Possible therapeutics for Pseudomyxoma peritonei: a rare, lethal, and the least investigated disease

Pseudomyxoma peritonei (PMP) refers to a growth disorder characterized by glycoprotein neoplasm in the peritoneum, where mucin oversecretion occurs. The tumors of the appendix region are well associated with PMP; however, ovarian, colon, stomach, pancreas, and urachus tumors have also been linked to PMP. Other mucinous tumors in the pelvis, paracolic gutters, greater omentum, retrohepatic space, and Treitz ligament can be the reason for PMP. Despite being rare and having a slow growth rate, PMP can be lethal without treatment. It is treated with neoadjuvant chemotherapy with the option of cytoreductive surgery and intraperitoneal chemotherapy. In the current study, we hypothesize that there may be novel gentle ways to inhibit or eliminate the mucin. Dr. David Morris has used mucolytics - such as bromelain and N-acetyl cysteine to solubilize mucin. In the present review, we aimed to study the regulation of mucin expression by promoter methylation, and drugs that can inhibit mucin, such as boldine, amiloride, naltrexone, dexamethasone, and retinoid acid receptors antagonist. This review also explored some possible pathways, such as inhibition of Na + , Ca2+ channels and induction of DNA methyltransferase along with inhibition of ten-eleven translocation enzymes, which can be good targets to control mucin. Mucins are strong adhesive molecules that play great roles in clinging to cells or cell to cell. Besides, they have been greatly involved in metastasis and also act as disease markers for cancers. Diagnostic markers may have exclusive roles in disease initiation and progression. Therefore, the present review explores various drugs to control and target mucin in various diseases, specifically cancers. (AU)

The ability of different formulations of artificial saliva to protect dentin from erosive wear / Ação protetora de diferentes formulações de saliva artificial no desgaste erosivo

Objective: Evaluate the protective effect of artificial saliva formulations associated or not with mucin on dentin. Materials and Methods: Bovine dentin specimens were randomly allocated to 10 groups (n = 20) according to the artificial saliva tested and the presence or absence of mucin: Amaechi et al. (1998); Klimek et al. (1982); Vieira et al. (2005) and Eisenburger et al. (2001) and deionized water (control). Samples were submitted to an erosive cycle consisting of two immersions of 120 min in the saliva, followed by 1 min in hydrochloric acid solution, and new storage in saliva for 120 min. Surface loss (µm) was measured before and after the cycle. Data were analyzed using 2-way ANOVA and Tukey's test (p < 0.05). Results: A significant difference was observed for the saliva formulation but not for the presence of mucin. The deionized water provided the highest surface loss and the Eisenburger's saliva formulation the lowest. The groups testing the Amaechi, Klimek, and Vieira saliva did not present significant differences. Conclusion: Eisenburger's saliva formulation provides a higher protective effect against dentin erosion. The presence of mucin did not increase the erosion-preventive effect of artificial saliva formulations. (AU)

Objetivo: Avaliar o efeito protetor de formulações de saliva artificial associadas ou não à mucina sobre a dentina submetida a erosão. Material e Métodos: Espécimes de dentina bovina foram alocados em 10 grupos (n = 20) de acordo com a saliva testada e a presença ou ausência de mucina: . Amaechi et al. (1998); Klimek et al. (1982); Vieira e cols. (2005), Eisenburger et al (2001) e agua deionizada (controle). As amostras foram submetidas a um ciclo erosivo composto por duas imersões de 120 min na saliva, seguidas de 1 min em solução de ácido clorídrico e novo armazenamento na saliva por 120 min. A perda de superfície (µm) foi medida antes e depois do ciclo. Os dados foram analisados usando ANOVA 2 fatores e teste de Tukey (p <0,05). Resultados: Foi observada diferença significativa para a formulação de saliva, mas não para a presença de mucina. A água deionizada proporcionou a maior perda de superfície e a formulação de saliva de Eisenburger a menor. Os grupos que testaram a saliva Amaechi, Klimek e Vieira não apresentaram diferenças significativas entre si. Conclusão: A formulação de saliva de Eisenburger fornece o maior efeito protetor contra a erosão dentinária e a presença de mucina não aumentou o efeito preventivo de erosão de formulações de saliva artificial (AU).

Immunology of a unique biological structure: the Echinococcus laminated layer

The larval stages of the cestode parasites belonging to the genus Echinococcus grow within internal organs of humans and a range of animal species. The resulting diseases, collectively termed echinococcoses, include major neglected tropical diseases of humans and livestock. Echinococcus larvae are outwardly protected by the laminated layer (LL), an acellular structure that is unique to this genus. The LL is based on a fibrillar meshwork made up of mucins, which are decorated by galactose-rich O-glycans. In addition, in the species cluster termed E. granulosus sensu lato, the LL features nano-deposits of the calcium salt of myo-inositol hexakisphosphate (Insp6). The main purpose of our article is to update the immunobiology of the LL. Major recent advances in this area are (i) the demonstration of LL "debris" at the infection site and draining lymph nodes, (ii) the characterization of the decoy activity of calcium Insp6 with respect to complement, (iii) the evidence that the LL mucin carbohydrates interact specifically with a lectin receptor expressed in Kupffer cells (Clec4F), and (iv) the characterization of what appear to be receptor-independent effects of LL particles on dendritic cells and macrophages. Much information is missing on the immunology of this intriguing structure: we discuss gaps in knowledge and propose possible avenues for research.

Histochemical assessment of mucin-secreting cells in the stomach of domestic rabbit / Evaluación histoquímica de células secretoras de mucina en el estómago de conejo doméstico

SUMMARY: The mucous substances of the stomach in mammals are important not only for the protection of the gastric epithelium from the acid environment and grinding actions, but it facilitates some other functions of the stomach such as antibacterial, antimetastatic, and immunological roles. The goal of the study is to highlight the distribution of mucin-secreting cells in the gastric mucosa in domestic rabbits, including the type of mucus synthesized. The gastric samples collected from ten individual rabbits were fixed in 10 % buffered formalin and underwent later standard paraffin tissue sample processing, which included dehydration, clarification, and embedding in paraffin. The tissue sections were eventually stained histochemically by PAS reaction and by Alcian blue method (pH 2.5) for neutral and acidic mucins detection, respectively. The quantification of mucins in the cytoplasm of mucus-secreting cells was performed by grading the gastric tissue samples from negative (-) to intensely positive (++). The mucus elaboration was observed in all the regions of the stomach (i.e., cardial, fundic, and pyloric regions), but only for the neutral mucin. The acidic mucin synthesis occurred only in the secretory units of the gastric glands from the cardial region in the stomach. Pyloric glands synthesized the largest amounts of neutral mucins, followed by moderate amounts elaborated by cardial glands, while the fundic region does not synthesize it at all. The description of new microscopic features of the stomach in rabbits is fundamental not only for comprehending species-related physiological features but gastric pathological processes.

RESUMEN: Las sustancias mucosas del estómago en los mamíferos son importantes no solo para la protección del epitelio gástrico del ambiente ácido y las acciones de trituración, sino que facilitan además otras funciones del estómago, como son las funciones antibacterianas, antimetastásicas e inmunológicas. El objetivo del estudio fue resaltar la distribución de las células secretoras de mucina en la mucosa gástrica de conejos domésticos, incluido el tipo de moco sintetizado. Las muestras gástricas recolectadas de diez conejos se fijaron en formalina tamponada al 10 % y se sometieron a un procesamiento que incluyó deshidratación, clarificación e inclusión en parafina. Las secciones de tejido finalmente se tiñeron histoquímicamente mediante la reacción de PAS y el método del azul de Alcian (pH 2,5) para la detección de mucinas neutras y ácidas, respectivamente. La cuantificación de mucinas en el citoplasma de las células secretoras de moco se realizó clasificando las muestras de tejido gástrico desde negativas (-) hasta intensamente positivas (++). La elaboración de moco se observó en todas las regiones del estómago (es decir, cardias, fúndica y pilórica), pero solo para la mucina neutra. La síntesis de mucina ácida ocurrió solo en las unidades secretoras de las glándulas gástricas de la región correspondiente al cardias del estómago. Las glándulas pilóricas sintetizaron la mayor cantidad de mucinas neutras, seguidas de cantidades moderadas elaboradas por las glándulas cardiales, mientras que la región fúndica no las sintetizó en abso- luto. La descripción de nuevas características microscópicas del estómago en conejos es fundamental no solo para comprender las características fisiológicas relacionadas con las especies sino también para entender los procesos patológicos gástricos.

Aberrant Expression and Glycosylation of Mucins in Gastric Mucosal Disease / 中国医学科学院学报

Mucins,a family of heavily glycosylated proteins,present mainly in epithelial cells.They function as essential barriers for epithelium and play important roles in cellular physiological processes.Aberrant expression and glycosylation of mucins in gastric epithelium occur at pathological conditions,such as Helicobacter pylori infection,chronic atrophic gastritis,intestinal metastasis,dysplasia,and gastric cancer.This review addresses the major roles played by mucins and associated O-glycan structures in normal gastric epithelium.Further,we expound the alterations of expression patterns and glycan signatures of mucins at those pathological conditions.

Mucina salival en pacientes obesos en relación al tratamiento de la enfermedad periodontal / Salivary mucin in obese patients in relation to the treatment of periodontal disease

Introducción: La mucina salival (Ms) modula otras proteínas salivales que participan en múltiples funciones fisiológicas de la cavidad oral. Los niveles de Ms pueden proporcionar información sobre el estado de inflamación de los tejidos periodontales. Por tanto, el objetivo del presente estudio fue evaluar los niveles Ms en pacientes obesos y no obesos, antes y después del tratamiento periodontal. Material y métodos: Un total de 60 pacientes fueron distribuidos en seis grupos, de acuerdo al índice de masa corporal (IMC) y la gravedad de la enfermedad periodontal (EP). Valores del IMC superiores a 27 correspondían a obesidad. La EP en el momento del diagnóstico se designó como leve, moderada o severa. Se recolectaron muestras de saliva completa, antes (MU-A) y después (MU-D) del tratamiento periodontal. Se evaluaron los niveles de Ms utilizando el método de Azul Alcian. Los resultados se analizaron con el Software InfoStat, mediante estadística descriptiva e inferencial. Resultados: Los valores de MU-A fueron superiores a los contenidos de MU-D (p < 0.0001). Las variaciones entre los pacientes no obesos y obesos fueron mínimas. A medida que aumentó el nivel de la EP, las variables MU-A y MU-D mostraron una disminución progresiva (p = 0.0032). Conclusiones: El nivel de Ms fue mayor en la saliva de los pacientes con EP no tratada. Ms se puede utilizar como marcador inflamatorio para la detección de EP (AU)

Introduction: Salivary mucin (sM) modulates other salivary proteins that participate in multiple physiological functions of the oral cavity. sM levels can provide information on the state of inflammation of the periodontium. Therefore, the objective of the present study was to evaluate sM levels in obese and non-obese patients, before and after periodontal treatment. Material and methods: A total of 60 patients were distributed into six groups, according to the body mass index (BMI) and the severity of the periodontal disease (PD). BMI values higher than 27 corresponded to obesity. PD at the time of diagnosis was designated as mild, moderate, or severe. Complete saliva samples were collected before (MU-B) and after (MU-A) the periodontal treatment. sM levels were evaluated using the Alcian Blue method. The results were analyzed with the InfoStat Software, using descriptive and inferential statistics. Results: MU-B values were higher than MU-A contents (p < 0.0001). Variations between non-obese and obese patients were minimal. As the level of PD increased, the variables MU-A and MU-D showed a progressive decrease (p = 0.0032). Conclusions: The level of sM was higher in the saliva of patients with untreated PD. sM can be used as an inflammatory marker for the detection of PD (AU)

Mucina y Enfermedad Periodontal / Mucin and periodontal disease

La enfermedad periodontal (EP) es una patología que afecta principalmente los tejidos que rodean a la pieza dentaria (PD) y se caracteriza, en la mayoría de los casos, por una exposición bacteriana que favorece una respuesta destructiva e inflamatoria del huésped, que conduce a la pérdida de inserción periodontal de la PD, provocando una marcada reabsorción ósea y la posible pérdida de las PD. El diagnóstico de EP implica evaluaciones clínicas y radiográficas, en la actualidad se están realizando diversas investigaciones para evaluar posibles compuestos en los fluidos orales a través de lo cual puede ser posible evaluar la presencia y gravedad de estas enfermedades, como así también el riesgo en los pacientes. Hay evidencias de la interacción de macromoléculas salivales, como las mucinas, con microorganismos específicos. De esta manera las mucinas, junto con otros productos de la saliva, ayudan a modular tanto el número como el tipo de proliferación de ciertos organismos y provocar la disminución de otros. La revisión de la literatura actual concluye que las mucinas salivales pueden servir como un parámetro bioquímico de la inflamación del periodonto (AU)

Periodontal disease (PD) is a pathology that mainly affects the tissues surrounding the tooth (PD) and is characterized, in most cases, by a bacterial exposure that favors a destructive and inflammatory response of the host, which leads to the loss of periodontal insertion of the PD, causing a marked bone resorption and the possible loss of the PD. The diagnosis of PD involves clinical and radiographic evaluations, at present several investigations are being carried out to evaluate possible compounds in oral fluids through which it may be possible to evaluate the presence and severity of these diseases, as well as the risk in patients. There is evidence of the interaction of salivary macromolecules, such as mucins, with specific microorganisms. In this way, mucins, together with other saliva products, help modulate both the number and type of proliferation of certain organisms and cause the decrease of others. The review of the current literature concludes that salivary mucins can serve as a biochemical parameter of inflammation of the periodontium (AU)

Concentración de mucina salival en pacientes con enfermedad periodontal / Concentração de mucina salivar em pacientes com doença periodontal / Salivary mucin concentration in patients with periodontal disease

Resumen El objetivo de este trabajo fue estudiar la relación entre la concentración de mucina salival y la enfermedad periodontal. La muestra se dividió en tres grupos de 20 individuos cada uno: Grupo 1 sin enfermedad periodontal; Grupo 2 con gingivitis; y Grupo 3 con periodontitis. En todas las muestras salivales se confirmó la presencia de mucina, el Grupo 1 presentó un valor promedio de 1,27 mg/ml. En el Grupo 2 se registró un promedio de 1,93 mg/ml. En el Grupo 3 se observó un promedio de 3,01 mg/ml. El Análisis de la Variancia y posterior prueba de F (F = 25,01, p < 0,0001) confirman diferencias significativas en los contenidos de mucina entre grupos. El aumento de la concentración de mucina salival en pacientes periodontales podría representar un marcador químico de utilidad como coadyuvante en el diagnóstico clínico de esta enfermedad.

Resumo O objetivo deste trabalho foi estudar a relação entre a concentração de mucina salivar e a doença periodontal. A amostra foi dividida em três grupos de 20 indivíduos cada: Grupo 1 sem doença periodontal; Grupo 2 com gengivite; e Grupo 3 com periodontite. Em todas as amostras salivares foi confirmada a presença de mucina, o Grupo 1 apresentou valor médio de 1,27 mg / ml. No Grupo 2, foi registrada uma média de 1,93 mg / ml. No Grupo 3 foi observada uma média de 3,01 mg / ml. A Análise de Variância e o teste F subsequente (F = 25,01, p <0,0001) confirmam diferenças significativas nos conteúdos de mucina entre os grupos. O aumento da concentração de mucina salivar em pacientes periodontais pode representar um marcador químico útil como adjuvante no diagnóstico clínico desta doença.

Abstract This work aimed to study the relationship between salivary mucin concentration and periodontal disease. The sample was divided into three groups of 20 individuals each: Group 1 with no periodontal disease, Group 2 with gingivitis, and Group 3 with periodontitis. Mucin was detected in all the saliva samples. Group 1 had an average value of 1.27 mg/ml. Group 2 had an average value of 1.93 mg/ml. Group 3 had an average value of 3.01 mg/ml. The analysis of variance and subsequent F test (F = 25.01, p < 0.0001) confirmed significant differences in mucin content between the groups. Increased salivary mucin concentration in periodontal patients could be a useful chemical marker for the clinical diagnosis of periodontal disease.

Biomarcadores para la evaluación y diagnóstico del síndrome de ojo seco: una revisión / Biomarkers for the evaluation and diagnosis of the dry eye syndrome: a review

Resumen Introducción: El síndrome de ojo seco es una enfermedad en la que se generan signos y síntomas que conducen a alteraciones oculares prolongadas, por lo tanto, es relevante establecer con precisión la etiología de la enfermedad con la finalidad de establecer el tratamiento más efectivo, de allí, la importancia del desarrollo de exámenes innovadores como son los biomarcadores, los cuales permiten identificar con mayor precisión el cuadro clínico. Por esta razón, el presente trabajo pretende describir los principales avances de los biomarcadores de la superficie ocular y reconocer su aplicación clínica para el diagnóstico de ojo seco entre los años 2013 a 2018. Metodología: Se analizó literatura sobre biomarcadores empleados para el diagnóstico del ojo seco, mediante una revisión sistemática tipo narrativa de 2013 a 2018 por medio de los descriptores controlados "Dry Eye Syndrome" "biomarkers" "tear proteins" "eye proteins" seleccionados en DeCS y Pubmed; la búsqueda arrojó 48 estudios, de los cuales seleccionamos 21 para el análisis. Resultados: Son diversas las proteínas lagrimales que pueden ser relacionadas con la presencia y ausencia de la enfermedad, es vital que los biomarcadores sean valorados como una herramienta alternativa para diagnosticar con facilidad y precisión la enfermedad del ojo seco. Discusión: Los biomarcadores permiten reconocer los procesos patógenos y biológicos del síndrome de ojo seco, al reflejar el estado de la superficie ocular en presencia o ausencia de signos y síntomas, facilitando el diagnóstico precoz, seguimiento, tratamiento y control de la enfermedad.

Abstract Introduction: Dry eye syndrome is a disease in which signs and symptoms that lead to prolonged ocular alterations occur, therefore, it is relevant to accurately establish the etiology of the disease with the configuration of establishing the most effective treatment, hence the development of innovative exams such as biomarkers selected with greater precision the clinical picture. For this reason, the present work aims to describe the main advances of biomarkers of the ocular surface and to recognize their clinical application for the diagnosis of dry eye between 2013 and 2018. Metodology: Literature on biomarkers used for the diagnosis of dry eye was analyzed, by means of a systematic narrative review from 2013 to 2018 by means of the controlled descriptors "Dry Eye Syndrome" "biomarkers" "tear proteins" "eye proteins" selected in DeCS and Pubmed; The search yielded 48 studies and 21 studies were selected for the analysis. Results: There are several tear proteins that can be related to the presence and absence of the disease, it is vital that biomarkers are evaluated as an alternative tool to easily and accurately diagnose dry eye disease. Discussion: Biomarkers allow to recognize the pathogenic and biological processes of dry eye syndrome, reflecting the state of the ocular surface in the presence or absence of signs and symptoms, facilitating early diagnosis, monitoring, treatment and control of the disease.

A prospective study of discrepancy between clinical and pathological diagnosis of appendiceal mucinous neoplasm

PURPOSE: Appendiceal tumoral lesions can occur as benign, malignant, or borderline disease. Determination of the extent of surgery through accurate diagnosis is important in these tumoral lesions. In this study, we assessed the accuracy of preoperative CT and identified the factors affecting diagnosis.METHODS: Patients diagnosed or strongly suspected from July 2016 to June 2019 with appendiceal mucocele or mucinous neoplasm using abdominal CT were included in the study. All the patients underwent single-incision laparoscopic cecectomy with the margin of cecum secured at least 2 cm from the appendiceal base. To compare blood test results and CT findings, the patients were divided into a mucinous and a nonmucinous group according to pathology.RESULTS: The total number of patients included in this study was 54 and biopsy confirmed appendiceal mucinous neoplasms in 39 of them. With CT, the accuracy of diagnosis was 89.7%. The mean age of the mucinous group was greater than that of the nonmucinous group (P = 0.035). CT showed that the maximum diameter of appendiceal tumor in the mucinous group was greater than that in the nonmucinous group (P < 0.001). Calcification was found only in the appendix of patients in the mucinous group (P = 0.012). Multivariate analysis revealed that lager tumor diameter was a factor of diagnosis for appendiceal mucinous neoplasm.CONCLUSION: The accuracy of preoperative diagnosis of appendiceal mucinous neoplasms in this study was 89.7%. Blood test results did not provide differential diagnosis, and the larger the diameter of appendiceal tumor on CT, the more accurate the diagnosis.

JL1 Antigen Expression on Bone Marrow Lymphoma Cells from Patients With Non-Hodgkin Lymphoma

BACKGROUND: JL1, a CD43 epitope and mucin family cell surface glycoprotein, is expressed on leukemic cells. An anti-JL1 antibody combined with a toxic substance can have targeted therapeutic effects against JL1-positive leukemia; however, JL1 expression on bone marrow (BM) lymphoma cells has not been assessed using flow cytometry. We investigated JL1 expression on BM lymphoma cells from patients with non-Hodgkin lymphoma (NHL) to assess the potential of JL1 as a therapeutic target. METHODS: Patients with BM involvement of mature B-cell (N=44) or T- and natural killer (NK)-cell (N=4) lymphomas were enrolled from May 2015 to September 2016. JL1 expression on BM lymphoma cells was investigated using flow cytometry. Clinical, pathological, and cytogenetic characteristics, and treatment responses were compared according to JL1 expression status. RESULTS: Of the patients with NHL and BM involvement, 37.5% (18/48) were JL1-positive. Among mature B-cell lymphomas, 100%, 38.9%, 33.3%, 100%, and 25.0% of Burkitt lymphomas, diffuse large B-cell leukemias, mantle cell leukemias, Waldenstrom macroglobulinemia, and other B-cell lymphomas, respectively, were JL1-positive. Three mature T- and NK-cell NHLs were JL1-positive. JL1 expression was associated with age (P=0.045), complete response (P=0.004), and BM involvement at follow-up (P=0.017), but not with sex, performance status, the B symptoms, packed marrow pattern, cytogenetic abnormalities, or survival. CONCLUSIONS: JL1 positivity was associated with superior complete response and less BM involvement in NHL following chemotherapy.

Lichen myxedematosus: a rare group of cutaneous mucinosis

Abstract: Cutaneous mucinoses are a heterogeneous group of dermatoses in which excess deposition of mucin in the dermis gives the skin a waxy appearance, with papules and plaques that can vary from self-healing mucinosis to even disrupting the normal shape of a patient's face, conferring a leonine facies, or be part of life threatening diseases like scleromyxedema. This review will describe the most recent classification on lichen myxedematosus in the generalized (scleromyxedema) and the localized forms, as well as the different organ systems involved in scleromyxedema, diagnostic workup, current management, and prognosis.

Clinical, dermoscopic, and histologic aspects of two cases of cutaneous focal mucinosis

Abstract: Cutaneous mucinoses are a complex and diverse group of connective tissue disorders characterized by the accumulation of mucin and/or glycosaminoglycan in the skin and adnexa. Cutaneous focal mucinosis appears as a solitary, asymptomatic, skin-colored to white papule, nodule, or plaque located anywhere on the body or in the oral cavity. It presents mainly in adults and is characterized on histopathology by mucin throughout the upper and mid dermis. We describe the dermoscopy of two cases of cutaneous focal mucinosis. Both lesions presented a nonspecific homogenous whitish pattern; the first case also exhibited a sharply demarcated yellow border.

Coexisting Mucinous Cystic Neoplasm of the Pancreas and Type 1 Autoimmune Pancreatitis

Type 1 autoimmune pancreatitis (AIP1) is an IgG4-related systemic disease that mimics tumors. We report a rare case of AIP1 accompanied by mucinous cystic neoplasm (MCN). A pancreatic lesion was incidentally detected in a woman in her 60s. After 6 years of follow-up, the lesion abruptly increased in size. Computed tomography showed a 3.5 cm unilocular cyst in the tail of the pancreas and distal pancreatectomy was performed. On microscopic examination, the cyst was lined by mucinous and non-mucinous epithelial cells with mild cytologic atypia. The surrounding stroma comprised ovarian-type spindle cells with progesterone receptor positivity. The pericystic pancreas exhibited multifocal lymphoid follicles, lymphoplasmacytic infiltrations, obliterative phlebitis, and storiform fibrosis. IgG4-positive plasma cell infiltration (215 cells high-power field) and the IgG4/IgG ratio (57%) were increased. Cases of MCN coexisting with AIP1 are extremely rare; only two such cases have been reported in the English-language literature. This third case featured low-grade MCN with AIP1.

Accuracy of frozen section diagnosis and factors associated with final pathological diagnosis upgrade of mucinous ovarian tumors / 부인종양

OBJECTIVE: To determine the accuracy of frozen section diagnosis and factors associated with final pathological diagnosis upgrade in patients with mucinous ovarian tumors. METHODS: This study included 1,032 patients with mucinous ovarian tumors who underwent frozen section diagnosis during surgery. Sensitivity, specificity, and diagnostic accuracy of frozen section diagnosis was calculated. Univariate and multivariate regression analyses were performed to determine factors associated with diagnosis upgrade in the final pathology report. RESULTS: The sensitivity and specificity of frozen section diagnosis were 99.1% (95% confidence interval [CI]=98%–99.6%) and 82.2% (95% CI=77.9%–85.7%), respectively, for benign mucinous tumors; 74.6% (95% CI=69.1%–79.4%) and 96.7% (95% CI=95.2%–97.8%), respectively, for mucinous borderline ovarian tumors; and 72.5% (95% CI=62.9%–80.3%) and 98.8% (95% CI=97.9%–99.3%), respectively, for invasive mucinous carcinomas. The multivariate analysis revealed that mixed tumor histology (odds ratio [OR]=2.8; 95% CI=1.3–6.3; p=0.012), tumor size >12 cm (OR=2.5; 95% CI=1.5–4.3; p=0.001), multilocular tumor (OR=2.9; 95% CI=1.4–6.0; p=0.006), and presence of a solid component in the tumor (OR=3.1; 95% CI=1.8–5.1; p12 cm, multilocular tumor, and presence of a solid component in the tumor were independent risk factors for final pathological diagnosis upgrade based on frozen section diagnosis.

Human Epidermal Growth Factor Receptor 2-positive Mucinous Carcinoma with Signet Ring Cell Differentiation, Which Showed Complete Response after Neoadjuvant Chemotherapy / 한국유방암학회지

Mucinous carcinoma (MC) is a rare subtype of breast cancer, which is composed of tumor cells floating in the abundant extracellular mucin. This form of cancer is usually estrogen receptor/progesterone receptor positive and human epidermal growth factor receptor 2 (HER2) negative. Here, we present a case of HER2-positive MC with an unusual signet ring cell differentiation. It is very rare that a breast tumor consists entirely of signet ring cells. The tumor showed pathologic complete response (pCR) after neoadjuvant chemotherapy with trastuzumab and pertuzumab. pCR of HER2-positive MC has rarely been described in literature. It is important to consider the biological heterogeneity of MCs for effective management.

Characterization of Intraductal Papillary Neoplasm of the Bile Duct with Respect to the Histopathologic Similarities to Pancreatic Intraductal Papillary Mucinous Neoplasm

Intraductal papillary neoplasms of the bile duct (IPNBs) are known to show various pathologic features and biological behaviors. Recently, two categories of IPNBs have been proposed based on their histologic similarities to pancreatic intraductal papillary mucinous neoplasms (IPMNs): type 1 IPNBs, which share many features with IPMNs; and type 2 IPNBs, which are variably different from IPMNs. The four IPNB subtypes were re-evaluated with respect to these two categories. Intestinal IPNBs showing a predominantly villous growth may correspond to type 1, while those showing papillay-tubular or papillay-villous growth correspond to type 2. Regarding gastric IPNB, those with regular foveolar structures with varying numbers of pyloric glands may correspond to type 1, while those with papillary-foveolar structures with gastric immunophenotypes and complicated structures may correspond to type 2. Pancreatobiliary IPNBs that show fine ramifying branching may be categorized as type 1, while others containing many complicated structures may be categorized as type 2. Oncocytic type, which displays solid growth or irregular papillary structures, may correspond to type 2, while papillary configurations with pseudostratified oncocytic lining cells correspond to type 1. Generally, type 1 IPNBs of any subtype develop in the intrahepatic bile ducts, while type 2 IPNBs develop in the extrahepatic bile duct. These findings suggest that IPNBs arising in the intrahepatic ducts are biliary counterparts of IPMNs, while those arising in the extrahepatic ducts display differences from prototypical IPMNs. The recognition of these two categories of IPNBs with reference to IPMNs and their anatomical location along the biliary tree may deepen our understanding of IPNBs.

Endoplasmic Reticulum Stress Induces MUC5AC and MUC5B Expression in Human Nasal Airway Epithelial Cells

OBJECTIVES: Endoplasmic reticulum (ER) stress is known to be associated with inflammatory airway diseases, and three major transmembrane receptors: double-stranded RNA-activated protein kinase-like ER kinase, inositol requiring enzyme 1, and activating transcription factor 6 (ATF6) play important roles in ER stress-related proinflammatory signaling. However, the effects of ER stress and these three major signaling pathways on the regulation of the production of airway mucins in human nasal airway epithelial cells have not been elucidated. METHODS: In primary human nasal epithelial cells, the effect of tunicamycin (an ER stress inducer) and 4-phenylbutyric acid (4-PBA, ER stress inhibitor) on the expression of MUC5AC and MUC5B was investigated by reverse transcriptasepolymerase chain reaction, real-time polymerase chain reaction, enzyme immunoassay, and immunoblot analysis. Small interfering RNA (siRNA) transfection was used to identify the mechanisms involved. RESULTS: Tunicamycin increased the expressions of MUC5AC and MUC5B and the mRNA expressions of ER stress-related signaling molecules, including spliced X-box binding protein 1 (XBP-1), transcription factor CCAAT-enhancer-binding protein homologous protein (CHOP), and ATF6. In addition, 4-PBA attenuated the tunicamycin-induced expressions of MUC5AC and MUC5B and the mRNA expressions of ER stress-related signaling molecules. Furthermore, siRNA knockdowns of XBP-1, CHOP, and ATF6 blocked the tunicamycin-induced mRNA expressions and glycoprotein productions of MUC5AC and MUC5B. CONCLUSION.: These results demonstrate that ER stress plays an important role in the regulation of MUC5AC and MUC5B via the activations of XBP-1, CHOP, and ATF6 in human nasal airway epithelial cells.

Impact of Mucin Proportion in the Pretreatment MRI on the Outcomes of Rectal Cancer Patients Undergoing Neoadjuvant Chemoradiotherapy / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The purpose of this study was to evaluate treatment response to neoadjuvant chemoradiotherapy (CRT) with regard to mucin status in pathology and pretreatment magnetic resonance imaging (MRI) in locally advanced rectal cancer. MATERIALS AND METHODS: Between 2003 and 2011, 306 patients with locally advanced rectal cancer received neoadjuvant CRT followed by surgery, and mucinous adenocarcinoma (MAC) was found in 27 (8.8%). All MAC patients had MRI before and after CRT and mucin proportion at MRI was measured. Therapeutic response was assessed by pathology after total mesorectal excision. To determine the optimal cut-off for mucin proportion in predicting good CRT response (near total or total regression) and negative circumferential resection margin (CRM), the receiver-operating characteristic analysis was performed. RESULTS: After neoadjuvant CRT, overall downstaging occurred in 44.4% of MAC and 72.4% of non-MAC (p=0.001), and positive CRM (≤1 mm) was observed more frequently in MAC (p<0.001). The optimal threshold for treatment response was 30% for mucin proportion, and there are nine with low mucin proportion (<30%) and 18 with high mucin proportion (≥30%) in pretreatment MRI. Negative CRM and tumor downstaging occurred more common in patients with mucin <30%, although statistically insignificant (p=0.071 and p=0.072, respectively). Regarding oncologic outcomes, lower mucin proportion in pretreatment MRI was associated with better disease-free and overall survival in MAC group (p=0.092 and 0.056, respectively), but the difference did not reach statistical significance. CONCLUSION: Poor treatment outcome with neoadjuvant CRT was observed in patients with MAC, especially those with high mucin proportion at pretreatment MRI.

A rare case of gastric-type mucinous adenocarcinoma in a woman with Peutz-Jeghers syndrome

Adenocarcinoma of the cervix is less common than squamous cell carcinoma. Minimal deviation adenocarcinoma (adenoma malignum) is considered an extremely well-differentiated variant of GAS. An association exists between GAS and Peutz-Jeghers syndrome, which is a rare autosomal dominant disorder characterized by mucocutaneous pigmentation and multiple hamartomatous polyps in the gastrointestinal tracts. The incidence of GAS in patients with Peutz-Jeghers syndrome is estimated to be 11–17%. We present a rare case of adenoma malignum, diagnosed using colposcopic biopsy in a woman with Peutz-Jeghers syndrome, which was histopathologically confirmed to be GAS after surgery.