary mucinous

Structural Diversity of Human Gastric Mucin Glycans*

PubMed Central

Jin, Chunsheng; Kenny, Diarmuid T.; Skoog, Emma C.; Padra, Médea; Adamczyk, Barbara; Vitizeva, Varvara; Thorell, Anders; Venkatakrishnan, Vignesh; Lindén, Sara K.; Karlsson, Niclas G.

2017-01-01

The mucin O-glycosylation of 10 individuals with and without gastric disease was examined in depth in order to generate a structural map of human gastric glycosylation. In the stomach, these mucins and their O-glycosylation protect the epithelial surface from the acidic gastric juice and provide the first point of interaction for pathogens such as Helicobacter pylori, reported to cause gastritis, gastric and duodenal ulcers and gastric cancer. The rational of the present study was to map the O-glycosylation that the pathogen may come in contact with. An enormous diversity in glycosylation was found, which varied both between individuals and within mucins from a single individual: mucin glycan chain length ranged from 2–13 residues, each individual carried 34–103 O-glycan structures and in total over 258 structures were identified. The majority of gastric O-glycans were neutral and fucosylated. Blood group I antigens, as well as terminal α1,4-GlcNAc-like and GalNAcβ1–4GlcNAc-like (LacdiNAc-like), were common modifications of human gastric O-glycans. Furthemore, each individual carried 1–14 glycan structures that were unique for that individual. The diversity and alterations in gastric O-glycosylation broaden our understanding of the human gastric O-glycome and its implications for gastric cancer research and emphasize that the high individual variation makes it difficult to identify gastric cancer specific structures. However, despite the low number of individuals, we could verify a higher level of sialylation and sulfation on gastric O-glycans from cancerous tissue than from healthy stomachs. PMID:28461410

PIK3CA Mutations in Mucinous Cystic Neoplasms of the Pancreas

PubMed Central

Garcia-Carracedo, Dario; Chen, Zong-Ming; Qiu, Wanglong; Huang, Alicia S.; Tang, Sophia M.; Hruban, Ralph H.; Su, Gloria H.

2014-01-01

Objectives Mucinous cystic neoplasms (MCNs) are rare, potentially curable, mucin-producing neoplasms of the pancreas. We have previously reported PIK3CA (phosphoinositide-3-kinase catalytic subunit, p110α) mutations in intraductal papillary mucinous neoplasms, another mucin-producing neoplasm of the pancreas. In this study, we analyzed the presence of PIK3CA and AKT1/PKB (V-akt murine thymoma viral oncogene homolog 1) hot-spot mutations in MCN specimens. Methods Using the genomic DNA sequencing of tumor tissues isolated by laser capture microdissection, we evaluated 15 well-characterized MCNs for the E542K, E545K(exon 9), and H1047R (exon 20) hot-spotmutations in the PIK3CA gene and the E17K mutation in the AKT1 gene. Results A hot-spotmutation (E545K) of the PIK3CA gene was detected in 1 of the 15 MCNs and further confirmed by a mutant-enriched method. Interestingly, this mutation was found to be present only in the high-grade but not in low-grade dysplastic epithelium obtained from this neoplasm and coexisted with a KRASG12D mutation. No mutations were identified in the AKT1 gene. Conclusions Our data, when combined with previous reports on intraductal papillary mucinous neoplasms, indicate that oncogenic activation of the PI3K pathway involving PIK3CA gene mutations can contribute to the progression of mucin-producing neoplasms but not pancreatic intraepithelial neoplasia. PIK3CA status could be useful for understanding their progression to malignancy. PMID:24518503

Clinical significance of isolated biliary candidiasis in patients with unresectable cholangiocarcinoma.

PubMed

Kim, In-Ho; Choi, Jae-Ki; Lee, Dong-Gun; Lee, In Seok; Hong, Tae Ho; You, Young Kyoung; Chun, Ho Jong; Lee, Myung Ah

2016-10-01

The frequency of isolated biliary candidiasis is increasing in cancer patients. The clinical significance of isolated biliary candidiasis remains unclear. We analyzed the risk factors of biliary candidiasis and outcomes of the patients with unresectable cholangiocarcinoma after percutaneous transhepatic biliary drainage (PTBD). Among 430 patients who underwent PTBD between January 2012 and March 2015, 121 patients had unresectable cholangiocarcinoma. Bile and blood samples were collected for consecutive fungal culture. The study cohort included 49 women and 72 men with a median age of 71 years. Multivariate analysis showed that cancer progression (P=0.013), concurrent presence of another microorganism (P=0.010), and previous long-term (>7 days) antibiotic use (P=0.011) were potential risk factors of biliary candidiasis. Chemotherapy was not associated with overall biliary candidiasis (P=0.196), but was significantly related to repeated biliary candidiasis (P=0.011). Patients with isolated biliary candidiasis showed remarkably reduced survival compared with those without [median overall survival (OS): 32 vs 62 days, P=0.011]. Subgroup analysis was also performed. Patients with repeated candidiasis had markedly decreased survival compared with those with transient candidiasis (median OS: 30 vs 49 days, P=0.046). Biliary candidiasis was identified as a poor prognostic factor by univariate and multivariate analyses (P=0.033). Four cases of repeated candidiasis (4/19, 21%) showed Candida species in consecutive blood culture until the end of the study, but others showed no candidemia. Isolated biliary candidiasis may be associated with poor prognosis in patients with unresectable cholangiocarcinoma. Especially, repeated biliary candidiasis may have the possibility of progression to candidemia. We suggest that biliary dilatation treatment or antifungal agents might be helpful for patients with biliary candidiasis.

Biliary obstruction - slideshow

MedlinePlus

... ency/presentations/100199.htm Biliary obstruction - series—Normal anatomy To use the sharing ... Overview Bile is a digestive fluid secreted by the liver and stored in the gallbladder which normally is ...

Current status of mucins in the diagnosis and therapy of cancer

PubMed Central

Rachagani, Satyanarayana; Torres, Maria P.; Moniaux, Nicolas; Batra, Surinder K.

2010-01-01

Mucins are the most abundant high molecular weight glycoproteins in mucus. Their nature and glycosylation content dictates the biochemical and biophysical properties of viscoelastic secretions, pointing out an important role in diverse biological functions, such as differentiation, cell adhesions, immune responses, and cell signaling. Mucins are expressed in tubular organs by specialized epithelial cells in the body. Their aberrant expression is well documented in a variety of inflammatory or malignant diseases. From a prognosis point of view, their expression and alterations in glycosylation are associated with the development and progression of malignant diseases. Therefore, mucins can be used as valuable markers to distinguish between normal and disease conditions. Indeed, this alteration in glycosylation patterns generates several epitopes in the oligosaccharide side chains that can be used as diagnostic and/or prognostic markers. Furthermore, these characteristic tumor-associated epitopes are extensively used as appropriate immunotargets of malignant epithelial cells. Therefore, in an effort to detect and treat cancer at the earliest stage possible, mucins are analyzed as potential markers of disease for diagnosis, progression, and for therapeutic purposes. In this review, we focused on the current status of the distribution of mucins in normal and pathologic conditions and their clinical use both in cancer diagnosis and therapeutics treatments. PMID:19904814

Spontaneous external biliary fistula uncomplicated by gallstones.

PubMed Central

Birch, B. R.; Cox, S. J.

1991-01-01

External biliary fistulae are rare. Only 65 cases have been reported in the literature and in each instance gallstones were a complicating factor. We report in this paper the first case of spontaneous external (cholecystocutaneous) biliary fistula uncomplicated by gallstones. PMID:2068038

Comparative Genomic Analysis of the Human Gut Microbiome Reveals a Broad Distribution of Metabolic Pathways for the Degradation of Host-Synthetized Mucin Glycans and Utilization of Mucin-Derived Monosaccharides

PubMed Central

Ravcheev, Dmitry A.; Thiele, Ines

2017-01-01

The colonic mucus layer is a dynamic and complex structure formed by secreted and transmembrane mucins, which are high-molecular-weight and heavily glycosylated proteins. Colonic mucus consists of a loose outer layer and a dense epithelium-attached layer. The outer layer is inhabited by various representatives of the human gut microbiota (HGM). Glycans of the colonic mucus can be used by the HGM as a source of carbon and energy when dietary fibers are not sufficiently available. Both commensals and pathogens can utilize mucin glycans. Commensals are mostly involved in the cleavage of glycans, while pathogens mostly utilize monosaccharides released by commensals. This HGM-derived degradation of the mucus layer increases pathogen susceptibility and causes many other health disorders. Here, we analyzed 397 individual HGM genomes to identify pathways for the cleavage of host-synthetized mucin glycans to monosaccharides as well as for the catabolism of the derived monosaccharides. Our key results are as follows: (i) Genes for the cleavage of mucin glycans were found in 86% of the analyzed genomes, which significantly higher than a previous estimation. (ii) Genes for the catabolism of derived monosaccharides were found in 89% of the analyzed genomes. (iii) Comparative genomic analysis identified four alternative forms of the monosaccharide-catabolizing enzymes and four alternative forms of monosaccharide transporters. (iv) Eighty-five percent of the analyzed genomes may be involved in potential feeding pathways for the monosaccharides derived from cleaved mucin glycans. (v) The analyzed genomes demonstrated different abilities to degrade known mucin glycans. Generally, the ability to degrade at least one type of mucin glycan was predicted for 81% of the analyzed genomes. (vi) Eighty-two percent of the analyzed genomes can form mutualistic pairs that are able to degrade mucin glycans and are not degradable by any of the paired organisms alone. Taken together, these

Comparative Genomic Analysis of the Human Gut Microbiome Reveals a Broad Distribution of Metabolic Pathways for the Degradation of Host-Synthetized Mucin Glycans and Utilization of Mucin-Derived Monosaccharides.

PubMed

Ravcheev, Dmitry A; Thiele, Ines

2017-01-01

The colonic mucus layer is a dynamic and complex structure formed by secreted and transmembrane mucins, which are high-molecular-weight and heavily glycosylated proteins. Colonic mucus consists of a loose outer layer and a dense epithelium-attached layer. The outer layer is inhabited by various representatives of the human gut microbiota (HGM). Glycans of the colonic mucus can be used by the HGM as a source of carbon and energy when dietary fibers are not sufficiently available. Both commensals and pathogens can utilize mucin glycans. Commensals are mostly involved in the cleavage of glycans, while pathogens mostly utilize monosaccharides released by commensals. This HGM-derived degradation of the mucus layer increases pathogen susceptibility and causes many other health disorders. Here, we analyzed 397 individual HGM genomes to identify pathways for the cleavage of host-synthetized mucin glycans to monosaccharides as well as for the catabolism of the derived monosaccharides. Our key results are as follows: (i) Genes for the cleavage of mucin glycans were found in 86% of the analyzed genomes, which significantly higher than a previous estimation. (ii) Genes for the catabolism of derived monosaccharides were found in 89% of the analyzed genomes. (iii) Comparative genomic analysis identified four alternative forms of the monosaccharide-catabolizing enzymes and four alternative forms of monosaccharide transporters. (iv) Eighty-five percent of the analyzed genomes may be involved in potential feeding pathways for the monosaccharides derived from cleaved mucin glycans. (v) The analyzed genomes demonstrated different abilities to degrade known mucin glycans. Generally, the ability to degrade at least one type of mucin glycan was predicted for 81% of the analyzed genomes. (vi) Eighty-two percent of the analyzed genomes can form mutualistic pairs that are able to degrade mucin glycans and are not degradable by any of the paired organisms alone. Taken together, these

Percutaneous Intraductal Radiofrequency Ablation Combined with Biliary Stent Placement for Nonresectable Malignant Biliary Obstruction Improves Stent Patency but not Survival.

PubMed

Wang, Jianfeng; Zhao, Lizhen; Zhou, Chuanguo; Gao, Kun; Huang, Qiang; Wei, Baojie; Gao, Jun

2016-04-01

Although radiofrequency (RF) ablation has been accepted as a curative treatment modality for solid organ tumors, intraductal RF ablation for malignant biliary obstruction has not been widely described. The aim of this study was to evaluate the feasibility, safety, and efficacy (in terms of stent patency and survival) of intraductal RF ablation combined with biliary stent placement for nonresectable malignant biliary obstruction. A search of the nonresectable malignant extrahepatic biliary obstruction database (179 patients) identified 18 consecutive patients who were treated with biliary intraluminal RF ablation during percutaneous transhepatic cholangiodrainage and inner stent placement (RF ablation group) and 18 patients who underwent inner stent placement without biliary intraluminal RF ablation (control group). The patients were matched for tumor type, location of obstruction, tumor stage, and Child-Pugh class status. Primary endpoints included safety, stent patency time, and survival rates. The secondary endpoint was effectiveness of the technique. The RF ablation and control groups were closely matched in terms of age, diagnosis, presence of metastases, presence of locally advanced tumor, American Society of Anesthesiologists (ASA) grade, and chemotherapy regimen (all P > 0.05). The technical success rate for both groups was 100%. The median time of stent patency in the RF ablation and control groups were 5.8 (2.8-11.5) months and 4.5 (2.4-8.0) months, respectively (Kaplan-Meier analysis: P = 0.03). The median survival times in the RF ablation and control groups were 6.1 (4.8-15.2) months and 5.8 (4.2-16.5) months, with no significant difference according to Kaplan-Meier analysis (P = 0.45). In univariate and multivariate analyses, poorer overall survival was associated with advanced age and presence of metastases (P < 0.05). Intraductal RF ablation combined with biliary stent placement for nonresectable malignant biliary obstruction is safe

Noninvasive Imaging of the Biliary System Relevant to Percutaneous Interventions

PubMed Central

Thomas, Stephen; Jahangir, Kayleen

2016-01-01

Clinical data such as history, physical examination, and laboratory tests are useful in identifying patients with biliary obstruction and biliary sources of infection. However, if intervention is planned, noninvasive imaging is needed to confirm the presence, location, and extent of the disease process. Currently, the most commonly available and used noninvasive modalities are ultrasound (US), computed tomography (CT), magnetic resonance (MR), and nuclear medicine hepatobiliary scintigraphy (HIDA). US is quick, portable, readily available, and is commonly the first imaging modality used when biliary pathology is suspected. It is excellent in the detection of cholelithiasis and acute cholecystitis but is limited in detecting choledocholithiasis. CT is excellent at detecting infected postoperative fluid collections, bilomas, biliary obstruction, and biliary infection but is limited in the detection of cholelithiasis. Therefore, US may be more useful than CT for the initial screening of acute biliary disease. MR has inherent advantages over CT, as it does not use ionizing radiation, can be done without intravenous contrast, and its detection of cholelithiasis is not affected by the internal composition of the stone. Magnetic resonance cholangiopancreatography can be used to determine the cause and location of biliary obstruction but is limited in the detection of small stones and the evaluation of the biliary tract near the ampulla. HIDA is used to evaluate for cholecystitis, biliary obstruction, and bile leaks. The main limitation is its lack of anatomical detail, and it is therefore frequently performed in conjunction with other described modalities. PMID:27904246

Overexpression or ectopic expression of MUC2 is the common property of mucinous carcinomas of the colon, pancreas, breast, and ovary.

PubMed

Hanski, C; Hofmeier, M; Schmitt-Gräff, A; Riede, E; Hanski, M L; Borchard, F; Sieber, E; Niedobitek, F; Foss, H D; Stein, H; Riecken, E O

1997-08-01

Mucinous carcinomas of the colorectum have been reported to overexpress the intestinal mucin MUC2. The purpose of this study was to determine whether this alteration is shared by mucinous tumours of the ovary, breast, and pancreas. A total of 40 breast carcinomas (22 of mucinous and 18 of ductal invasive type), 39 ovarian adenocarcinomas (16 mucinous, 23 serous), 47 colorectal carcinomas (25 mucinous and 22 non-mucinous), and 41 pancreatic adenocarcinomas (14 mucinous, 27 non-mucinous) were investigated by immunohistochemistry with the anti-MUC2 monoclonal antibody 4F1 and the expression pattern was ranked. MUC2 mucin is expressed in the normal colonic epithelium; in the normal epithelium of the breast, ovary, and pancreas, it was not detectable by immunohistochemistry or by reverse transcriptase-polymerase chain reaction (RT-PCR). In agreement with previous reports, the colonic mucinous carcinomas differed significantly from the non-mucinous carcinomas by strong MUC2 expression. In all mucinous carcinomas of the ovary, breast, and pancreas, de novo expression of the MUC2 gene was observed, which differentiated mucinous and non-mucinous carcinomas of these tissues (P < 0.001). The overexpression or ectopic expression of the MUC2 gene exhibited by mucinous carcinomas of four organs indicates a common genetic lesion associated with the mucinous tumour phenotype.

The eicosanoid, 15-(S)-HETE, stimulates secretion of mucin-like glycoprotein by the corneal epithelium.

PubMed

Jackson , R S; Van Dyken, S J; McCartney, M D; Ubels, J L

2001-07-01

The eicosanoid, 15-(S)-hydroxyeicosa-5Z, 8Z-11Z, 13E-tetraenoic acid (15-(S)-HETE), is known to stimulate production of mucin glycoprotein by airway epithelium. This study investigated the effect of 15-(S)-HETE on the mucin glycoprotein secretion by the corneal epithelium. To determine the effect of dose, corneas of anesthetized New Zealand White rabbits were treated with 50, 500, or 5,000 nM 15-(S)-HETE in artificial tears for 120 minutes. To determine the time to onset of the response, corneas were treated with 500 or 1,000 nM 15-(S)-HETE in balanced salt solution for periods ranging from 5 to 120 minutes. Corneas were fixed for electron microscopy in fixative containing 0.5% cetylpyridinium chloride (CPC) to stabilize the layer of mucin-like glycoprotein on the corneal surface. The mucin layer thickness was measured by image analysis of electron micrographs. The layer of CPC-fixed mucin-like glycoprotein on the surface of control corneas was 0.46 +/- 0.04 microm thick. After treatment with 15-(S)-HETE, the thickness of the mucin layer increased to 0.64 +/- 0.1 microm at 50 or 5,000 nM HETE and as much as 1.02 +/- 0.2 microm in response to 500 nM HETE. Mucin thickness reached a statistical maximum of 0.59 +/- 0.1 microm after only 5 minutes of exposure to 500 or 1,000 nM HETE. Exposure of the cornea to 15-(S)-HETE causes a rapid-onset increase in the thickness of a layer of mucin-like glycoprotein on the surface of the corneal epithelium. This supports previous reports that corneal epithelial cells produce mucin and suggests that treatment with topical 15-(S)-HETE may be effective in treating ocular surface mucin deficiency in dry eye syndrome.

Covered biliary stents with proximal bare stent extension for the palliation of malignant biliary disease: can we reduce tumour overgrowth rate?

PubMed

Krokidis, Miltiadis; Hatzidakis, Adam

2017-08-01

Covered biliary stents have shown significant effectiveness in the palliative management of patients with malignant biliary disease due to prevention of tumour ingrowth. However, stent dysfunction may still occur due to growth of tumour at the borders of the covered stent (tumour overgrowth). The aim of this study is to assess the effectiveness of a bare extension in the prevention of tumour overgrowth when covered stents are used in the palliative treatment of malignant biliary strictures. This is a prospective, single arm, cohort study. Twenty-two patients with inoperable malignant biliary strictures in the distal common bile duct (Bismuth I-II) and life expectancy more than 6 months were included in the study. The combination of a fully covered biliary stent and a bare proximal and distal extension was used in all cases. All patients were followed-up until death. Primary patency, survival, complication rates and dysfunction cause were assessed. Mean survival was 263.7 days (median 255, SD: 77.6). Mean patency was 240 days (median: 237, SD: 87). The primary patency rate at 3, 6 and 12 months was 90%, 86% and 86% respectively. Tumour inor overgrowth did not occur in any of the patients. Dysfunction due to sludge formation occurred in three cases; all three were treated with bilioplasty. The combined use of a covered biliary stent and a bare extension appears to be a very effective tool in the palliation of malignant biliary disease, offering long-term patency for patients with inoperable malignant distal common bile duct strictures and increasing the quality of life of such patients.

Structure and Biological Roles of Mucin-type O-glycans at the Ocular Surface

PubMed Central

Guzman-Aranguez, Ana; Argüeso, Pablo

2010-01-01

Mucins are major components in mucus secretions and apical cell membranes on wet-surfaced epithelia. Structurally, they are characterized by the presence of tandem repeat domains containing heavily O-glycosylated serine and threonine residues. O-glycans contribute to maintaining the highly extended and rigid structure of mucins, conferring to them specific physical and biological properties essential for their protective functions. At the ocular surface epithelia, mucin-type O-glycan chains are short and predominantly sialylated, perhaps reflecting specific requirements of the ocular surface. Traditionally, secreted mucins and their O-glycans in the tear film have been involved in the clearance of debris and pathogens from the surface of the eye. New evidence, however, shows that O-glycans on the cell-surface glycocalyx have additional biological roles in the protection of corneal and conjunctival epithelia, such as preventing bacterial adhesion, promoting boundary lubrication, and maintaining the epithelial barrier function through their interaction with galectin-3. Abnormalities in mucin-type O-glycosylation have been identified in many disorders where the stability of the ocular surface is compromised. This review summarizes recent advances in understanding the structure, biosynthesis, and function of mucin-type O-glycans at the ocular surface and their alteration in ocular surface disease. PMID:20105403

A case of Krukenberg carcinoma metastasized from colon cancer resembling mucinous cystadenocarcinoma of the ovary

PubMed Central

Shiono, Saori; Saito, Tsuyoshi; Fujii, Hiroaki; Arakawa, Atsushi; Nakamura, Takanori; Yao, Takashi

2014-01-01

We report a case of a 44-year-old woman with bilateral ovarian carcinoma that had metastasized from the colon and mimicked primary mucinous cystadenocarcinoma. Macroscopically, both ovarian tumors were large, multiloculated cystic masses with abundant mucinous content. Histologically, they were lined with mucinous epithelium with mild to moderate nuclear atypia and showed stromal invasion and surface involvement. At first, the tumors were diagnosed as bilateral primary ovarian mucinous cystadenocarcinomas. However, three months after surgery, a large villous tumor was discovered in the ascending colon by colonoscopic examination and was surgically resected. Histologically, the colonic tumor was a villous adenomatous tumor with invasive components of mucinous adenocarcinoma composed of well-differentiated adenocarcinoma and exhibited abundant extracellular mucin production. As a villous adenomatous component was present in the mucosal area, the colonic tumor was considered a primary tumor. Therefore, the original diagnosis of bilateral ovarian tumors was revised for consistent with metastasis from the colon carcinoma, in line with the findings of immunohistochemistry and loss of heterozygosity analysis. This case highlights the importance of considering the possibility of metastatic tumors from the gastrointestinal tract in the diagnosis of mucinous ovarian tumors. PMID:24427362

Use of biliary stent in laparoscopic common bile duct exploration.

PubMed

Lyon, Matthew; Menon, Seema; Jain, Abhiney; Kumar, Harish

2015-05-01

It is well supported in the literature that laparoscopic common bile duct exploration (LCBDE) for choledocholithiasis has equal efficacy when compared to ERCP followed by laparoscopic cholecystectomy. Decompression after supra-duodenal choledochotomy is common practice as it reduced the risk of bile leaks. We conducted a prospective non-randomized study to compare outcomes and length of stay in patients undergoing biliary stent insertion versus T-tube drainage following LCBDE via choledochotomy. The study involved 116 patients with choledocholithiasis who underwent LCBDE and decompression of the biliary system by either ante-grade biliary stent or T-tube insertion. A 7 French straight/duodenal curve biliary Diagmed™ stent (9-11 cm) was placed in 82 patients (Biliary Stent Group). T-tube insertion was used for 34 patients (T-tube group). The length of hospital stay and complications for the selected patients were recorded. All trans-cystic common bile duct explorations were excluded from the study. The mean hospital stay for patients who underwent ante-grade biliary stent or T-tube insertion after LBCDE were 1 and 3.4 days, respectively. This is a statistically significant result with a p value of less than 0.001. Of the T-tube group, two patients required laparoscopic washout due to bile leaks, one had ongoing biliary stasis and one reported ongoing pain whilst the T-tube was in situ. A complication rate of 11.2%, this was a significant finding. There were no complications or concerns reported for the Biliary Stent Group. Our results show that there is a significant reduction in length of hospital stay and morbidity for patients that have ante-grade biliary stent decompression of the CBD post laparoscopic choledochotomy when compared T-tube drainage. This implies that ante-grade biliary stent insertion is likely to reduce costs and increase overall patient satisfaction. We support the use of ante-grade biliary stent insertion during LCBDE when primary closure is

Laparoscopic Transcystic Treatment Biliary Calculi by Laser Lithotripsy

PubMed Central

Jin, Lan; Zhang, Zhongtao

2016-01-01

Background and Objectives: Laparoscopic transcystic common bile duct exploration (LTCBDE) is a complex procedure requiring expertise in laparoscopic and choledochoscopic skills. The purpose of this study was to investigate the safety and feasibility of treating biliary calculi through laparoscopic transcystic exploration of the CBD via an ultrathin choledochoscope combined with dual-frequency laser lithotripsy. Methods: From August 2011 through September 2014, 89 patients at our hospital were treated for cholecystolithiasis with biliary calculi. Patients underwent laparoscopic cholecystectomy and exploration of the CBD via the cystic duct and the choledochoscope instrument channel. A dual-band, dual-pulse laser lithotripsy system was used to destroy the calculi. Two intermittent laser emissions (intensity, 0.12 J; pulse width 1.2 μs; and pulse frequency, 10 Hz) were applied during each contact with the calculi. The stones were washed out by water injection or removed by a stone-retrieval basket. Results: Biliary calculi were removed in 1 treatment in all 89 patients. No biliary tract injury or bile leakage was observed. Follow-up examination with type-B ultrasonography or magnetic resonance cholangiopancreatography 3 months after surgery revealed no instances of retained-calculi–related biliary tract stenosis. Conclusion: The combined use of laparoscopic transcystic CBD exploration by ultrathin choledochoscopy and dual-frequency laser lithotripsy offers an accurate, convenient, safe, effective method of treating biliary calculi. PMID:27904308

Enhanced bioavailability of polyaromatic hydrocarbons in the form of mucin complexes.

PubMed

Drug, Eyal; Landesman-Milo, Dalit; Belgorodsky, Bogdan; Ermakov, Natalia; Frenkel-Pinter, Moran; Fadeev, Ludmila; Peer, Dan; Gozin, Michael

2011-03-21

Increasing exposure of biological systems to large amounts of polycyclic aromatic hydrocarbons is of great public concern. Organisms have an array of biological defense mechanisms, and it is believed that mucosal gel (which covers the respiratory system, the gastrointestinal tract, etc.) provides an effective chemical shield against a range of toxic materials. However, in this work, we demonstrate, for the first time, that, upon complexation of polyaromatic hydrocarbons with mucins, enhanced bioavailability and, therefore, toxicity are obtained. This work was aimed to demonstrate how complexation of various highly hydrophobic polycyclic aromatic hydrocarbons with representative mucin glycoprotein could lead to the formation of previously undescribed materials, which exhibit increased toxicity versus pristine polycyclic aromatic hydrocarbons. In the present work, we show that a representative mucin glycoprotein, bovine submaxillary mucin, has impressive and unprecedented capabilities of binding and solubilizing water-insoluble materials in physiological solution. The complexes formed between the mucin and a series of polycyclic aromatic hydrocarbons were comprehensively characterized, and their toxicity was evaluated by both in vivo and in vitro assays. In addition, the bioavailability and membrane-penetration capabilities were tested using an internalization assay. Our results provide, for the first time, evidence of an unknown route by which hydrophobic materials may achieve higher bioavailability, penetrating some of the biological defense systems, in the form of water-soluble complexes with mucosal proteins.

[SURGICAL TACTICS IN CHRONIC PANCREATITIS WITH SIGNS OF BILIARY HYPERTENSION].

PubMed

Usenko, O Yu; Kopchak, V M; Pylypchuk, V I; Kopchak, K V; Andronik, S V

2015-08-01

The results of treatment of 84 patients for chronic pancreatitis with the biliary hypertension signs were depicted. In 83 patients operative interventions were performed, and in 1--positive results were achieved after pancreatic cyst puncture under ultrasonographic control. In 51 patients the conduction of Frey operation have permitted to achieve a lower pressure inside biliary system, in 25--the additional procedures were applied for a biliary hypertension elimination. In 20 patients a method of pressure measurement in biliary system was used.

Viscous fingering of HCI through gastric mucin

NASA Astrophysics Data System (ADS)

Bhaskar, K. Ramakrishnan; Garik, Peter; Turner, Bradley S.; Bradley, James Douglas; Bansil, Rama; Stanley, H. Eugene; Lamont, J. Thomas

1992-12-01

THE HCI in the mammalian stomach is concentrated enough to digest the stomach itself, yet the gastric epithelium remains undamaged. One protective factor is gastric mucus, which forms a protective layer over the surface epithelium1-4 and acts as a diffusion barrier5,6 Bicarbonate ions secreted by the gastric epithelium7 are trapped in the mucus gel, establishing a gradient from pH 1-2 at the lumen to pH 6-7 at the cell surface8-10. How does HCI, secreted at the base of gastric glands by parietal cells, traverse the mucus layer without acidifying it? Here we demonstrate that injection of HCI through solutions of pig gastric mucin produces viscous fingering patterns11-18 dependent on pH, mucin concentration and acid flow rate. Above pH 4, discrete fingers are observed, whereas below pH 4, HCI neither penetrates the mucin solution nor forms fingers. Our in vitro results suggest that HCI secreted by the gastric gland can penetrate the mucus gel layer (pH 5-7) through narrow fingers, whereas HC1 in the lumen (pH 2) is prevented from diffusing back to the epithelium by the high viscosity of gastric mucus gel on the luminal side.

Preoperative biliary drainage in hilar cholangiocarcinoma: When and how?

PubMed Central

Paik, Woo Hyun; Loganathan, Nerenthran; Hwang, Jin-Hyeok

2014-01-01

Hilar cholangiocarcinoma is a tumor of the extrahepatic bile duct involving the left main hepatic duct, the right main hepatic duct, or their confluence. Biliary drainage in hilar cholangiocarcinoma is sometimes clinically challenging because of complexities associated with the level of biliary obstruction. This may result in some adverse events, especially acute cholangitis. Hence the decision on the indication and methods of biliary drainage in patients with hilar cholangiocarcinoma should be carefully evaluated. This review focuses on the optimal method and duration of preoperative biliary drainage (PBD) in resectable hilar cholangiocarcinoma. Under certain special indications such as right lobectomy for Bismuth type IIIA or IV hilar cholangiocarcinoma, or preoperative portal vein embolization with chemoradiation therapy, PBD should be strongly recommended. Generally, selective biliary drainage is enough before surgery, however, in the cases of development of cholangitis after unilateral drainage or slow resolving hyperbilirubinemia, total biliary drainage may be considered. Although the optimal preoperative bilirubin level is still a matter of debate, the shortest possible duration of PBD is recommended. Endoscopic nasobiliary drainage seems to be the most appropriate method of PBD in terms of minimizing the risks of tract seeding and inflammatory reactions. PMID:24634710

Comparison of tumor markers and clinicopathological features in serous and mucinous borderline ovarian tumors.

PubMed

Alanbay, I; Aktürk, E; Coksuer, H; Ercan, C M; Karaşahin, E; Dede, M; Yenen, M C; Ozan, H; Dilek, S

2012-01-01

The aim of this study was to assess tumor markers and clinicopathological findings of patients with serous and mucinous borderline ovarian tumor (BOT) features. The study consisted of 50 patients that were diagnosed with and treated for BOT between 2005-2010 in three centers. CA125, CA19-9, and CA125+CA19-9 levels and clinicopathological features were compared in serous and mucinous histotypes. In serous and mucinous BOTs, correlations between tumor markers and demographics such as age, menopausal status, parity, clinical findings (stage, relapse, adjuvant chemotherapy, cytology, lymph node involvement and tumoral morphology (cystic-solid content, papilla, septation) were evaluated. There were no significant differences between serous and mucinous tumors in the clinicopathological features such as stage, tumor markers, age, menopausal status, or cytology. In serous BOTs we found a significant relation between elevated CA125+ CA19-9, CA19-9 and recurrence (p < 0.05). Also there was a significant relation between elevated CA125+ CA19-9, CA19-9 and cytology positivity (p < 0.05). We found a significant relation in serous BOTs between elevated CA125+CA19-9, adjuvant chemotherapy and lymph node metastases (p < 0.05). Also In mucinous BOTs with papilla formation we found a significant relation between elevated CA125 and CA125+ CA19-9 (p < 0.05). There was significant relation between cytology positivity and elevated CA19-9 in mucinous BOTs (p < 0.05). Serum tumor markers of serous and mucinous BOTs were different in relation to their clinicopathological features. This may reflect differences of serous and mucinous BOTs.

Biliary Tract Disorders, Gallbladder Disorders, and Gallstone Pancreatitis

MedlinePlus

... biliary disorders? What is the biliary tract? Enfermedades de la Vesicula y de la Via Biliar, Pancreatitis Biliar - Ricardo Morgenstern, MD and Ruben Acosta, MD Enfermedades de la Vesicula y de la Via Biliar, Pancreatitis ...

Molecular basis of the polydispersity of mucins: implications for the generation of saccharide diversity.

PubMed

Bhavanandan, V P; Gupta, D; Woitach, J; Guo, X; Jiang, W

1999-06-01

Secreted epithelial mucins are large macromolecules which exhibit extreme polydispersity, the molecular basis of which is not fully understood. We have obtained partial sequences of two genes (BSM1 and BSM2) coding for two distinct molecules. This is the first time that such closely-related genes have been identified for any mucin from an animal. We propose that a combination of multiple homologous genes, alternative splicing, differential glycosylation, and additional post-translational processing all contribute to the extreme polydispersity of mucins. The multiple domain structure and non-identical tandem repeats are also very important for the generation of the saccharide diversities of mucins.

Urgent endoscopic retrograde cholangiopancreatography is not superior to early ERCP in acute biliary pancreatitis with biliary obstruction without cholangitis.

PubMed

Lee, Hee Seung; Chung, Moon Jae; Park, Jeong Youp; Bang, Seungmin; Park, Seung Woo; Song, Si Young; Chung, Jae Bock

2018-01-01

Acute pancreatitis is a common diagnosis worldwide, with gallstone disease being the most prevalent cause (50%). The American College of Gastroenterology recommends urgent endoscopic retrograde cholangiopancreatography (ERCP) (within 24 h) for patients with biliary pancreatitis accompanied by cholangitis. Most international guidelines recommend that ERCP be performed within 72 h in patients with biliary pancreatitis and a bile duct obstruction without cholangitis, but the optimal timing for endoscopy is controversial. We investigated the optimal timing for ERCP in patients with biliary pancreatitis and a bile duct obstruction without cholangitis, and whether performing endoscopy within 24 h is superior to performing it after 24 h. We analyzed the clinical data of 505 patients with newly diagnosed acute pancreatitis, from January 1, 2005 to December 31, 2014. We divided the patients into two groups according to the timing of ERCP: < 24 h (urgent) and 24-72 h (early).Among the 505 patients, 73 were diagnosed with biliary pancreatitis and a bile duct obstruction without cholangitis. The mean age of the patients was 55 years (range: 26-90 years). Bile duct stones and biliary sludge were identified on endoscopy in 45 (61.6%) and 11 (15.0%) patients, respectively. The timing of ERCP within 72 h was not associated with ERCP-related complications (P = 0.113), and the total length of hospital stay was not different between urgent and early ERCP (5.9 vs. 5.7 days, P = 0.174). No significant differences were found in total length of hospitalization or procedural-related complications, in patients with biliary pancreatitis and a bile duct obstruction without cholangitis, according to the timing of ERCP (< 24 h vs. 24-72 h).

Complications and management of forgotten long-term biliary stents.

PubMed

Sohn, Se Hoon; Park, Jae Hyun; Kim, Kook Hyun; Kim, Tae Nyeun

2017-01-28

To evaluate complications and management outcomes of retained long-term plastic biliary stents. Endoscopic plastic biliary stent placement was performed in 802 patients at Yeungnam University Hospital between January 2000 and December 2014. Follow-up loss with a subsequently forgotten stent for more than 12 mo occurred in 38 patients. We retrospectively examined the cause of biliary stent insertion, status of stents, complications associated with biliary stents and management outcomes of long-term plastic biliary stents. Continuous variables were analyzed using the t test. Observed frequencies in subsets of the study population were compared using Fisher's exact test and χ 2 tests. Statistical significance was defined as P < 0.05 (two-tailed). Mean age of patients was 73.7 ± 12 years and male-to-female ratio was 2.2:1. Indications of plastic biliary stent insertion were bile duct stones (63.2%, 24/38) and benign bile duct stricture (52.6%, 20/38). Mean duration of retained plastic stent was 22.6 ± 12.2 mo, and in 10 cases (26.3%), stents were retained for more than 24 mo. Common bile duct (CBD) stones or sludge were found in most cases (92.1%, 35/38). The most common complication was acute cholangitis (94.7%, 36/38). Stent removal by endoscopic approach was successfully performed in 92.1% (35/38) of the cases. In 3 cases, an additional plastic stent was inserted alongside the previous stent due to failure of the stent removal. Endoscopic removal of bile duct stones was successful in 73.7% (28/38) of the cases. When patients were divided into two groups by duration of stent placement (12 to 24 mo vs over 24 mo), there were no differences in the development of cholangitis, presence of biliary stones, and success rate of endoscopic removal of stones and biliary stents. The most common complication of retained long-term plastic biliary stents was acute cholangitis associated with CBD stones. Endoscopic management was successfully performed in most cases.

Complications and management of forgotten long-term biliary stents

PubMed Central

Sohn, Se Hoon; Park, Jae Hyun; Kim, Kook Hyun; Kim, Tae Nyeun

2017-01-01

AIM To evaluate complications and management outcomes of retained long-term plastic biliary stents. METHODS Endoscopic plastic biliary stent placement was performed in 802 patients at Yeungnam University Hospital between January 2000 and December 2014. Follow-up loss with a subsequently forgotten stent for more than 12 mo occurred in 38 patients. We retrospectively examined the cause of biliary stent insertion, status of stents, complications associated with biliary stents and management outcomes of long-term plastic biliary stents. Continuous variables were analyzed using the t test. Observed frequencies in subsets of the study population were compared using Fisher’s exact test and χ2 tests. Statistical significance was defined as P < 0.05 (two-tailed). RESULTS Mean age of patients was 73.7 ± 12 years and male-to-female ratio was 2.2:1. Indications of plastic biliary stent insertion were bile duct stones (63.2%, 24/38) and benign bile duct stricture (52.6%, 20/38). Mean duration of retained plastic stent was 22.6 ± 12.2 mo, and in 10 cases (26.3%), stents were retained for more than 24 mo. Common bile duct (CBD) stones or sludge were found in most cases (92.1%, 35/38). The most common complication was acute cholangitis (94.7%, 36/38). Stent removal by endoscopic approach was successfully performed in 92.1% (35/38) of the cases. In 3 cases, an additional plastic stent was inserted alongside the previous stent due to failure of the stent removal. Endoscopic removal of bile duct stones was successful in 73.7% (28/38) of the cases. When patients were divided into two groups by duration of stent placement (12 to 24 mo vs over 24 mo), there were no differences in the development of cholangitis, presence of biliary stones, and success rate of endoscopic removal of stones and biliary stents. CONCLUSION The most common complication of retained long-term plastic biliary stents was acute cholangitis associated with CBD stones. Endoscopic management was successfully

JBP485 promotes tear and mucin secretion in ocular surface epithelia

PubMed Central

Nakamura, Takahiro; Hata, Yuiko; Nagata, Maho; Yokoi, Norihiko; Yamaguchi, Shumpei; Kaku, Taiichi; Kinoshita, Shigeru

2015-01-01

Dry eye syndrome (DES), a multifactorial disease of the tears and ocular surface, is one of the most common ocular disorders. Tear film contains ocular mucins and is essential for maintaining the homeostasis of the wet ocular surface. Since there are a limited number of clinical options for the treatment of DES, additional novel treatments are needed to improve the clinical results. In this study, we found that placental extract-derived dipeptide (JBP485) clearly promoted the expression and secretion of gel-forming mucin 5ac (Muc5ac) in rabbit conjunctival epithelium. JBP485 also elevated the expression level of cell surface-associated mucins (Muc1/4/16) in rabbit corneal epithelium. The Schirmer tear test results indicated that JBP485 induced tear secretion in the rabbit model. Moreover, JBP485 clinically improved corneal epithelial damage in a mouse dry eye model. Thus, our data indicate that JBP485 efficiently promoted mucin and aqueous tear secretion in rabbit ocular surface epithelium and has the potential to be used as a novel treatment for DES. PMID:25996902

JBP485 promotes tear and mucin secretion in ocular surface epithelia.

PubMed

Nakamura, Takahiro; Hata, Yuiko; Nagata, Maho; Yokoi, Norihiko; Yamaguchi, Shumpei; Kaku, Taiichi; Kinoshita, Shigeru

2015-05-21

Dry eye syndrome (DES), a multifactorial disease of the tears and ocular surface, is one of the most common ocular disorders. Tear film contains ocular mucins and is essential for maintaining the homeostasis of the wet ocular surface. Since there are a limited number of clinical options for the treatment of DES, additional novel treatments are needed to improve the clinical results. In this study, we found that placental extract-derived dipeptide (JBP485) clearly promoted the expression and secretion of gel-forming mucin 5ac (Muc5ac) in rabbit conjunctival epithelium. JBP485 also elevated the expression level of cell surface-associated mucins (Muc1/4/16) in rabbit corneal epithelium. The Schirmer tear test results indicated that JBP485 induced tear secretion in the rabbit model. Moreover, JBP485 clinically improved corneal epithelial damage in a mouse dry eye model. Thus, our data indicate that JBP485 efficiently promoted mucin and aqueous tear secretion in rabbit ocular surface epithelium and has the potential to be used as a novel treatment for DES.

Frey procedure combined with biliary diversion in chronic pancreatitis.

PubMed

Merdrignac, Aude; Bergeat, Damien; Rayar, Michel; Harnoy, Yann; Turner, Kathleen; Courtin-Tanguy, Laetitia; Boudjema, Karim; Meunier, Bernard; Sulpice, Laurent

2016-11-01

The Frey procedure has become the standard operative treatment in chronic painful pancreatitis. Biliary diversion could be combined when associated with common bile duct obstruction. The aim of the present study was to evaluate the impact of the type of biliary diversion combined with the Frey procedure on late morbidity. The data from consecutive patients undergoing the Frey procedure and having a minimum follow-up of 2 years were extracted from a maintained prospective database. The mean endpoint was the rate of secondary biliary stricture after the Frey procedure combined with biliary diversion (bilioenteric anastomosis or common bile duct reinsertion in the resection cavity). Between 2006 and 2013, 55 consecutive patients underwent the Frey procedure. Twenty-nine patients had common bile duct obstruction (52.7%). The technique of biliary diversion resulted in bilioenteric anastomosis in 19 patients (65.5%) and common bile duct reinsertion in 10 patients (34.5%). Preoperative characteristics and early surgical outcomes were comparable. Pain control was similar. There was significantly more secondary biliary stricture after common bile duct reinsertion than after bilioenteric anastomosis (60% vs 11%, P = .008). Combined bilioenteric anastomosis during the Frey procedure is an efficient technique for treating common bile duct obstruction that complicates chronic painful pancreatitis. Bilioenteric anastomosis was associated with less secondary biliary stricture than common bile duct reinsertion in the pancreatic resection cavity. Copyright © 2016 Elsevier Inc. All rights reserved.

Mucinous (colloid) adenocarcinomas secrete distinct O-acylated forms of sialomucins: a histochemical study of gastric, colorectal and breast adenocarcinomas.

PubMed

Sáez, C; Japón, M A; Poveda, M A; Segura, D I

2001-12-01

Mucinous (colloid) adenocarcinomas represent a distinct group of tumours defined by the presence of large amounts of extracellular mucins. By using histochemical methods, we analysed mucins secreted by mucinous versus non-mucinous adenocarcinomas and looked for differential secretion profiles. Sixty-four adenocarcinomas were studied (23 colorectal, 17 gastric, and 24 breast tumours). Thirty-two tumours were of the colloid type. The following methods were applied to paraffin tissue sections: (i) Alcian blue (pH 2.5) and periodic acid-Schiff (PAS); (ii) high iron diamine and Alcian blue (pH 2.5); (iii) periodic acid borohydride, potassium hydroxide, and PAS; (iv) periodic acid-thionine Schiff, potassium hydroxide, and PAS; and (v) periodic acid-borohydride and PAS. Most adenocarcinomas secreted acidic mucins, with sialomucins predominating over sulfomucins, except for non-mucinous adenocarcinomas of the breast which showed predominant neutral mucins. All mucinous adenocarcinomas contained C9-O-acyl sialic acid as mono, di(C8,C9)-, or tri(C7,C8,C9)-O-acyl forms. Acidic mucins secreted by the majority of non-colloid adenocarcinomas consisted of non-O-acylated sialomucins. C9-O-acylation of sialic acid is a characteristic feature of mucinous adenocarcinomas and can be readily detected by histochemical methods.

Surgical Treatment for Biliary Carcinoma Arising After Pancreatoduodenectomy

PubMed Central

Seki, Hitoshi; Kobayashi, Akira; Kawasaki, Seiji

1998-01-01

The clinicopathological features and surgical treatment of biliary carcinoma around the major hepatic duct confluence arising after pancreatoduodenectomy (PD) due to initial bile duct carcinoma are described in three patients. Occurrence of biliary carcinoma more than 12 years after initial surgery and a histological finding of cholangiocellular carcinoma mixed with hepatocellular carcinoma suggested metachronous incidence of biliary carcinoma after PD. Extended right hemihepatectomy with complete removal of the residual extrahepatic bile duct and segmental, resection of the jejunal loop were carried out safely without operative death or severe postoperative complications. Two patients died of tumor recurrence 6 months after surgery, and the remaining patient is currently living a normal life without evidence of recurrence 17 months after surgery. These surgical procedures are a therapeutic option in patients with biliary carcinoma around the major hepatic duct confluence arising after PD. PMID:9515238

Treatment and outcome of traumatic biliary injuries in children.

PubMed

Soukup, Elizabeth S; Russell, Katie W; Metzger, Ryan; Scaife, Eric R; Barnhart, Douglas C; Rollins, Michael D

2014-02-01

Traumatic biliary tract injuries in children are rare but may result in significant morbidity. The objective of this study was to review the occurrence of traumatic biliary tract injuries in children, management strategies, and outcome. We conducted a retrospective review of patients with biliary tract injury using the trauma registry at our level 1 pediatric trauma center from 2002-2012. Twelve out of 13,582 trauma patients were identified, representing 0.09% of all trauma patients. All were secondary to blunt trauma. Mean age was 9.7 years [range 4-15], and mean Injury Severity Score was 31 ± 14, with overall survival of 92%. Biliary injuries included major ductal injury (6), minor ductal injury with biloma (4), gallbladder injury (2), and intrahepatic ductal injury (1). Major ductal injuries were managed by endoscopic retrograde cholangiopancreatography (ERCP) and biliary stent (5) and Roux-en-Y hepaticojejunostomy (1). Associated gallbladder injury was managed by cholecystectomy. In addition, the associated biloma was managed with percutaneous drainage (7), laparoscopic drainage (2), or during laparotomy (3). Two patients with ductal injuries developed late strictures after initial management with ERCP and stent placement. One of the two patients ultimately required a left hepatectomy, and the other has been managed conservatively without evidence of cholangitis. Two patients required placement of additional drains and prolonged antibiotics for superinfection following biloma drainage. Biliary tract injuries are rare in children, and many are amenable to adjunctive therapy, including ERCP and biliary stent placement with or without placement of a peritoneal drain. Patients with a discrete ductal injury are at higher risk for stricture and require close follow up. Hepaticojejunostomy remains the definitive repair for large extrahepatic biliary tract injuries or transections. © 2014.

Mucinous Breast Cancer: a Review Study of 5 Year Experience from a Hospital-Based Series of Cases.

PubMed

Dumitru, Adrian; Procop, Alexandru; Iliesiu, Andreea; Tampa, Mircea; Mitrache, Luminita; Costache, Mariana; Sajin, Maria; Lazaroiu, Anca; Cirstoiu, Monica

2015-03-01

Mucinous carcinoma (also known as colloid carcinoma) is a particular type of breast cancer characterized by the presence of extracellular mucin and is linked with a more favorable prognosis than invasive breast carcinoma of no special type. Mucinous carcinoma of the breast is an uncommon form of breast tumor, often presenting as a lobulated, moderately well circumscribed mass on mammography, sonography, and MRI imaging. It accounts for 1 to 7% of all breast cancers. Pure mucinous breast carcinomas are rare and account for about 2% of all primary breast carcinomas. Metastatic disease happens at a lower rate than in other types of invasive carcinoma. We present our 5 year experience with this particular pathology in a retrospective review study. We identified 25 patients with mixed and pure mucinous breast cancer, the tumor size varied greatly from 2 to 19 cm in diameter. A subset of mixed mucinous carcinomas (8 cases) showed neuroendocrine differentiation or other associated premalignant lessions. Mucinous carcinoma of the breast is a rare entity with a favorable prognosis due to low incidence of lymph node metastases. Pure mucinous breast carcinoma has an even rare.

Mucinous Breast Cancer: a Review Study of 5 Year Experience from a Hospital-Based Series of Cases

PubMed Central

DUMITRU, Adrian; PROCOP, Alexandru; ILIESIU, Andreea; TAMPA, Mircea; MITRACHE, Luminita; COSTACHE, Mariana; SAJIN, Maria; LAZAROIU, Anca; CIRSTOIU, Monica

2015-01-01

Background: Mucinous carcinoma (also known as colloid carcinoma) is a particular type of breast cancer characterized by the presence of extracellular mucin and is linked with a more favorable prognosis than invasive breast carcinoma of no special type. Mucinous carcinoma of the breast is an uncommon form of breast tumor, often presenting as a lobulated, moderately well circumscribed mass on mammography, sonography, and MRI imaging. It accounts for 1 to 7% of all breast cancers. Pure mucinous breast carcinomas are rare and account for about 2% of all primary breast carcinomas. Metastatic disease happens at a lower rate than in other types of invasive carcinoma. Methods: We present our 5 year experience with this particular pathology in a retrospective review study. Results: We identified 25 patients with mixed and pure mucinous breast cancer, the tumor size varied greatly from 2 to 19 cm in diameter. A subset of mixed mucinous carcinomas (8 cases) showed neuroendocrine differentiation or other associated premalignant lessions. Conclusion: Mucinous carcinoma of the breast is a rare entity with a favorable prognosis due to low incidence of lymph node metastases. Pure mucinous breast carcinoma has an even rare. PMID:26225144

Risk factors for benign serous and mucinous epithelial ovarian tumors.

PubMed

Jordan, Susan J; Green, Adèle C; Whiteman, David C; Webb, Penelope M

2007-03-01

To investigate the risk factors for benign serous and mucinous epithelial ovarian tumors. Cases were women newly diagnosed with benign serous ovarian tumors (n=230) or benign mucinous tumors (n=133) between 2002 and 2005. Control women were selected at random from the general population (n=752). All participants completed a comprehensive reproductive and lifestyle questionnaire. Multivariable logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) and to simultaneously adjust for potential confounding factors. Current smoking was associated with a three-fold increase in risk of benign mucinous tumors (OR 3.25, 95% CI 1.97-5.34), and there was a trend of increasing risk with increasing amount smoked (P<.001). Both recent obesity (OR 1.93, 95% CI 1.30-2.88) and obesity at age 20 (OR 4.38, 95% CI 1.88-10.20) were associated with increased risk of benign serous ovarian tumors, and having had a hysterectomy was also related to increased risk of serous (OR 2.75, 95% CI 1.90-3.96), but not mucinous tumors. Ever having had a term pregnancy was inversely associated with both tumor types (combined OR 0.65, 95% CI 0.43-0.97), although greater numbers of pregnancies did not decrease risk further. Use of hormonal contraceptives was unrelated to risk. Our results suggest some differences in risk factors between benign serous and mucinous epithelial ovarian tumors and that risk factors for benign serous tumors differ from those well established for ovarian cancer. The results also suggest that there is potential for prevention of these common conditions through avoidance of smoking and obesity. II.

A Prospective Study of the Incidence of Juvenile-Onset Recurrent Respiratory Papillomatosis After Implementation of a National HPV Vaccination Program.

PubMed

Novakovic, Daniel; Cheng, Alan T L; Zurynski, Yvonne; Booy, Robert; Walker, Paul J; Berkowitz, Robert; Harrison, Henley; Black, Robert; Perry, Christopher; Vijayasekaran, Shyan; Wabnitz, David; Burns, Hannah; Tabrizi, Sepehr N; Garland, Suzanne M; Elliott, Elizabeth; Brotherton, Julia M L

2018-01-04

Recurrent respiratory papillomatosis is a rare but morbid disease caused by human papillomavirus (HPV) types 6 and 11. Infection is preventable through HPV vaccination. Following an extensive quadrivalent HPV vaccination program (females 12-26 years in 2007-2009) in Australia, we established a method to monitor incidence and demographics of juvenile-onset recurrent respiratory papillomatosis (JORRP) cases. The Australian Paediatric Surveillance Unit undertakes surveillance of rare pediatric diseases by contacting practitioners monthly. We enrolled pediatric otorhinolaryngologists and offered HPV typing. We report findings for 5 years to end 2016. The average annual incidence rate was 0.07 per 100000. The largest number of cases was reported in the first year, with decreasing annual frequency thereafter. Rates declined from 0.16 per 100000 in 2012 to 0.02 per 100000 in 2016 (P = .034). Among the 15 incident cases (60% male), no mothers were vaccinated prepregnancy, 20% had maternal history of genital warts, and 60% were first born; 13/15 were born vaginally. Genotyped cases were HPV-6 (n = 4) or HPV-11 (n = 3). To our knowledge, this is the first report internationally documenting decline in JORRP incidence in children following a quadrivalent HPV vaccination program. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Ischemic mass effect from biliary surgical clips.

PubMed

Mateo, Rod; Tsai, Steven; Stapfer, Maria V; Sher, Linda S; Selby, Rick; Genyk, Yuri S

2008-02-01

Migrating surgical clips in the hepatic hilum are known causes of biliary stricture or obstruction, most often due to direct intraluminal obstruction or secondary stone formation. Two cases are reported on patients with previous cholecystectomies presenting with delayed symptoms of biliary tract stricture. Both patients were successfully treated with a resection of the strictured area and a Roux-en-Y hepatico-jejunostomy. Resected specimens grossly demonstrated surgical clips adjacent to the stricture, but not directly within the lumen, suggestive of an ischemic mass effect, which was supported by histology. In addition to the direct intraluminal obstruction and lithogenic effects of migratory surgical clips, "clipomas" due to an ischemic mass effect can also lead to biliary tract strictures.

Fermentation of mucin and plant polysaccharides by strains of Bacteroides from the human colon.

PubMed Central

Salyers, A A; Vercellotti, J R; West, S E; Wilkins, T D

1977-01-01

Ten Bacteroides species found in the human colon were surveyed for their ability to ferment mucins and plant polysaccharides ("dietary fiber"). A number of strains fermented mucopolysaccharides (heparin, hyaluronate, and chondroitin sulfate) and ovomucoid. Only 3 of the 188 strains tested fermented beef submaxillary mucin, and none fermented porcine gastric mucin. Many of the Bacteroides strains tested were also able to ferment a variety of plant polysaccharides, including amylose, dextran, pectin, gum tragacanth, gum guar, larch arabinogalactan, alginate, and laminarin. Some plant polysaccharides such as gum arabic, gum karaya, gum ghatti and fucoidan, were not utilized by any of the strains tested. The ability to utilize mucins and plant polysaccharides varied considerably among the Bacteroides species tested. PMID:848954

Ocular melanoma and mammary mucinous carcinoma in an African lion.

PubMed

Cagnini, Didier Q; Salgado, Breno S; Linardi, Juliana L; Grandi, Fabrizio; Rocha, Rafael M; Rocha, Noeme S; Teixeira, Carlos R; Del Piero, Fabio; Sequeira, Julio L

2012-09-25

Reports of neoplasms in Panthera species are increasing, but they are still an uncommon cause of disease and death in captive wild felids. The presence of two or more primary tumor in large felids is rarely reported, and there are no documented cases of ocular melanoma and mammary mucinous carcinoma in African lions. An ocular melanoma and a mammary mucinous carcinoma are described in an African lion (Panthera leo). The first tumour was histologically characterized by the presence of epithelioid and fusiform melanocytes, while the latter was composed of mucus-producing cells with an epithelial phenotype that contained periodic acid-Schiff (PAS) and Alcian blue staining mucins. Metastases of both tumor were identified in various organs and indirect immunohistochemistry was used to characterize them. Peribiliary cysts were observed in the liver. This is the first description of these tumor in African lions.

Recurrent mucinous adenocarcinoma of the ovary presenting as an inguino-labial hernia.

PubMed

Ben-Hur, H; Schachter, M; Mashiah, A; Lifschitz-Mercer, B; Pfeffermann, R

1996-01-01

We report a case of a 65-year-old woman who nine years previously had undergone total abdominal hysterectomy and bilateral salpingoophorectomy for a large ovarian cyst. During surgery the cyst had ruptured and some mucinous material had been spilled intraabdominally. Histopathological studies demonstrated the cyst to be a mucinous adenocarcinoma of low malignant potential. Appendectomy had also been performed due to an enlarged appendix, which proved to be a mucocoele. The patient had been lost to subsequent follow-up. Her current presenting symptom was a giant inguino-labial hernia of 25 cm diameter with two small skin perforations leaking a gelatinous discharge. Subsequent laparotomy and inguinal exploration have disclosed herniated small intestine with an attached metastatic multicystic mucinous adenocarcinoma. This case represents a case of borderline mucinous adeno-carcinoma-pseudomyxoma peritonei recurring in a unique pattern as a huge inguino-labial hernia, and serves to emphasize the possible consequences of spillage of ovarian cyst contents during surgery.

Post-cholecystectomy syndrome: spectrum of biliary findings at magnetic resonance cholangiopancreatography

PubMed Central

Girometti, R; Brondani, G; Cereser, L; Como, G; Del Pin, M; Bazzocchi, M; Zuiani, C

2010-01-01

Post-cholecystectomy syndrome (PCS) is defined as a complex of heterogeneous symptoms, consisting of upper abdominal pain and dyspepsia, which recur and/or persist after cholecystectomy. Nevertheless, this term is inaccurate, as it encompasses biliary and non-biliary disorders, possibly unrelated to cholecystectomy. Biliary manifestations of PCS may occur early in the post-operative period, usually because of incomplete surgery (retained calculi in the cystic duct remnant or in the common bile duct) or operative complications, such as bile duct injury and/or bile leakage. A later onset is commonly caused by inflammatory scarring strictures involving the sphincter of Oddi or the common bile duct, recurrent calculi or biliary dyskinesia. The traditional imaging approach for PCS has involved ultrasound and/or CT followed by direct cholangiography, whereas manometry of the sphincter of Oddi and biliary scintigraphy have been reserved for cases of biliary dyskinesia. Because of its capability to provide non-invasive high-quality visualisation of the biliary tract, magnetic resonance cholangiopancreatography (MRCP) has been advocated as a reliable imaging tool for assessing patients with suspected PCS and for guiding management decisions. This paper illustrates the rationale for using MRCP, together with the main MRCP biliary findings and diagnostic pitfalls. PMID:20335441

Immunohistochemical study of mucins in human intestinal spirochetosis.

PubMed

Ogata, Sho; Shimizu, Ken; Tominaga, Susumu; Nakanishi, Kuniaki

2017-04-01

Most patients with human intestinal spirochetosis (HIS; a colorectal bacterial infection caused by Brachyspira species) seem asymptomatic, and its pathogenicity remains unclear. Recently, alterations in mucin expression were reported in animal Brachyspira infection. The present question was "Is mucin expression altered in HIS?" Using antibodies for MUCs 1, 2, 4, 5AC, and 6, we immunohistochemically compared 215 specimens from 83 histology-confirmed HIS cases with 106 specimens from 26 non-HIS cases. Positive staining (which included even focal positive staining) was rated "high (+)" or "low (+)." Results were analyzed for 4 categories of lesions, and associations between MUC expression and spirochetal presence were also analyzed. In the "specimens without polyps or adenocarcinoma" category, high (+) MUC2 positivity was more frequent in HIS than in control. In the hyperplasia/serrated polyp category, in HIS (versus control), the MUC5AC positivity rate was lower, whereas high (+) MUC4 positivity was more frequent. In the conventional adenoma category, in HIS (versus control), the MUC1 positivity rate was lower, whereas both high (+) MUC2 positivity and high (+) MUC5AC positivity were less frequent. In the adenocarcinoma category, high (+) MUC2 positivity was more frequent in HIS than in control. Among the above mucins, only MUC1 positivity was significantly associated with an absence of the so-called fringe formation, an absence of spiral organisms within mucus, and an absence of strong immunopositive materials within the epithelial layer and within the subepithelial layer. The results suggest that Brachyspira infection or a related change in the microbiome may alter the large intestine mucin expression profile in humans. Copyright © 2017 Elsevier Inc. All rights reserved.

Late-onset severe biliary bleeding after endoscopic pigtail plastic stent insertion.

PubMed

Yasuda, Muneji; Sato, Hideki; Koyama, Yuki; Sakakida, Tomoki; Kawakami, Takumi; Nishimura, Takeshi; Fujii, Hideki; Nakatsugawa, Yoshikazu; Yamada, Shinya; Tomatsuri, Naoya; Okuyama, Yusuke; Kimura, Hiroyuki; Ito, Takaaki; Morishita, Hiroyuki; Yoshida, Norimasa

2017-01-28

Here, we report our experience with a case of severe biliary bleeding due to a hepatic arterial pseudoaneurysm that had developed 1 year after endoscopic biliary plastic stent insertion. The patient, a 78-year-old woman, presented with hematemesis and obstructive jaundice. Ruptured hepatic arterial pseudoaneurysm was diagnosed, which was suspected to have been caused by long-term placement of an endoscopic retrograde biliary drainage (ERBD) stent. This episode of biliary bleeding was successfully treated by transarterial embolization (TAE). Pseudoaneurysm leading to hemobilia is a rare but potentially fatal complication in patients with long-term placement of ERBD. TAE is a minimally invasive procedure that offers effective treatment for biliary bleeding.

[Iatrogenic biliary lesions and stenosis].

PubMed

Latteri, S; Vecchio, R; Angilello, A

1997-01-01

Pathogenetic, diagnostic and therapeutic aspects of postoperative bile duct injuries are reviewed. Treatment options are discussed in relation to the time of diagnosis. Lesions detected during the same operation must be immediately repaired through an end-to-end biliary anastomosis or a bilioenteric anastomosis. In limited lesions of the bile duct a T-tube placement should be sufficient. Bile duct lesions recognized postoperatively can be managed through a multimodal surgical, endoscopic, and radiologic approach. In the early postoperative period, surgery is indicated when a complete section of the biliary tract or a severe peritonitis is recognized, or when endoscopic and radiologic treatment has failed. Surgery is also the treatment of choice in the late complete stenosis of the bile duct. Roux-en-Y hepatico-jejunostomy is the most common surgical procedure for the treatment of bile duct lesions and strictures. However, in high bile duct lesions, especially if the risk of anastomotic dehiscence is increased the Authors emphasize the Rodney-Smith technique for the reconstruction of the biliary tract.

Membrane-bound (MUC1) and secretory (MUC2, MUC3, and MUC4) mucin gene expression in human lung cancer.

PubMed

Nguyen, P L; Niehans, G A; Cherwitz, D L; Kim, Y S; Ho, S B

1996-01-01

Abnormalities of mucin-type glycoproteins have been described in lung cancers, but their molecular basis is unknown. In this study, mucin-core-peptide-specific antibodies and cDNA probes were used to determine the relative expression of mucin genes corresponding to one membrane-bound mucin (MUC1), two intestinal mucins (MUC2 and MUC3), and one tracheobronchial mucin (MUC4) in normal (nonneoplastic) lung, and in lung neoplasms. Normal lung tissues exhibited a distinct pattern of mucin gene expression, with high levels of MUC1 and MUC4 mRNA and low to absent levels of MUC2 and MUC3 mucin immunoreactivity and mRNA. In contrast, lung adenocarcinomas, especially well-differentiated cancers, exhibited increased MUC1, MUC3, and MUC4 mRNA levels. Lung squamous-cell, adenosquamous, and large-cell carcinomas were characterized by increased levels of MUC4 mucin only. We conclude that the expression of one membrane-bound and several secretory-type mucins is independently regulated and markedly altered in lung neoplasms. The frequent occurrence of increased MUC4 transcripts in a variety of non-small-cell lung cancers indicates the potential importance of this type of mucin in lung cancer biology.

Immunological response to quadrivalent HPV vaccine in treatment of recurrent respiratory papillomatosis.

PubMed

Tjon Pian Gi, Robin E A; San Giorgi, Michel R M; Pawlita, Michael; Michel, Angelika; van Hemel, Bettien M; Schuuring, Ed M D; van den Heuvel, Edwin R; van der Laan, Bernard F A M; Dikkers, Frederik G

2016-10-01

Aim of this study was to explore influence of the quadrivalent HPV vaccine (Gardasil(®)) on the immune status of recurrent respiratory papillomatosis (RRP) patients. In retrospective observational study, six RRP patients who received the quadrivalent HPV vaccine and whose HPV seroreactivity was measured were included. Multiplex HPV Serology was used to determine HPV-specific antibodies pre- and post-vaccination. Surgical interventions and patient records were analyzed. Five HPV6 and 1 HPV11 infected patient were included. Mean antibody reactivity against the associated HPV type rose from 1125 median fluorescence intensity (MFI) pre-vaccination to 4690 MFI post-vaccination (p < 0.001). Median post-vaccination follow-up was 4 years. Poisson regression analysis showed that the quadrivalent HPV vaccine decreased the incidence rate of surgeries. The immune system of RRP patients is able to increase antibody reactivity against the associated HPV type. A double blind randomized controlled trial is needed to determine whether this immunological increase can cause decrease in number of surgeries.

Hyaluronic Acid Molecular Weight-Dependent Modulation of Mucin Nanostructure for Potential Mucosal Therapeutic Applications.

PubMed

Hansen, Irene M; Ebbesen, Morten F; Kaspersen, Liselotte; Thomsen, Troels; Bienk, Konrad; Cai, Yunpeng; Malle, Birgitte Mølholm; Howard, Kenneth A

2017-07-03

This study investigates the effects of different molecular weight hyaluronic acids (HAs) on the mucosal nanostructure using a pig stomach mucin hydrogel as a mucosal barrier model. Microparticles (1.0 μm) and nanoparticles (200 nm) were used as probes, and their movement in mucin was studied by a three-dimensional confocal microscopy-based particle tracking technique and by Nanoparticle Tracking Analysis (NTA) after addition of high-molecular weight (900 kDa) and low-molecular weight (33 kDa) HA. This demonstrated a molecular weight-dependent HA modulation of the mucin nanostructure with a 2.5-fold decrease in the mobility of 200 nm nanoparticles. To further investigate these mechanisms and to verify that the natural viscoelastic properties of mucus are not undesirably altered, rheological measurements were performed on mucin hydrogels with or without HA. This suggested the observed particle mobility restriction was not attributed to alterations of the natural mucin cohesive and viscoelastic properties but, instead, indicates that the added high-molecular weight HA primarily modulates the mucin nanostructure and mesh size. This study, hereby, demonstrates how mucus nanostructure can be modulated by the addition of high-molecular weight HA that offers an opportunity to control mucosal pathogenesis and drug delivery.

Glycobiology of the ocular surface: Mucins and lectins

PubMed Central

Argüeso, Pablo

2013-01-01

Glycosylation is an important and common form of posttranscriptional modification of proteins in cells. A vast array of biological functions has been ascribed to glycans during the last decade thanks to a rapid evolution in glycomic technologies. Glycogenes highly expressed at the human ocular surface include families of glycosyltransferases, proteoglycans, glycan degradation proteins, as well as mucins and carbohydrate-binding proteins such as the galectins. On the apical glycocalyx, mucin O-glycans promote boundary lubrication, prevent bacterial adhesion and endocytic activity, and maintain epithelial barrier function through interactions with galectins. The emerging roles attributed to glycans are contributing to the appreciation of their biological capabilities at the ocular surface. PMID:23325272

The mucin-degradation strategy of Ruminococcus gnavus: The importance of intramolecular trans-sialidases.

PubMed

Crost, Emmanuelle H; Tailford, Louise E; Monestier, Marie; Swarbreck, David; Henrissat, Bernard; Crossman, Lisa C; Juge, Nathalie

2016-07-03

We previously identified and characterized an intramolecular trans-sialidase (IT-sialidase) in the gut symbiont Ruminococcus gnavus ATCC 29149, which is associated to the ability of the strain to grow on mucins. In this work we have obtained and analyzed the draft genome sequence of another R. gnavus mucin-degrader, ATCC 35913, isolated from a healthy individual. Transcriptomics analyses of both ATCC 29149 and ATCC 35913 strains confirmed that the strategy utilized by R. gnavus for mucin-degradation is focused on the utilization of terminal mucin glycans. R. gnavus ATCC 35913 also encodes a predicted IT-sialidase and harbors a Nan cluster dedicated to sialic acid utilization. We showed that the Nan cluster was upregulated when the strains were grown in presence of mucin. In addition we demonstrated that both R. gnavus strains were able to grow on 2,7-anyhydro-Neu5Ac, the IT-sialidase transglycosylation product, as a sole carbon source. Taken together these data further support the hypothesis that IT-sialidase expressing gut microbes, provide commensal bacteria such as R. gnavus with a nutritional competitive advantage, by accessing and transforming a source of nutrient to their own benefit.

Evaluation of endothelial mucin layer thickness after phacoemulsification with next generation ophthalmic irrigating solution.

PubMed

Ghate, Deepta A; Holley, Glenn; Dollinger, Harli; Bullock, Joseph P; Markwardt, Kerry; Edelhauser, Henry F

2008-10-01

To evaluate human corneal endothelial mucin layer thickness and ultrastructure after phacoemulsification and irrigation-aspiration with either next generation ophthalmic irrigating solution (NGOIS) or BSS PLUS. Paired human corneas were mounted in an artificial anterior chamber, exposed to 3 minutes of continuous ultrasound (US) at 80% power using the Alcon SERIES 20000 LEGACY surgical system (n = 9) or to 2 minutes of pulsed US at 50% power, 50% of the time at 20 pps using the Alcon INFINITI Vision System (n = 5), and irrigated with 250 mL of either NGOIS or BSS PLUS. A control group of paired corneas did not undergo phacoemulsification or irrigation-aspiration (n = 5). Corneas were divided and fixed for mucin staining or transmission electron microscopy. Mucin layer thickness was measured on the transmission electron microscopy prints. The mucin layer thickness in the continuous phaco group was 0.77 +/- 0.02 microm (mean +/- SE) with NGOIS and 0.51 +/- 0.01 microm with BSS PLUS (t test, P < 0.001). The mucin layer thickness in the pulsed phaco group was 0.79 +/- 0.02 microm with NGOIS and 0.54 +/- 0.01 microm with BSS PLUS (P < 0.001). The mucin layer thickness in the untreated control group was 0.72 +/- 0.02 microm. The endothelial ultrastructure was normal in all corneas. In this in vitro corneal model, NGOIS, due to its lower surface tension and higher viscosity, preserved endothelial mucin layer thickness better than BSS PLUS with both the INFINITI Vision System (pulsed US) and the LEGACY surgical system (continuous US).

Comparison of intraductal ultrasonography-directed and cholangiography-directed endoscopic retrograde biliary drainage in patients with a biliary obstruction.

PubMed

Rew, Soo-Jung; Lee, Du-Hyeon; Park, Chang-Hwan; Jeon, Jin; Kim, Hyun-Soo; Choi, Sung-Kyu; Rew, Jong-Sun

2016-09-01

Endoscopic retrograde biliary drainage (ERBD) has become a standard procedure in patients with a biliary obstruction. Intraductal ultrasonography (IDUS) has emerged as a new tool for managing extrahepatic biliary diseases. IDUS-directed ERBD can be performed without conventional cholangiography (CC). The goal of this study was to assess the effectiveness and safety of IDUS-directed ERBD compared to CC-directed ERBD in patients with an extrahepatic biliary obstruction. A total of 210 patients who had undergone IDUS-directed ERBD (IDUS-ERBD, n = 105) and CC-directed ERBD (CC-ERBD, n = 105) between October 2013 and April 2014 were analyzed retrospectively. The primary outcome measure was the procedural success rate. Secondary outcome measures included clinical outcomes, total procedure time, radiation exposure time, and overall complication rates. The total technical success rate of ERBD was 100% (105/105) in the IDUS-ERBD and CC-ERBD groups. Mean procedure time was slightly prolonged in the IDUS-ERBD group than that in the CC-ERBD group (32.1 ± 9.9 minutes vs. 28.4 ± 11.6 minutes, p = 0.023). Mean radiation exposure time was one-third less in the IDUS-ERBD group than that in the CC-ERBD group (28.0 ± 49.3 seconds vs. 94.2 ± 57.3 seconds, p < 0.001). No significant differences in complication rates were detected between the groups. IDUS-ERBD was equally effective and safe as CC-ERBD in patients with an extrahepatic biliary obstruction. Although IDUS-ERBD increased total procedure time, it significantly decreased radiation exposure.

[Extrahepatic biliary atresia: diagnostic methods].

PubMed

Cauduro, Sydney M

2003-01-01

To emphasize the importance of precocious diagnosis of extrahepatic biliary atresia and its direct relationship with the surgical re-establishment of the biliary flow before the second month of life. To discuss several complementary methods with the aim of selecting the ones that present better evidence, and avoiding delays in diagnosis and worse prognostic. Bibliographical researching regarding the period of 1985-2001, in Medline and MdConsult, using the following key words: neo-natal cholestasis; extrahepatic biliary atresia; neo-natal hepatitis. National and foreign articles were also elected based on the bibliography of consulted publications, and when necessary, for better understanding of the theme, opinions emitted in theses and textbooks were referred. The revision of the consulted bibliography led to the assumption that early diagnosis of EHBA and surgical treatment to reestablish the biliary flow up to 60 days of life are fundamental in order to achieve good results. Among several complementary methods of diagnosis, cholangiography by MR, US and the hepatic biopsy are the ones that provide the largest success indexes. The referring of patients bearers of EHBA to centers of references in Brazil, is still made tardily, probably due to lack of enlightenment of the doctors of primary attention, allied to bureaucratic and technological difficulties. The experience in England in relation to the "Yellow Alert" program, allowed that the number of children referred to surgical treatment before the 60 days of life increased significantly. Among the complementary methods, the MR cholangiography, ultrasonography and hepatic biopsy should be used, depending on the technological resources of the diagnosis units.

Eosinophilic Cholangitis--A Challenging Diagnosis of Benign Biliary Stricture: A Case Report.

PubMed

Fragulidis, Georgios Panagiotis; Vezakis, Antonios I; Kontis, Elissaios A; Pantiora, Eirini V; Stefanidis, Gerasimos G; Politi, Aikaterini N; Koutoulidis, Vasilios K; Mela, Maria K; Polydorou, Andreas A

2016-01-01

When confronting a biliary stricture, both benign and malignant etiologies must be carefully considered as a variety of benign biliary strictures can masquerade as hilar cholangiocarcinoma (CCA). Therefore, patients could undergo a major surgery despite the possibility of a benign biliary disease. Approximately 15% to 24% of patients undergoing surgical resection for suspected biliary malignancy will have benign pathology. Eosinophilic cholangitis (EC) is a rare benign disorder of the biliary tract, which can cause obstructive jaundice and can pose a difficult diagnostic task. We present a rare case of a young woman who was referred to our hospital with obstructive painless jaundice due to a biliary stricture at the confluence of the hepatic bile ducts, with a provisional diagnosis of cholangiocarcinoma. Though, during her work up she was found to have EC, an extremely rare benign cause of biliary stricture, which is characterized by a dense eosinophilic infiltration of the biliary tree causing stricturing, fibrosis, and obstruction and which is reversible with short-term high-dose steroids. Despite its rarity, EC should be taken into consideration when imaging modalities demonstrate a biliary stricture, especially if preoperative diagnosis of malignancy cannot be made, in the setting of peripheral eosinophilia and the absence of cardinal symptoms of malignancy.

Plastic Biliary Stent Occlusion: Factors Involved and Possible Preventive Approaches

PubMed Central

Donelli, Gianfranco; Guaglianone, Emilio; Di Rosa, Roberta; Fiocca, Fausto; Basoli, Antonio

2007-01-01

Endoscopic biliary stenting is today the most common palliative treatment for patients suffering from obstructive jaundice associated with malignant hepatobiliary tumors or benign strictures. However, recurrent jaundice, with or without cholangitis, is a major complication of a biliary endoprosthesis insertion. Thus, stent removal and replacement with a new one frequently occurs as a consequence of device blockage caused by microbial biofilm growth and biliary sludge accumulation in the lumen. Factors and mechanisms involved in plastic stent clogging arising from epidemiological, clinical and experimental data, as well as the possible strategies to prevent biliary stent failure, will be reviewed and discussed. PMID:17456835

[Diagnostic performance of biliary ultrasound vs. magnetic resonance cholangiogram in patients with recurrent biliary obstruction.].

PubMed

Chávez-Valencia, V; Espinosa-Ortega, H F; Espinoza-Peralta, D; Arce-Salinas, C A

2009-01-01

Obstructive jaundice in patients with previous cholecystectomy requires a precise diagnosis. In the diagnostic algorithm, biliary ultrasound (BUS) and magnetic resonance cholangiogram (MRC) are used, although the accuracy of each method is unknown in our setting. No previous comparison of US and MRC in subjects with cholecystectomy has been made. To determine diagnostic accuracy of BUS and MRC in patients with recurrent biliary obstruction. Patients with endoscopic retrograde cholangiopacreatography (ERCP) demonstrating recurrent biliary obstruction by stones were included. All patients underwent BUS and MRC. We determined the diagnostic performance of each image study compared with ERCP. Twenty-seven patients with a mean age of 62.9 +/- 17.3 years-old were included. Sensitivity and specificity of BUS were 0.12 and 0.58, respectively. Figures for MRC were 0.88 and 0.82. Diagnostic agreement between ERCP and MRC was k= 0.66 whereas BUS had a k of only 0.26. MRC had good diagnostic performance for recurrent choledocolithiasis. BUS demonstrated lower accuracy compared with previous reports, so should not be considered in the initial approach of recurrent choledocus obstruction.

Role of stents and laser therapy in biliary strictures

NASA Astrophysics Data System (ADS)

Chennupati, Raja S.; Trowers, Eugene A.

2001-05-01

The most frequent primary cancers causing malignant obstructive jaundice were pancreatic cancer (57%), hilar biliary cancer (19% including metastatic disease), nonhilar biliary cancer (14%) and papillary cancer (10%). Endoscopic stenting has widely replaced palliative surgery for malignant biliary obstruction because of its lower risk and cost. Self-expandable metal stents are the preferred mode of palliation for hilar malignancies. Plastic stents have a major role in benign biliary strictures. Major complications and disadvantages associated with metallic stents include high cost, cholangitis. malposition, migration, unextractability, and breakage of the stents, pancreatitis and stent dysfunction. Dysfunction due to tumor ingrowth can be relieved by thermal methods (argon plasma coagulator therapy). We present a concise review of the efficacy of metallic stents for palliation of malignant strictures.

Percutaneous biliary covered stent insertion in patients with malignant duodenobiliary obstruction.

PubMed

Lee, Eunsol; Gwon, Dong Il; Ko, Gi-Young; Sung, Kyu-Bo; Yoon, Hyun-Ki; Shin, Ji Hoon; Kim, Jin Hyoung; Ko, Heung Kyu; Song, Ho-Young

2015-02-01

Although the use of polytetrafluoroethylene (PTFE)-covered biliary stents has proven to be feasible for the treatment of benign and malignant biliary disease, less is known regarding the outcomes of percutaneous placement of a covered stent in patients with malignant duodenobiliary obstruction. To investigate the technical and clinical efficacy of the percutaneous placement of a PTFE-covered biliary stent in patients with malignant duodenobiliary obstruction. From April 2007 to September 2012, the medical records of 45 consecutive patients with malignant duodenobiliary obstruction were retrospectively reviewed. All percutaneous biliary stent deployment was performed using PTFE-covered stents, whereas duodenal stent insertion was performed either fluoroscopically or endoscopically using covered or uncovered stents. Biliary stent deployment was technically successful in all patients. None of the stents migrated after deployment. Procedure-related minor complications, including self-limiting hemobilia, occurred in three (7%) patients. Successful internal drainage was achieved in 39 (87%) of the 45 patients. The median survival time after biliary stent placement was 62 days (95% confidence interval, 8-116 days), and the cumulative stent patency rates at 1, 3, 6, and 12 months were 96%, 92%, 75%, and 38%, respectively. The causes of biliary stent dysfunction included stent occlusion caused by a subsequently inserted duodenal stent (n = 7), food impaction (n = 3), and sludge incrustation (n = 1). One patient developed acute cholecystitis 131 days after biliary stent placement and underwent percutaneous transhepatic gallbladder drainage. Percutaneous insertion of a PTFE-covered stent is a safe and effective method for palliative treatment of patients with malignant duodenobiliary obstruction. If possible, subsequent biliary stent insertion is preferable in order to prevent possible biliary stent dysfunction caused by subsequent insertion of a duodenal stent. �

Benign Biliary Strictures and Leaks.

PubMed

Devière, Jacques

2015-10-01

The major causes of benign biliary strictures include surgery, chronic pancreatitis, primary sclerosing cholangitis, and autoimmune cholangitis. Biliary leaks mainly occur after surgery and, rarely, abdominal trauma. These conditions may benefit from a nonsurgical approach in which endoscopic retrograde cholangiopancreatography (ERCP) plays a pivotal role in association with other minimally invasive approaches. This approach should be evaluated for any injury before deciding about the method for repair. ERCP, associated with peroral cholangioscopy, plays a growing role in characterizing undeterminate strictures, avoiding both unuseful major surgeries and palliative options that might compromise any further management. Copyright © 2015 Elsevier Inc. All rights reserved.

[Biliary atresia - signs and symptoms, diagnosis, clinical management].

PubMed

Orłowska, Ewa; Czubkowski, Piotr; Socha, Piotr

Biliary atresia is a chronic cholangiopathy leading to progressive fibrosis of both intra- and extrahepatic bile ducts. The cause of the condition is unknown. Fundamental management of biliary atresia is surgical intervention and the outcomes of the treatment depend on the child's age with best results when performed within the first 2 months of life. Thus, the main role of pediatric healthcare is an urgent differential diagnosis and prompt qualification for the surgery, optimal postoperative management and early qualification for the liver transplantation in patients with persistent cholestasis. The authors discuss the clinical presentation, diagnosis and management of biliary atresia.

Repair of a mal-repaired biliary injury: a case report.

PubMed

Aldumour, Awad; Aseni, Paolo; Alkofahi, Mohmmad; Lamperti, Luca; Aldumour, Elias; Girotti, Paolo; De Carlis, Luciano-Gregorio

2009-05-14

Iatrogenic bile-duct injury post-laparoscopic cholecystectomy remains a major serious complication with unpredictable long-term results. We present a patient who underwent laparoscopic cholecystectomy for gallstones, in which the biliary injury was recognized intraoperatively. The surgical procedure was converted to an open one. The first surgeon repaired the injury over a T-tube without recognizing the anatomy and type of the biliary lesion, which led to an unusual biliary mal-repair. Immediately postoperatively, the abdominal drain brought a large amount of bile. A T-tube cholangiogram was performed. Despite the contrast medium leaking through the abdominal drain, the mal-repair was unrecognized. The patient was referred to our hospital for biliary leak. Ultrasound and cholangiography was repeated, which showed an unanatomical repair (right to left hepatic duct anastomosis over the T-tube), with evidence of contrast medium coming out through the abdominal drain. Eventually the patient was subjected to a definitive surgical treatment. The biliary continuity was re-established by a Roux-en-Y hepatico-jejunostomy, over transanastomotic external biliary stents. The patient is now doing well 4 years after the second surgical procedure. In reviewing the literature, we found a similar type of injury but we did not find a similar surgical mal-repair. We propose an algorithm for the treatment of early and late biliary injuries.

Repair of a mal-repaired biliary injury: A case report

PubMed Central

Aldumour, Awad; Aseni, Paolo; Alkofahi, Mohmmad; Lamperti, Luca; Aldumour, Elias; Girotti, Paolo; Carlis, Luciano Gregorio De

2009-01-01

Iatrogenic bile-duct injury post-laparoscopic cholecystectomy remains a major serious complication with unpredictable long-term results. We present a patient who underwent laparoscopic cholecystectomy for gallstones, in which the biliary injury was recognized intraoperatively. The surgical procedure was converted to an open one. The first surgeon repaired the injury over a T-tube without recognizing the anatomy and type of the biliary lesion, which led to an unusual biliary mal-repair. Immediately postoperatively, the abdominal drain brought a large amount of bile. A T-tube cholangiogram was performed. Despite the contrast medium leaking through the abdominal drain, the mal-repair was unrecognized. The patient was referred to our hospital for biliary leak. Ultrasound and cholangiography was repeated, which showed an unanatomical repair (right to left hepatic duct anastomosis over the T-tube), with evidence of contrast medium coming out through the abdominal drain. Eventually the patient was subjected to a definitive surgical treatment. The biliary continuity was re-established by a Roux-en-Y hepatico-jejunostomy, over transanastomotic external biliary stents. The patient is now doing well 4 years after the second surgical procedure. In reviewing the literature, we found a similar type of injury but we did not find a similar surgical mal-repair. We propose an algorithm for the treatment of early and late biliary injuries. PMID:19437572

Palliation of Malignant Biliary and Duodenal Obstruction with Combined Metallic Stenting

DOE Office of Scientific and Technical Information (OSTI.GOV)

Akinci, Devrim, E-mail: akincid@hotmail.com; Akhan, Okan; Ozkan, Fuat

2007-11-15

Purpose. The purpose of this study is to evaluate the efficacy of palliation of malignant biliary and duodenal obstruction with combined metallic stenting under fluoroscopy guidance. Materials and Methods. A retrospective analysis of 9 patients (6 men and 3 women) who underwent biliary and duodenal stenting was performed. The mean age of patients was 61 years (range: 42-80 years). The causes of obstruction were pancreatic carcinoma in 7 patients, cholangiocellular carcinoma in one, and duodenal carcinoma in the other. Biliary and duodenal stents were placed simultaneously in 4 patients. In other 5 patients dudodenal stents were placed after biliary stentingmore » when the duodenal obstruction symptoms have developed. In two patients duodenal stents were advanced via transgastric approach. Results. Technical success rate was 100 %. After percutaneous biliary drainage and stenting bilirubin levels decreased to normal levels in 6 patients and in remaining 3 patients mean reduction of 71% in bilirubin levels was achieved. Tumoral ingrowth occurred in one patient and percutaneous biliary restenting was performed 90 days after the initial procedure. Of the 9 patients, 6 patients were able to tolerate solid diet, whereas 2 patients could tolerate liquid diet and one patient did not show any improvement. Mean survival periods were 111 and 73 days after biliary and duodenal stenting, respectively. Conclusion. Combined biliary and duodenal stent placement which can be performed under fluoroscopic guidance without assistance of endoscopy is feasible and an effective method of palliation of malignant biliary and duodenal obstructions. If transoral and endoscopic approaches fail, percutaneous gastrostomy route allows duodenal stenting.« less

Office-based 532-nm pulsed KTP laser treatment of glottal papillomatosis and dysplasia.

PubMed

Zeitels, Steven M; Akst, Lee M; Burns, James A; Hillman, Robert E; Broadhurst, Matthew S; Anderson, R Rox

2006-09-01

Treatment of glottal papillomatosis and dysplasia was mirror-guided and done in surgeons' offices in the 19th century. It migrated to the operating room in the 20th century to accommodate direct laryngoscopic surgery, which required assistants to administer anesthesia and procedural support. The primary treatment goals, which are disease regression and voice restoration and/or maintenance, are tempered by the morbidity of general anesthesia and potential treatment-induced vocal deterioration. To obviate general anesthesia, office-based laser laryngeal surgery was first done in 2001 with the 585-nm pulsed dye laser (PDL), because it employs a fiber delivery system and its energy is selectively absorbed by oxyhemoglobin. Since then, this new angiolytic laser treatment paradigm has become a mainstay of management for many surgeons; however, there are a number of shortcomings of the PDL. To further develop this concept and address the limitations of the PDL, we used a 532-nm pulsed potassium titanyl phosphate (KTP) laser. A prospective assessment was performed on 48 patients in 72 cases of recurrent glottal dysplasia (36) or papillomatosis (36). All individuals had previously undergone microlaryngoscopic management with histopathologic evaluation. Two dysplasia patients did not tolerate the procedure. Of the treatable dysplasia cases, there was follow-up in 29 of 34. Disease regression was at least 75% in 18 of 29 cases (62%), 50% to 75% in 7 of 29 (24%), and 25% to 50% in the remaining 4 of 29 (14%). Papilloma patients returned for treatment when symptoms recurred, so disease regression could not be assessed accurately. Similar to data obtained with the PDL, these data confirmed that dysplastic mucosa could normalize without resection. Our observations revealed that the 532-nm pulsed KTP laser provided enhanced performance over the PDL laser in a number of ways. The ability to use smaller glass fibers precluded mechanical trauma to the channels of the flexible

Reversible surgical model of biliary inflammation and obstructive jaundice in mice.

PubMed

Kirkland, Jacob G; Godfrey, Cody B; Garrett, Ryan; Kakar, Sanjay; Yeh, Benjamin M; Corvera, Carlos U

2010-12-01

Common bile duct (CBD) ligation is used in animal models to induce biliary inflammation, fibrosis, and cholestatic liver injury, but results in a high early postoperative mortality rate, probably from traumatic pancreatitis. We modified the CBD ligation model in mice by placing a small metal clip across the lower end of the CBD. To reverse biliary obstruction, a suture was incorporated within the clip during its placement. The suture and clip were removed on postoperative d 5 or 10 for biliary decompression. After 5 d of biliary obstruction, the gallbladder showed an 8-fold increase in wall thickness and a 17-fold increase in tissue myeloperoxidase activity. Markedly elevated serum levels of alkaline phosphatase and bilirubin indicated injury to the biliary epithelium and hepatocytes. Early postoperative (d 0-2) survival was 100% and later (d 3-5) survival was 85% (n=54 mice). We successfully reversed biliary obstruction in 20 mice (37%). Overall survival after reversal was 70%. In surviving mice, biliary decompression was complete, inflammation was reduced, and jaundice resolved. Histologic features confirmed reduced epithelial damage, edema, and neutrophil infiltration. Our technique minimized postoperative death, maintained an effective inflammatory response, and was easily reversible without requiring repeat laparotomy. This reversible model can be used to further define molecular mechanisms of biliary inflammation, fibrosis, and liver injury in genetically altered mice. Copyright © 2010. Published by Elsevier Inc.

Insulin hypersecretion together with high luteinizing hormone concentration augments androgen secretion in oral glucose tolerance test in women with polycystic ovarian disease.

PubMed

Anttila, L; Koskinen, P; Jaatinen, T A; Erkkola, R; Irjala, K; Ruutiainen, K

1993-08-01

Female hyperandrogenism is often associated with hyperinsulinaemia and insulin resistance. We evaluated the hormone responses in an oral glucose tolerance test to investigate the interactions of gonadotrophins, insulin, C-peptide and androgens in women with polycystic ovarian disease (PCOD). In 28 patients with ultrasonographically diagnosed PCOD, hyperinsulinaemia and insulin resistance were mainly associated with obesity. Both basal and cumulative sum of insulin to C-peptide ratios were high in obese subjects, suggesting decreasing hepatic removal of insulin caused by obesity. Nevertheless, in some lean PCOD women, despite normal fasting insulin concentrations, insulin hypersecretion existed. The mean concentration of testosterone decreased significantly during the oral glucose tolerance test both in PCOD and control women, and of androstenedione in the PCOD patients only. However, an increase in androgen responses was found in a subgroup of PCOD patients, who had both elevated luteinizing hormone (LH) concentrations and hyperinsulinaemic response to oral glucose. In the remaining PCOD patients an inverse correlation between LH and insulin was found. The patients with hyperinsulinaemia together with LH hypersecretion may represent a subgroup of PCOD with deranged regulation of androgen secretion.

Surface topography and ultrastructural changes of mucinous carcinoma breast cells.

PubMed

Voloudakis, G E; Baltatzis, G E; Agnantis, N J; Arnogianaki, N; Misitzis, J; Voloudakis-Baltatzis, I

2007-01-01

Mucinous carcinoma of the breast (MCB) is histologically classified into 2 groups: (1) pure MCB and (2) mixed MCB. Pure MCB carries a better diagnosis than mixed MCB. This research relates to the cell surface topography and ultrastructure of the cells in the above cases and aims to find the differences between them, by means of two methods: scanning electron microscopy (SEM) and transmission electron microscopy (TEM). For the SEM examination, it was necessary to initially culture the MCB tissues and then proceed with the usual SEM method. In contrast, for the TEM technique, MCB tissues were initially fixed followed by the classic TEM method. The authors found the topography of pure MCB cases to be without nodes. The cell membrane was smooth, with numerous pores and small ruffles that covered the entire cell. The ultrastructural appearance of the same cases was with a normal cell membrane containing abundant collagen fibers. They also had many small vesicles containing mucin as well as secretory droplets. In contrast the mixed MCB had a number of lymph nodes and their cell surface topography showed stronger changes such as microvilli, numerous blebs, ruffles and many long projections. Their ultrastructure showed very long microvilli with large cytoplasmic inclusions and extracellular mucin collections, electron-dense material vacuoles, and many important cytoplasmic organelles. An important fact is that mixed MCB also contains areas of infiltrating ductal carcinoma. These cells of the cytoplasmic organelles are clearly responsible for the synthesis, storage, and secretion of the characteristic mucin of this tumor type. Evidently, this abnormal mucin production and the abundance of secretory granules along with the long projections observed in the topographical structure might be responsible for transferring tumor cells to neighboring organs, thus being responsible for metastatic disease.

Mucinous cystic neoplasms of the mesentery: a case report and review of the literature

PubMed Central

Metaxas, Georgios; Tangalos, Athanasios; Pappa, Polyxeni; Papageorgiou, Irene

2009-01-01

Background Mucinous cystic neoplasms arise in the ovary and various extra-ovarian sites. While their pathogenesis remains conjectural, their similarities suggest a common pathway of development. There have been rare reports involving the mesentery as a primary tumour site. Case presentation A cystic mass of uncertain origin was demonstrated radiologically in a 22 year old female with chronic abdominal pain. At laparotomy, the mass was fixed within the colonic mesentery. Histology demonstrated a benign mucinous cystadenoma. Methods and results We review the literature on mucinous cystic neoplasms of the mesentery and report on the pathogenesis, biologic behavior, diagnosis and treatment of similar extra-ovarian tumors. We propose an updated classification of mesenteric cysts and cystic tumors. Conclusion Mucinous cystic neoplasms of the mesentery present almost exclusively in women and must be considered in the differential diagnosis of mesenteric tumors. Only full histological examination of a mucinous cystic neoplasm can exclude a borderline or malignant component. An updated classification of mesenteric cysts and cystic tumors is proposed. PMID:19454018

CFTR, Mucins, and Mucus Obstruction in Cystic Fibrosis

PubMed Central

Kreda, Silvia M.; Davis, C. William; Rose, Mary Callaghan

2012-01-01

Mucus pathology in cystic fibrosis (CF) has been known for as long as the disease has been recognized and is sometimes called mucoviscidosis. The disease is marked by mucus hyperproduction and plugging in many organs, which are usually most fatal in the airways of CF patients, once the problem of meconium ileus at birth is resolved. After the CF gene, CFTR, was cloned and its protein product identified as a cAMP-regulated Cl− channel, causal mechanisms underlying the strong mucus phenotype of the disease became obscure. Here we focus on mucin genes and polymeric mucin glycoproteins, examining their regulation and potential relationships to a dysfunctional cystic fibrosis transmembrane conductance regulator (CFTR). Detailed examination of CFTR expression in organs and different cell types indicates that changes in CFTR expression do not always correlate with the severity of CF disease or mucus accumulation. Thus, the mucus hyperproduction that typifies CF does not appear to be a direct cause of a defective CFTR but, rather, to be a downstream consequence. In organs like the lung, up-regulation of mucin gene expression by inflammation results from chronic infection; however, in other instances and organs, the inflammation may have a non-infectious origin. The mucus plugging phenotype of the β-subunit of the epithelial Na+ channel (βENaC)-overexpressing mouse is proving to be an archetypal example of this kind of inflammation, with a dehydrated airway surface/concentrated mucus gel apparently providing the inflammatory stimulus. Data indicate that the luminal HCO3 − deficiency recently described for CF epithelia may also provide such a stimulus, perhaps by causing a mal-maturation of mucins as they are released onto luminal surfaces. In any event, the path between CFTR dysfunction and mucus hyperproduction has proven tortuous, and its unraveling continues to offer its own twists and turns, along with fascinating glimpses into biology. PMID:22951447

Innate immune defense in the inner ear - mucines are expressed by the human endolymphatic sac.

PubMed

Møller, Martin N; Kirkeby, Svend; Cayé-Thomasen, Per

2017-02-01

The human endolymphatic sac has been shown recently to have immunological capacities and has thus been proposed as the main entity protecting the inner ear from pathogen invasion, equivalent to mucosa-associated lymphoid tissue (MALT). Although the sac expresses molecules of the innate immune system, the potential expression of members of the important mucin family has not been detailed. Thus, this paper explores endolymphatic sac expression of a number of mucins and mucin precursors. Twelve fresh tissue samples from the human endolymphatic sac were obtained during translabyrinthine surgery. The expression of Mucin 1, 2, 5B/AC and 16, as well as the core structure elements (mucin precursors) T-antigen, Tn-antigen and Sialyl-Tn-antigen was investigated by immunohistochemistry. The endolymphatic sac epithelium expressed MUC1 (both apically towards the endolymphatic sac (ES) lumen and basally towards the capillary network), MUC 16 and Tn-antigen. There was no labeling after incubation with antibodies against T-antigen, sialyl-Tn-antigen, MUC2 and MUC5B/AC. We conclude that the human endolymphatic sac epithelium expresses a number of mucin molecules, which supports the hypothesis of the sac as the primary immunological tissue structure of the inner ear, equivalent to MALT in other organs. The mucins may also play a role in the formation and continuous homeostasis of the inner ear fluids, as well as the pathogenesis of Meniere's disease. © 2016 Anatomical Society.

Ovarian mucinous tumors arising from mature cystic teratomas--a molecular genetic approach for understanding the cellular origin.

PubMed

Fujii, Kaho; Yamashita, Yoriko; Yamamoto, Toshimichi; Takahashi, Koji; Hashimoto, Katsunori; Miyata, Tomoko; Kawai, Kumi; Kikkawa, Fumitaka; Toyokuni, Shinya; Nagasaka, Tetsuro

2014-04-01

Mucinous tumors of the ovary are frequently associated with mature cystic teratomas, and it has been speculated that the mucinous tumors arise from teratoma components. The cellular origins of mature cystic teratomas are believed to be post-meiotic ovarian germ cells, and the analysis of microsatellite markers such as short tandem repeats is suitable for determining the cellular origin of tumors. In this study, we analyzed 3 ovarian mature cystic teratomas, all of which were associated with simultaneous ovarian mucinous tumors within the same ovary. Two of the 3 mucinous tumors were intestinal-type and the other was endocervical type. A laser capture microdissection technique was used to separate the epithelial component of the mucinous tumor, the components of the mature cystic teratoma, and control ovarian somatic tissue. Using short tandem repeat analysis based on 6 markers (D20S480, D6S2439, D6S1056, D9S1118, D4S2639, and D17S1290), we could distinguish the germ cell (homozygous) or somatic (heterozygous) origin of a given component in each sample. The epithelial components of the intestinal-type mucinous tumors in cases 1 and 2 were homozygous, and the epithelial component in case 3 (endocervical type) was heterozygous. All teratomatous components were homozygous, and the control components were heterozygous. In addition, we analyzed 3 mature cystic teratomas without mucinous tumors, and all 3 were homozygous in the tumor component. Our data suggest that the origin of mucinous tumors in the ovary may differ among histological subtypes, and intestinal-type mucinous tumors may arise from mature cystic teratomas, although endocervical-type mucinous tumors may not. Copyright © 2014 Elsevier Inc. All rights reserved.

A Gastric Glycoform of MUC5AC Is a Biomarker of Mucinous Cysts of the Pancreas

PubMed Central

Sinha, Jessica; Cao, Zheng; Dai, Jianliang; Tang, Huiyuan; Partyka, Katie; Hostetter, Galen; Simeone, Diane M.; Feng, Ziding; Allen, Peter J.; Brand, Randall E.; Haab, Brian B.

2016-01-01

Molecular indicators to specify the risk posed by a pancreatic cyst would benefit patients. Previously we showed that most cancer-precursor cysts, termed mucinous cysts, produce abnormal glycoforms of the proteins MUC5AC and endorepellin. Here we sought to validate the glycoforms as a biomarker of mucinous cysts and to specify the oligosaccharide linkages that characterize MUC5AC. We hypothesized that mucinous cysts secrete MUC5AC displaying terminal N-acetylglucosamine (GlcNAc) in either alpha or beta linkage. We used antibody-lectin sandwich assays to detect glycoforms of MUC5AC and endorepellin in cyst fluid samples from three independent cohorts of 49, 32, and 66 patients, and we used monoclonal antibodies to test for terminal, alpha-linked GlcNAc and the enzyme that produces it. A biomarker panel comprising the previously-identified glycoforms of MUC5AC and endorepellin gave 96%, 96%, and 87% accuracy for identifying mucinous cysts in the three cohorts with an average sensitivity of 92% and an average specificity of 94%. Glycan analysis showed that MUC5AC produced by a subset of mucinous cysts displays terminal alpha-GlcNAc, a motif expressed in stomach glands. The alpha-linked glycoform of MUC5AC was unique to intraductal papillary mucinous neoplasms (IPMN), whereas terminal beta-linked GlcNAc was increased in both IPMNs and mucinous cystic neoplasms (MCN). The enzyme that synthesizes alpha-GlcNAc, A4GNT, was expressed in the epithelia of mucinous cysts that expressed alpha-GlcNAc, especially in regions with high-grade dysplasia. Thus IPMNs secrete a gastric glycoform of MUC5AC that displays terminal alpha-GlcNAc, and the combined alpha-GlcNAc and beta-GlcNAc glycoforms form an accurate biomarker of mucinous cysts. PMID:27992432

DA-6034-induced mucin secretion via Ca2+-dependent pathways through P2Y receptor stimulation.

PubMed

Lee, Hun; Kim, Eung Kweon; Kim, Ji Yeon; Yang, Yu-Mi; Shin, Dong Min; Kang, Kyung Koo; Kim, Tae-im

2014-09-11

We evaluated whether DA-6034 is involved in mucin secretion via P2Y receptor activation and/or intracellular Ca2+ concentration ([Ca2+]i) change. Also, we investigated the effect of P2Y receptor inhibitors or Ca2+ chelators on the DA-6034-induced mucin secretion and [Ca2+]i increases. Effects of DA-6034 on mucin expression in primary, cultured, conjunctival epithelial cells was studied using RT-PCR, Western blot analysis, and periodic acid-schiff (PAS) staining. To evaluate thin film layer thickness generated by mucin and fluid secretion, cells were incubated in DA-6034 with/without P2Y antagonists or extracellular/intracellular Ca2+ chelators, and were imaged with confocal microscope using Texas Red-dextran dye. In addition, DA-6034-induced Ca2+-dependent Cl- channels opening was evaluated using perforated patch clamp. Fluo-4/AM was used to measure changes in [Ca2+]i induced by DA-6034 in Ca2+-free or Ca2+-containing buffered condition, as well as P2Y antagonists. DA-6034 induced the expression of mucin genes, production of mucin protein, and increase of number of mucin-secreting cells. P2Y antagonists inhibited DA-6034-induced mucin and fluid secretion, which was also affected by extracellular/intracellular Ca2+ chelators. DA-6034 stimulated Cl- channel opening and [Ca2+]i elevation. Further, [Ca2+]i increases induced by DA-6034 were lacking in either P2Y antagonists or Ca2+-free buffered condition, and diminished when endoplasmic reticulum Ca2+ was depleted by cyclopiazonic acid in Ca2+-free buffered condition. This study demonstrated that DA-6034 has a potential to induce mucin secretion via Ca2+-dependent pathways through P2Y receptors in multilayer, cultured, human conjunctival epithelial cells. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

Antiadhesive Character of Mucin O-glycans at the Apical Surface of Corneal Epithelial Cells

PubMed Central

Sumiyoshi, Mika; Ricciuto, Jessica; Tisdale, Ann; Gipson, Ilene K.; Mantelli, Flavio; Argüeso, Pablo

2008-01-01

Purpose Prolonged contact of opposite mucosal surfaces, which occurs on the ocular surface, oral cavity, reproductive tract, and gut, requires a specialized apical cell surface that prevents adhesion. The purpose of this study was to evaluate the contribution of mucin O-glycans to the antiadhesive character of human corneal–limbal epithelial (HCLE) cells. Methods Mucin O-glycan biosynthesis in HCLE cells was disrupted by metabolic interference with benzyl-α-GalNAc. The cell surface mucin MUC16 and its carbohydrate epitope H185 were detected by immunofluorescence and Western blot. HCLE cell surface features were assessed by field emission scanning electron microscopy. Cell–cell adhesion assays were performed under static conditions and in a parallel plate laminar flow chamber. Results Benzyl-α-GalNAc disrupted the biosynthesis of O-glycans without affecting apomucin biosynthesis or cell surface morphology. Static adhesion assays showed that the apical surface of differentiated HCLE cells expressing MUC16 and H185 was more antiadhesive than undifferentiated HCLE cells, which lacked MUC16. Abrogation of mucin O-glycosylation in differentiated cultures with benzyl-α-GalNAc resulted in increased adhesion of applied corneal epithelial cells and corneal fibroblasts. The antiadhesive effect of mucin O-glycans was further demonstrated by fluorescence video microscopy in dynamic flow adhesion assays. Cationized ferritin labeling of the cell surface indicated that anionic repulsion did not contribute to the antiadhesive character of the apical surface. Conclusions These results indicate that epithelial O-glycans contribute to the antiadhesive properties of cell surface–associated mucins in corneal epithelial cells and suggest that alterations in mucin O-glycosylation are involved in the pathology of drying mucosal diseases (e.g., dry eye). PMID:18172093

Stool color card screening for biliary atresia.

PubMed

Tseng, Jui-Ju; Lai, Mei-Su; Lin, Ming-Chih; Fu, Yun-Ching

2011-11-01

Biliary atresia is a major cause of extrahepatic obstructive jaundice in neonates. Early Kasai operation is the gold standard of treatment. In this study, we evaluated the effectiveness of stool color card screening by using claims data from the National Health Insurance Research Database. This was a retrospective cohort study. Data from medical charts of all inpatients who were diagnosed with biliary atresia from 1996 to 2008 were collected from Taiwan's National Health Insurance Research Database. Patients who received a Kasai operation or liver transplant were identified by the Operation code. The patients' gender, age at admission, and type of operation were collected and analyzed. From 1996 to 2008, the overall incidence of biliary atresia was 1.48 per 10,000 live births. The median age at first admission for patients with suspected biliary atresia decreased after the implementation of stool color card screening (47 vs 43 days). The proportion of very late referral decreased from 9.5% to 4.9%. The median age of Kasai operation advanced from 51 to 48 days. The proportions of Kasai operation within 60 days of age were 68.9% before and 73.6% after screening program. Stool color card screening seemed to increase parents' and physicians' awareness of biliary atresia. It also was associated with a decline in the proportion of late referral. Thus, screening might be especially effective in areas with high a proportion of late referral. Improvements in the speed of workup and the operation room should be the focus of education and training in the future.

Mucin-Microbiota Interaction During Postnatal Maturation of the Intestinal Ecosystem: Clinical Implications.

PubMed

Rokhsefat, Sana; Lin, Aifeng; Comelli, Elena M

2016-06-01

The mucus layer and gut microbiota interplay contributes to host homeostasis. The mucus layer serves as a scaffold and a carbon source for gut microorganisms; conversely, gut microorganisms, including mucin degraders, influence mucin gene expression, glycosylation, and secretion. Conjointly they shield the epithelium from luminal pathogens, antigens, and toxins. Importantly, the mucus layer and gut microbiota are established in parallel during early postnatal life. During this period, the development of gut microbiota and mucus layer is coupled with that of the immune system. Developmental changes of different mucin types can impact the age-dependent patterns of intestinal infection in terms of incidence and severity. Altered mucus layer, dysbiotic microbiota, and abnormal mucus-gut microbiota interaction have the potential for inducing systemic effects, and accompany several intestinal diseases such as inflammatory bowel disease, colorectal cancer, and radiation-induced mucositis. Early life provides a pivotal window of opportunity to favorably modulate the mucus-microbiota interaction. The support of a health-compatible mucin-microbiota maturation in early life is paramount for long-term health and serves as an important opportunity for clinical intervention.

The association between body mass index and severe biliary infections: a multivariate analysis.

PubMed

Stewart, Lygia; Griffiss, J McLeod; Jarvis, Gary A; Way, Lawrence W

2012-11-01

Obesity has been associated with worse infectious disease outcomes. It is a risk factor for cholesterol gallstones, but little is known about associations between body mass index (BMI) and biliary infections. We studied this using factors associated with biliary infections. A total of 427 patients with gallstones were studied. Gallstones, bile, and blood (as applicable) were cultured. Illness severity was classified as follows: none (no infection or inflammation), systemic inflammatory response syndrome (fever, leukocytosis), severe (abscess, cholangitis, empyema), or multi-organ dysfunction syndrome (bacteremia, hypotension, organ failure). Associations between BMI and biliary bacteria, bacteremia, gallstone type, and illness severity were examined using bivariate and multivariate analysis. BMI inversely correlated with pigment stones, biliary bacteria, bacteremia, and increased illness severity on bivariate and multivariate analysis. Obesity correlated with less severe biliary infections. BMI inversely correlated with pigment stones and biliary bacteria; multivariate analysis showed an independent correlation between lower BMI and illness severity. Most patients with severe biliary infections had a normal BMI, suggesting that obesity may be protective in biliary infections. This study examined the correlation between BMI and biliary infection severity. Published by Elsevier Inc.

Rescue EUS-guided intrahepatic biliary drainage for malignant hilar biliary stricture after failed transpapillary re-intervention.

PubMed

Minaga, Kosuke; Takenaka, Mamoru; Kitano, Masayuki; Chiba, Yasutaka; Imai, Hajime; Yamao, Kentaro; Kamata, Ken; Miyata, Takeshi; Omoto, Shunsuke; Sakurai, Toshiharu; Watanabe, Tomohiro; Nishida, Naoshi; Kudo, Masatoshi

2017-11-01

Treatment of unresectable malignant hilar biliary stricture (UMHBS) is challenging, especially after failure of repeated transpapillary endoscopic stenting. Endoscopic ultrasonography-guided intrahepatic biliary drainage (EUS-IBD) is a recent technique for intrahepatic biliary decompression, but indications for its use for complex hilar strictures have not been well studied. The aim of this study was to assess the feasibility and safety of EUS-IBD for UMHBS after failed transpapillary re-intervention. Retrospective analysis of all consecutive patients with UMHBS of Bismuth II grade or higher who, between December 2008 and May 2016, underwent EUS-IBD after failed repeated transpapillary interventions. The technical success, clinical success, and complication rates were evaluated. Factors associated with clinical ineffectiveness of EUS-IBD were explored. A total of 30 patients (19 women, median age 66 years [range 52-87]) underwent EUS-IBD for UMHBS during the study period. Hilar biliary stricture morphology was classified as Bismuth II, III, or IV in 5, 13, and 12 patients, respectively. The median number of preceding endoscopic interventions was 4 (range 2-14). EUS-IBD was required because the following procedures failed: duodenal scope insertion (n = 4), accessing the papilla after duodenal stent insertion (n = 5), or achieving desired intrahepatic biliary drainage (n = 21). Technical success with EUS-IBD was achieved in 29 of 30 patients (96.7%) and clinical success was attained in 22 of these 29 (75.9%). Mild peritonitis occurred in three of 30 (10%) and was managed conservatively. Stent dysfunction occurred in 23.3% (7/30). There was no procedure-related mortality. On multivariable analysis, Bismuth IV stricture predicted clinical ineffectiveness (odds ratio = 12.7, 95% CI 1.18-135.4, P = 0.035). EUS-IBD may be a feasible and effective rescue alternative with few major complications after failed transpapillary endoscopic re-intervention in patients

Mucin Expression in the Esophageal Malignant and Pre-malignant States: A Systematic Review and Meta-analysis.

PubMed

Niv, Yaron; Ho, Samuel B; Fass, Ronnie; Rokkas, Theodore

2018-02-01

Mucins are heavily glycosylated glycoproteins, synthesized by mucosal surfaces and have an important role in healthy state and malignant diseases. Change in mucins synthesis or secretion may be primary event or secondary to inflammation or carcinogenesis. The aim of this study is to assess the current knowledge about mucin expression in esophageal lesions, and to establish a role for different mucin expressions as prognostic markers. English Medical literature searches were conducted for "mucin" and "esophagus." Observational studies were included. Meta-analysis was performed using comprehensive meta-analysis software. Pooled odds ratios (OR) and 95% confidence intervals (CI) were calculated. In the random-effect model, mucin expression was significantly higher in esophageal lesions than in normal esophageal mucosa with OR=5.456 (95% CI, 1.883-15.807, P=0.002). Measure of heterogeneity, demonstrated in the included studies, was high: Q=287.501, df (Q)=44.00, P<0.0001, I=84.696%. There is a gradient of mucin expression and complexity in esophageal premalignant to malignant lesions, lower in Barrett's mucosa with low grade dysplasia (LGD), increased in high grade dysplasia (HGD), and highest in esophageal adenocarcinoma (EAC). MUC2, MUC3, MUC5AC, and MUC6 expression was higher in EAC than HGD, and higher in HGD than in LGD mucosa. The opposite was found for MUC1 and MUC4. Increased expression of certain mucin genes in esophageal mucosa may be further studied as a potential diagnostic tool, and this may add important information in the surveillance of Barrett's esophagus.

Biliary Ascariasis: MR Cholangiography Findings in Two Cases

PubMed Central

Hwang, Cheol Mok; Ha, Hyun Kwon; Kim, Pyo Nyun; Lee, Moon-Gyu

2001-01-01

We describe the imaging features of two cases of biliary ascariasis. Ultrasonography and CT showed no specific abnormal findings, but MR cholangiography clearly demonstrated an intraductal linear filling defect that led to the correct diagnosis. MR cholangiography is thus a useful technique for the diagnosis of biliary ascariasis. PMID:11752990

Gallbladder and Biliary Tract

MedlinePlus

... switch to the Professional version Home Digestive Disorders Biology of the Digestive System Gallbladder and Biliary Tract ... Version. DOCTORS: Click here for the Professional Version Biology of the Digestive System Overview of the Digestive ...

Drug-eluting stent in malignant biliary obstruction

NASA Astrophysics Data System (ADS)

Lee, Dong-Ki; Jang, Sung Ill

2012-10-01

Endoscopic stent insertion is the treatment of choice for patients with malignant biliary obstruction. However, conventional stents enable only mechanical palliation of the obstruction, without any anti-tumor effects. Drugeluting stent (DES), which was first introduced in coronary artery disease, are currently under investigation for sustaining stent patency and prolonging patient survival by inhibiting tumor ingrowth in malignant biliary obstruction. Many factors affecting efficient drug delivery have been studied to determine how drugs with antitumor effects suppress tumor ingrowth, including the specific drugs incorporated, means of incorporating the drugs, mode of drug release, and stent structure. Advances have resulted in the construction of more effective non-vascular DES and ongoing clinical research. Non-vascular DES is expected to play a vital role in prolonging the survival of patients with malignant biliary obstruction.

The isolated MUC5AC gene product from human ocular mucin displays intramolecular conformational heterogeneity.

PubMed

Round, Andrew N; McMaster, Terence J; Miles, Mervyn J; Corfield, Anthony P; Berry, Monica

2007-06-01

Atomic force microscopy (AFM) has been used to show that human ocular mucins contain at least three distinct polymer conformations, separable by isopycnic density gradient centrifugation. In this work we have used affinity purification against the anti(mucin peptide core) monoclonal antibody 45M1 to isolate MUC5AC gene products, a major component of human ocular mucins. AFM images confirm that the affinity-purified polymers adopt distinct conformations that coidentify with two of those observed in the parent population, and further reveal that these two different conformations can be present within the same polymer. AFM images of the complexes formed after incubation of 45M1 with the parent sample reveal different rates of binding to the two MUC5AC polymer types. The variability of gene products within a mucin population was revealed by analyzing the height distributions along the polymer contour and periodicities in distances between occupied antibody binding sites. AFM analysis of mucin polymers at the single molecule level provides new information about the genetic origins of individual polymers and the contributions of glycosylation to the physicochemical properties of mucins, which can be correlated with information obtained from biochemistry, antibody binding assays, and molecular biology techniques.

Unique characteristics of pyogenic liver abscesses of biliary origin.

PubMed

Shi, Shaohua; Xia, Weiliang; Guo, Haijun; Kong, Haishen; Zheng, Shusen

2016-05-01

Pyrogenic liver abscesses (PLA) can be caused by cholangitis associated with hepatolithiasis and cholangitis related to an abnormal bilioenteric communication, such as a hepaticojejunostomy or the presence of indwelling biliary stents. Our aim was to evaluate the clinical characteristics of PLA of biliary origin. We compared patients with PLA related to biliary tract disease (PLA-B; n = 125) with patients with PLA not related to biliary tract disease (PLA-NB; n = 444). We also separated the patients with PLA-B into PLA related to biliary tract disease that involved an abnormal bilioenteric communication, including hepaticojejunostomy and indwelling biliary stents (PLA-B-AC; n = 38), and PLA-B not related to abnormal communication (n = 87), and compared them. Among the 569 patients with PLA from 2008 to 2013, the most common etiologies were cryptogenic (n = 341; 60%) and biliary (n = 125; 22%). Patients with PLA-B tended to have a higher maximum body temperature and a greater leukocytosis. The incidences of bacteremia, septic shock, death, and postdischarge recurrence were greater in the PLA-B group when compared with the PLA-NB group. The most commonly isolated pathogenic bacteria in PLA-B group were Escherichia coli (36%) and Klebsiella pneumonia (23%). In contrast, in the PLA-NB group, the most common pathogen was K pneumonia (64%), whereas E coli was uncommon (only 5%). Independent risk factors for the occurrence of PLA-B were isolates with multidrug resistant (MDR) bacteria, bacteremia, E coli, and polymicrobial infection. In the group of PLA-B-AC, risk factors included MDR bacteria and a history of malignancy. The occurrences of PLA-B are often infected with MDR bacteria and mixed infections caused mainly by E coli and other isolates and associated with bacteremia; PLA-B-AC are associated with MDR bacteria and a history of malignancy. Copyright © 2016. Published by Elsevier Inc.

Biliary tract cancer stem cells - translational options and challenges

PubMed Central

Mayr, Christian; Ocker, Matthias; Ritter, Markus; Pichler, Martin; Neureiter, Daniel; Kiesslich, Tobias

2017-01-01

Management of biliary tract cancer remains challenging. Tumors show high recurrence rates and therapeutic resistance, leading to dismal prognosis and short survival. The cancer stem cell model states that a tumor is a heterogeneous conglomerate of cells, in which a certain subpopulation of cells - the cancer stem cells - possesses stem cell properties. Cancer stem cells have high clinical relevance due to their potential contributions to development, progression and aggressiveness as well as recurrence and metastasis of malignant tumors. Consequently, reliable identification of as well as pharmacological intervention with cancer stem cells is an intensively investigated and promising research field. The involvement of cancer stem cells in biliary tract cancer is likely as a number of studies demonstrated their existence and the obvious clinical relevance of several established cancer stem cell markers in biliary tract cancer models and tissues. In the present article, we review and discuss the currently available literature addressing the role of putative cancer stem cells in biliary tract cancer as well as the connection between known contributors of biliary tract tumorigenesis such as oncogenic signaling pathways, micro-RNAs and the tumor microenvironment with cancer stem cells. PMID:28465631

Endoscopic management of biliary complications following liver transplantation after donation from cardiac death donors.

PubMed

Croome, Kris P; McAlister, Vivian; Adams, Paul; Marotta, Paul; Wall, William; Hernandez-Alejandro, Roberto

2012-09-01

Previous studies have shown a higher incidence of biliary complications following donation after cardiac death (DCD) liver transplantation compared with donation after brain death (DBD) liver transplantation. The endoscopic management of ischemic type biliary strictures in patients who have undergone DCD liver transplants needs to be characterized further. A retrospective institutional review of all patients who underwent DCD liver transplant from January 2006 to September 2011 was performed. These patients were compared with all patients who underwent DBD liver transplantation in the same time period. A descriptive analysis of all DCD patients who developed biliary complications and their subsequent endoscopic management was also performed. Of the 36 patients who received DCD liver transplants, 25% developed biliary complications compared with 13% of patients who received DBD liver transplants (P=0.062). All DCD allograft recipients who developed biliary complications became symptomatic within three months of transplantation. Ischemic type biliary strictures in DCD allograft recipients included disseminated biliary strictures in two patients, biliary strictures of the hepatic duct bifurcation in three patients and biliary strictures of the donor common hepatic duct in three patients. There was a trend toward increasing incidence of total biliary complications in recipients of DCD liver allografts compared with those receiving DBD livers, and the rate of diffuse ischemic cholangiopathy was significantly higher. Focal ischemic type biliary strictures can be treated effectively in DCD liver transplant recipients with favourable results. Diffuse ischemic type biliary strictures in DCD liver transplant recipients ultimately requires retransplantation.

Association of Cell Surface Mucins with Galectin-3 Contributes to the Ocular Surface Epithelial Barrier*

PubMed Central

Argüeso, Pablo; Guzman-Aranguez, Ana; Mantelli, Flavio; Cao, Zhiyi; Ricciuto, Jessica; Panjwani, Noorjahan

2009-01-01

Maintenance of an intact mucosal barrier is critical to preventing damage to and infection of wet-surfaced epithelia. The mechanism of defense has been the subject of much investigation, and there is evidence now implicating O-glycosylated mucins on the epithelial cell surface. Here we investigate a new role for the carbohydrate-binding protein galectin-3 in stabilizing mucosal barriers through its interaction with mucins on the apical glycocalyx. Using the surface of the eye as a model system, we found that galectin-3 colocalized with two distinct membrane-associated mucins, MUC1 and MUC16, on the apical surface of epithelial cells and that both mucins bound to galectin-3 affinity columns in a galactose-dependent manner. Abrogation of the mucin-galectin interaction in four different mucosal epithelial cell types using competitive carbohydrate inhibitors of galectin binding, β-lactose and modified citrus pectin, resulted in decreased levels of galectin-3 on the cell surface with concomitant loss of barrier function, as indicated by increased permeability to rose bengal diagnostic dye. Similarly, down-regulation of mucin O-glycosylation using a stable tetracycline-inducible RNA interfering system to knockdown c1galt1 (T-synthase), a critical galactosyltransferase required for the synthesis of core 1 O-glycans, resulted in decreased cell surface O-glycosylation, reduced cell surface galectin-3, and increased epithelial permeability. Taken together, these results suggest that galectin-3 plays a key role in maintaining mucosal barrier function through carbohydrate-dependent interactions with cell surface mucins. PMID:19556244

Fascin and EMMPRIN expression in primary mucinous tumors of ovary: a tissue microarray study.

PubMed

Alici, Omer; Kefeli, Mehmet; Yildiz, Levent; Baris, Sancar; Karagoz, Filiz; Kandemir, Bedri

2014-12-01

The aim of this study was to compare the expressions of fascin and EMMPRIN in primary malignant, borderline and benign mucinous ovarian tumors, and to investigate the relationship of these markers with tumor progression and their applicability to differential diagnosis. An immunohistochemical study was performed for fascin and EMMPRIN using the tissue microarray technique. Eighty-one cases were included in the study; there were 37 benign, 25 borderline and 19 malignant primary mucinous ovarian tumors. For each case, a total staining score was determined, consisting of scores for extent of staining and intensity of staining. The cases were allocated to negative, weakly positive and strongly positive staining categories, according to the total staining score. Both of the markers were significantly negative in benign tumors as compared with borderline and malignant tumors. There was no significant difference between borderline and malignant groups for both markers. Sixty-eight percent of malignant tumors were stained positive by fascin, while this rate was 40% for borderline mucinous tumors. All malignant tumors were strongly stained positive for EMMPRIN, while this rate was 92% for borderline mucinous tumors. The rest of the cases stained weakly positive. No significant difference in staining score was found between fascin and EMMPRIN expression. In ovarian primary mucinous tumors, fascin and EMMPRIN may play an important role in tumor progression from benign tumor to carcinoma. In that context, EMMPRIN and fascin expression may have potential application in the differential diagnosis of some diagnostically problematic mucinous ovarian tumors. However, the differential diagnostic applicability of EMMPRIN appears to be more limited than that of fascin due to its wide spectrum of staining in mucinous ovarian tumors. Copyright © 2014 Elsevier GmbH. All rights reserved.

Bile salts stimulate mucin secretion by cultured dog gallbladder epithelial cells independent of their detergent effect.

PubMed

Klinkspoor, J H; Yoshida, T; Lee, S P

1998-05-15

1. Bile salts stimulate mucin secretion by the gallbladder epithelium. We have investigated whether this stimulatory effect is due to a detergent effect of bile salts. 2. The bile salts taurocholic acid (TC) and tauroursodeoxycholic acid (TUDC) and the detergents Triton X-100 (12.5-400 microM) and Tween-20 (0.1-3.2 mM) were applied to monolayers of cultured dog gallbladder epithelial cells. Mucin secretion was studied by measuring the secretion of [3H]N-acetyl-d-glucosamine-labelled glycoproteins. We also attempted to alter the fluidity of the apical membrane of the cells through extraction of cholesterol with beta-cyclodextrin (2.5-15 mM). The effect on TUDC-induced mucin secretion was studied. Cell viability was assessed by measuring lactate dehydrogenase (LDH) leakage or 51Cr release. 3. In contrast with the bile salts, the detergents were not able to cause an increase in mucin secretion without causing concomitant cell lysis. Concentrations of detergent that increased mucin release (>100 microM Triton X-100, >0.8 mM Tween-20), caused increased LDH release. Incubation with beta-cyclodextrin resulted in effective extraction of cholesterol without causing an increase in 51Cr release. However, no effect of the presumed altered membrane fluidity on TUDC (10 mM)-induced mucin secretion was observed. 4. The stimulatory effect of bile salts on mucin secretion by gallbladder epithelial cells is not affected by the fluidity of the apical membrane of the cells and also cannot be mimicked by other detergents. We conclude that the ability of bile salts to cause mucin secretion by the gallbladder epithelium is not determined by their detergent properties.

Aggressive Management of Peritoneal Carcinomatosis from Mucinous Appendiceal Neoplasms

PubMed Central

Austin, Frances; Mavanur, Arun; Sathaiah, Magesh; Steel, Jennifer; Lenzner, Diana; Ramalingam, Lekshmi; Holtzman, Matthew; Ahrendt, Steven; Pingpank, James; Zeh, Herbert J.; Bartlett, David L.; Choudry, Haroon A.

2014-01-01

Background Peritoneal carcinomatosis (PC) in the setting of mucinous appendiceal neoplasms is characterized by the intraperitoneal accumulation of mucinous ascites and mucin-secreting epithelial cells that leads to progressive compression of intra-abdominal organs, morbidity, and eventual death. We assessed postoperative and oncologic outcomes after aggressive surgical management by experienced surgeons. Methods We analyzed clinicopathologic, perioperative, and oncologic outcome data in 282 patients with PC from appendiceal adenocarcinomas between 2001 and 2010 from a prospective database. Kaplan–Meier survival curves and multivariate Cox-regression models were used to identify prognostic factors affecting oncologic outcomes. Results Adequate cytoreduction was achieved in 82% of patients (completeness of cytoreduction score (CC)-0: 49%; CC-1: 33%). Median simplified peritoneal cancer index (SPCI), operative time, and estimated blood loss were 14 (range, 0–21), 483.5 min (range, 46–1,402), and 800 ml (range, 0–14,000), respectively. Pathology assessment demonstrated high-grade tumors in 36% of patients and lymph node involvement in 23% of patients. Major postoperative morbidity occurred in 70 (25%) patients. Median overall survival was 6.72 years (95% confidence interval (CI), 4.17 years not reached), with 5 year overall survival probability of 52.7% (95% CI, 42.4, 62%). In a multivariate Cox-regression model, tumor grade, age, preoperative SPCI and chemo-naïve status at surgery were joint significant predictors of overall survival. Tumor grade, postoperative CC-score, prior chemotherapy, and preoperative SPCI were joint significant predictors of time to progression. Conclusions Aggressive management of PC from mucinous appendiceal neoplasms, by experienced surgeons, to achieve complete cytoreduction provides long-term survival with low major morbidity. PMID:22302270

Best option for preoperative biliary drainage in Klatskin tumor

PubMed Central

Tang, Zengwei; Yang, Yuan; Meng, Wenbo; Li, Xun

2017-01-01

Abstract The operative treatment combined with preoperative biliary drainage (PBD) has been established as a safe Klatskin tumor (KT) treatment strategy. However, there has always been a dispute for the preferred technique for PBD technique. This meta-analysis was conducted to compare the biliary drainage-related cholangitis, pancreatitis, hemorrhage, and the success rates of palliative relief of cholestasis between percutaneous transhepatic biliary drainage (PTBD) and endoscopic biliary drainage (EBD), to identify the best technique in the management of KT. PubMed, EMBASE, and Web of Science were searched systematically for prospective or retrospective studies reporting the biliary drainage-related cholangitis, pancreatitis, hemorrhage, and the success rates of palliative relief of cholestasis in patients with KT. A meta-analysis was performed, using the fixed or random-effect model, with Review Manager 5.3. PTBD was associated with lower risk of cholangitis (risk ratio [RR] = 0.49, 95% confidence interval [CI]: 0.36–0.67; P < .00001), particularly in patients with Bismuth-Corlette type II, III, IV KT (RR = 0.50, 95% CI: 0.33–0.77; P = .05). Compared with EBD, PTBD was also associated with a lower risk of pancreatitis (RR = 0.35, 95% CI: 0.17–0.69; P = 0.003) and with higher successful rates of palliative relief of cholestasis (RR = 1.20, 95% CI: 1.10–1.31; P < .0001). The incidence of hemorrhage was similar in these 2 groups (RR 1.29, 95% CI: 0.51–3.27; P = .59). The risk of biliary drainage-related cholangitis (RR = 1.96, 95% CI: 0.96–4.01; P = .06) and pancreatitis (RR = 1.62, 95% CI: 0.76–3.47; P = .21) was similar between endoscopic nasobiliary drainage groups and biliary stenting. In patients with type II or type III or IV KT who need to have PBD, PTBD should be performed as an initial method of biliary drainage in terms of reducing the incidence of procedure related cholangitis, pancreatitis

Diffusion through Pig Gastric Mucin: Effect of Relative Humidity

PubMed Central

Runnsjö, Anna; Dabkowska, Aleksandra P.; Sparr, Emma; Kocherbitov, Vitaly; Arnebrant, Thomas; Engblom, Johan

2016-01-01

Mucus covers the epithelium found in all intestinal tracts, where it serves as an important protecting barrier, and pharmaceutical drugs administrated by the oral, rectal, vaginal, ocular, or nasal route need to penetrate the mucus in order to reach their targets. Furthermore, the diffusion in mucus as well as the viscosity of mucus in the eyes, nose and throat can change depending on the relative humidity of the surrounding air. In this study we have investigated how diffusion through gels of mucin, the main protein in mucus, is affected by changes in ambient relative humidity (i.e. water activity). Already a small decrease in water activity was found to give rise to a significant decrease in penetration rate through the mucin gel of the antibacterial drug metronidazole. We also show that a decrease in water activity leads to decreased diffusion rate in the mucin gel for the fluorophore fluorescein. This study shows that it is possible to alter transport rates of molecules through mucus by changing the water activity in the gel. It furthermore illustrates the importance of considering effects of the water activity in the mucosa during development of potential pharmaceuticals. PMID:27336158

Low-grade appendiceal mucinous neoplasm mimicking an adnexal mass.

PubMed

Cristian, Daniel Alin; Grama, Florin Andrei; Becheanu, Gabriel; Pop, Anamaria; Popa, Ileana; Şurlin, Valeriu; Stănilescu, Sorin; Bratu, Ana Magdalena; Burcoş, Traean

2015-01-01

We present a rare case of malignant epithelial neoplasm of the appendix, an uncommon disorder encountered in clinical practice, which poses a variety of diagnostic and therapeutic challenges. We report a particular case in which the appendix was abnormally located in the pelvis, mimicking an adnexal mass. Therefore, it was difficult to make the preoperative diagnosis on clinical examination, imaging studies and laboratory tests and we discovered the lesion during the diagnostic laparoscopy. No lymphadenopathy or mucinous ascites were found. The case was completely handled via the laparoscopic approach keeping the appendix intact during the operation. The frozen section, the detailed histopathology overview as well as multiple immunostaining with a complex panel of markers report diagnosed a low-grade appendiceal mucinous neoplasm (LAMN) with no invasion of the wall. No adjuvant therapy was considered needed. At a one-year follow-up oncological assessment, the patient was free of disease. In women with cystic mass in the right iliac fossa an appendiceal mucocele should be considered in the differential diagnosis. Laparoscopic appendectomy can represent an adequate operation for the appendiceal mucinous neoplasm if the histological report is clear and surgical precautionary measures are taken.

Tea Derived Galloylated Polyphenols Cross-Link Purified Gastrointestinal Mucins

PubMed Central

Georgiades, Pantelis; Pudney, Paul D. A.; Rogers, Sarah; Thornton, David J.; Waigh, Thomas A.

2014-01-01

Polyphenols derived from tea are thought to be important for human health. We show using a combination of particle tracking microrheology and small-angle neutron scattering that polyphenols acts as cross-linkers for purified gastrointestinal mucin, derived from the stomach and the duodenum. Both naturally derived purified polyphenols, and green and black tea extracts are shown to act as cross-linkers. The main active cross-linking component is found to be the galloylated forms of catechins. The viscosity, elasticity and relaxation time of the mucin solutions experience an order of magnitude change in value upon addition of the polyphenol cross-linkers. Similarly small-angle neutron scattering experiments demonstrate a sol-gel transition with the addition of polyphenols, with a large increase in the scattering at low angles, which is attributed to the formation of large scale (>10 nm) heterogeneities during gelation. Cross-linking of mucins by polyphenols is thus expected to have an impact on the physicochemical environment of both the stomach and duodenum; polyphenols are expected to modulate the barrier properties of mucus, nutrient absorption through mucus and the viscoelastic microenvironments of intestinal bacteria. PMID:25162539

Genome-wide analysis of Atlantic salmon (Salmo salar) mucin genes and their role as biomarkers

PubMed Central

Grammes, Fabian Thomas; Ytteborg, Elisabeth; Takle, Harald; Jørgensen, Sven Martin

2017-01-01

The aim of this study was to identify potential mucin genes in the Atlantic salmon genome and evaluate tissue-specific distribution and transcriptional regulation in response to aquaculture-relevant stress conditions in post-smolts. Seven secreted gel-forming mucin genes were identified based on several layers of evidence; annotation, transcription, phylogeny and domain structure. Two genes were annotated as muc2 and five genes as muc5. The muc2 genes were predominantly transcribed in the intestinal region while the different genes in the muc5 family were mainly transcribed in either skin, gill or pyloric caeca. In order to investigate transcriptional regulation of mucins during stress conditions, two controlled experiments were conducted. In the first experiment, handling stress induced mucin transcription in the gill, while transcription decreased in the skin and intestine. In the second experiment, long term intensive rearing conditions (fish biomass ~125 kg/m3) interrupted by additional confinement led to increased transcription of mucin genes in the skin at one, seven and fourteen days post-confinement. PMID:29236729

Early biliary decompression versus conservative treatment in acute biliary pancreatitis (APEC trial): study protocol for a randomized controlled trial.

PubMed

Schepers, Nicolien J; Bakker, Olaf J; Besselink, Marc G H; Bollen, Thomas L; Dijkgraaf, Marcel G W; van Eijck, Casper H J; Fockens, Paul; van Geenen, Erwin J M; van Grinsven, Janneke; Hallensleben, Nora D L; Hansen, Bettina E; van Santvoort, Hjalmar C; Timmer, Robin; Anten, Marie-Paule G F; Bolwerk, Clemens J M; van Delft, Foke; van Dullemen, Hendrik M; Erkelens, G Willemien; van Hooft, Jeanin E; Laheij, Robert; van der Hulst, René W M; Jansen, Jeroen M; Kubben, Frank J G M; Kuiken, Sjoerd D; Perk, Lars E; de Ridder, Rogier J J; Rijk, Marno C M; Römkens, Tessa E H; Schoon, Erik J; Schwartz, Matthijs P; Spanier, B W Marcel; Tan, Adriaan C I T L; Thijs, Willem J; Venneman, Niels G; Vleggaar, Frank P; van de Vrie, Wim; Witteman, Ben J; Gooszen, Hein G; Bruno, Marco J

2016-01-05

Acute pancreatitis is mostly caused by gallstones or sludge. Early decompression of the biliary tree by endoscopic retrograde cholangiography (ERC) with sphincterotomy may improve outcome in these patients. Whereas current guidelines recommend early ERC in patients with concomitant cholangitis, early ERC is not recommended in patients with mild biliary pancreatitis. Evidence on the role of routine early ERC with endoscopic sphincterotomy in patients without cholangitis but with biliary pancreatitis at high risk for complications is lacking. We hypothesize that early ERC with sphincterotomy improves outcome in these patients. The APEC trial is a randomized controlled, parallel group, superiority multicenter trial. Within 24 hours after presentation to the emergency department, patients with biliary pancreatitis without cholangitis and at high risk for complications, based on an Acute Physiology and Chronic Health Evaluation (APACHE-II) score of 8 or greater, Modified Glasgow score of 3 or greater, or serum C-reactive protein above 150 mg/L, will be randomized. In 27 hospitals of the Dutch Pancreatitis Study Group, 232 patients will be allocated to early ERC with sphincterotomy or to conservative treatment. The primary endpoint is a composite of major complications (that is, organ failure, pancreatic necrosis, pneumonia, bacteremia, cholangitis, pancreatic endocrine, or exocrine insufficiency) or death within 180 days after randomization. Secondary endpoints include ERC-related complications, infected necrotizing pancreatitis, length of hospital stay and an economical evaluation. The APEC trial investigates whether an early ERC with sphincterotomy reduces the composite endpoint of major complications or death compared with conservative treatment in patients with biliary pancreatitis at high risk of complications. Current Controlled Trials ISRCTN97372133 (date registration: 17-12-2012).

Potential signaling pathways as therapeutic targets for overcoming chemoresistance in mucinous ovarian cancer

PubMed Central

Niiro, Emiko; Morioka, Sachiko; Iwai, Kana; Yamada, Yuki; Ogawa, Kenji; Kawahara, Naoki; Kobayashi, Hiroshi

2018-01-01

Cases of mucinous ovarian cancer are predominantly resistant to chemotherapies. The present review summarizes current knowledge of the therapeutic potential of targeting the Wingless (WNT) pathway, with particular emphasis on preclinical and clinical studies, for improving the chemoresistance and treatment of mucinous ovarian cancer. A review was conducted of English language literature published between January 2000 and October 2017 that concerned potential signaling pathways associated with the chemoresistance of mucinous ovarian cancer. The literature indicated that aberrant activation of growth factor and WNT signaling pathways is specifically observed in mucinous ovarian cancer. An evolutionarily conserved signaling cascade system including epidermal growth factor/RAS/RAF/mitogen-activated protein kinase kinase/extracellular signal-regulated protein kinase, phosphoinositide 3-kinase/Akt and WNT signaling regulates a variety of cellular functions; their crosstalk mutually enhances signaling activity and induces chemoresistance. Novel antagonists, modulators and inhibitors have been developed for targeting the components of the WNT signaling pathway, namely Frizzled, low-density lipoprotein receptor-related protein 5/6, Dishevelled, casein kinase 1, AXIN, glycogen synthase kinase 3β and β-catenin. Targeted inhibition of WNT signaling represents a rational and promising novel approach to overcome chemoresistance, and several WNT inhibitors are being evaluated in preclinical studies. In conclusion, the WNT receptors and their downstream components may serve as novel therapeutic targets for overcoming chemoresistance in mucinous ovarian cancer. PMID:29564122

Regulation of membrane-associated mucins in the human corneal epithelial cells by dexamethasone.

PubMed

Seo, Kyoung Yul; Chung, So-Hyang; Lee, Joon H; Park, Mi Young; Kim, Eung Kweon

2007-07-01

To study the influence of dexamethasone on membrane-associated mucins produced by human corneal epithelial cells. Human corneal epithelial cells were cultured in medium supplemented with various concentrations of dexamethasone (ranging from 10 to 10 M). Reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis using monoclonal antibodies specific for human MUC1 (HMFG-1), MUC4 (1G8), and MUC16 (OC125) were performed to evaluate the effect of dexamethasone on membrane-associated mucin expression. The effect of glucocorticoid receptor antagonist (RU38486) on dexamethasone-induced mucin expression was estimated. RT-PCR revealed that MUC1 and MUC16 gene expression were upregulated 48 hours after addition of dexamethasone and that MUC4 gene expression was downregulated in the same condition. Western blot analysis showed that MUC1 and MUC16 proteins were increased after addition of dexamethasone. However, MUC4 was not detected by anti-MUC4 monoclonal antibody (1G8) for ASGP-2 under our conditions. Treatment with RU38486 inhibited the changes of MUC1, MUC4, and MUC16 by dexamethasone; thus, the effect of dexamethasone on mucin expression is mediated by glucocorticoid receptors. This study shows that MUC1, MUC4, and MUC16 are regulated differently by dexamethasone in human corneal epithelial cells. External application of dexamethasone might affect the precorneal mucin.

Therapeutic experience of 289 elderly patients with biliary diseases

PubMed Central

Zhang, Zong-Ming; Liu, Zhuo; Liu, Li-Min; Zhang, Chong; Yu, Hong-Wei; Wan, Bai-Jiang; Deng, Hai; Zhu, Ming-Wen; Liu, Zi-Xu; Wei, Wen-Ping; Song, Meng-Meng; Zhao, Yue

2017-01-01

AIM To present clinical characteristics, diagnosis and treatment strategies in elderly patients with biliary diseases. METHODS A total of 289 elderly patients with biliary diseases were enrolled in this study. The clinical data relating to these patients were collected in our hospital from June 2013 to May 2016. Patient age, disease type, coexisting diseases, laboratory examinations, surgical methods, postoperative complications and therapeutic outcomes were analyzed. RESULTS The average age of the 289 patients with biliary diseases was 73.9 ± 8.5 years (range, 60-102 years). One hundred and thirty-one patients (45.3%) had one of 10 different biliary diseases, such as gallbladder stones, common bile duct stones, and cholangiocarcinoma. The remaining patients (54.7%) had two types of biliary diseases. One hundred and seventy-nine patients underwent 9 different surgical treatments, including pancreaticoduodenectomy, radical resection of hilar cholangiocarcinoma and laparoscopic cholecystectomy. Ten postoperative complications occurred with an incidence of 39.3% (68/173), and hypopotassemia showed the highest incidence (33.8%, 23/68). One hundred and sixteen patients underwent non-surgical treatments, including anti-infection, symptomatic and supportive treatments. The cure rate was 97.1% (168/173) in the surgical group and 87.1% (101/116) in the non-surgical group. The difference between these two groups was statistically significant (χ2 = 17.227, P < 0.05). CONCLUSION Active treatment of coexisting diseases, management of indications and surgical opportunities, appropriate selection of surgical procedures, improvements in perioperative therapy, and timely management of postoperative complications are key factors in enhancing therapeutic efficacy in elderly patients with biliary diseases. PMID:28428722

Impact of Ebola mucin-like domain on antiglycoprotein antibody responses induced by Ebola virus-like particles.

PubMed

Martinez, Osvaldo; Tantral, Lee; Mulherkar, Nirupama; Chandran, Kartik; Basler, Christopher F

2011-11-01

Ebola virus (EBOV) glycoprotein (GP), responsible for mediating host-cell attachment and membrane fusion, contains a heavily glycosylated mucin-like domain hypothesized to shield GP from neutralizing antibodies. To test whether the mucin-like domain inhibits the production and function of anti-GP antibodies, we vaccinated mice with Ebola virus-like particles (VLPs) that express vesicular stomatitis virus G, wild-type EBOV GP (EBGP), EBOV GP without its mucin-like domain (ΔMucGP), or EBOV GP with a Crimean-Congo hemorrhagic fever virus mucin-like domain substituted for the EBOV mucin-like domain (CMsubGP). EBGP-VLP immunized mice elicited significantly higher serum antibody titers toward EBGP or its mutants, as detected by western blot analysis, than did VLP-ΔMucGP. However, EBGP-, ΔMucGP- and CMsubGP-VLP immunized mouse sera contained antibodies that bound to cell surface-expressed GP at similar levels. Furthermore, low but similar neutralizing antibody titers, measured against a vesicular stomatitis virus (VSV) expressing EBGP or ΔMucGP, were present in EBGP, ΔMucGP, and CMsubGP sera, although a slightly higher neutralizing titer (2- to 2.5-fold) was detected in ΔMucGP sera. We conclude that the EBOV GP mucin-like domain can increase relative anti-GP titers, however these titers appear to be directed, at least partly, to denatured GP. Furthermore, removing the mucin-like domain from immunizing VLPs has modest impact on neutralizing antibody titers in serum.

Quality and readability assessment of websites related to recurrent respiratory papillomatosis

PubMed Central

de Groot, Olivier S.D.; Dikkers, Frederik G.

2017-01-01

Objective Recurrent respiratory papillomatosis (RRP) is a rare disease for which a limited number of information sources for patients exist. The role of the Internet in the patient–physician relationship is increasing. More and more patients search for online health information, which should be of good quality and easy readable. The study aim was to investigate the quality and readability of English online health information about RRP. Study Design Quality and readability assessment of online information. Methods Relevant information was collected using three different search engines and seven different search terms. Quality was assessed with the DISCERN instrument. The Flesch Reading Ease Score (FRES) and average grade level (AGL) were determined to measure readability of the English websites. Results Fifty‐one English websites were included. The mean DISCERN score of the websites is 28.1 ± 9.7 (poor quality); the mean FRES is 41.3 ± 14.9 (difficult to read); and the mean AGL is 12.6 ± 2.3. Conclusion The quality and readability of English websites about RRP is alarmingly poor. Level of Evidence NA. Laryngoscope, 127:2293–2297, 2017 PMID:28233911

Differentiation of pancreatobiliary cancer from benign biliary strictures using neutrophil gelatinase-associated lipocalin.

PubMed

Budzynska, A; Nowakowska-Dulawa, E; Marek, T; Boldys, H; Nowak, A; Hartleb, M

2013-02-01

Aim of the study was to investigate the value of serum and bile neutrophil gelatinase-associated lipocalin (NGAL) for distinguishing malignant strictures caused by cholangiocarcinoma (CCA) or pancreatic cancer from benign biliary strictures. The study was performed prospectively on patients admitted for endoscopic or radiologic biliary decompression. Forty patients with dilated biliary ducts, including 16 cases of CCA, 6 cases of pancreatic cancer, and 18 cases of benign biliary stricture were enrolled. Their sera and bile were collected to measure NGAL. Routine biochemistry including measurement of serum levels of carbohydrate antigens (CA) 19-9 and carcinoembryonic antigen (CEA) was also performed. The serum CA19-9, serum CEA, and bile NGAL levels were significantly increased in patients with malignant strictures as compared with patients with benign biliary diseases. Serum NGAL had no significant value for discriminating between malignant and benign biliary strictures. Bile NGAL levels had a receiver characteristic area under the curve of 0.74, sensitivity 77.3, and specificity 72.2% for discriminating between pancreatobiliary cancer and benign biliary diseases. Bile NGAL and serum CA19-9 were independent parameters and their combined use improved diagnostic accuracy (sensitivity 91%, negative predictive value 85.7%). We conclude that measurement of biliary, but not serum NGAL, may differentiate malignant pancreatobiliary from benign biliary strictures, serving as a complementary biomarker for serum CA19-9.

Utility of Shear Wave Elastography for Differentiating Biliary Atresia From Infantile Hepatitis Syndrome.

PubMed

Wang, Xiaoman; Qian, Linxue; Jia, Liqun; Bellah, Richard; Wang, Ning; Xin, Yue; Liu, Qinglin

2016-07-01

The purpose of this study was to investigate the potential utility of shear wave elastography (SWE) for diagnosis of biliary atresia and for differentiating biliary atresia from infantile hepatitis syndrome by measuring liver stiffness. Thirty-eight patients with biliary atresia and 17 patients with infantile hepatitis syndrome were included, along with 31 healthy control infants. The 3 groups underwent SWE. The hepatic tissue of each patient with biliary atresia had been surgically biopsied. Statistical analyses for mean values of the 3 groups were performed. Optimum cutoff values using SWE for differentiation between the biliary atresia and control groups were calculated by a receiver operating characteristic (ROC) analysis. The mean SWE values ± SD for the 3 groups were as follows: biliary atresia group, 20.46 ± 10.19 kPa; infantile hepatitis syndrome group, 6.29 ± 0.99 kPa; and control group, 6.41 ± 1.08 kPa. The mean SWE value for the biliary atresia group was higher than the values for the control and infantile hepatitis syndrome groups (P < .01). The mean SWE values between the control and infantile hepatitis syndrome groups were not statistically different. The ROC analysis showed a cutoff value of 8.68 kPa for differentiation between the biliary atresia and control groups. The area under the ROC curve was 0.997, with sensitivity of 97.4%, specificity of 100%, a positive predictive value of 100%, and a negative predictive value of 96.9%. Correlation analysis suggested a positive correlation between SWE values and age for patients with biliary atresia, with a Pearson correlation coefficient of 0.463 (P < .05). The significant increase in liver SWE values in neonates and infants with biliary atresia supports their application for differentiating biliary atresia from infantile hepatitis syndrome.

Expression of mucins on the mucosal surface of lungs of 4-week-old pigs.

PubMed

Kim, Chung Hyun; Lee, Kichan; Han, Kiwon; Oh, Yeonsu; Kim, Duyeol; Seo, Hwi Won; Park, Changhoon; Ha, Mi-Kyoung; Kim, Sung-Hoon; Cho, Kyung-Dong; Lee, Bog-Hieu; Chae, Chanhee

2011-04-01

The aim of this study was to determine the immunoreactivity of normal small bronchial, bronchiolar, respiratory bronchiolar, and interalveolar epithelium using antibodies to six mucins: MUC1, MUC2, MUC4, MUC5AC, MUC5B, and MUC6. The large, gel-forming secreted mucins MUC2, MUC5AC, and MUC5B were widely expressed in the lower respiratory tract. The results of this study demonstrate that these secreted mucins form a gel to cover and protect the mucosal surface in the lower respiratory tract of pigs. © Springer Science+Business Media B.V. 2011

[Self-expandable metallic biliary endoprosthesis in malignant obstructive jaundice].

PubMed

Güitrón-Cantú, Alfredo; Adalid-Martínez, Raúl; Gutiérrez-Bermúdez, José A

2005-01-01

Implantation of metallic stents for malignant biliary strictures has been recognized to be effective alternatives. To show our experience in metallic stents for palliation of malignant biliary strictures. Seventy three patients (38 males, 35 females, mean age 64.26) with malignant biliary strictures have been treated by implantation of metallic stents. Causes of obstruction were pancreatic carcinoma (23/73, 31.5%), bile duct carcinoma (31/73, 42.5%), carcinoma of ampula of Vater (11/73, 15%) and Klatskin tumor (3/73, 4.1%). Endoscopic procedure was successful in all cases. Neither procedure-related morbidity nor mortality was observed. Life surviving curve was 9 months and showed significant difference (p < 0.0071) in patients with carcinoma of ampula of Vater. Self-expanding metal endoprosthesis is a recognized method of palliation in malignant biliary obstruction. It efficiently relieves jaundice and generally improves comfort and nutritional status during the patient's remaining lifetime. The metallic stents are advantageous in patients surviving 6 months or less.

Salivary mucin MG1 is comprised almost entirely of different glycosylated forms of the MUC5B gene product.

PubMed

Thornton, D J; Khan, N; Mehrotra, R; Howard, M; Veerman, E; Packer, N H; Sheehan, J K

1999-03-01

The MG1 population of mucins was isolated from human whole salivas by gel chromatography followed by isopycnic density gradient centrifugation. The reduced and alkylated MG1 mucins, separated by anion exchange chromatography, were of similar size (radius of gyration 55-64 nm) and molecular weight (2.5-2.9 x 10(6) Da). Two differently-charged populations of MG1 subunits were observed which showed different reactivity with monoclonal antibodies to glycan epitopes. Monosaccharide and amino acid compositional analyses indicated that the MG1 subunits had similar glycan structures on the same polypeptide. An antiserum recognizing the MUC5B mucin was reactive across the entire distribution, whereas antisera raised against the MUC2 and MUC5AC mucins showed no reactivity. Western blots of agarose gel electrophoresis of fractions across the anion exchange distribution indicated that the polypeptide underlying the mucins was the product of the MUC5B gene. Amino acid analysis and peptide mapping performed on the fragments produced by trypsin digestion of the two MG1 populations yielded data similar to that obtained for MUC5B mucin subunits prepared from respiratory mucus (Thornton et al., 1997) and confirmed that the MUC5B gene product was the predominant mucin polypeptide present. Isolation of the MG1 mucins from the secretions of the individual salivary glands (palatal, sublingual, and submandibular) indicate that the palatal gland is the source of the highly charged population of the MUC5B mucin.

Analysis of cell cycle-related proteins in gastric intramucosal differentiated-type cancers based on mucin phenotypes: a novel hypothesis of early gastric carcinogenesis based on mucin phenotype

PubMed Central

2010-01-01

Background Abnormalities of cell cycle regulators are common features in human cancers, and several of these factors are associated with the early development of gastric cancers. However, recent studies have shown that gastric cancer tumorigenesis was characterized by mucin expression. Thus, expression patterns of cell cycle-related proteins were investigated in the early phase of differentiated-type gastric cancers to ascertain any mechanistic relationships with mucin phenotypes. Methods Immunostaining for Cyclins D1, A, E, and p21, p27, p53 and β-catenin was used to examine impairments of the cell cycle in 190 gastric intramucosal differentiated-type cancers. Mucin phenotypes were determined by the expressions of MUC5AC, MUC6, MUC2 and CD10. A Ki-67 positive rate (PR) was also examined. Results Overexpressions of p53, cyclin D1 and cyclin A were significantly more frequent in a gastric phenotype than an intestinal phenotype. Cyclin A was overexpressed in a mixed phenotype compared with an intestinal phenotype, while p27 overexpression was more frequent in an intestinal phenotype than in a mixed phenotype. Reduction of p21 was a common feature of the gastric intramucosal differentiated-type cancers examined. Conclusions Our results suggest that the levels of some cell cycle regulators appear to be associated with mucin phenotypes of early gastric differentiated-type cancers. PMID:20525401

Secreted mucins and airway bacterial colonization in non-CF bronchiectasis.

PubMed

Sibila, Oriol; Suarez-Cuartin, Guillermo; Rodrigo-Troyano, Ana; Fardon, Thomas C; Finch, Simon; Mateus, Eder Freddy; Garcia-Bellmunt, Laia; Castillo, Diego; Vidal, Silvia; Sanchez-Reus, Ferran; Restrepo, Marcos I; Chalmers, James D

2015-10-01

Secreted mucins play a key role in antibacterial defence in the airway, but have not previously been characterized in non-cystic fibrosis (CF) bronchiectasis patients. We aim to investigate the relationship between secreted mucins levels and the presence of bacterial colonization due to potentially pathogenic microorganisms (PPM) in the airways of stable bronchiectasis patients. Clinically stable bronchiectasis patients were studied prospectively at two centres. Patients with other pulmonary conditions were excluded. Spontaneous sputum was subject to bacterial culture, and secreted mucins (MUC2, MUC5AC and MUC5B) were measured in sputum supernatants by ELISA. A total of 50 patients were included. PPM were identified from sputum samples in 30 (60%), with Pseudomonas aeruginosa (n = 10) and Haemophilus influenzae (n = 10) as the most common PPM. There were no baseline differences among airway colonized and non-colonized patients. Patients with airways colonized by PPM presented higher levels of airway MUC2. No differences in MUC5AC levels were found among groups, whereas MUC5B levels were undetectable. Patients with P. aeruginosa colonization expressed the highest levels of MUC2. High levels of MUC2 and MUC5AC are also correlated with disease severity using the Bronchiectasis Severity Index. Airway MUC2 levels were higher in bronchiectasis patients colonized with PPM compared with those without airway colonization, especially in patients with P. aeruginosa. These findings suggest that airway-secreted mucins levels may play a role in the pathogenesis of airway infection in non-CF bronchiectasis. © 2015 Asian Pacific Society of Respirology.

Current diagnosis and treatment of benign biliary strictures after living donor liver transplantation

PubMed Central

Chang, Jae Hyuck; Lee, Inseok; Choi, Myung-Gyu; Han, Sok Won

2016-01-01

Despite advances in surgical techniques, benign biliary strictures after living donor liver transplantation (LDLT) remain a significant biliary complication and play an important role in graft and patient survival. Benign biliary strictures after transplantation are classified into anastomotic or non-anastomotic strictures. These two types differ in presentation, outcome, and response to therapy. The leading causes of biliary strictures include impaired blood supply, technical errors during surgery, and biliary anomalies. Because patients usually have non-specific symptoms, a high index of suspicion should be maintained. Magnetic resonance cholangiography has gained widespread acceptance as a reliable noninvasive tool for detecting biliary complications. Endoscopy has played an increasingly prominent role in the diagnosis and treatment of biliary strictures after LDLT. Endoscopic management in LDLT recipients may be more challenging than in deceased donor liver transplantation patients because of the complex nature of the duct-to-duct reconstruction. Repeated aggressive endoscopic treatment with dilation and the placement of multiple plastic stents is considered the first-line treatment for biliary strictures. Percutaneous and surgical treatments are now reserved for patients for whom endoscopic management fails and for those with multiple, inaccessible intrahepatic strictures or Roux-en-Y anastomoses. Recent advances in enteroscopy enable treatment, even in these latter cases. Direct cholangioscopy, another advanced form of endoscopy, allows direct visualization of the inner wall of the biliary tree and is expected to facilitate stenting or stone extraction. Rendezvous techniques can be a good option when the endoscopic approach to the biliary stricture is unfeasible. These developments have resulted in almost all patients being managed by the endoscopic approach. PMID:26819525

Barrier role of actin filaments in regulated mucin secretion from airway goblet cells.

PubMed

Ehre, Camille; Rossi, Andrea H; Abdullah, Lubna H; De Pestel, Kathleen; Hill, Sandra; Olsen, John C; Davis, C William

2005-01-01

Airway goblet cells secrete mucin onto mucosal surfaces under the regulation of an apical, phospholipase C/G(q)-coupled P2Y(2) receptor. We tested whether cortical actin filaments negatively regulate exocytosis in goblet cells by forming a barrier between secretory granules and plasma membrane docking sites as postulated for other secretory cells. Immunostaining of human lung tissues and SPOC1 cells (an epithelial, mucin-secreting cell line) revealed an apical distribution of beta- and gamma-actin in ciliated and goblet cells. In goblet cells, actin appeared as a prominent subplasmalemmal sheet lying between granules and the apical membrane, and it disappeared from SPOC1 cells activated by purinergic agonist. Disruption of actin filaments with latrunculin A stimulated SPOC1 cell mucin secretion under basal and agonist-activated conditions, whereas stabilization with jasplakinolide or overexpression of beta- or gamma-actin conjugated to yellow fluorescent protein (YFP) inhibited secretion. Myristoylated alanine-rich C kinase substrate, a PKC-activated actin-plasma membrane tethering protein, was phosphorylated after agonist stimulation, suggesting a translocation to the cytosol. Scinderin (or adseverin), a Ca(2+)-activated actin filament severing and capping protein was cloned from human airway and SPOC1 cells, and synthetic peptides corresponding to its actin-binding domains inhibited mucin secretion. We conclude that actin filaments negatively regulate mucin secretion basally in airway goblet cells and are dynamically remodeled in agonist-stimulated cells to promote exocytosis.

CT differentiation of mucin-producing cystic neoplasms of the liver from solitary bile duct cysts.

PubMed

Kim, Hyoung Jung; Yu, Eun Sil; Byun, Jae Ho; Hong, Seung-Mo; Kim, Kyoung Won; Lee, Jong Seok; Kim, So Yeon

2014-01-01

The purpose of this study was to identify the CT features required for differentiating mucin-producing cystic neoplasms of the liver (mucinous cystic neoplasms and cyst-forming intraductal papillary neoplasms of the bile duct) from solitary bile duct cysts. CT images of pathologically confirmed mucinous cystic neoplasms (n = 15), cyst-forming intraductal papillary neoplasms of the bile duct (n = 16), and solitary bile duct cysts (n = 31) were reviewed. Analysis of the CT findings included shape, presence of septa, location of septa (peripheral vs central), thickness of septa (thin vs thick), mosaic pattern, mural nodules, intracystic debris, calcification, upstream bile duct dilatation, downstream bile duct dilatation, and communication between a cystic lesion and the bile duct. The maximum size of a cystic lesion and the maximum size of the largest mural nodule were measured. The presence of septa, central septa, mural nodules, upstream bile duct dilatation, and downstream bile duct dilatation were found to be significant CT findings for differentiating mucinous cystic neoplasms and cyst-forming intraductal papillary neoplasms of the bile duct from solitary bile duct cysts (p < 0.05 for each finding). When two of these five criteria were used in combination, the sensitivity and specificity for diagnosing mucin-producing cystic neoplasms and cyst-forming intraductal papillary neoplasms of the bile duct were 87% (27 of 31) and 87% (27 of 31), respectively. When two of these five criteria were used in combination, the sensitivity and specificity for diagnosing mucinous cystic neoplasms and cyst-forming intraductal papillary neoplasms of the bile duct were 87% (27 of 31) and 87% (27 of 31), respectively [corrected]. With the use of specific CT criteria, mucin-producing cystic neoplasms of the liver can be differentiated from solitary bile duct cysts with a high degree of accuracy.

Microrheology study of human mucins varying in Helicobacter pylori binding affinity

NASA Astrophysics Data System (ADS)

Su, Clover; Sharba, Sinan; Linden, Sara; Bansil, Rama

Helicobacter pylori is the pathogen that colonizes the human stomach and causes gastric ulcers and cancer. One of the key mechanisms by which H. pylori establishes an infection on the gastric mucosa is by expressing adhesins that facilitate the binding of the bacterium to the host epithelial cell. We present the motility and microrheology study of a clinical isolate strain of H. pylori, J99, and its mutant with and without particular adhesins that bind to mucins with specific alterations in their glycans coat. Our microrheology experiments show that mucin viscosity depends on the glycans coat and decreases in the presence of bacteria. We found no significant changes in bacterial motility between J99 wild type and mutant in culture broth. Unlike previous observations made with other H. pylori strains, we did not see reversals in J99 strains. Bacteria tracking measurements are underway to examine the motility in these altered mucin solutions. Supported by NSF PHY 1410798.

The surface activity of purified ocular mucin at the air-liquid interface and interactions with meibomian lipids.

PubMed

Millar, Thomas J; Tragoulias, Sophia T; Anderton, Philip J; Ball, Malcolm S; Miano, Fausto; Dennis, Gary R; Mudgil, Poonam

2006-01-01

Ocular mucins are thought to contribute to the stability of the tear film by reducing surface tension. The purpose of this study was to compare the effect of different mucins and hyaluronic acid (HA) alone and mixed with meibomian lipids on the surface pressure at an air-liquid interface. A Langmuir trough and Wilhelmy balance were used to measure and compare the surface activity of bovine submaxillary gland mucin (BSM), purified BSM, purified bovine ocular mucin and HA, and mixtures of these with meibomian lipids, phosphatidylcholine, and phosphatidylglycerol. Their appearance at the surface of an air-buffer interface was examined using epifluorescence microscopy. Purified ocular mucin had no surface activity even at concentrations that were 100 times more than normally occur in tears. By contrast, commercial BSM caused changes to surface pressure that were concentration dependent. The surface pressure-area profiles showed surface activity with maximum surface pressures of 12.3-22.5 mN/m depending on the concentration. Purified BSM showed no surface activity at low concentrations, whereas higher concentrations reached a maximum surface pressure of 25 mN/m. HA showed no surface activity, at low or high concentrations. Epifluorescence showed that the mucins were located at the air-buffer interface and changed the appearance of lipid films. Purified bovine ocular mucin and HA have no surface activity. However, despite having no surface activity in their own right, ocular mucins are likely to be present at the surface of the tear film, where they cause an increase in surface pressure by causing a compression of the lipids (a reorganization of the lipids) and alter the viscoelastic properties at the surface.

Biliary atresia in Vietnam: Management and the burden of disease.

PubMed

Liu, Max Bolun; Huong, Thuy Bui; Hoang, Xuyen; Doan, Lan; Trinh, Shauna; Anh Nguyen, Hoa Pham; Thanh Le, Hai; Holterman, Ai-Xuan

2017-02-01

Biliary atresia is an idiopathic, neonatal liver disease of the bile ducts. The natural evolution of biliary atresia is known in developed countries. This study describes the clinical course of biliary atresia in Vietnam, a developing country. Chart reviews were undertaken of patients treated with or without the Kasai procedure between January 2010 and July 2013 at a children's hospital in Vietnam. Of 287 children with biliary atresia, 149 (52%) were treated without the Kasai procedure and 138 (48%) were treated with the Kasai procedure. Median age at diagnosis was 2.4 months for children treated without the Kasai procedure vs 2.3 months for those treated with the procedure. The percentages of patients in the group treated without the Kasai procedure presenting at <2 months, 2 to <3 months, 3 to <4 months, 4-6 months, and >6 months of age were 31%, 35%, 15%, 10%, and 9%, respectively, compared to those treated with the Kasai procedure at 36% (P = .38), 44% (P = .12), 16% (P = 1.0), 4% (P = .037), and 0% (P < .001), respectively. The group treated without the Kasai procedure had 1- and 2-year survivals of 52% and 28%, respectively (median survival 6.6 months); in contrast, the group treated with the Kasai procedure had 1- and 2-year transplant-free survivals of 84% and 71%. No patients were treated by liver transplantation because of lack of a liver transplantation program in Vietnam. The majority of biliary atresia in Vietnam remains untreated despite early presentation and reasonable outcomes after a Kasai procedure relative to Western countries. These data illustrate the high health care burden for biliary atresia in Vietnam and the need to improve education about biliary atresia and its treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

Mucinous expression in benign and neoplastic glandular lesions of the uterine cervix.

PubMed

Baker, Allyson C; Eltoum, Isam; Curry, Rebecca O; Stockard, Cecil R; Manne, Upender; Grizzle, William E; Chhieng, David

2006-10-01

Mucins are glycoproteins produced by both normal and neoplastic glandular epithelial cells including endocervix. To determine the expression of mucins in uterine cervical glandular lesions and whether mucin expression correlates with the nature and origin of the glandular lesions. Antibodies to MUC1, MUC2, MUC4, and MUC5AC were applied on 52 cases including 14 endocervical adenocarcinomas (including 4 adenosquamous carcinomas), 9 endometrial carcinomas (8 endometrioid adenocarcinomas and 1 adenosquamous carcinoma), 8 adenocarcinoma in situ (AIS), 2 glandular dysplasias, 6 tubal metaplasias, 10 microglandular hyperplasias, and 3 normal endocervix. The presence of any staining was considered positive. All benign endocervical epithelia, including tubal metaplasia and microglandular hyperplasia, expressed MUC1, MUC4, and MUC5AC but not MUC2. Almost all endocervical AIS and carcinomas and all endometrial adenocarcinomas expressed MUC1; the exceptions were 2 cases of endocervical adenocarcinoma and 1 case of adenosquamous carcinoma of the endocervix. MUC2 staining was noted in 25%, 40%, and 22% of AIS, endocervical adenocarcinomas, and endometrial adenocarcinomas, respectively. About 38% of AIS, 75% of endocervical adenocarcinomas, and 44% of endometrial adenocarcinomas expressed MUC4. Half of AIS, most of endocervical adenocarcinomas, and 22% of endometrial adenocarcinomas expressed MUC5AC. The difference in MUC4 and MUC5AC expression between benign endocervical lesions and AIS and the difference in MUC5AC expression between endocervical and endometrial neoplasms were statistically significant. Mucin expressions differed among benign endocervical lesions and AIS and among endocervical and endometrial malignancies. These results suggest that mucin staining may potentially be helpful in differentiating various uterine cervical glandular lesions.

Linking human beta retrovirus infection with primary biliary cirrhosis.

PubMed

Mason, A L; Zhang, G

2010-01-01

Several environmental agents have been linked with primary biliary cirrhosis (PBC) that include bacteria, xenobiotics and viruses. A human beta retrovirus (HBRV) related to mouse mammary tumor virus has been cloned and characterized from patients with PBC. This agent can be detected in the majority of patients' perihepatic lymph nodes by immunochemistry and RT-PCR. The HBRV has recently been isolated in culture and integration sites have been identified in the genome of patients to provide convincing evidence of beta retrovirus infection in patients. Three lines of evidence support a role for the virus in PBC. First, the beta retrovirus is linked with aberrant expression of mitochondrial protein(s) on the biliary epithelium cell (BEC) surface, a disease specific phenotype. Second, the related agent, mouse mammary tumor virus has been linked with autoimmune biliary disease in the NOD.c3c4 mouse model for PBC. In this mouse model, the virus is localized to diseased biliary epithelium that also display aberrant expression of the mitochondrial autoantigens. In translational studies, both patients with PBC and NOD.c3c4 mice demonstrate significant improvement in biliary disease with combination antiviral therapy. An overview of the biological relevance of the beta retrovirus infection in PBC will be discussed in this review. Copyright 2010 Elsevier Masson SAS. All rights reserved.

Safety evaluation of probiotic bifidobacteria by analysis of mucin degradation activity and translocation ability.

PubMed

Abe, Fumiaki; Muto, Masamichi; Yaeshima, Tomoko; Iwatsuki, Keiji; Aihara, Hiroaki; Ohashi, Yuji; Fujisawa, Tomohiko

2010-04-01

Although probiotic-containing nutrient formulas for infants and toddlers have become very popular, some adverse effects related to translocation of probiotic strains have been reported. We assessed the safety of probiotic bifidobacteria that have been used in clinical investigations and proven to have beneficial effects, by analyzing mucin degradation activity and translocation ability. Mucin degradation activities of three probiotic bifidobacteria strains; Bifidobacterium longum BB536, Bifidobacterium breve M-16V and Bifidobacterium infantis M-63, were evaluated by three in vitro tests comprising growth in liquid medium, SDS-PAGE analysis of degraded mucin residues, and degradation assay in Petri dish. All test strains and control type strains failed to grow in the liquid medium containing mucin as the only carbon source, although good growth was obtained from fecal sample. In the SDS-PAGE analyses of mucin residues and observation of mucinolytic zone in agar plate, the three test strains also showed no mucin degradation activity as the type strains, although fecal sample yielded positive results. In another study, a high dose of B. longum BB536 was administered orally to conventional mice to examine the translocation ability. No translocation into blood, liver, spleen, kidney and mesenteric lymph nodes was observed and no disturbance of epithelial cells and mucosal layer in the ileum, cecum and colon was detected, indicating that the test strain had no translocation ability and induced no damage to intestinal surface. These results resolve the concern about bacterial translocation when using bifidobacteria strains as probiotics, which have been tested in various clinical trials, supporting the continuous use of these probiotic strains without anxiety. Copyright 2009 Elsevier Ltd. All rights reserved.

Pattern of HER-2 Gene Amplification and Protein Expression in Benign, Borderline, and Malignant Ovarian Serous and Mucinous Neoplasms.

PubMed

Mohammed, Rabab A A; Makboul, Rania; Elsers, Dalia A H; Elsaba, Tarek M A M; Thalab, Abeer M A B; Shaaban, Omar M

2017-01-01

Amplification of HER-2 gene and overexpression of HER-2 receptor play a significant role in the progression of a number of malignancies such as breast cancer. Trastuzumab (anti-HER-2 therapeutic agent) has been used successfully in treatment of breast cancer. The aim of this study was to assess the pattern of HER-2 gene amplification and of HER-2 receptor expression in a spectrum of serous and mucinous ovarian tumors to determine whether HER-2 is altered in these neoplasms similar to that occurring in breast cancer. Formalin-fixed paraffin-embedded microarray tissue sections from 212 specimens were stained with HER-2 antibody using immunohistochemistry and with anti-HER-2 DNA probe using chromogenic in situ hybridization. Specimens consisted of 65 benign tumors (50 serous and 15 mucinous), 26 borderline (13 serous and 13 mucinous), 73 malignant tumors (53 serous carcinoma and 20 mucinous carcinoma), 18 metastatic deposits (13 serous and 5 mucinous), in addition to 30 normal tissues (16 ovarian surface and 14 normal fallopian tube). HER-2 protein-positive expression was not detected in the normal or the benign tissues. Borderline neoplasms showed positive staining, but no overexpression. HER-2 overexpression was seen only in 4 carcinoma specimens: 1/53 (1.8%) primary serous carcinomas and 3/20 (15%) primary mucinous carcinomas. HER-2 gene amplification was seen in 4 specimens: 2 primary mucinous carcinomas and 2 malignant deposits of these 2 mucinous carcinomas. In conclusion, alteration of HER-2 was not detected in ovarian serous neoplasms; however, in mucinous carcinoma, HER-2 amplification and overexpression occur.

National assessment of early biliary complications after liver transplantation: economic implications.

PubMed

Axelrod, David A; Dzebisashvilli, Nino; Lentine, Krista L; Xiao, Huiling; Schnitzler, Mark; Tuttle-Newhall, Janet E; Segev, Dorry L

2014-12-15

Despite improvement in surgical technique and medical management of liver transplant recipients, biliary complications remain a frequent cause of posttransplant morbidity and graft loss. Biliary complications require potentially expensive interventions including radiologic procedures and surgical revisions. A national data set linking transplant registry and Medicare claims data for 12,803 liver transplant recipients was developed to capture information on complications, treatments, and associated direct medical costs up to 3 years after transplantation. Biliary complications were more common in recipients of donation after cardiac death compared to donation after brain death allografts (23% vs. 19% P<0.001). Among donation after brain death recipients, biliary complications were associated with $54,699 (95% confidence interval [CI], $49,102 to $60,295) of incremental spending in the first year after transplantation and $7,327 in years 2 and 3 (95% CI, $4,419-$10,236). Biliary complications in donation after cardiac death recipients independently increased spending by $94,093 (95% CI, $64,643-$124,542) in the first year and $12,012 (95% CI, $-1,991 to $26,016) in years 2 and 3. This national study of biliary complications demonstrates the significant economic impact of this common perioperative complication and suggests a potential target for quality of care improvements.

Expression of cancer-associated simple mucin-type O-glycosylated antigens in parasites.

PubMed

Osinaga, Eduardo

2007-01-01

Simple mucin-type O-glycan structures, such as Tn, TF, sialyl-Tn and Tk antigens, are among of the most specific human cancer-associated structures. These antigens are involved in several types of receptor-ligand interactions, and they are potential targets for immunotherapy. In the last few years several simple mucin-type O-glycan antigens were identified in different species belonging to the main two helminth parasite phyla, and sialyl-Tn bearing glycoproteins were detected in Trypanosoma cruzi. These results are of interest to understand new aspects in parasite glycoimmunology and may help identify new biological characteristics of parasites as well of the host-parasite relationship. Considering that different groups reported a negative correlation between certain parasite infections and cancer development, we could hypothesize that simple mucin-type O-glycosylated antigens obtained from parasites could be good potential targets for cancer immunotherapy.

A Sensitive and Rapid Method to Determin the Adhesion Capacity of Probiotics and Pathogenic Microorganisms to Human Gastrointestinal Mucins.

PubMed

Ringot-Destrez, Bélinda; D'Alessandro, Zéa; Lacroix, Jean-Marie; Mercier-Bonin, Muriel; Léonard, Renaud; Robbe-Masselot, Catherine

2018-05-29

Mucus is the habitat for the microorganisms, bacteria and yeast that form the commensal flora. Mucins, the main macromolecules of mucus, and more specifically, the glycans that cover them, play essential roles in microbial gastrointestinal colonization. Probiotics and pathogens must also colonize mucus to have lasting positive or deleterious effects. The question of which mucin-harboured glycan motifs favour the adhesion of specific microorganisms remains very poorly studied. In the current study, a simple test based on the detection of fluorescent-labeled microorganisms raised against microgram amounts of mucins spotted on nitrocellulose was developed. The adhesion of various probiotic, commensal and pathogenic microorganisms was evaluated on a panel of human purified gastrointestinal mucins and compared with that of commercially available pig gastric mucins (PGM) and of mucins secreted by the colonic cancer cell line HT29-MTX. The latter two proved to be very poor indicators of adhesion capacity on intestinal mucins. Our results show that the nature of the sialylated cores of O -glycans, determined by MALDI MS-MS analysis, potentially enables sialic acid residues to modulate the adhesion of microorganisms either positively or negatively. Other identified factors affecting the adhesion propensity were O -glycan core types and the presence of blood group motifs. This test should help to select probiotics with enhanced adhesion capabilities as well as deciphering the role of specific mucin glycotopes on microbial adhesion.

Mucin- and carbohydrate-stimulated adhesion and subproteome changes of the probiotic bacterium Lactobacillus acidophilus NCFM.

PubMed

Celebioglu, Hasan Ufuk; Olesen, Sita Vaag; Prehn, Kennie; Lahtinen, Sampo J; Brix, Susanne; Abou Hachem, Maher; Svensson, Birte

2017-06-23

Adhesion to intestinal mucosa is a crucial property for probiotic bacteria. Adhesion is thought to increase host-bacterial interactions, thus potentially enabling health benefits to the host. Molecular events connected with adhesion and surface proteome changes were investigated for the probiotic Lactobacillus acidophilus NCFM cultured with established or emerging prebiotic carbohydrates as carbon source and in the presence of mucin, the glycoprotein of the epithelial mucus layer. Variation in adhesion to HT29-cells and mucin was associated with carbon source and mucin-induced subproteome abundancy differences. Specifically, while growth on fructooligosaccharides (FOS) only stimulated adhesion to intestinal HT-29 cells, cellobiose and polydextrose in addition increased adhesion to mucin. Adhesion to HT-29 cells increased by about 2-fold for bacteria grown on mucin-supplemented glucose. Comparative 2DE-MS surface proteome analysis showed different proteins in energy metabolism appearing on the surface, suggesting they exert moonlighting functions. Mucin-supplemented bacteria had relative abundance of pyruvate kinase and fructose-bisphosphate aldolase increased by about 2-fold while six spots with 3.2-2.1 fold reduced relative abundance comprised elongation factor G, phosphoglycerate kinase, BipAEFTU family GTP-binding protein, ribonucleoside triphosphate reductase, adenylosuccinate synthetase, 30S ribosomal protein S1, and manganese-dependent inorganic pyrophosphatase. Surface proteome of cellobiose- compared to glucose-grown L. acidophilus NCFM had phosphate starvation inducible protein stress-related, thermostable pullulanase, and elongation factor G increasing 4.4-2.4 fold, while GAPDH, elongation factor Ts, and pyruvate kinase were reduced by 2.0-1.5 fold in relative abundance. Addition of recombinant L. acidophilus NCFM elongation factor G and pyruvate kinase to a coated mucin layer significantly suppressed subsequent adhesion of the bacterium. Human diet is

Surgical Management of Benign Biliary Stricture in Chronic Pancreatitis: A Single-Center Experience.

PubMed

Ray, Sukanta; Ghatak, Supriyo; Das, Khaunish; Dasgupta, Jayanta; Ray, Sujay; Khamrui, Sujan; Sonar, Pankaj Kumar; Das, Somak

2015-12-01

Biliary stricture in chronic pancreatitis (CP) is not uncommon. Previously, all cases were managed by surgery. Nowadays, three important modes of treatment in these patients are observation, endoscopic therapy, and surgery. In the modern era, surgery is recommended only in a subset of patients who develop biliary symptoms or those who have asymptomatic biliary stricture and require surgery for intractable abdominal pain. We want to report on our experience regarding surgical management of CP-induced benign biliary stricture. Over a period of 5 years, we have managed 340 cases of CP at our institution. Bile duct stricture was found in 62 patients. But, surgical intervention was required in 44 patients, and the remaining 18 patients were managed conservatively. Demographic data, operative procedures, postoperative complications, and follow-up parameters of these patients were collected from our prospective database. A total 44 patients were operated for biliary obstruction in the background of CP. Three patients were excluded, so the final analysis was based on 41 patients. The indication for surgery was symptomatic biliary stricture in 27 patients and asymptomatic biliary stricture with intractable abdominal pain in 14 patients. The most commonly performed operation was Frey's procedure. There was no inhospital mortality. Thirty-five patients were well at a mean follow-up of 24.4 months (range 3 to 54 months). Surgery is still the best option for CP-induced benign biliary stricture, and Frey's procedure is a versatile operation unless you suspect malignancy as the cause of biliary obstruction.

Risk factors for isolated biliary atresia, National Birth Defects Prevention Study, 1997-2002.

PubMed

The, Natalie S; Honein, Margaret A; Caton, Alissa R; Moore, Cynthia A; Siega-Riz, Anna Maria; Druschel, Charlotte M

2007-10-01

Biliary atresia is a rare birth defect that affects 1 in 12,000 to 1 in 19,500 live births. We used data from the National Birth Defects Prevention Study, a multistate case-control study, to identify potential risk factors for isolated biliary atresia (no additional unrelated major birth defects diagnosed). Infants were identified from eight states from 1997 to 2002, with clinical information abstracted from medical records. Potential risk factors assessed include: demographic factors, seasonality, preterm birth, maternal smoking, maternal alcohol use, maternal illicit drug use, maternal health, maternal medication use, maternal vitamin use, and maternal nutrition. Infants of non-Hispanic black mothers were more likely to have biliary atresia than infants of non-Hispanic white mothers (adjusted odds ratio (aOR) = 2.29, 95% confidence interval (CI) 1.07-4.93) and infants conceived during the spring season were more likely to have biliary atresia than infants conceived in winter (aOR = 2.33, 95%CI 1.05-5.16). Low intakes of vitamin E, copper, phosphorus, and beta tocopherol were associated with the occurrence of isolated biliary atresia (borderline significance). Low iron intake had a borderline inverse association with biliary atresia. While this analysis provides support for previous reports of a possible association between seasonal variation and the occurrence of biliary atresia, more data are needed to evaluate whether the seasonal variation is related to infectious agents. The role of nutrients in the development of biliary atresia remains unclear. Further studies of genetic, infectious, and nutrient exposures and the association of biliary atresia are warranted. 2007 Wiley-Liss, Inc

Progesterone alters biliary flow dynamics.

PubMed

Tierney, S; Nakeeb, A; Wong, O; Lipsett, P A; Sostre, S; Pitt, H A; Lillemoe, K D

1999-02-01

To test the hypothesis that progesterone alters sphincter of Oddi and gallbladder function and, therefore, bile flow dynamics. Although the effects of progesterone on the biliary tract have been implicated in the increased incidence of gallstones among women, the specific effects of prolonged elevation of progesterone levels, such as occurs with contraceptive progesterone implants and during pregnancy, on the sphincter of Oddi and biliary flow dynamics are still incompletely understood. Adult female prairie dogs were randomly assigned to receive subcutaneous implants containing either progesterone or inactive pellet matrix only. Hepatic bile partitioning and gallbladder emptying were determined 14 days later using 99mTc-Mebrofenin cholescintigraphy. Significantly less hepatic bile partitioned into the gallbladder in progesterone-treated than in control animals. The gallbladder ejection fraction was significantly reduced from 73+/-6% in controls to 59+/-3% in the progesterone-treated animals. The rate of gallbladder emptying was significantly reduced from 3.6+/-0.3%/minute to 2.9+/-0.1%/minute. Progesterone administered as subcutaneous implants alters partitioning of hepatic bile between gallbladder and small intestine and, therefore, gallbladder filling. Progesterone also significantly impairs gallbladder emptying in response to cholecystokinin. The effects of progesterone on the sphincter of Oddi and the gallbladder may contribute to the greater prevalence of gallstones and biliary motility disorders among women.

Multicenter study of endoscopic preoperative biliary drainage for malignant hilar biliary obstruction: E-POD hilar study.

PubMed

Nakai, Yousuke; Yamamoto, Ryuichi; Matsuyama, Masato; Sakai, Yuji; Takayama, Yukiko; Ushio, Jun; Ito, Yukiko; Kitamura, Katsuya; Ryozawa, Shomei; Imamura, Tsunao; Tsuchida, Kouhei; Hayama, Jo; Itoi, Takao; Kawaguchi, Yoshiaki; Yoshida, Yu; Sugimori, Kazuya; Shimura, Kenji; Mizuide, Masafumi; Iwai, Tomohisa; Nishikawa, Ko; Yagioka, Hiroshi; Nagahama, Masatsugu; Toda, Nobuo; Saito, Tomotaka; Yasuda, Ichiro; Hirano, Kenji; Togawa, Osamu; Nakamura, Kenji; Maetani, Iruru; Sasahira, Naoki; Isayama, Hiroyuki

2018-05-01

Endoscopic nasobiliary drainage (ENBD) is often recommended in preoperative biliary drainage (PBD) for hilar malignant biliary obstruction (MBO), but endoscopic biliary stent (EBS) is also used in the clinical practice. We conducted this large-scale multicenter study to compare ENBD and EBS in this setting. A total of 374 cases undergoing PBD including 281 ENBD and 76 EBS for hilar MBO in 29 centers were retrospectively studied. Extrahepatic cholangiocarcinoma (ECC) accounted for 69.8% and Bismuth-Corlette classification was III or more in 58.8% of the study population. Endoscopic PBD was technically successful in 94.6%, and adverse event rate was 21.9%. The rate of post-endoscopic retrograde cholangiopancreatography pancreatitis was 16.0%, and non-endoscopic sphincterotomy was the only risk factor (odds ratio [OR] 2.51). Preoperative re-intervention was performed in 61.5%: planned re-interventions in 48.4% and unplanned re-interventions in 31.0%. Percutaneous transhepatic biliary drainage was placed in 6.4% at the time of surgery. The risk factors for unplanned procedures were ECC (OR 2.64) and total bilirubin ≥ 10 mg/dL (OR 2.18). In surgically resected cases, prognostic factors were ECC (hazard ratio [HR] 0.57), predraiange magnetic resonance cholangiopancreatography (HR 1.62) and unplanned re-interventions (HR 1.81). EBS was not associated with increased adverse events, unplanned re-interventions, or a poor prognosis. Our retrospective analysis did not demonstrate the advantage of ENBD over EBS as the initial PBD for resectable hilar MBO. Although the technical success rate of endoscopic PBD was high, its re-intervention rate was not negligible, and unplanned re-intervention was associated with a poor prognosis in resected hilar MBO. © 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Biliary complications after right lobe living donor liver transplantation: a single-centre experience

PubMed Central

Yaprak, Onur; Dayangac, Murat; Akyildiz, Murat; Demirbas, Tolga; Guler, Necdet; Bulutcu, Fisun; Bassullu, Nuray; Akun, Elif; Yuzer, Yildiray; Tokat, Yaman

2012-01-01

Background Biliary complications that developed after right lobe liver transplantation from living donors were studied in a single centre. Methods From 2004 to 2010, 200 consecutive living donor right lobe liver transplantations were performed. The database was evaluated retrospectively. Biliary complications were diagnosed according to clinical, biochemical and radiological tests. The number of biliary ducts in the transplanted graft, the surgical techniques used for anastomosis, biliary strictures and bile leakage rates were analysed. Results Of a total of 200 grafts, 117 invloved a single bile duct, 77 had two bile ducts and in six grafts there were three bile ducts. In 166 transplants, the anastomosis was performed as a single duct to duct, in 21 transplants double duct to ducts, in one transplant, three duct to ducts and in 12 transplants as a Roux-en-Y reconstruction. In all, 40 bile leakages (20%) and 17 biliary strictures (8.5%) were observed in 49 patients resulting in a total of 57 biliary complications (28.5%). Seventeen patients were re-operated (12 as a result of bile leakages and five owing to biliary strictures). Conclusion Identification of more than one biliary orifice in the graft resulted in an increase in the complication rates. In grafts containing multiple orifices, performing multiple duct-to-duct (DD) or Roux-en-Y anastomoses led to a lower number of complications. PMID:22151451

Advanced Stage Mucinous Adenocarcinoma of the Ovary is both Rare and Highly Lethal: A Gynecologic Oncology Group Study

PubMed Central

Zaino, Richard J.; Brady, Mark F.; Lele, Subodh M.; Michael, Helen; Greer, Benjamin; Bookman, Michael A.

2010-01-01

Background Primary mucinous adenocarcinomas of the ovary are uncommon and their biologic behavior uncertain. Retrospective studies suggest that many mucinous carcinomas diagnosed as primary to the ovary were actually metastatic from another site. A prospective randomized trial provided an opportunity to estimate the frequency of mucinous tumors, diagnostic reproducibility, and clinical outcomes. Methods A phase III trial enrolled 4000 women with stage III or IV ovarian carcinoma, treated by surgical staging and debulking, with randomization to one of five chemotherapeutic arms. Slides and pathology reports classified as primary mucinous carcinoma were reviewed independently by three pathologists. Cases were re-classified as primary or metastatic to the ovary according to two methods. Overall survival (OS) of reclassified groups was compared with each other and with that of patients with serous carcinomas. Results Forty-four cases were classified as mucinous adenocarcinoma at review. Using either method, only about one third were interpreted by the three reviewers as primary mucinous carcinomas. Reproducibility of interpretations among the reviewers was high with unanimity of opinion in 30 of the 44 (68%) cases. The median survival (MS) did not differ significantly between the groups interpreted as primary or metastatic, but the OS was significantly less than that for women with serous carcinoma (14 vs 42 months, p<0.001). Conclusion Advanced stage mucinous carcinoma of the ovary is very rare and is associated with poor OS. Many mucinous adenocarcinomas that are diagnosed as primary ovarian neoplasms appear to be metastatic to the ovary. PMID:20862744

Utilisation of mucin glycans by the human gut symbiont Ruminococcus gnavus is strain-dependent.

PubMed

Crost, Emmanuelle H; Tailford, Louise E; Le Gall, Gwenaelle; Fons, Michel; Henrissat, Bernard; Juge, Nathalie

2013-01-01

Commensal bacteria often have an especially rich source of glycan-degrading enzymes which allow them to utilize undigested carbohydrates from the food or the host. The species Ruminococcus gnavus is present in the digestive tract of ≥90% of humans and has been implicated in gut-related diseases such as inflammatory bowel diseases (IBD). Here we analysed the ability of two R. gnavus human strains, E1 and ATCC 29149, to utilize host glycans. We showed that although both strains could assimilate mucin monosaccharides, only R. gnavus ATCC 29149 was able to grow on mucin as a sole carbon source. Comparative genomic analysis of the two R. gnavus strains highlighted potential clusters and glycoside hydrolases (GHs) responsible for the breakdown and utilization of mucin-derived glycans. Transcriptomic and functional activity assays confirmed the importance of specific GH33 sialidase, and GH29 and GH95 fucosidases in the mucin utilisation pathway. Notably, we uncovered a novel pathway by which R. gnavus ATCC 29149 utilises sialic acid from sialylated substrates. Our results also demonstrated the ability of R. gnavus ATCC 29149 to produce propanol and propionate as the end products of metabolism when grown on mucin and fucosylated glycans. These new findings provide molecular insights into the strain-specificity of R. gnavus adaptation to the gut environment advancing our understanding of the role of gut commensals in health and disease.

Mucin gene expression in the intestine of ulcerative colitis patients: a systematic review and meta-analysis.

PubMed

Niv, Yaron

2016-11-01

The mucus layer of the colon is the main barrier between luminal microbes and the mucosa, and plays a significant role in the body defense mechanisms. Several studies have examined mucin gene (MUC) expression in ulcerative colitis (UC) without conclusive results. The aim of the study was to establish the knowledge of mucin expression in UC as a basis for further investigation. English medical literature searches were performed for mucin expression in the colonic mucosa of UC patients in comparison with controls. Case-control studies were included. A meta-analysis was carried out using 'Comprehensive meta-analysis' software. Pooled odds ratios (ORs) and 95% confidence intervals were calculated. Altogether, we found 311 eligible studies. Only 10 case-control studies from five countries fulfilled the inclusion criteria. A moderate heterogeneity was found in the studies included: Q=52.703, d.f. (Q)=15.000, I=71.539%. OR for mucin expression in UC patients versus healthy controls was 1.868 with a 95% confidence interval (CI) 1.263-2.764, P=0.002. Thus, we could find a significant increase of 87% of mucin expression in UC patients. OR for MUC2 was 2.520, 95% CI 1.320-4.809, P<0.001. MUC3 was also increased with OR 2.599, 95% CI 1.389-4.861, P=0.003. Funnel plot did not indicate a significant publication bias. We found a global increase in mucin expression in UC patients, specifically in MUC2 and MUC3. Further studies are needed, especially in patients treated with biologics for mucosal healing, to understand the role of mucin expression in the natural history of UC.

Palliation double stenting for malignant biliary and duodenal obstruction

PubMed Central

ZHAO, LIANG; XU, HAITAO; ZHANG, YUBAO

2016-01-01

The surgical management of patients with malignant biliary and duodenal obstruction is complex. Tumor excision is no longer possible in the majority of patients with malignant obstructive jaundice and duodenal obstruction. The aim of the present study was to evaluate the effectiveness of intraluminal dual stent placement in malignant biliary and duodenal obstruction. In total, 20 patients with malignant obstructive jaundice and duodenal obstruction, including 6 with pancreatic carcinoma, 11 with cholangiocarcinoma, 1 with duodenal carcinoma and 2 with abdominal lymph node metastasis, were treated with intraluminal stent placement. Bile duct obstruction with late occurrence of duodenal obstruction was observed in 16 cases, and duodenal obstruction followed by a late occurrence of bile duct obstruction was observed in 3 cases, while, in 1 case, bile duct obstruction and duodenal obstruction occurred simultaneously. After X-ray fluoroscopy revealed obstruction in the bile duct and duodenum, stents were placed into the respective lumens. Percutaneous transhepatic placement was employed for the biliary stent, while the duodenal stent was placed perioraly. The clinical outcomes, including complications associated with the procedures and patency of the stents, were evaluated. The biliary and duodenal stents were successfully implanted in 18 patients and the technical success rate was 90% (18/20). A total of 39 stents were implanted in 20 patients. In 2 cases, duodenal stent placement failed following biliary stent placement. Duodenal obstruction remitted in 15 patients, and 1 patient succumbed to aspiration pneumonia 5 days after the procedure. No severe complications were observed in any other patient. The survival time of the 18 patients was 5–21 months (median, 9.6 months), and 6 of those patients survived for >12 months. The present study suggests that X-ray fluoroscopy-guided intraluminal stent implantation is an effective procedure for the treatment of malignant

Biliary atresia: evaluation on two distinct periods at a reference pediatric service.

PubMed

Queiroz, Thais Costa Nascentes; Ferreira, Alexandre Rodrigues; Fagundes, Eleonora Druve Tavares; Roquete, Mariza Leitão Valadares; Penna, Francisco José

2014-01-01

Biliary atresia is a progressive, idiopathic, fibro-obliterative disease of the extrahepatic biliary tree that presents with biliary obstruction exclusively in the neonatal period. To assess the differences regarding age at referral, age at surgery, duration of propaedeutics and waiting time for surgery between two groups of infants in different periods. Retrospective study of infants diagnosed with biliary atresia on two periods: 1983-1993 and 1998-2011. Biliary atresia was diagnosed in 129 infants, being 48 in casuistic I and 81 in casuistic II. The median age at admission was 94 and 60 days, respectively (P = 0.0001). On evaluating patients who had undergone portoenterostomy before 120 days of age, no difference was observed regarding the duration of propaedeutics or waiting time for surgery (P = 0.15), but difference was found when comparing the age at surgery (P = 0.002). Among those infants with no biliary flow and without liver transplantation or death after 18 post-operative months, the estimated probability of survival was 44.6% and 38.7% in casuistics I and II, respectively. In casuistic I, all infants who showed biliary flow were alive during the observation period and, in casuistic II, 80.3% were alive after 7 years of follow-up. Even though patients were admitted and treated earlier, it is clear that surgery could be done sooner. Delay in referral and timely propaedeutics were the main contributors.

[Pancreatic mucinous cystadenoma doubly complicated by acute pancreatitis and retroperitoneal rupture].

PubMed

Maghrebi, Houcine; Makni, Amine

2017-01-01

Mucinous cystadenomas are benign tumors with malignant potential. They are often revealed by non-specific abdominal pain, jaundice or an episode of acute pancreatitis. We here report an exceptional case of mucinous cystadenoma doubly complicated by acute pancreatitis and retroperitoneal rupture. The study involved a 30-year old non-weighted female patient, presenting with epigastric pain associated with left hypochondrium evolving over the last three months and which had intensified without fever or jaundice in the last 3 days. Clinical examination showed impingement on palpation of the epigastrium and of the left hypochondrium. There was no palpable mass. Laboratory tests were without abnormalities, except for lipasemia that was 8-times the upper normal. Abdominal CT scan showed bi-loculated cystic mass in the pancreas tail, measuring 111 mm * 73 mm, with a thin wall and a fluid content, associated with an infiltration of the left perirenal fascia. MRI (Panel A) showed mucinous cystadenoma with retroperitoneal rupture. The caudal portion of the main pancreatic duct was slightly dilated and communicated with the pancreatic cyst. The patient underwent surgery via bi-sub-costal approach. A cystic mass in the pancreas tail with retroperitoneal rupture associated with acute pancreatitis (outflow of necrotic content from left anterior prerenal space) was found. Caudal splenopancreatectomy was performed (Panel B). The postoperative course was uneventful. The anatomo-pathological examination of the surgical specimen showed pancreatic mucinous cystadenoma with low-grade dysplasia.

[Surgical treatment of chronic pancreatitis complicated by biliary hypertension].

PubMed

Pylypchuk, V I

2015-01-01

The results of 29 patients treatment, suffering chronic pancreatitis, complicated by biliary hypertension, in whom operative interventions in Department of Surgery of Regional Ivano-Frankivsk clinical hospital in 2009 - 2014 yrs, were analyzed. The drainage, resectional and combined interventions were performed. Direct intervention on pancreatic gland was not applied in 5 (17.2%) patients. Operation to Frey was performed in 7 (24.1%) patients, in 4--it was added by choledochojejunoanastomosis formation, longitudinal pancreatojejunostomy--in 13 (44.8%). In 4 (14.8%) patients while functional disorders of adjacent organs present a pancreaticoduodenal resection to Whipple was done. For biliary hypertension diagnosis (including the occult one) the method of intraoperative pressure measurement in common biliary duct (CBD) was proposed. The operation was added by biliodigestive anastomosis formation, using choledochoenterostomy to Roux method if while operations to Frey or Beger after intervention on pancreatic head with the intrapancreatic CBD freeing the intraductal pressure witnessed the biliary hypertension presence. In all the patients good and satisfactory results of operative treatment were noted.

Safety and Efficacy of Percutaneous Biliary Covered Stent Placement in Patients with Malignant Biliary Hilar Obstruction; Correlation with Liver Function.

PubMed

Hyun, Hyeran; Choi, Sun Young; Kim, Kyung Ah; Ko, Soo Bin

2016-09-01

To estimate the safety and efficacy of percutaneous ePTFE-covered biliary stent placement and the relationship between underlying liver function and stent patency in patients with malignant hilar obstruction. From March 2012 to June 2015, 41 patients [22 females, 19 males; mean age 69.8 (range 34-94) years] with malignant biliary obstruction underwent percutaneous biliary stent placement (31 patients with unilateral, 10 patients with bilateral side-by-side). Cumulative patient survival and stent patency rate curves were derived using the Kaplan-Meier method. A Cox model was used to explore the relationship between liver function and patient survival, and also biliary stent patency. Pearson correlation coefficient was used to analyze the relationship between patient survival and stent patency. Technical success rate was 100 % and clinical success rate was 95 %. During follow-up, four complications occurred (two bilomas and two cases of acute cholecystitis) and were treated successfully with percutaneous drainage. No other complication occurred. Mean serum bilirubin level was 11.34 ± 7.35 mg/dL before drainage and 5.00 ± 4.83 mg/dL 2 weeks after stent placement. The median patent survival duration was 147 days (95 % CI, 69.6-224.4 days). The median stent patency duration was 101 days (95 % CI, 70.0-132.0 days). The cumulative stent patency rates at 1, 3, 6, and 12 months were 97, 57.6, 30.3, and 17.0 %, respectively. Child-Pugh score was correlated significantly with patient survival (P = 0.011) and stent patency (P = 0.007). MELD score was correlated significantly with stent patency (P = 0.044). There was a correlation between patient survival and stent patency (r = 0.778, P < 0.001). Percutaneous placement of ePTFE-covered biliary stent was a safe and an effective method for malignant biliary obstruction. Underlying liver function seemed to be one of the important factors affecting patient survival and stent patency, and stent patency

Safety and Efficacy of Percutaneous Biliary Covered Stent Placement in Patients with Malignant Biliary Hilar Obstruction; Correlation with Liver Function

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hyun, Hyeran; Choi, Sun Young, E-mail: medmath@hanmail.net; Kim, Kyung Ah

PurposeTo estimate the safety and efficacy of percutaneous ePTFE-covered biliary stent placement and the relationship between underlying liver function and stent patency in patients with malignant hilar obstruction.Materials and MethodsFrom March 2012 to June 2015, 41 patients [22 females, 19 males; mean age 69.8 (range 34–94) years] with malignant biliary obstruction underwent percutaneous biliary stent placement (31 patients with unilateral, 10 patients with bilateral side-by-side). Cumulative patient survival and stent patency rate curves were derived using the Kaplan–Meier method. A Cox model was used to explore the relationship between liver function and patient survival, and also biliary stent patency. Pearsonmore » correlation coefficient was used to analyze the relationship between patient survival and stent patency.ResultsTechnical success rate was 100 % and clinical success rate was 95 %. During follow-up, four complications occurred (two bilomas and two cases of acute cholecystitis) and were treated successfully with percutaneous drainage. No other complication occurred. Mean serum bilirubin level was 11.34 ± 7.35 mg/dL before drainage and 5.00 ± 4.83 mg/dL 2 weeks after stent placement. The median patent survival duration was 147 days (95 % CI, 69.6–224.4 days). The median stent patency duration was 101 days (95 % CI, 70.0–132.0 days). The cumulative stent patency rates at 1, 3, 6, and 12 months were 97, 57.6, 30.3, and 17.0 %, respectively. Child–Pugh score was correlated significantly with patient survival (P = 0.011) and stent patency (P = 0.007). MELD score was correlated significantly with stent patency (P = 0.044). There was a correlation between patient survival and stent patency (r = 0.778, P < 0.001).ConclusionPercutaneous placement of ePTFE-covered biliary stent was a safe and an effective method for malignant biliary obstruction. Underlying liver function seemed to be one of the important factors

Risk factors and outcome in patients with primary sclerosing cholangitis with persistent biliary candidiasis.

PubMed

Rupp, Christian; Bode, Konrad Alexander; Chahoud, Fadi; Wannhoff, Andreas; Friedrich, Kilian; Weiss, Karl-Heinz; Sauer, Peter; Stremmel, Wolfgang; Gotthardt, Daniel Nils

2014-10-23

Candidiasis is commonly observed in patients with primary sclerosing cholangitis (PSC), but the clinical risk factors associated with its presence have not been fully investigated. In this study, we aimed to analyse the incidence, risk factors, and transplantation-free survival in primary sclerosing cholangitis (PSC) patients with persistent biliary candidiasis. We retrospectively analysed patients diagnosed with PSC who were admitted to our department during 2002 to 2012. One-hundred fifty patients whose bile cultures were tested for fungal species were selected, and their clinical and laboratory parameters were investigated. The results of endoscopic retrograde cholangiography (ERC) and bile cultures were analysed using chart reviews. The cases of biliary candidiasis were sub-classified as transient or persistent. Thirty out of 150 (20.0%) patients had biliary candidiasis. Although all patients demonstrated comparable baseline characteristics, those with biliary candidiasis showed significantly reduced transplantation-free survival (p < 0.0001) along with a markedly elevated frequency of cholangiocarcinoma (CCA) (p = 0.04). The patients were further sub-classified according to the transient (15/30) or persistent (15/30) nature of their biliary candidiasis. A subgroup analysis showed reduced survival with a greater necessity for orthotopic liver transplantation (OLT) only in patients with persistence of Candida (p = 0.007). The survival in the patients with transient biliary candidiasis was comparable to that in candidiasis-free patients. In a multivariate regression analysis that included Mayo risk score (MRS), sex, age, dominant stenosis, inflammatory bowel disease, autoimmune hepatitis overlap syndrome, and number of times ERC was performed, biliary candidiasis was an independent risk factor for reduced survival (p = 0.008). Risk factors associated with acquisition of biliary candidiasis were age at PSC diagnosis and number of ERCs. The persistence of biliary

In-office vs. operating room procedures for recurrent respiratory papillomatosis.

PubMed

Miller, Anya J; Gardner, Glendon M

2017-01-01

We conducted a study to analyze hospital and patient costs, outcomes, and patient satisfaction among adults undergoing in-office and operating room procedures for the treatment of recurrent respiratory papillomatosis. Our final study population was made up of 17 patients-1 man and 16 women, aged 30 to 86 years (mean: 62). The mean number of in-office laser procedures per patient was 4.2, and the mean interval between procedures was 5.4 months (although 10 patients underwent only 1 office procedure); the mean number of operating room procedures was 13.5, and the mean interval between procedures was 14.3 months. An equal number of patients reported complications or adverse events with the two types of procedures-5 each. The difference in cost between the office procedure (mean: $3,413.00) and the operating room procedure (mean: $12,382.59) was almost $9,000, but these savings were offset by the fact that the office procedures needed to be performed three times as often. Patients reported slightly more anxiety and discomfort during the office procedures and, overall, they appeared to prefer the operating room procedure. We conclude that office procedures are significantly more cost-effective than operating room procedures, but their use may be limited by patient tolerance and the increased frequency of the procedure.

Percutaneous transhepatic biliary stenting in patients with intradiverticular papillae and biliary strictures caused by ampullary carcinoma: A case report

PubMed Central

NIU, HONG-TAO; HUANG, QIANG; ZHAI, REN-YOU

2014-01-01

Endoscopic retrograde cholangiopancreatography with endoscopic sphincterotomy is a well-established procedure for the treatment of bile duct strictures. However, the procedure is difficult to perform in patients with intradiverticular papillae or tumor infiltration of the major papilla. Percutaneous transhepatic biliary stenting (PTBS) is commonly used in the management of malignant biliary stricture. The current study reports two cases of PTBS performed to treat malignant obstructive jaundice caused by ampullary carcinoma complicated with intradiverticular papillae. PTBS is potentially a safe technique for this relatively rare condition. PMID:24944703

Percutaneous transhepatic biliary stenting in patients with intradiverticular papillae and biliary strictures caused by ampullary carcinoma: A case report.

PubMed

Niu, Hong-Tao; Huang, Qiang; Zhai, Ren-You

2014-04-01

Endoscopic retrograde cholangiopancreatography with endoscopic sphincterotomy is a well-established procedure for the treatment of bile duct strictures. However, the procedure is difficult to perform in patients with intradiverticular papillae or tumor infiltration of the major papilla. Percutaneous transhepatic biliary stenting (PTBS) is commonly used in the management of malignant biliary stricture. The current study reports two cases of PTBS performed to treat malignant obstructive jaundice caused by ampullary carcinoma complicated with intradiverticular papillae. PTBS is potentially a safe technique for this relatively rare condition.

Chronic anti-inflammatory drug therapy inhibits gel-forming mucin production in a murine xenograft model of human pseudomyxoma peritonei.

PubMed

Choudry, Haroon Asif; Mavanur, Arun; O'Malley, Mark E; Zeh, Herbert J; Guo, Z Sheng; Bartlett, David L

2012-05-01

Intraperitoneal accumulation of mucinous ascites in pseudomyxoma peritonei (PMP) promotes an inflammatory/fibrotic reaction that progresses to bowel obstruction and eventual patient demise. Cytokines and inflammation-associated transcription factor binding sites, such as glucocorticoid response elements and COX-2, regulate secretory mucin, specifically MUC2, production. We hypothesized that anti-inflammatory drugs targeting inflammation-associated pathways may reduce mucin production and subsequent disease morbidity in PMP. The effects of dexamethasone and Celebrex were assessed in mucin-secreting human colon cancer LS174T cells in vitro and murine xenograft models of LS174T and human appendiceal PMP in vivo by serial parametric measurements, MUC2 transcripts via real-time RT-PCR, and MUC2 protein expression via immunofluorescence assays. Dexamethasone significantly inhibited basal MUC2 mRNA levels in LS174T cells, inhibited mucinous tumor accumulation in an intraperitoneal PMP xenograft model, and prolonged survival in a subcutaneous LS174T xenograft model. Celebrex significantly inhibited sodium butyrate-stimulated MUC2 mRNA levels in LS174T cells and demonstrated a statistically nonsignificant trend toward reduced mucinous tumor growth and prolonged survival in the xenograft models. MUC2 protein analysis by immunofluorescence demonstrated a dual effect of dexamethasone on mucin production and tumor cell count. Inflammatory mediators are known to regulate mucin production and may promote overexpression of MUC2 by neoplastic cells with goblet cell phenotype in PMP. Anti-inflammatory drugs, dexamethasone and Celebrex, could inhibit extracellular mucin production in PMP by targeting inflammatory cascades and, therefore, may decrease compressive symptoms, increase the disease-free interval, and reduce the extent or frequency of morbid cytoreductive surgeries.

Benign biliary strictures refractory to standard bilioplasty treated using polydoxanone biodegradable biliary stents: retrospective multicentric data analysis on 107 patients.

PubMed

Mauri, Giovanni; Michelozzi, Caterina; Melchiorre, Fabio; Poretti, Dario; Pedicini, Vittorio; Salvetti, Monica; Criado, Eva; Falcò Fages, Joan; De Gregorio, Miguel Ángel; Laborda, Alicia; Sonfienza, Luca Maria; Cornalba, Gianpaolo; Monfardini, Lorenzo; Panek, Jiri; Andrasina, Tomas; Gimenez, Mariano

2016-11-01

To assess mid-term outcome of biodegradable biliary stents (BBSs) to treat benign biliary strictures refractory to standard bilioplasty. Institutional review board approval was obtained and patient consent was waived. 107 patients (61 males, 46 females, mean age 59 ± 16 years), were treated. Technical success and complications were recorded. Ninety-seven patients (55 males, 42 females, aged 57 ± 17 years) were considered for follow-up analysis (mean follow-up 23 ± 12 months). Fisher's exact test and Mann-Whitney U tests were used and a Kaplan-Meier curve was calculated. The procedure was always feasible. In 2/107 cases (2 %), stent migration occurred (technical success 98 %). 4/107 patients (4 %) experienced mild haemobilia. No major complications occurred. In 19/97 patients (18 %), stricture recurrence occurred. In this group, higher rate of subsequent cholangitis (84.2 % vs. 12.8 %, p = 0.001) and biliary stones (26.3 % vs. 2.5 %, p = 0.003) was noted. Estimated mean time to stricture recurrence was 38 months (95 % C.I 34-42 months). Estimated stricture recurrence rate at 1, 2, and 3 years was respectively 7.2 %, 26.4 %, and 29.4 %. Percutaneous placement of a BBS is a feasible and safe strategy to treat benign biliary strictures refractory to standard bilioplasty, with promising results in the mid-term period. • Percutaneous placement of a BBS is 100 % feasible. • The procedure appears free from major complications, with few minor complications. • BBSs offer promising results in the mid-term period. • With a BBS, external catheter/drainage can be removed early. • BBSs represent a new option in treating benign biliary stenosis.

Intraductal ultrasonographic anatomy of biliary varices in patients with portal hypertension.

PubMed

Takagi, Tadayuki; Irisawa, Atsushi; Shibukawa, Goro; Hikichi, Takuto; Obara, Katsutoshi; Ohira, Hiromasa

2015-01-01

The term, portal biliopathy, denotes various biliary abnormalities, such as stenosis and/or dilatation of the bile duct, in patients with portal hypertension. These vascular abnormalities sometimes bring on an obstructive jaundice, but they are not clear which vessels participated in obstructive jaundice. The aim of present study was clear the bile ductal changes in patients with portal hypertension in hopes of establishing a therapeutic strategy for obstructive jaundice caused by biliary varices. Three hundred and thirty-seven patients who underwent intraductal ultrasound (IDUS) during endoscopic retrograde cholangiography for biliary abnormalities were enrolled. Portal biliopathy was analyzed using IDUS. Biliary varices were identified in 11 (2.7%) patients. IDUS revealed biliary varices as multiple, hypoechoic features surrounding the bile duct wall. These varices could be categorized into one of two groups according to their location in the sectional image of bile duct: epicholedochal and paracholedochal. Epicholedochal varices were identified in all patients, but paracholedochal varices were observed only in patients with extrahepatic portal obstruction. IDUS was useful to characterize the anatomy of portal biliopathy in detail.

Anaplastic carcinoma occurring in association with a mucinous cystic neoplasm of the pancreas.

PubMed

Lane, R B; Sangüeza, O P

1997-05-01

Anaplastic carcinomas of the pancreas are considered variants of ductal adenocarcinoma. They typically occur in elderly men. They have rarely been reported to occur in association with mucinous cystic neoplasms of the pancreas. We report a case of anaplastic carcinoma occurring in association with a pancreatic mucinous cystic neoplasm, borderline-type, in a 25-year-old woman who presented with lymph node and hepatic metastases.

Fine-needle aspiration cytology of intraductal papillary-mucinous tumors: a retrospective analysis.

PubMed

Layfield, Lester J; Cramer, Harvey

2005-01-01

Intraductal papillary-mucinous tumor (IPMT) of the pancreas has become the accepted terminology for a group of mucin-producing epithelial proliferations lying within ectatic segments of the main pancreatic duct or its large branches. These neoplasms generally are associated with an indolent course, characteristic endoscopic ultrasonographic (EUS) findings, and a variable histo- and cytomorphology ranging from hyperplasia to carcinoma. Cytological specimens obtained by endoscopic ultrasound-guided or percutaneous fine-needle aspiration (FNA) are characterized by a background containing abundant mucin in which are entrapped single or loosely cohesive clusters of neoplastic cells characteristically showing a goblet-cell morphology. The degree of nuclear atypia, cell crowding, and cell shape varies between smears within a single case and between cases. Cytomorphological examination, when coupled with EUS features, is accurate for the diagnosis of these lesions but often it underdiagnoses the grade of the neoplasm. (c) 2005 Wiley-Liss, Inc.

A comparative evaluation of early stent occlusion among biliary conventional versus wing stents.

PubMed

Khashab, Mouen A; Hutfless, Susan; Kim, Katherine; Lennon, Anne Marie; Canto, Marcia I; Jagannath, Sanjay B; Okolo, Patrick I; Shin, Eun Ji; Singh, Vikesh K

2012-06-01

Conventional plastic stents with a lumen typically have limited patency. The lumenless wing stent was engineered to overcome this problem. The objective of this study was to compare the incidence of early stent occlusion (symptomatic occlusion/cholangitis necessitating re-insertion within 90 days) for wing stents and conventional plastic stents. Patients with biliary pathology treated with plastic biliary stenting during the period 2003-2009 comprised the study cohort. Patients who had at least one biliary wing stent placed comprised the wing stent group, whereas patients who underwent only conventional stent plastic placement comprised the conventional stent group. Patients were stratified by indication: benign biliary strictures (group 1), malignant biliary strictures (group 2), or benign biliary non-stricture pathology (group 3). The association of stent type with the occurrence of primary outcome by indication was analyzed by use of multivariable logistic regression. Three-hundred and forty-six patients underwent 612 ERCP procedures with placement of plastic biliary stent(s). On multivariate analysis, early stent occlusion did not differ between the wing and conventional groups in groups 1, 2, and 3. Among patients who achieved primary outcome in group 2, significantly fewer patients in the wing group had cholangitis (6.7% vs. 39.1%, P = 0.03). Among patients who achieved primary outcome in group 3, significantly fewer patients in the wing group had cholangitis (10% vs. 50%, P = 0.03). Early stent occlusion was similar for wing stents and conventional plastic stents. Wing stents, however, were associated with a lower incidence of cholangitis in patients with malignant biliary obstruction and benign non-stricturing biliary pathology.

Spontaneous biliary perforation in an infant: an unusual chronic presentation.

PubMed

Vijay, Babu Balakrishnan; Kumar, Rakesh; Gupta, Devendra K; Ragavan, Muniswamy; Mohapatra, Tushar; Dhanpathi, Halanaik; Sharma, Sanjay; Malhotra, Arun

2008-04-01

Spontaneous perforation of the biliary ducts is a rare disorder in infants. Early diagnosis of this entity is important because it can be treated surgically. We report on a 4-month-old child presenting with jaundice and progressive abdominal distention present since birth. Hepatobiliary scintigraphy, which was done to rule out any obstructive pathology, showed a biliary leak from the porta hepatis region leading to biliary ascites and bilateral hydroceles. Surgical exploration and intraoperative cholangiogram confirmed cystic duct perforation. Cholecystectomy and inguinal herniorrhaphy were performed. Follow-up hepatobiliary scintigraphy demonstrated complete resolution of the bile leak and hydroceles.

Analysis of biliary anatomy according to different classification systems.

PubMed

Deka, Pranjal; Islam, Mahibul; Jindal, Deepti; Kumar, Niteen; Arora, Ankur; Negi, Sanjay Singh

2014-01-01

Variations in biliary anatomy are common, and different classifications have been described. These classification systems have not been compared to each other in a single cohort. We report such variations in biliary anatomy on magnetic resonance cholangiopancreatography (MRCP) using six different classification systems. In 299 patients undergoing MRCP for various indications, biliary anatomy was classified as described by Couinaud (1957), Huang (1996), Karakas (2008), Choi (2003), Champetier (1994), and Ohkubo (2004). Correlation with direct cholangiography and vascular anatomy was done. Bile duct dimensions were measured. Cystic duct junction and pancreaticobiliary ductal junction (PBDJ) were classified. Normal biliary anatomy was noted in 57.8 %. The most common variants were Couinaud type D2, Choi type 3A, Huang type A1, Champetier type a, Ohkubo types D and J, and Karakas type 2a. The Ohkubo classification was the most appropriate; 3.1 % of right ducts and 6.3 % of left ducts with variant anatomy could not be classified using the Ohkubo classification. There was a good agreement between MRCP and direct cholangiography (ĸ = 0.9). Anomalous PBDJ was noted in 8.7 %. Variant biliary anatomy was not associated with gender (p = 0.194) or variant vascular anatomy (p = 0.24). Although each classification system has its merits and demerits, some anatomical variations cannot be classified using any of the previously described classifications. The Ohkubo classification system is the most applicable as it considers most clinically relevant variations pertinent to hepatobiliary surgery.

Covered self-expandable metal stents for benign biliary tract diseases.

PubMed

Baron, Todd H

2011-05-01

Benign biliary diseases are often managed endoscopically using plastic stents. Benign biliary strictures (BBS) respond to placement of multiple large-bore plastic stents, though requiring multiple procedures to place stents, and to exchange stents to prevent and/or treat stent occlusion. Bile leaks close using plastic stents, which divert bile away from the leak into the duodenum. Covered self-expandable metal stents (CSEMS), intended for palliation of malignant biliary obstruction, have been used to treat benign biliary diseases. Advantages include small predeployment and large postexpansion diameters. Lack of imbedding of the metal into the bile duct wall enables removability. For strictures, one CSEMS is inserted without need for dilation and remains in place for up to 6 months. Successful removal has been reported in all cases. Long-term stricture resolution is achieved in up to 92%. Adverse events include migration and new stricture formation. For treatment of complex bile leaks, the covering and large diameter allow successful closure in nearly all cases. Other uses of CSEMS include treatment of postsphincterotomy bleeding and closure of perforations. CSEMS show promise for treatment of BBS and complex biliary leaks. Successful resolution can be achieved in the majority of patients with the advantage of fewer procedures, which offsets their higher cost.

Mucin gene expression in bile of patients with and without gallstone disease, collected by endoscopic retrograde cholangiography

PubMed Central

Vilkin, Alexander; Geller, Alex; Levi, Zohar; Niv, Yaron

2009-01-01

AIM: To investigate the pattern of mucin expression and concentration in bile obtained during endoscopic retrograde cholangiography (ERC) in relation to gallstone disease. METHODS: Bile samples obtained at ERC from 29 consecutive patients, 17 with and 12 without gallstone disease were evaluated for mucin content by gel filtration on a Sepharose CL-4B column. Dot blot analysis for bile mucin apoproteins was performed with antibodies to Mucin 1 (MUC1), MUC2, MUC3, MUC5AC, MUC5B and MUC6. Staining intensity score (0-3) was used as a measure of antigen expression. RESULTS: MUC1, MUC2, MUC3, MUC5AC, MUC5B and MUC6 were demonstrated in 34.4%, 34.4%, 51.7%, 51.7%, 55.1% and 27.5% of bile samples, respectively. The staining intensity scores were 0.62 ± 0.94, 0.58 ± 0.90, 0.79 ± 0.97, 1.06 ± 1.22, 1.20 ± 1.26 and 0.41 ± 0.73, respectively. Mean mucin concentration measured in bile by the Sepharose CL-4B method was 22.8 ± 24.0 mg/mL (range 3.4-89.0 mg/mL). Mean protein concentration was 8.1 ± 4.8 mg/mL (range 1.7-23.2 mg/mL). CONCLUSION: High levels of MUC3, MUC5AC and MUC5B are expressed in bile aspirated during ERC examination. A specific pattern of mucin gene expression or change in mucin concentration was not found in gallstone disease. PMID:19452580

Arterio-biliary fistula as rare complication of chemoradiation therapy for intrahepatic cholangiocarcinoma

PubMed Central

Hayano, Koichi; Miura, Fumihiko; Amano, Hodaka; Toyota, Naoyuki; Wada, Keita; Kato, Kenichiro; Takada, Tadahiro; Asano, Takehide

2010-01-01

Significant hemobilia due to arterio-biliary fistula is a very rare complication of chemoradiation therapy (CRT) for unresectable intrahepatic cholangiocarcinoma (ICC). Here we report a case of arterio-biliary fistula after CRT for unresectable ICC demonstrated by angiographic examinations. This fistula was successfully treated by endovascular embolization. Hemobilia is a rare complication, but arterio-biliary fistula should be considered after CRT of ICC. PMID:21160700

Quality and readability assessment of websites related to recurrent respiratory papillomatosis.

PubMed

San Giorgi, Michel R M; de Groot, Olivier S D; Dikkers, Frederik G

2017-10-01

Recurrent respiratory papillomatosis (RRP) is a rare disease for which a limited number of information sources for patients exist. The role of the Internet in the patient-physician relationship is increasing. More and more patients search for online health information, which should be of good quality and easy readable. The study aim was to investigate the quality and readability of English online health information about RRP. Quality and readability assessment of online information. Relevant information was collected using three different search engines and seven different search terms. Quality was assessed with the DISCERN instrument. The Flesch Reading Ease Score (FRES) and average grade level (AGL) were determined to measure readability of the English websites. Fifty-one English websites were included. The mean DISCERN score of the websites is 28.1 ± 9.7 (poor quality); the mean FRES is 41.3 ± 14.9 (difficult to read); and the mean AGL is 12.6 ± 2.3. The quality and readability of English websites about RRP is alarmingly poor. NA. Laryngoscope, 127:2293-2297, 2017. © 2017 The Authors The Laryngoscope published by Wiley Periodicals, Inc. on behalf of American Laryngological, Rhinological and Otological Society Inc, “The Triological Society” and American Laryngological Association (ALA).

Molecular subtypification of human papillomavirus in male adult individuals with recurrent respiratory papillomatosis.

PubMed

García-Romero, Carmen S; Akaki-Caballero, Matsuharu; Saavedra-Mendoza, Ana G; Guzmán-Romero, Ana K; Canto, Patricia; Coral-Vázquez, Ramón M

2015-10-01

This study aimed to identify the isotype of human papillomavirus (HPV) in fresh tissue samples of 35 male adults with adult recurrent adult respiratory papillomatosis which may be important to define the precise etiology of the disease, and determine the therapeutic and prophylactic measures. A total of 35 adult male patients diagnosed with active RRP who have been treated for several years were included in the study. DNA of patients was extracted from fresh biological samples and analyzed by PCR and a Linear Array® HPV Genotyping system. Most cases (95%) corresponded to adult-onset of RRP. A questionnaire was applied to obtain demographic and clinical data. Using a PCR-based detection system all patients showed the presence of HPV; 80% were positive for HPV-6, 8% for HPV-11 and one for HPV-16. Most patients presented HPV-6 and consequently it was not feasible to correlate clinical and demographic characteristics with viral type. Besides, co-infections were not evident. This knowledge may be relevant to delineate therapeutic and preventive measures. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Intestinal mucin dynamics: response of broiler chicks and White Pekin ducklings to dietary threonine.

PubMed

Horn, N L; Donkin, S S; Applegate, T J; Adeola, O

2009-09-01

Mucin dynamics may be particularly sensitive to a Thr deficiency due to the high concentration and structural importance of Thr in the mucin protein backbone. Intestinal mucin secretion, expression of mucin gene (MUC2), and histological characteristics were investigated in male broilers and White Pekin ducklings offered diets containing 3.3, 5.8, or 8.2 g of Thr/kg in 4 studies. Seventy-two birds of each species were fed a standard broiler starter diet from 1 to 14 d of age followed by assignment to 3 dietary treatments in a randomized complete block design for a 7-d feeding trial in experiment 1 (broilers) and experiment 2 (ducklings). The dietary treatments consisted of an isonitrogenous corn-soybean meal-based diet with the addition of crystalline amino acids and graded levels of Thr. Dietary treatments contained 3.3, 5.8, or 8.2 g of Thr/kg. Dietary formulation and experimental design for experiments 3 (broilers) and 4 (ducklings) were similar to experiments 1 and 2 except that birds were fed 3.3 or 8.2 g of Thr/kg for durations of 7 or 14 d. For chicks, increased dietary Thr resulted in higher levels of intestinal crude mucin excretion in experiment 1 (P=0.04) but not in experiment 3, whereas intestinal sialic acid excretion increased in experiment 3 (P=0.02) but not in experiment 1. Furthermore, there was no effect of Thr on intestinal goblet cell density or MUC2 mRNA abundance for broilers. For ducklings, there was an increase in intestinal crude mucin excretion in both experiments (P<0.05) as dietary Thr increased, although there was no effect of Thr on intestinal sialic acid excretion. There was a tendency for an increase in intestinal goblet cell density (cells/microm of villus length; P=0.09) as dietary Thr increased in experiment 2. For experiment 4, intestinal MUC2 mRNA abundance increased (P=0.03) as dietary Thr increased for the 14-d feeding trial but not for the 7-d feeding trial. The data establish a link between dietary Thr and intestinal crude

Endoscopic management with inside stent for proximal benign biliary stricture after laparoscopic cholecystectomy.

PubMed

Sasahira, Naoki; Isayama, Hiroyuki; Kogure, Hirofumi; Tsujino, Takeshi; Koike, Kazuhiko

2012-05-01

Endoscopic placement of a plastic stent is the standard drainage for a symptomatic benign biliary stricture. Although a removable fully covered self-expandable metal stent has been applied for distal benign biliary stricture, placement of a plastic stent remains the standard treatment for proximal benign biliary stricture. Placement of a plastic stent above the papilla (inside stent) is an alternative to the conventional method because of its preventive effect against the dysfunction of the stent in patients with proximal benign biliary stricture. © 2012 The Authors. Digestive Endoscopy © 2012 Japan Gastroenterological Endoscopy Society.

Prospective observational multicenter study to define a diagnostic algorithm for biliary candidiasis

PubMed Central

Lenz, Philipp; Eckelskemper, Franziska; Erichsen, Thomas; Lankisch, Tim; Dechêne, Alexander; Lubritz, Gabriele; Lenze, Frank; Beyna, Torsten; Ullerich, Hansjörg; Schmedt, Andre; Domagk, Dirk

2014-01-01

AIM: To develop an algorithm to improve the diagnosis and treatment of patients with biliary candidiasis. METHODS: We performed a prospective study of 127 patients who underwent endoscopic retrograde cholangiopancreatography, for various biliary disorders, at 3 tertiary referral centers in Germany from July 2011 through July 2012 (ClinicalTrials.gov: NCT01109550). Bile, buccal, and stool samples were collected. When indicated, endoscopic transpapillary bile duct biopsies were performed to clarify the etiology of bile duct strictures and to prove invasive fungal infections. RESULTS: Candida species were detected in 38 of the 127 bile samples (29.9%). By multivariate analysis patients’ age and previous endoscopic sphincterotomy were independent risk factors for biliary candidiasis (P < 0.05). Patients with immunosuppression (P = 0.058) and recent long-term antibiotic therapy (> 7 d) (P = 0.089) tend to be at risk for biliary candidiasis. One patient was negative in mycological culture of bile fluid but invasive biliary candidiasis was diagnosed histologically. Of Candida subspecies detected, 36.7% were azole-resistant, such as C glabrata. Eight patients received anti-mycotic therapy, based on our algorithm. Of these, 3 had cancer with biliary tract involvement, 2 had secondary sclerosing cholangitis, 1 had retroperitoneal fibrosis, and 5 had septicemia. In all patients contamination was ruled out by smears of the endoscope channel. CONCLUSION: Gastroenterologists should be aware of frequent candida colonization in patients with cholangitis and biliary disorders. Our suggested algorithm facilitates the further clinical management. PMID:25232260

Prospective observational multicenter study to define a diagnostic algorithm for biliary candidiasis.

PubMed

Lenz, Philipp; Eckelskemper, Franziska; Erichsen, Thomas; Lankisch, Tim; Dechêne, Alexander; Lubritz, Gabriele; Lenze, Frank; Beyna, Torsten; Ullerich, Hansjörg; Schmedt, Andre; Domagk, Dirk

2014-09-14

To develop an algorithm to improve the diagnosis and treatment of patients with biliary candidiasis. We performed a prospective study of 127 patients who underwent endoscopic retrograde cholangiopancreatography, for various biliary disorders, at 3 tertiary referral centers in Germany from July 2011 through July 2012 (ClinicalTrials.gov: NCT01109550). Bile, buccal, and stool samples were collected. When indicated, endoscopic transpapillary bile duct biopsies were performed to clarify the etiology of bile duct strictures and to prove invasive fungal infections. Candida species were detected in 38 of the 127 bile samples (29.9%). By multivariate analysis patients' age and previous endoscopic sphincterotomy were independent risk factors for biliary candidiasis (P < 0.05). Patients with immunosuppression (P = 0.058) and recent long-term antibiotic therapy (> 7 d) (P = 0.089) tend to be at risk for biliary candidiasis. One patient was negative in mycological culture of bile fluid but invasive biliary candidiasis was diagnosed histologically. Of Candida subspecies detected, 36.7% were azole-resistant, such as C glabrata. Eight patients received anti-mycotic therapy, based on our algorithm. Of these, 3 had cancer with biliary tract involvement, 2 had secondary sclerosing cholangitis, 1 had retroperitoneal fibrosis, and 5 had septicemia. In all patients contamination was ruled out by smears of the endoscope channel. Gastroenterologists should be aware of frequent candida colonization in patients with cholangitis and biliary disorders. Our suggested algorithm facilitates the further clinical management.

Interfacial Interaction between Transmembrane Ocular Mucins and Adhesive Polymers and Dendrimers Analyzed by Surface Plasmon Resonance

PubMed Central

Noiray, M.; Briand, E.; Woodward, A. M.; Argüeso, P.; Molina Martínez, I. T.; Herrero-Vanrell, R.; Ponchel, G.

2013-01-01

Purpose Development of the first in vitro method based on biosensor chip technology designed for probing the interfacial interaction phenomena between transmembrane ocular mucins and adhesive polymers and dendrimers intended for ophthalmic administration. Methods The surface plasmon resonance (SPR) technique was used. A transmembrane ocular mucin surface was prepared on the chip surface and characterized by QCM-D (Quartz Crystal Microbalance with Dissipation) and XPS (X-ray photoelectron spectroscopy). The mucoadhesive molecules tested were: hyaluronic acid (HA), carboxymethyl cellulose (CMC), hydroxypropylmethyl cellulose (HPMC), chitosan (Ch) and polyamidoamine dendrimers (PAMAM). Results While Ch originated interfacial interaction with ocular transmembrane mucins, for HA, CMC and HPMC, chain interdiffusion seemed to be mandatory for bioadherence at the concentrations used in ophthalmic clinical practise. Interestingly, PAMAM dendrimers developed permanent interfacial interactions with transmembrane ocular mucins whatever their surface chemical groups, showing a relevant importance of co-operative effect of these multivalent systems. Polymers developed interfacial interactions with ocular membrane-associated mucins in the following order: Ch(1 %) > G4PAMAM-NH2(2 %) = G4PAMAM-OH(2 %) > G3.5PAMAM-COOH(2 %)≫ CMC(0.5 %) = HA(0.2 %) = HPMC(0.3 %). Conclusions The method proposed is useful to discern between the mucin-polymer chemical interactions at molecular scale. Results reinforce the usefulness of chitosan and den-drimers as polymers able to increase the retention time of drugs on the ocular surface and hence their bioavailability. PMID:22565639

E6 and E7 oncogene expression by human papilloma virus (HPV) and the aggressive behavior of recurrent laryngeal papillomatosis (RLP).

PubMed

Shehata, Bahig M; Otto, Kristen J; Sobol, Steven E; Stockwell, Christina A; Foulks, Cora; Lancaster, Wayne; Gregoire, Lucie; Hill, Charles E

2008-01-01

Recurrent laryngeal papillomatosis (RLP), a chronic disease associated with human papilloma virus (HPV), requires serial surgical procedures for debulking, resulting in debilitating long-term dysphonia, laryngeal scarring, and rarely malignant degeneration. Human papilloma virus 11 tumors have been widely accepted as more aggressive than HPV 6 tumors; however, the clinical course has been difficult to predict at disease onset, and the biologic mediators of proliferation have not been well characterized. A retrospective case review of 43 patients (4 months to 10 years at diagnosis) was performed on children treated for recurrent laryngeal papillomatosis. Patient charts were reviewed for demographic information, age at RLP diagnosis, approximate frequency of surgical intervention, and absolute number of surgical procedures performed. Human papilloma virus subtyping was performed. Expression analysis of the HPV-encoded E6 and E7 oncogenes was performed by reverse-transcriptase polymerase chain reaction. Fourteen patients had subtype 11 (33%) and 29 patients had subtype 6 (67%). As expected, HPV 11 patients showed a more aggressive clinical course than HPV 6 patients. However, 38% of patients with subtype 6 (11 patients) followed a clinical course that mirrored the more severe subtype 11 patients. These patients expressed the disease at a younger age (P < 0.0002) and showed higher levels of E6 and E7 oncogenes compared to the patients with the more indolent course. Although HPV subtype and early onset of RLP are well characterized prognostic factors, our study documents the significance of E6 and E7 oncogene expression as potential biologic mediators of proliferation and thereby clinical behavior.

Importance of early diagnosis of pancreaticobiliary maljunction without biliary dilatation

PubMed Central

Takuma, Kensuke; Kamisawa, Terumi; Tabata, Taku; Hara, Seiichi; Kuruma, Sawako; Inaba, Yoshihiko; Kurata, Masanao; Honda, Goro; Tsuruta, Koji; Horiguchi, Shin-ichiro; Igarashi, Yoshinori

2012-01-01

AIM: To clarify the strategy for early diagnosis of pancreaticobiliary maljunction (PBM) without biliary dilatation and to pathologically examine gallbladder before cancer develops. METHODS: The anatomy of the union of the pancreatic and bile ducts was assessed by using endoscopic retrograde cholangiopancreatography (ERCP). Patients with a long common channel in which communication between the pancreatic and bile ducts was maintained even during sphincter contraction were diagnosed as having PBM. Of these, patients in which the maximal diameter of the bile duct was less than 10 mm were diagnosed with PBM without biliary dilatation. The process of diagnosing 54 patients with PBM without biliary dilatation was retrospectively investigated. Histopathological analysis of resected gallbladder specimens from 8 patients with PBM without biliary dilatation or cancer was conducted. RESULTS: Thirty-six PBM patients without biliary dilatation were diagnosed with gallbladder cancer after showing clinical symptoms such as abdominal or back pain (n = 16) or jaundice (n = 12). Radical surgery for gallbladder cancer was only possible in 11 patients (31%) and only 4 patients (11%) survived for 5 years. Eight patients were suspected as having PBM without biliary dilatation from the finding of gallbladder wall thickening on ultrasound and the diagnosis was confirmed by ERCP and/or magnetic resonance cholangiopancreatography (MRCP). The median age of these 8 patients was younger by a decade than PBM patients with gallbladder cancer. All 8 patients underwent prophylactic cholecystectomy and bile duct cancer has not occurred. Wall thickness and mucosal height of the 8 resected gallbladders were significantly greater than controls, and hyperplastic changes, hypertrophic muscular layer, subserosal fibrosis, and adenomyomatosis were detected in 7 (88%), 5 (63%), 7 (88%) and 5 (63%) patients, respectively. Ki-67 labeling index was high and K-ras mutation was detected in 3 of 6 patients

The role of airway mucus in pulmonary toxicology.

PubMed Central

Samet, J M; Cheng, P W

1994-01-01

Airway mucus is a complex airway secretion whose primary function as part of the mucociliary transport mechanism is to to serve as renewable and transportable barrier against inhaled particulates and toxic agents. The rheologic properties necessary for this function are imparted by glycoproteins, or mucins. Some respiratory disease states, e.g., asthma, cystic fibrosis, and bronchitis, are characterized by quantitative and qualitative changes in mucus biosynthesis that contribute to pulmonary pathology. Similar alterations in various aspects of mucin biochemistry and biophysics, leading to mucus hypersecretion and altered mucus rheology, result from inhalation of certain air pollutants, such as ozone, sulfur dioxide, nitrogen dioxide, and cigarette smoke. The consequences of these pollutant-induced alterations in mucus biology are discussed in the context of pulmonary pathophysiology and toxicology. PMID:7925190

Adaptive remodeling of the biliary tree: the essence of liver progenitor cell expansion.

PubMed

Kok, Cindy Yuet-Yin; Miyajima, Atsushi; Itoh, Tohru

2015-07-01

The liver progenitor cell population has long been thought to exist within the liver. However, there are no standardized criteria for defining the liver progenitor cells, and there has been intense debate about the origin of these cells in the adult liver. The characteristics of such cells vary depending on the disease model used and also on the method of analysis. Visualization of three-dimensional biliary structures has revealed that the emergence of liver progenitor cells essentially reflects the adaptive remodeling of the hepatic biliary network in response to liver injury. We propose that the progenitor cell exists as a subpopulation in the biliary tree and show that the appearance of liver progenitor cells in injured parenchyma is reflective of extensive remodeling of the biliary structure. © 2015 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

Primary biliary cirrhosis: an epidemiological study.

PubMed Central

Triger, D R

1980-01-01

A three-year study (1977-9) of primary biliary cirrhosis in the city of Sheffield disclosed 34 cases, a point prevalence of 54 per million population. Closer inspection showed an apparent clustering of cases, and the prevalence in relation to one water reservoir appeared to be more than ten times that of the other reservoirs. Nevertheless, analyses of the water showed no significant relevant differences between the reservoir serving areas with a high prevalence of cirrhosis and other reservoirs. Despite the inconclusive results of the water analyses, these findings do suggest that an environmental agent may be a cause of primary biliary cirrhosis and that further epidemiological studies may help to elucidate the cause. PMID:7427444

Biliary atresia: the Canadian experience.

PubMed

Schreiber, Richard A; Barker, Collin C; Roberts, Eve A; Martin, Steven R; Alvarez, Fernando; Smith, Lesley; Butzner, J Decker; Wrobel, Iwona; Mack, David; Moroz, Stanley; Rashid, Mohsin; Persad, Rabin; Levesque, Dominique; Brill, Herbert; Bruce, Garth; Critch, Jeff

2007-12-01

To determine the outcomes of Canadian children with biliary atresia. Health records of infants born in Canada between January 1, 1985 and December 31, 1995 (ERA I) and between January 1, 1996 and December 31, 2002 (ERA II) who were diagnosed with biliary atresia at a university center were reviewed. 349 patients were identified. Median patient age at time of the Kasai operation was 55 days. Median age at last follow-up was 70 months. The 4-year patient survival rate was 81% (ERA I = 74%; ERA II = 82%; P = not significant [NS]). Kaplan-Meier survival curves for patients undergoing the Kasai operation at age < or = 30, 31 to 90, and > 90 days showed 49%, 36%, and 23%, respectively, were alive with their native liver at 4 years (P < .0001). This difference continued through 10 years. The 2- and 4-year post-Kasai operation native liver survival rates were 47% and 35% for ERA I and 46% and 39% for ERA II (P = NS). A total of 210 patients (60%) underwent liver transplantation; the 4-year transplantation survival rate was 82% (ERA I = 83%, ERA II = 82%; P = NS). This is the largest outcome series of North American children with biliary atresia at a time when liver transplantation was available. Results in each era were similar. Late referral remains problematic; policies to ensure timely diagnosis are required. Nevertheless, outcomes in Canada are comparable to those reported elsewhere.

Progesterone alters biliary flow dynamics.

PubMed Central

Tierney, S; Nakeeb, A; Wong, O; Lipsett, P A; Sostre, S; Pitt, H A; Lillemoe, K D

1999-01-01

OBJECTIVE: To test the hypothesis that progesterone alters sphincter of Oddi and gallbladder function and, therefore, bile flow dynamics. SUMMARY BACKGROUND DATA: Although the effects of progesterone on the biliary tract have been implicated in the increased incidence of gallstones among women, the specific effects of prolonged elevation of progesterone levels, such as occurs with contraceptive progesterone implants and during pregnancy, on the sphincter of Oddi and biliary flow dynamics are still incompletely understood. METHODS: Adult female prairie dogs were randomly assigned to receive subcutaneous implants containing either progesterone or inactive pellet matrix only. Hepatic bile partitioning and gallbladder emptying were determined 14 days later using 99mTc-Mebrofenin cholescintigraphy. RESULTS: Significantly less hepatic bile partitioned into the gallbladder in progesterone-treated than in control animals. The gallbladder ejection fraction was significantly reduced from 73+/-6% in controls to 59+/-3% in the progesterone-treated animals. The rate of gallbladder emptying was significantly reduced from 3.6+/-0.3%/minute to 2.9+/-0.1%/minute. CONCLUSIONS: Progesterone administered as subcutaneous implants alters partitioning of hepatic bile between gallbladder and small intestine and, therefore, gallbladder filling. Progesterone also significantly impairs gallbladder emptying in response to cholecystokinin. The effects of progesterone on the sphincter of Oddi and the gallbladder may contribute to the greater prevalence of gallstones and biliary motility disorders among women. Images Figure 1. Figure 2. Figure 3. Figure 4. PMID:10024101

Percutaneous imaging-guided interventions for acute biliary disorders in high surgical risk patients

PubMed Central

Donkol, Ragab Hani; Latif, Nahed Abdel; Moghazy, Khaled

2010-01-01

AIM: To evaluate the efficacy of percutaneous imaging-guided biliary interventions in the management of acute biliary disorders in high surgical risk patients. METHODS: One hundred and twenty two patients underwent 139 percutaneous imaging-guided biliary interventions during the period between January 2007 to December 2009. The patients included 73 women and 49 men with a mean age of 61 years (range 35-90 years). Fifty nine patients had acute biliary obstruction, 26 patients had acute biliary infection and 37 patients had abnormal collections. The procedures were performed under computed tomography (CT)- (73 patients), sonographic- (41 patients), and fluoroscopic-guidance (25 patients). Success rates and complications were determined. The χ2 test with Yates’ correction for continuity was applied to compare between these procedures. A P value < 0.05 was considered significant. RESULTS: The success rates for draining acute biliary obstruction under CT- , fluoroscopy- or ultrasound-guidance were 93.3%, 62.5% and 46.1%, respectively with significant P values (P = 0.026 and 0.002, respectively). In acute biliary infection, successful drainage was achieved in 22 patients (84.6%). The success rates in patients drained under ultrasound- and CT-guidance were 46.1% and 88.8%, respectively and drainage under CT-guidance was significantly higher (P = 0.0293). In 13 patients with bilomas, percutaneous drainage was successful in 11 patients (84.6%). Ten out of 12 cases with hepatic abscesses were drained with a success rate of 83.3%. In addition, the success rate of drainage in 12 cases with pancreatic pseudocysts was 83.3%. The reported complications were two deaths, four major and seven minor complications. CONCLUSION: Percutaneous imaging-guided biliary interventions help to promptly diagnose and effectively treat acute biliary disorders. They either cure the disorders or relieve sepsis and jaundice before operations. PMID:21160698

Interventional Endoscopy Database for Pancreatico-biliary, Gastrointestinal and Esophageal Disorders

ClinicalTrials.gov

2017-02-16

Ampullary Cancer; Duodenal Cancer; Bile Duct Cancer; Bile Duct Disorders; Gallstones; Obstructive Jaundice; Pancreatic Disorders (Noncancerous); Colorectal Cancer; Esophageal Cancer; Barrett's Esophagus; Gastric Malignancies; Pancreatic Cancer; Pediatric Gastroenterology; Cholangiocarcinoma; Pancreatic Pseudocysts; Acute and Chronic Pancreatitis; Recurrent Pancreatitis; Cholangitis; Bile Leak; Biliary Strictures; Pancreatic Divisum; Biliary and Pancreatic Stones; Choledocholithiasis

Design of Stomach Acid-Stable and Mucin-Binding Enzyme Polymer Conjugates.

PubMed

Cummings, Chad S; Campbell, Alan S; Baker, Stefanie L; Carmali, Sheiliza; Murata, Hironobu; Russell, Alan J

2017-02-13

The reduced immunogenicity and increased stability of protein-polymer conjugates has made their use in therapeutic applications particularly attractive. However, the physicochemical interactions between polymer and protein, as well as the effect of this interaction on protein activity and stability, are still not fully understood. In this work, polymer-based protein engineering was used to examine the role of polymer physicochemical properties on the activity and stability of the chymotrypsin-polymer conjugates and their degree of binding to intestinal mucin. Four different chymotrypsin-polymer conjugates, each with the same polymer density, were synthesized using "grafting-from" atom transfer radical polymerization. The influence of polymer charge on chymotrypsin-polymer conjugate mucin binding, bioactivity, and stability in stomach acid was determined. Cationic polymers covalently attached to chymotrypsin showed high mucin binding, while zwitterionic, uncharged, and anionic polymers showed no mucin binding. Cationic polymers also increased chymotrypsin activity from pH 6-8, while zwitterionic polymers had no effect, and uncharged and anionic polymers decreased enzyme activity. Lastly, cationic polymers decreased the tendency of chymotrypsin to structurally unfold at extremely low pH, while uncharged and anionic polymers induced unfolding more quickly. We hypothesized that when polymers are covalently attached to the surface of a protein, the degree to which those polymers interact with the protein surface is the predominant determinant of whether the polymer will stabilize or inactivate the protein. Preferential interactions between the polymer and the protein lead to removal of water from the surface of the protein, and this, we believe, inactivates the enzyme.

Primary mammary mucinous cystadenocarcinoma: cytological and histological findings.

PubMed

Sentani, Kazuhiro; Tashiro, Takashi; Uraoka, Naohiro; Aosaki, Yoriyuki; Yano, Satomi; Takaeko, Fumio; Yasui, Wataru

2012-07-01

Mucinous cystadenocarcinoma (MCA), commonly encountered in the ovary or pancreas, is rare in the breast and was only recently described as a distinct variant of invasive ductal carcinoma of the breast. Only 11 cases of primary mammary MCA have been reported. In this article, we report a case of primary mammary MCA with focus on cytological and histological findings. A 65-year-old female noticed right palpable breast mass. Sonography showed an irregularly shaped 2.8 × 2.4 cm lesion in the upper outer quadrant of the right breast. Fine-needle aspiration cytology was performed on the right breast nodule, and cytopathologic examination suggested an adenocarcinoma composed of tall columnar cells with mucin. A partial mastectomy of the right breast and the axillary lymph nodes dissection was performed. The gross examination revealed a well-demarcated and mucus-filled tumor. Histologically, it had complex papillae, some of which were supported by delicate fibrovascular stroma lined by simple to slightly stratified columnar neoplastic epithelial cells with intracellular mucin, coexisting with MCA in situ and ordinary intraductal carcinoma component (ICC). Immunohistochemically, ICC was HER2-negative and estrogen receptor/progesterone receptor-positive, while MCA was triple negative. MCA might be derived from a metaplasia of ordinary ICC, but its pathogenesis and biologic behavior remains unclear. Despite the invasive nature of mammary MCA, these carcinomas appear to be associated with a good prognosis. The patient has remained well and disease-free for 6 months after the operation. Copyright © 2011 Wiley Periodicals, Inc.

Internal stenting in malignant biliary obstruction.

PubMed

Cowling, M G; Adam, A N

2001-03-01

Internal stenting in inoperable malignant biliary obstruction plays an important role in patient management. Surgical bypass may still be undertaken where there is also duodenal obstruction, though the need for gastroenterostomy may be reduced with the increasing use of metallic stents for the relief of malignant gastric outlet obstruction. Stents may be placed endoscopically or percutaneously, though in most centers the endoscopic route is usually tried first, with the percutaneous route being reserved for endoscopic failures. Plastic and self-expanding metallic biliary stents are available, each with its own advantages and disadvantages. In general, longer periods of patency are observed with metallic stents, though they are more expensive. Plastic stents can be changed endoscopically relatively easily when they have blocked, and in practice it is common for plastic stents to be inserted via this route for initial biliary drainage. If there is prolonged survival thereafter, many workers insert a metallic stent in an attempt to reduce the number of interventions required. If the percutaneous route is being employed, the histologic diagnosis has been confirmed, and the malignancy is inoperable, our practice is to use a self-expanding metallic stent, as the delivery system is relatively small and subsequent occlusion less likely.

Reality named endoscopic ultrasound biliary drainage

PubMed Central

Guedes, Hugo Gonçalo; Lopes, Roberto Iglesias; de Oliveira, Joel Fernandez; Artifon, Everson Luiz de Almeida

2015-01-01

Endoscopic ultrasound (EUS) is used for diagnosis and evaluation of many diseases of the gastrointestinal (GI) tract. In the past, it was used to guide a cholangiography, but nowadays it emerges as a powerful therapeutic tool in biliary drainage. The aims of this review are: outline the rationale for endoscopic ultrasound-guided biliary drainage (EGBD); detail the procedural technique; evaluate the clinical outcomes and limitations of the method; and provide recommendations for the practicing clinician. In cases of failed endoscopic retrograde cholangiopancreatography (ERCP), patients are usually referred for either percutaneous transhepatic biliary drainage (PTBD) or surgical bypass. Both these procedures have high rates of undesirable complications. EGBD is an attractive alternative to PTBD or surgery when ERCP fails. EGBD can be performed at two locations: transhepatic or extrahepatic, and the stent can be inserted in an antegrade or retrograde fashion. The drainage route can be transluminal, duodenal or transpapillary, which, again, can be antegrade or retrograde [rendezvous (EUS-RV)]. Complications of all techniques combined include pneumoperitoneum, bleeding, bile leak/peritonitis and cholangitis. We recommend EGBD when bile duct access is not possible because of failed cannulation, altered upper GI tract anatomy, gastric outlet obstruction, a distorted ampulla or a periampullary diverticulum, as a minimally invasive alternative to surgery or radiology. PMID:26504507

The potential health and economic benefits of preventing recurrent respiratory papillomatosis through quadrivalent human papillomavirus vaccination.

PubMed

Chesson, Harrell W; Forhan, Sara E; Gottlieb, Sami L; Markowitz, Lauri E

2008-08-18

We estimated the health and economic benefits of preventing recurrent respiratory papillomatosis (RRP) through quadrivalent human papillomavirus (HPV) vaccination. We applied a simple mathematical model to estimate the averted costs and quality-adjusted life years (QALYs) saved by preventing RRP in children whose mothers had been vaccinated at age 12 years. Under base case assumptions, the prevention of RRP would avert an estimated USD 31 (range: USD 2-178) in medical costs (2006 US dollars) and save 0.00016 QALYs (range: 0.00001-0.00152) per 12-year-old girl vaccinated. Including the benefits of RRP reduced the estimated cost per QALY gained by HPV vaccination by roughly 14-21% in the base case and by <2% to >100% in the sensitivity analyses. More precise estimates of the incidence of RRP are needed, however, to quantify this impact more reliably.

An autoinflammatory neurological disease due to interleukin 6 hypersecretion

PubMed Central

2013-01-01

Autoinflammatory diseases are rare illnesses characterized by apparently unprovoked inflammation without high-titer auto-antibodies or antigen-specific T cells. They may cause neurological manifestations, such as meningitis and hearing loss, but they are also characterized by non-neurological manifestations. In this work we studied a 30-year-old man who had a chronic disease characterized by meningitis, progressive hearing loss, persistently raised inflammatory markers and diffuse leukoencephalopathy on brain MRI. He also suffered from chronic recurrent osteomyelitis of the mandible. The hypothesis of an autoinflammatory disease prompted us to test for the presence of mutations in interleukin-1−pathway genes and to investigate the function of this pathway in the mononuclear cells obtained from the patient. Search for mutations in genes associated with interleukin-1−pathway demonstrated a novel NLRP3 (CIAS1) mutation (p.I288M) and a previously described MEFV mutation (p.R761H), but their combination was found to be non-pathogenic. On the other hand, we uncovered a selective interleukin-6 hypersecretion within the central nervous system as the likely pathogenic mechanism. This is also supported by the response to the anti-interleukin-6−receptor monoclonal antibody tocilizumab, but not to the recombinant interleukin-1−receptor antagonist anakinra. Exome sequencing failed to identify mutations in other genes known to be involved in autoinflammatory diseases. We propose that the disease described in this patient might be a prototype of a novel category of autoinflammatory diseases characterized by prominent neurological involvement. PMID:23432807

Specificity of dermal mucin in the diagnosis of lupus erythematosus: comparison with other dermatitides and normal skin.

PubMed

Vincent, Jeremy G; Chan, May P

2015-10-01

Increased dermal mucin is a feature of lupus erythematosus (LE); however, its amount and distribution have not been well characterized. The differentiation of LE from other forms of dermatitis can be challenging when other features of LE are subtle or equivocal. One hundred and thirty-five skin specimens showing LE, graft vs. host disease, erythema multiforme/fixed drug eruption, lichen planus, polymorphous light eruption (PMLE), urticaria, eczematous dermatitis and psoriasis and normal skin with and without photodamage were collected. The amounts of mucin in the papillary, superficial reticular and deep reticular dermis were scored from 0 to 3 on hematoxylin-eosin (H&E) and alcian blue (AB) stains, and compared between groups. The mean scores in the reticular dermis were significantly higher in LE than in other categories except PMLE and eczematous dermatitis. A combined H&E + AB score of ≥5 in the superficial reticular dermis gave an overall specificity of 85.7% for LE. Mucin in the papillary dermis failed to distinguish among entities. Normal photodamaged skin showed significantly more mucin in the superficial reticular dermis compared to non-photodamaged skin. While LE is associated with increased mucin deposition, scant to moderate amount of mucin alone has limited specificity and is common in other dermatitides or photodamaged skin. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Bile Culture and Susceptibility Testing of Malignant Biliary Obstruction via PTBD

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yu Haipeng; Guo Zhi, E-mail: jieruke@yahoo.com.cn; Xing Wenge

Purpose: To assess the information obtained by bile culture and susceptibility testing for malignant biliary obstruction by a retrospective one-center study. Methods: A total of 694 patients with malignant biliary obstruction received percutaneous transhepatic biliary drainage during the period July 2003 to September 2010, and subsequently, bile specimens were collected during the procedure. Among the 694 patients, 485 were men and 209 were women, ranging in age from 38 to 78 years (mean age 62 years). Results: A total of 42.9% patients had a positive bile culture (298 of 694). Further, 57 species of microorganisms and 342 strains were identified;more » gram-positive bacteria accounted for 50.9% (174 of 342) and gram-negative bacteria accounted for 41.5% (142 of 342) of these strains. No anaerobes were obtained by culture during this study. The most common microorganisms were Enterococcus faecalis (41 of 342, 11.9%), Escherichia coli (34 of 342, 9.9%), Klebsiella pneumoniae (28 of 342, 8.2%), Staphylococcus epidermidis (19 of 342, 5.5%), Enterococcus (18 of 342, 5.3%), and Enterobacter cloacae (16 of 342, 4.7%). The percentage of {beta}-lactamase-producing gram-positive bacteria was 27.6% (48 of 174), and the percentage of gram-negative bacteria was 19.7% (28 of 142). The percentage of enzyme-producing Escherichia coli was 61.7% (21 of 34). Conclusion: The bile cultures in malignant biliary obstruction are different from those in the Tokyo Guidelines and other benign biliary obstruction researches, which indicates that a different antibacterial therapy should be applied. Thus, knowledge of the antimicrobial susceptibility data could aid in the better use of antibiotics for the empirical therapy of biliary infection combined with malignant biliary obstruction.« less

Biliary excretion of intravenous (/sup 14/C) omeprazole in humans

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lind, T.; Andersson, T.; Skanberg, I.O.

1987-11-01

We have studied the biliary excretion of (/sup 14/C) omeprazole in humans. The study was performed in eight healthy subjects and the technique used was based on multiple marker dilution principles with double-lumen tubes placed in both the stomach and intestine. The results obtained show a 16% biliary excretion of (/sup 14/C) omeprazole. These data suggest a minimal spillover of omeprazole from the gastric mucosa into the gastric lumen in humans. The results also agree with previous data of the fecal recovery of radiolabeled omeprazole that suggest that the fecal excretion of intravenous omeprazole in humans is entirely accounted formore » by biliary excretion.« less

Sequential algorithm analysis to facilitate selective biliary access for difficult biliary cannulation in ERCP: a prospective clinical study.

PubMed

Lee, Tae Hoon; Hwang, Soon Oh; Choi, Hyun Jong; Jung, Yunho; Cha, Sang Woo; Chung, Il-Kwun; Moon, Jong Ho; Cho, Young Deok; Park, Sang-Heum; Kim, Sun-Joo

2014-02-17

Numerous clinical trials to improve the success rate of biliary access in difficult biliary cannulation (DBC) during ERCP have been reported. However, standard guidelines or sequential protocol analysis according to different methods are limited in place. We planned to investigate a sequential protocol to facilitate selective biliary access for DBC during ERCP. This prospective clinical study enrolled 711 patients with naïve papillae at a tertiary referral center. If wire-guided cannulation was deemed to have failed due to the DBC criteria, then according to the cannulation algorithm early precut fistulotomy (EPF; cannulation time > 5 min, papillary contacts > 5 times, or hook-nose-shaped papilla), double-guidewire cannulation (DGC; unintentional pancreatic duct cannulation ≥ 3 times), and precut after placement of a pancreatic stent (PPS; if DGC was difficult or failed) were performed sequentially. The main outcome measurements were the technical success, procedure outcomes, and complications. Initially, a total of 140 (19.7%) patients with DBC underwent EPF (n = 71) and DGC (n = 69). Then, in DGC group 36 patients switched to PPS due to difficulty criteria. The successful biliary cannulation rate was 97.1% (136/140; 94.4% [67/71] with EPF, 47.8% [33/69] with DGC, and 100% [36/36] with PPS; P < 0.001). The mean successful cannulation time (standard deviation) was 559.4 (412.8) seconds in EPF, 314.8 (65.2) seconds in DGC, and 706.0 (469.4) seconds in PPS (P < 0.05). The DGC group had a relatively low successful cannulation rate (47.8%) but had a shorter cannulation time compared to the other groups due to early switching to the PPS method in difficult or failed DGC. Post-ERCP pancreatitis developed in 14 (10%) patients (9 mild, 1 moderate), which did not differ significantly among the groups (P = 0.870) or compared with the conventional group (P = 0.125). Based on the sequential protocol analysis, EPF, DGC, and PPS may be safe and feasible for DBC. The use of

Expanding endourology for biliary stone disease: the efficacy of intracorporeal lithotripsy on refractory biliary calculi.

PubMed

Sninsky, Brian C; Sehgal, Priyanka D; Hinshaw, J Louis; McDermott, John C; Nakada, Stephen Y

2014-07-01

We evaluated the efficacy of ureteroscopic therapy (electrohydraulic lithotripsy [EHL] and intraductal laser lithotripsy [ILL]) in patients with challenging biliary stones secondary to anatomic variations resulting from a previous surgical procedure, including liver transplantation. A retrospective chart review was performed for all patients with previous surgical alteration of the gastrointestinal (GI) tract who underwent EHL or ILL via peroral or percutaneous access for choledocholithiasis by a single surgeon at our institution from 2000 to 2012. A database containing clinical and surgical variables was created, and long-term follow-up was conducted (3-138 months; median, 99 months). Thirteen patients (51.7±20.0 years; M:F, 10:3) in whom endoscopic retrograde cholangiopancreatography (ERCP), percutaneous transhepatic cholangiography (PTHC), or both failed were identified. Failure of ERCP/PTHC was because of inaccessibility of the calculi in all cases. Stone clearance was achieved in 12/13 (93%) patients; 8/12 (62%) after one procedure, and 4/12 (31%) after two procedures. One patient with biliary cast syndrome needed four interventions over 9 years. Major complications were low, with only one patient with hypotension and cholangitis that resolved with 24 hours of administration of intravenous fluids and antibiotics. Both endoscopic and percutaneous lithotripsies are effective treatments for refractory biliary calculi resulting from the post-surgical GI tract. Although a staged second procedure may be necessary in patients with significant stone burden, this is significantly better than extensive open surgery.

Biliary metal stents for proximal esophageal or hypopharyngeal strictures.

PubMed

Bechtler, Matthias; Wagner, Florian; Fuchs, Erik-Sebastian; Jakobs, Ralf

2015-11-01

Endoscopic dilation is the standard of care for stenoses of the cervical esophagus, but refractory strictures require some form of stenting. Most endoscopists avoid the placement of metal stents near the upper esophageal sphincter as they can cause major problems like severe cervical pain and globus sensation. We report our results with the use of biliary SEMS in the upper esophagus, which have a smaller diameter than regular esophageal stents and therefore exert less expansive force. We retrospectively reviewed all patients in our center between July 2011 and June 2014 who received a biliary metal stent because of a refractory stricture in the cervical esophagus. We implanted biliary SEMS (Wallflex, Boston Scientific) with a diameter of 1 cm and length of 6-8 cm. Technical and clinical success, adverse events and duration of stenting were evaluated. Ten patients were treated with biliary SEMS in the upper esophagus. Strictures were located between 10 and 19 cm from incisor teeth. Stent placement was successful in all (10/10) patients. One stent had to be extracted because of pain and globus sensation. Apart from that stent tolerability was good. All remaining patients (9/9) reported improvement of dysphagia with a decrease in mean dysphagia score from 3.2 to 1.78. Mean duration of stenting was 68 days. Because of a high clinical success rate and good tolerability, biliary metal stents are a reasonable alternative for difficult strictures in the cervical esophagus, especially in the palliative setting.

Pigment gallstone pathogenesis: slime production by biliary bacteria is more important than beta-glucuronidase production.

PubMed

Stewart, L; Ponce, R; Oesterle, A L; Griffiss, J M; Way, L W

2000-01-01

Pigment stones are thought to form as a result of deconjugation of bilirubin by bacterial beta-glucuronidase, which results in precipitation of calcium bilirubinate. Calcium bilirubinate is then aggregated into stones by an anionic glycoprotein. Slime (glycocalyx), an anionic glycoprotein produced by bacteria causing foreign body infections, has been implicated in the formation of the precipitate that blocks biliary stents. We previously showed that bacteria are present within the pigment portions of gallstones and postulated a bacterial role in pigment stone formation through beta-glucuronidase or slime production. Ninety-one biliary bacterial isolates from 61 patients and 12 control stool organisms were tested for their production of beta-glucuronidase and slime. The average slime production was 42 for biliary bacteria and 2.5 for stool bacteria (P <0.001). Overall, 73% of biliary bacteria and 8% of stool bacteria produced slime (optical density >3). In contrast, only 38% of biliary bacteria produced beta-glucuronidase. Eighty-two percent of all patients, 90% of patients with common bile duct (CBD) stones, 100% of patients with primary CBD stones, and 93% of patients with biliary tubes had one or more bacterial species in their stones that produced slime. By comparison, only 47% of all patients, 60% of patients with CBD stones, 62% of patients with primary CBD stones, and 50% of patients with biliary tubes had one or more bacteria that produced beta-glucuronidase. Most biliary bacteria produced slime, and slime production correlated better than beta-glucuronidase production did with stone formation and the presence of biliary tubes or stents. Patients with primary CBD stones and biliary tubes had the highest incidence of slime production. These findings suggest that bacterial slime is important in gallstone formation and the blockage of biliary tubes.

[Fissures in biliary calculi. Personal contribution (author's transl)].

PubMed

Nano, M; Potenzoni, F; Camandona, M; Casalegno, P A

1979-04-01

In a series of 70 patients suffering from biliary lithiasis, the roentgenologic findings of fissures in the calculi was observed in 5 cases examined by means of cholecystography and in 7 cases who underwent cholangiocholecystography. Fissures were demonstrated 11 times in calculi after surgery. The "Mercedes-Benz" sign was never observed at the abdominal examination without contrast medium. The presence of fissures may be an additional sign in the radiologic diagnosis of biliary calculi, but its value is not determinant.

Anthony Eden’s (Lord Avon) Biliary Tract Saga

PubMed Central

Braasch, John W.

2003-01-01

Anthony Eden (Lord Avon) was the youngest foreign secretary in Great Britain’s history. He subsequently became Prime Minister, succeeding Winston Churchill. Eden had the misfortune to have, during cholecystectomy, a biliary tract injury which required four subsequent biliary tract operations. He was subject to recurrent fevers and postoperative disability at important times in his career and during international crises. This report details the operative procedures used and his clinical status at crucial times in national and international affairs. PMID:14578742

Goblet cell mucins as the selective barrier for the intestinal helminths: T-cell-independent alteration of goblet cell mucins by immunologically 'damaged' Nippostrongylus brasiliensis worms and its significance on the challenge infection with homologous and heterologous parasites.

PubMed Central

Ishikawa, N; Horii, Y; Oinuma, T; Suganuma, T; Nawa, Y

1994-01-01

The aim of this study was to examine the role of T cells on the alteration of terminal sugars of goblet cell mucins in the small intestinal mucosa of parasitized rats and to clarify the biological significance of the altered mucins in the mucosal defence against intestinal helminths. For this purpose, Nippostrongylus brasiliensis adult worms obtained from donor rats at 7 ('normal' worms) or 13 days ('damaged' worms) post-infection were implanted intraduodenally into euthymic and hypothymic (rnu/rnu) rats. Expulsion of implanted normal worms and associated goblet cell changes were extremely delayed in hypothymic recipients compared with euthymic recipients. In contrast, intraduodenally implanted damaged worms were expelled by day 5 regardless of the strains. Around the time of expulsion of implanted damaged worms, euthymic recipients showed both goblet cell hyperplasia and alteration of mucins, whereas hypothymic rats showed only the latter. Dexamethasone treatment completely abolished goblet cell changes of both strains of recipients. To clarify the importance of the constitutional changes of goblet cell mucins in mucosal defence, euthymic rats were primed by implantation of damaged worms to induce goblet cell changes, and then 3 or 5 days later they were challenged by implantation with normal worms. The results show that when goblet cell changes were induced by priming with damaged worms, recipient rats could completely prevent the establishment of normal worms. When hypothymic rats were primed and challenged in the same manner, a similar but slightly less preventive effect was observed. Such a protective effect of altered mucins seems to be selective because priming of euthymic rats with damaged N. brasiliensis did not affect the establishment of Strongyloides venezuelensis. These results suggest that: (1) once N. brasiliensis adult worms are 'damaged' by the host's T-cell-dependent immune mechanisms, they can induce alteration of sugar residues of goblet cell

Endometrial carcinomas with significant mucinous differentiation associated with higher frequency of k-ras mutations: a morphologic and molecular correlation study.

PubMed

Xiong, Jinjun; He, Mai; Jackson, Cynthia; Ou, Joyce J; Sung, C James; Breese, Virgina; Steinhoff, Margaret M; Quddus, M Ruhul; Tejada-Berges, Trevor; Lawrence, W Dwayne

2013-09-01

K-ras gene product in the mitogen-activated protein kinase/extracellular signal-regulated kinase pathway is critical in the development of certain types of malignancies. K-ras mutation-associated pancreatic and ovarian carcinomas often display mucinous differentiation. Previous studies have shown that k-ras mutation is found in 10% to 30% of endometrial carcinomas. We investigated k-ras mutations in several morphologic subtypes of endometrial carcinomas with particular emphasis on various degrees of mucinous differentiation. Genomic DNA was extracted from formalin-fixed paraffin-embedded (FFPE) tissue sections. Polymerase chain reaction amplification for k-ras codons 12 and 13 were performed, followed by sequencing using capillary electrophoresis. The Fisher exact test is used to compare the prevalent difference of k-ras mutation among the groups. P < 0.05 was considered significant. K-ras mutations were detected in 8 (80%) of 10 mucinous carcinomas, 12 (67%) of 18 endometrioid carcinomas (ECs) with significant mucinous differentiation (ECMD), 4 (25%) of 16 ECs, and 1 (9%) of 11 serous carcinomas. The differences were statistically significant between mucinous carcinomas versus EC (P < 0.01) and ECMD versus EC (P < 0.05). The findings suggest that mucinous carcinoma and endometrioid carcinoma with significant mucinous component are more likely to be associated with k-ras mutation. Potential clinical implications of k-ras mutation lies in the management of recurrent or higher-stage endometrial mucinous tumors, which would not be responsive to treatment protocols containing epidermal growth factor receptor inhibitors.

Genome-Scale Model and Omics Analysis of Metabolic Capacities of Akkermansia muciniphila Reveal a Preferential Mucin-Degrading Lifestyle

PubMed Central

Suarez-Diez, Maria; Boeren, Sjef; Schaap, Peter J.; Martins dos Santos, Vitor A. P.; Smidt, Hauke; Belzer, Clara

2017-01-01

ABSTRACT The composition and activity of the microbiota in the human gastrointestinal tract are primarily shaped by nutrients derived from either food or the host. Bacteria colonizing the mucus layer have evolved to use mucin as a carbon and energy source. One of the members of the mucosa-associated microbiota is Akkermansia muciniphila, which is capable of producing an extensive repertoire of mucin-degrading enzymes. To further study the substrate utilization abilities of A. muciniphila, we constructed a genome-scale metabolic model to test amino acid auxotrophy, vitamin biosynthesis, and sugar-degrading capacities. The model-supported predictions were validated by in vitro experiments, which showed A. muciniphila to be able to utilize the mucin-derived monosaccharides fucose, galactose, and N-acetylglucosamine. Growth was also observed on N-acetylgalactosamine, even though the metabolic model did not predict this. The uptake of these sugars, as well as the nonmucin sugar glucose, was enhanced in the presence of mucin, indicating that additional mucin-derived components are needed for optimal growth. An analysis of whole-transcriptome sequencing (RNA-Seq) comparing the gene expression of A. muciniphila grown on mucin with that of the same bacterium grown on glucose confirmed the activity of the genes involved in mucin degradation and revealed most of these to be upregulated in the presence of mucin. The transcriptional response was confirmed by a proteome analysis, altogether revealing a hierarchy in the use of sugars and reflecting the adaptation of A. muciniphila to the mucosal environment. In conclusion, these findings provide molecular insights into the lifestyle of A. muciniphila and further confirm its role as a mucin specialist in the gut. IMPORTANCE Akkermansia muciniphila is among the most abundant mucosal bacteria in humans and in a wide range of other animals. Recently, A. muciniphila has attracted considerable attention because of its capacity to

Effect of guaifenesin on mucin production, rheology, and mucociliary transport in differentiated human airway epithelial cells.

PubMed

Seagrave, JeanClare; Albrecht, Helmut; Park, Yong Sung; Rubin, Bruce; Solomon, Gail; Kim, K Chul

2011-12-01

Guaifenesin is widely used to alleviate symptoms of excessive mucus accumulation in the respiratory tract. However, its mechanism of action is poorly understood. The authors hypothesized that guaifenesin improves mucociliary clearance in humans by reducing mucin release, by decreasing mucus viscoelasticity, and by increasing mucociliary transport. To test these hypotheses, human differentiated airway epithelial cells, cultured at an air-liquid interface, were treated with clinically relevant concentrations of guaifenesin by addition to the basolateral medium. To evaluate the effect on mucin secretion, the authors used an anzyme-linked immunosorbent assay (ELISA) to measure the amounts of MUC5AC protein in apical surface fluid and cell lysates. To measure mucociliary transportability, additional cultures were treated for 1 or 6 hours with guaifenesin, and the movement of cell debris was measured from video data. Further, the authors measured mucus dynamic viscoelasticity using a micro cone and plate rheometer with nondestructive creep transformation. Guaifenesin suppressed mucin production in a dose-dependent manner at clinically relevant concentrations. The reduced mucin production was associated with increased mucociliary transport and decreased viscoelasticity of the mucus. Viability of the cultures was not significantly affected. These results suggest that guaifenesin could improve mucociliary clearance in humans by reducing the release and/or production of mucins, thereby altering mucus rheology.

Impaired viscosity of gastric secretion and its mucin content as potential contributing factors to the development of chronic constipation.

PubMed

Castro-Combs, Juan; Garcia, Cesar J; Majewski, Marek; Wallner, Grzegorz; Sarosiek, Jerzy

2014-11-01

The alimentary tract mucosa continuously releases mucus-rich secretion. Mucin, the major component of mucus, determines its viscosity and provides lubrication for the luminal content of indigestible food particles. To measure mucin secretion rate and its viscosity in patients with chronic constipation (CC) and in asymptomatic volunteers. Nineteen patients with symptoms of CC and 19 controls were included in the study. Mucin secretion and viscosity were assessed in aspirated gastric juice in basal conditions and after stimulation with pentagastrin (1 h each). Mucin content was tested by PAS methodology. Viscosity was measured using cone/plate digital viscometer. Mucin secretion rates in basal and stimulated conditions in controls were 65 and 42 % higher than in patients with CC (P < 0.05 and P < 0.001, respectively). Basal viscosity in controls was 48 % higher than in CC (P < 0.05) at the lowest and 55 % higher (P < 0.05) at the middle velocities. Viscosity in pentagastrin-stimulated conditions in controls was 71 % higher than in CC (P < 0.01) at the lowest and 35 % higher (P < 0.05) at the middle velocities. (1) The significantly lower rate of soluble mucin secretion in patients with CC than in normal volunteers may reflect impairment in mucin-related lubrication. (2) Significantly lower viscosity of gastric secretion in patients with CC may result from the lower rate of mucin secretion and may also diminish lubrication within the alimentary tract. (3) This may potentially set the stage for the development of symptoms related to chronic constipation and open a new therapeutic avenue for this patient population.

Endoscopic management of benign biliary strictures.

PubMed

Rustagi, Tarun; Jamidar, Priya A

2015-01-01

Benign biliary strictures are a common indication for endoscopic retrograde cholangiopancreatography (ERCP). Endoscopic management has evolved over the last 2 decades as the current standard of care. The most common etiologies of strictures encountered are following surgery and those related to chronic pancreatitis. High-quality cross-sectional imaging provides a road map for endoscopic management. Currently, sequential placement of multiple plastic biliary stents represents the preferred approach. There is an increasing role for the treatment of these strictures using covered metal stents, but due to conflicting reports of efficacies as well as cost and complications, this approach should only be entertained following careful consideration. Optimal management of strictures is best achieved using a team approach with the surgeon and interventional radiologist playing an important role.

Managing malignant biliary obstruction in pancreas cancer: Choosing the appropriate strategy

PubMed Central

Boulay, Brian R; Parepally, Mayur

2014-01-01

Most patients with pancreatic cancer develop malignant biliary obstruction. Treatment of obstruction is generally indicated to relieve symptoms and improve morbidity and mortality. First-line therapy consists of endoscopic biliary stent placement. Recent data comparing plastic stents to self-expanding metallic stents (SEMS) has shown improved patency with SEMS. The decision of whether to treat obstruction and the means for doing so depends on the clinical scenario. For patients with resectable disease, preoperative biliary decompression is only indicated when surgery will be delayed or complications of jaundice exist. For patients with locally advanced disease, self-expanding metal stents are superior to plastic stents for long-term patency. For patients with advanced disease, the choice of metallic or plastic stent depends on life expectancy. When endoscopic stent placement fails, percutaneous or surgical treatments are appropriate. Endoscopic therapy or surgical approach can be used to treat concomitant duodenal and biliary obstruction. PMID:25071329

Activity of chemotherapy in mucinous ovarian cancer with a recurrence free interval of more than 6 months: results from the SOCRATES retrospective study

PubMed Central

Pignata, Sandro; Ferrandina, Gabriella; Scarfone, Giovanna; Scollo, Paolo; Odicino, Franco; Cormio, Gennaro; Katsaros, Dionyssios; Villa, Antonella; Mereu, Liliana; Ghezzi, Fabio; Manzione, Luigi; Lauria, Rossella; Breda, Enrico; Alletti, Desiderio Gueli; Ballardini, Michela; Lombardi, Alessandra Vernaglia; Sorio, Roberto; Mangili, Giorgia; Priolo, Domenico; Magni, Giovanna; Morabito, Alessandro

2008-01-01

Background Mucinous ovarian carcinoma have a poorer prognosis compared with other histological subtypes. The aim of this study was to evaluate, retrospectively, the activity of chemotherapy in patients with platinum sensitive recurrent mucinous ovarian cancer. Methods The SOCRATES study retrospectively assessed the pattern of care of a cohort of patients with recurrent platinum-sensitive ovarian cancer observed in the years 2000–2002 in 37 Italian centres. Data were collected between April and September 2005. Patients with recurrent ovarian cancer with > 6 months of platinum free interval were considered eligible. Results Twenty patients with mucinous histotype and 388 patients with other histotypes were analyzed. At baseline, mucinous tumours differed from the others for an higher number of patients with lower tumor grading (p = 0.0056) and less advanced FIGO stage (p = 0.025). At time of recurrence, a statistically significant difference was found in performance status (worse in mucinous, p = 0.024). About 20% of patients underwent secondary cytoreduction in both groups, but a lower number of patients were optimally debulked in the mucinous group (p = 0.03). Patients with mucinous cancer received more frequently single agent platinum than platinum based-combination therapy or other non-platinum schedules as second line therapy (p = 0.026), with a response rate lower than in non-mucinous group (36.4% vs 62.6%, respectively, p = 0.04). Median time to progression and overall survival were worse for mucinous ovarian cancer. Finally, mucinous cancer received a lower number of chemotherapy lines (p = 0.0023). Conclusion This analysis shows that platinum sensitive mucinous ovarian cancer has a poor response to chemotherapy. Studies dedicated to this histological subgroup are needed. PMID:18761742