Perspectives for Combining Viral Oncolysis With Additional Immunotherapies for the Treatment of Melanoma.

Melanoma is the deadliest type of skin cancer with steadily increasing incidence worldwide during the last few decades. In addition to its tumor associated antigens (TAAs), melanoma has a high mutation rate compared to other tumors, which promotes the appearance of tumor specific antigens (TSAs) as well as increased lymphocytic infiltration, inviting the use of therapeutic tools that evoke new or restore pre-existing immune responses. Innovative therapeutic proposals, such as immune checkpoint inhibitors (ICIs), have emerged as effective options for melanoma. However, a significant portion of these patients relapse and become refractory to treatment. Likewise, strategies using viral vectors, replicative or not, have garnered confidence and approval by different regulatory agencies around the world. It is possible that further success of immune therapies against melanoma will come from synergistic combinations of different approaches. In this review we outline molecular features inherent to melanoma and how this supports the use of viral oncolysis and immunotherapies when used as monotherapies or in combination.

Environmental control of mammary carcinoma cell expansion by acidification and spheroid formation in vitro.

Breast cancer is the leading cause of cancer death among women worldwide. Like other cancers, mammary carcinoma progression involves acidification of the tumor microenvironment, which is an important factor for cancer detection and treatment strategies. However, the effects of acidity on mammary carcinoma cell morphology and phenotype have not been thoroughly characterized. Here, we evaluated fundamental effects of environmental acidification on mammary carcinoma cells in standard two-dimensional cultures and three-dimensional spheroids. Acidification decreased overall mammary carcinoma cell viability, while increasing their resistance to the anthracycline doxorubicin. Environmental acidification also increased extracellular vesicle production by mammary carcinoma cells. Conditioned media containing these vesicles appeared to increase fibroblast motility. Acidification also increased mammary carcinoma cell motility when cultured with fibroblasts in spheroids. Taken together, results from this study suggest that environmental acidification induces drug resistance and extracellular vesicle production by mammary carcinoma cells that promote tumor expansion.

Combined p14ARF and Interferon-ß Gene Transfer to the Human Melanoma Cell Line SK-MEL-147 Promotes Oncolysis and Immune Activation.

Immune evasion is an important cancer hallmark and the understanding of its mechanisms has generated successful therapeutic approaches. Induction of immunogenic cell death (ICD) is expected to attract immune cell populations that promote innate and adaptive immune responses. Here, we present a critical advance for our adenovirus-mediated gene therapy approach, where the combined p14ARF and human interferon-ß (IFNß) gene transfer to human melanoma cells led to oncolysis, ICD and subsequent activation of immune cells. Our results indicate that IFNß alone or in combination with p14ARF was able to induce massive cell death in the human melanoma cell line SK-MEL-147, though caspase 3/7 activation was not essential. In situ gene therapy of s.c. SK-MEL-147 tumors in Nod-Scid mice revealed inhibition of tumor growth and increased survival in response to IFNß alone or in combination with p14ARF. Emission of critical markers of ICD (exposition of calreticulin, secretion of ATP and IFNß) was stronger when cells were treated with combined p14ARF and IFNß gene transfer. Co-culture of previously transduced SK-MEL-147 cells with monocyte-derived dendritic cells (Mo-DCs) derived from healthy donors resulted in increased levels of activation markers HLA-DR, CD80, and CD86. Activated Mo-DCs were able to prime autologous and allogeneic T cells, resulting in increased secretion of IFNγ, TNF-α, and IL-10. Preliminary data showed that T cells primed by Mo-DCs activated with p14ARF+IFNß-transduced SK-MEL-147 cells were able to induce the loss of viability of fresh non-transduced SK-MEL-147 cells, suggesting the induction of a specific cytotoxic population that recognized and killed SK-MEL-147 cells. Collectively, our results indicate that p14ARF and IFNß delivered by our adenoviral system induced oncolysis in human melanoma cells accompanied by adaptive immune response activation and regulation.

No association between periodontitis and preterm low birth weight: a case-control study.

PURPOSE: This study aimed to investigate the association between periodontitis in pregnant women and adverse pregnancy outcomes by heeding confounding risk factors for preterm low birth weight infants. METHODS: This study was reported according to The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement. A case-control study was conducted. Medical records of all pregnant women attending a prenatal care clinic were screened. Those between 21 and 34 years and gestational age of 28-32 weeks were initially enrolled in the study. The exclusion criteria were then applied: diabetes mellitus, genitourinary tract infections, or HIV infection; previous multiple gestations; previous preterm birth/low birth weight infants; in vitro fertilization procedures; placental, cervical/uterine abnormalities; history of infertility; history of drug abuse; and any medical conditions that required antibiotics prophylaxis. Patients' anthropometric, demographic, and behavioral characteristics were collected. The periodontal clinical parameters were obtained from six sites per tooth: clinical attachment level, probing pocket depth, dental plaque index, and gingival bleeding index. Women were then allocated into two groups: mothers of preterm and/or low birth weight newborns (cases) and mothers of full-term and normal birth weight newborns (controls). RESULTS: Periodontal clinical parameters were analyzed and reported separately for each group, and no significant differences were observed (p > 0.05). Logistic regression analysis revealed that periodontal clinical parameters were not associated with the adverse pregnancy outcomes. CONCLUSION(S): After controlling for confounding factors, our results suggest that maternal periodontal disease is not a risk factor associated with preterm low birth weight infants.

Chemokine (C-C motif) ligand 25 expressed by trophoblast cells and leukocytes bearing its receptor Ccr9: An alliance during embryo implantation?

PROBLEM: We hypothesized that trophoblast expression of Ccl25 attracts a specific leukocyte cell population to the implantation site for local regulation. METHOD OF STUDY: Mice blastocysts, ectoplacental cones, and decidua at gestational days 3.5-7.5 were evaluated for Ccl25 and Ccr9 expressions. Peripheral availability and characterization of Ccr9+ leukocytes were determined by flow cytometry. Leukocyte chemotaxis was assessed in the presence of Ccl25 recombinant protein and embryos using antisense oligomers (ODNs) to Ccl25 and Ccr9 neutralizing antibody. RESULTS: Ccl25 was expressed by embryonic cells, whereas Ccr9 expression was strong at the maternal compartment and in PBMC. Immunolocalization confirmed this expression. In vitro, chemotaxis assays showed that the embryonic Ccl25 signals to Ccr9+ PBMCs. Maternal Ccr9+α4ß7+ monocytes switch from an anti-inflammatory phenotype (F4/80+11b+Ly6C-TGF-ß+ cells, pre-implantation) to an inflammatory profile (F4/80+11b+Ly6C+TNF-α+ cells, post-implantation). CONCLUSION: Our data support the establishment of a CCL25/CCR9-axis at the maternal-fetal interface in mice, which may be involved in immune regulatory mechanisms during embryo implantation.

Anisakidose en el hombre: zoonosis con riesgo potencial para los consumidores del pescado crudo / Human anisakidose: zoonosis with potential hazard to consumers of raw fish / Anisakidose humana: zoonose com risco potencial para consumidores de pescado cru

En los últimos años en Brasil y en todo el mundo, se observo un aumento en el consumo de pescado de agua dulce y marina. Los alimentos de origen animal tienen un gran potencial como diseminador de enfermedades y con el pescado no es diferente. Los helmintos que parasitan el pescado y intoxican el hombre son trematodos y nematodos, y las larvas de los nematodos de la família Anisakidae producen patologia en el hombre con más frecuencia. La anisakiosis es una parasitosis que se produce en el hombre debido al consumo de pescado crudo o insuficientemente cocinado parasitado con larvas de Anisakis sp. y reacciones alérgicas pueden manifestarse. Las larvas Anisakis se inactivan ao someter los pescados a tratamientos térmicos que se alcancen temperaturas superiores a 60C en un tiempo de 10 minutos. El hombre se intoxica con la ingesta de peces e cefalópodes en estado crudo o no bien cocidos. Para consumir pescado crudo o practicamente en crudo deberán congelarse a una temperatura igual o inferior a -20C durante un período de al menos 24 horas

Over the last years in Brazil and in the world, has been an increase of the consumption of fish from freshwater and marine. Animal foods have great potential to causing foodborne and the fish is no different. Trematodes and nematodes are common parasites in freshwater and marine fish. The nematodes of the Aniskidaes famally occur more frequently. Aniskiasis is a human disease caused by ingestion of larval nematodes belonging to the family Anisakidae. It is a parasitic disease with a worldwide distribution that presents some difficulties for the diagnosis in humans. The control of this disease can be done with a correct cooking of the fish and seafood at high temperatures over 60C for 10 minutes and before eating raw fish or seafood, submit it at freezing temperature of -20C for 24 hours for inactivation of the larvae

Ao longo dos últimos anos no Brasil e no mundo, vem se observando um aumento no consumo de pescado de água doce e marinha. Alimentos de origem animal apresentam um grande potencial como veiculador de doenças, as chamadas DTAs (doenças veiculadas por alimentos) e com o pescado não é diferente. Dentre os agentes que podem parasitar o pescado e infectar humanos, têm-se os tremátodos e nemátodos, sendo que as larvas de nematódos infectantes da família Anisakidose ocorrem com maior frequência. A anisakíose ou anisakidose humana é uma parasitose gastrointestinal causada pela ingestão acidental de larvas infectantes de nemátodos da família Anisakidae presente no pescado e que em alguns casos, pode se manifestar com reações de hipersensibilidade. É uma parasitose de distribuição mundial que apresenta algumas dificuldades para o diagnóstico da doença em humanos. Seu controle pode ser feito com o adequado preparo e cocção do pescado, em temperaturas superiores a 60C por no mínimo 10 minutos. Para evitar a infecção humana por larvas da família Anisakidae quando do consumo de pescado cru, além de se preconizar o consumo de um produto de qualidade sanitária satisfatória, é importante que o mesmo tenha sido submetido à temperatura de congelamento de -20ºC por um período de pelo menos 24 horas para inativação das larvas

Anisakidose en el hombre: zoonosis con riesgo potencial para los consumidores del pescado crudo / Human anisakidose: zoonosis with potential hazard to consumers of raw fish / Anisakidose humana: zoonose com risco potencial para consumidores de pescado cru

En los últimos años en Brasil y en todo el mundo, se observo un aumento en el consumo de pescado de agua dulce y marina. Los alimentos de origen animal tienen un gran potencial como diseminador de enfermedades y con el pescado no es diferente. Los helmintos que parasitan el pescado y intoxican el hombre son trematodos y nematodos, y las larvas de los nematodos de la família Anisakidae producen patologia en el hombre con más frecuencia. La anisakiosis es una parasitosis que se produce en el hombre debido al consumo de pescado crudo o insuficientemente cocinado parasitado con larvas de Anisakis sp. y reacciones alérgicas pueden manifestarse. Las larvas Anisakis se inactivan ao someter los pescados a tratamientos térmicos que se alcancen temperaturas superiores a 60C en un tiempo de 10 minutos. El hombre se intoxica con la ingesta de peces e cefalópodes en estado crudo o no bien cocidos. Para consumir pescado crudo o practicamente en crudo deberán congelarse a una temperatura igual o inferior a -20C durante un período de al menos 24 horas(AU)

Over the last years in Brazil and in the world, has been an increase of the consumption of fish from freshwater and marine. Animal foods have great potential to causing foodborne and the fish is no different. Trematodes and nematodes are common parasites in freshwater and marine fish. The nematodes of the Aniskidaes famally occur more frequently. Aniskiasis is a human disease caused by ingestion of larval nematodes belonging to the family Anisakidae. It is a parasitic disease with a worldwide distribution that presents some difficulties for the diagnosis in humans. The control of this disease can be done with a correct cooking of the fish and seafood at high temperatures over 60C for 10 minutes and before eating raw fish or seafood, submit it at freezing temperature of -20C for 24 hours for inactivation of the larvae(AU)

Ao longo dos últimos anos no Brasil e no mundo, vem se observando um aumento no consumo de pescado de água doce e marinha. Alimentos de origem animal apresentam um grande potencial como veiculador de doenças, as chamadas DTAs (doenças veiculadas por alimentos) e com o pescado não é diferente. Dentre os agentes que podem parasitar o pescado e infectar humanos, têm-se os tremátodos e nemátodos, sendo que as larvas de nematódos infectantes da família Anisakidose ocorrem com maior frequência. A anisakíose ou anisakidose humana é uma parasitose gastrointestinal causada pela ingestão acidental de larvas infectantes de nemátodos da família Anisakidae presente no pescado e que em alguns casos, pode se manifestar com reações de hipersensibilidade. É uma parasitose de distribuição mundial que apresenta algumas dificuldades para o diagnóstico da doença em humanos. Seu controle pode ser feito com o adequado preparo e cocção do pescado, em temperaturas superiores a 60C por no mínimo 10 minutos. Para evitar a infecção humana por larvas da família Anisakidae quando do consumo de pescado cru, além de se preconizar o consumo de um produto de qualidade sanitária satisfatória, é importante que o mesmo tenha sido submetido à temperatura de congelamento de -20ºC por um período de pelo menos 24 horas para inativação das larvas(AU)

Niemann-Pick disease type C: a case series of Brazilian patients.

UNLABELLED: The aim of the study was to analyze a series of Brazilian patients with Niemann-Pick disease type C (NP-C). METHOD: Correlations between clinical findings, laboratory data, molecular findings and treatment response are presented. RESULT: The sample consisted of 5 patients aged 8 to 26 years. Vertical supranuclear gaze palsy, cerebellar ataxia, dementia, dystonia and dysarthria were present in all cases. Filipin staining showed the "classical" pattern in two patients and a "variant" pattern in three patients. Molecular analysis found mutations in the NPC1 gene in all alleles. Miglustat treatment was administered to 4 patients. CONCLUSION: Although filipin staining should be used to confirm the diagnosis, bone marrow sea-blue histiocytes often help to diagnosis of NP-C. The p.P1007A mutation seems to be correlated with the "variant" pattern in filipin staining. Miglustat treatment response seems to be correlated with the age at disease onset and disability scale score at diagnosis.

Niemann-Pick disease type C: a case series of Brazilian patients / Doenca de Niemann-Pick tipo C: serie de casos de pacientes brasileiros

The aim of the study was to analyze a series of Brazilian patients with Niemann-Pick disease type C (NP-C). Method Correlations between clinical findings, laboratory data, molecular findings and treatment response are presented. Result The sample consisted of 5 patients aged 8 to 26 years. Vertical supranuclear gaze palsy, cerebellar ataxia, dementia, dystonia and dysarthria were present in all cases. Filipin staining showed the “classical” pattern in two patients and a “variant” pattern in three patients. Molecular analysis found mutations in the NPC1 gene in all alleles. Miglustat treatment was administered to 4 patients. Conclusion Although filipin staining should be used to confirm the diagnosis, bone marrow sea-blue histiocytes often help to diagnosis of NP-C. The p.P1007A mutation seems to be correlated with the “variant” pattern in filipin staining. Miglustat treatment response seems to be correlated with the age at disease onset and disability scale score at diagnosis. .

O objetivo desse estudo foi analisar uma série de casos de pacientes brasileiros com doença de Niemann-Pick tipo C (NP-C). Método Correlação entre manifestações clínicas, alterações laboratoriais, estudo molecular e resposta ao tratamento foram realizadas. Resultado A amostra consiste de 5 pacientes com idade entre 8 e 26 anos. Paralisia do olhar vertical supranuclear, ataxia cerebelar, demência, distonia e disartria estavam presentes em todos os casos. Coloração de filipina na cultura de fibroblastos mostrou padrão “clássico” em dois pacientes e padrão “variante” em três casos. O estudo molecular encontrou mutações no gene NPC1 em todos os alelos. O tratamento com miglustate foi realizado em 4 pacientes. Conclusão Embora coloração de filipina seja utilizada para confirmar o diagnóstico, o histiócito azul-marinho no aspirado de medula óssea frequentemente auxilia a confirmar o diagnóstico de NP-C. A mutação p.P1007A está correlacionada com o padrão “ variante” na coloração de filipina. A resposta ao tratamento com miglustate parece estar correlacionada com a idade e escore de desabilidade no momento do diagnóstico. .

Upregulation of innate antiviral restricting factor expression in the cord blood and decidual tissue of HIV-infected mothers.

Programs for the prevention of mother-to-child transmission of HIV have reduced the transmission rate of perinatal HIV infection and have thereby increased the number of HIV-exposed uninfected (HEU) infants. Natural immunity to HIV-1 infection in both mothers and newborns needs to be further explored. In this study, we compared the expression of antiviral restricting factors in HIV-infected pregnant mothers treated with antiretroviral therapy (ART) in pregnancy (n=23) and in cord blood (CB) (n=16), placental tissues (n=10-13) and colostrum (n=5-6) samples and compared them to expression in samples from uninfected (UN) pregnant mothers (n=21). Mononuclear cells (MNCs) were prepared from maternal and CB samples following deliveries by cesarean section. Maternal (decidua) and fetal (chorionic villus) placental tissues were obtained, and colostrum was collected 24 h after delivery. The mRNA and protein expression levels of antiviral factors were then evaluated. We observed a significant increase in the mRNA expression levels of antiviral factors in MNCs from HIV-infected mothers and CB, including the apolipoprotein B mRNA-editing enzyme 3G (A3G), A3F, tripartite motif family-5α (TRIM-5α), TRIM-22, myxovirus resistance protein A (MxA), stimulator of interferon (IFN) genes (STING) and IFN-ß, compared with the levels detected in uninfected (UN) mother-CB pairs. Moreover, A3G transcript and protein levels and α-defensin transcript levels were decreased in the decidua of HIV-infected mothers. Decreased TRIM-5α protein levels in the villi and increased STING mRNA expression in both placental tissues were also observed in HIV-infected mothers compared with uninfected (UN) mothers. Additionally, colostrum cells from infected mothers showed increased tetherin and IFN-ß mRNA levels and CXCL9 protein levels. The data presented here indicate that antiviral restricting factor expression can be induced in utero in HIV-infected mothers. Future studies are warranted to determine whether this upregulation of antiviral factors during the perinatal period has a protective effect against HIV-1 infection.

TLR7/TLR8 Activation Restores Defective Cytokine Secretion by Myeloid Dendritic Cells but Not by Plasmacytoid Dendritic Cells in HIV-Infected Pregnant Women and Newborns.

Mother-to-child transmission (MTCT) of HIV-1 has been significantly reduced with the use of antiretroviral therapies, resulting in an increased number of HIV-exposed uninfected infants. The consequences of HIV infection on the innate immune system of both mother-newborn are not well understood. In this study, we analyzed peripheral blood and umbilical cord blood (CB) collected from HIV-1-infected and uninfected pregnant women. We measured TNF-α, IL-10 and IFN-α secretion after the stimulation of the cells with agonists of both extracellular Toll-like receptors (TLRs) (TLR2, TLR4 and TLR5) and intracellular TLRs (TLR7, TLR7/8 and TLR9). Moreover, as an indicator of the innate immune response, we evaluated the responsiveness of myeloid dendritic cells (mDCs) and plasmacytoid DCs (pDCs) to TLRs that are associated with the antiviral response. Our results showed that peripheral blood mononuclear cells (PBMCs) from HIV-1-infected mothers and CB were defective in TNF-α production after activation by TLR2, TLR5, TLR3 and TLR7. However, the TNF-α response was preserved after TLR7/8 (CL097) stimulation, mainly in the neonatal cells. Furthermore, only CL097 activation was able to induce IL-10 and IFN-α secretion in both maternal and CB cells in the infected group. An increase in IFN-α secretion was observed in CL097-treated CB from HIV-infected mothers compared with control mothers. The effectiveness of CL097 stimulation was confirmed by observation of similar mRNA levels of interferon regulatory factor-7 (IRF-7), IFN-α and TNF-α in PBMCs of both groups. The function of both mDCs and pDCs was markedly compromised in the HIV-infected group, and although TLR7/TLR8 activation overcame the impairment in TNF-α secretion by mDCs, such stimulation was unable to reverse the dysfunctional type I IFN response by pDCs in the HIV-infected samples. Our findings highlight the dysfunction of innate immunity in HIV-infected mother-newborn pairs. The activation of the TLR7/8 pathway could function as an adjuvant to improve maternal-neonatal innate immunity.

Profile of autoantibodies against phosphorylcholine and cross-reactivity to oxidation-specific neoantigens in selective IgA deficiency with or without autoimmune diseases.

Immunoglobulin A deficiency (IgAD) is considered the most common form of primary immunodeficiency. The majority of IgA-deficient individuals are considered asymptomatic, even though IgAD has been associated with an increased frequency of recurrent infections, allergy, and autoimmune diseases. In this study we evaluate the Natural autoantibodies (NatAbs) reactivity to phosphorylcholine (PC) and to some pro-inflammatory molecules in IgAD with or without autoimmune disorders. We observed that in the absence of IgA there is an enhancement of IgG subclasses functioning as NatAbs against PC. Immunoglobulin G (IgG) against lipopolysaccharide, C-reactive protein, and IgA was found in IgAD, regardless of the autoimmune manifestations. Nonetheless, IgAD patients with autoimmune disease showed significantly higher IgG reactivity against pro-inflammatory molecules, such as cardiolipin, oxidized low-density lipoproteins, and phosphatidylserine, with positive correlation between them. In conclusion, the IgG NatAbs against PC may represent a compensatory defense mechanism against infections and control excess of inflammation, explaining the asymptomatic status in the IgA deficiency.

Pineal melatonin and the innate immune response: the TNF-alpha increase after cesarean section suppresses nocturnal melatonin production.

The nocturnal surge of melatonin is the endocrine expression of the circadian system and is essential for organizing the timing of various endogenous processes. Previous works suggest that, in the beginning of a defense response, the increase in circulating tumor necrosis factor-alpha (TNF-alpha) leads to a transient block of nocturnal melatonin production and promotes a disruption of internal time organization. In the present paper, the concentration of melatonin and cytokines [TNF-alpha, interferon-gamma (IFN-gamma), interleukin (IL)-2, IL-4, IL-5, IL-10, IL-12] in the colostrum (postdelivery day 3) and in the milk (postdelivery days 10, 15, 20 and 30) obtained at midday and midnight from mothers who gave birth by vaginal or cesarean section were compared. The nocturnal melatonin surge observed 3 days after vaginal delivery was absent after cesarean section. IL-12 presented no daily variation in either case, while daily variations in IFN-gamma, IL-10, IL-4 and IL-5 were observed after vaginal delivery and cesarean section. On the other hand, the increase in TNF-alpha after cesarean section resulted in suppression of the nocturnal melatonin surge. Daily variation of IL-2 was only observed after recovery of the nocturnal melatonin surge, 30 days after cesarean section. The present paper supports the hypothesis of a cross-talk between the pineal gland and the immune system, which could represent a putative immune-pineal axis.

Injury switches melatonin production source from endocrine (pineal) to paracrine (phagocytes) - melatonin in human colostrum and colostrum phagocytes.

A large number of data show that melatonin has immunomodulatory properties and is produced by immunocompetent cells; also, some evidence suggests a 'feedback' of the activated immune system on the pineal gland. In this paper, we studied immune-pineal interactions in colostrum obtained from healthy puerperae and mothers with mastitis taking into account that, (a) melatonin levels in milk reflects pineal activity and (b) colostrum quiescent mononuclear and polymorphonuclear phagocytes from healthy mothers in culture are adequate for evaluating the ability of immunocompetent cells to produce melatonin. Here we compared the diurnal and nocturnal melatonin levels in colostrum from healthy puerperae and mothers with mastitis; this is a unique noninvasive model for determining pineal activity in the proinflammatory phase of a defense response. In addition, we determined the 'in vitro' production of melatonin by colostrum immunocompetent cells stimulated by enteropathogenic Escherichia coli or zymosan. Suppression of nocturnal melatonin rise in mothers with mastitis was highly correlated with increased tumor necrosis factor-alpha (TNF-alpha) secretion. This result, interpreted taking into account the presence of the transcription factor nuclear factor kappa B in pineal gland, suggest that the proinflammatory cytokine can inhibit nocturnal pineal melatonin production. On the other hand, stimulated, but not quiescent, immunocompetent cells secreted in the colostrum produced melatonin in vitro. In addition, this production ceases after bacteria killing. These results suggest that during the response to an injury the production of melatonin can be transiently shifted from an endocrine (pineal) to a paracrine (immunocompetent cells) source.

Tumor gástrico de células estromais hemorrágico apresentando-se como hematoma encistado no pequeno saco omental / Hemorrhage stromall cell tumorpresenting as lesser sac haematoma

Relatamos um caso de tumor gástrico de células estromais em paciente jovem, cuja apresentaçäo clínica foi de massa abdominal causada por hematoma encistado de pequena cavidade omental, com 4000cmü. A peça ressecada pesava cerca de 400g e era formada pelo epíplon, corpo e antro gástricos. Ao exame macroscópico, o tumor consistia em uma massa sólida no estômago e sólida e microcísticano epíplon, enquanto, microscopicamente, era formada por neoplasia mesenquimal com padräo fusocelular, algo epitelóide, com raras mitoses atípicas. O perfil imunohistoquímico foi positivo apenas para o marcador CD34, o que reforça o diagnóstico de tumor estromal. Os tumores estromais gastrointestinais säo um raro subtipo de tumor mesenquimal e, por esse fato, é difícil se chegar a este diagnóstico pré-operatoriamente. Este é um dos fatores que praticamente obrigam o cirurgiäo a uma ampla ressecçäo quando suspeitar de tumor desta linhagem. A raridade do tumor gástrico de células estromais, bem como de sua apresentaçäo na forma hematoma retrogástrico, foi que nos levou a relatar o caso

Vesícula biliardupla: raro achado em cirurgia de vias biliares / Double gallbladder: a rare finding in biliary surgery

As anormalias de anatomia de vias biliares säo relativamente freqüentes, porém, a duplicaçäo da vesícula biliar é muita rara. Apresentamos um caso de uma paciente jovem, operada em vigência de abdômen agudo, com colecistite aguda, cujo diagnóstico de vesícula dupla foi realizado transoperatoriamente

Cirurgia de Hartmann - análise de 41 casos em hospital de referência do norte do Paraná / Hartmann's procedure - analysis of 41 cases in a reference hospital in north Paraná

A cirurgia de Hartmann é um procedimento cirúrgico de grande importância para o cirurgiäo do aparelho digestivo e do trauma. Consiste na ressecçäo do segmento colônico doente associado a uma colostomia proximal com fechamento do coto distal. A falta de segurança para a realizaçäo de anastomose primária por falta do preparo do cólon ou por condiçöes näo ideais do paciente constitui uma das suas principais indicaçöes. Dois meses ou mais após o primeiro procedimento, realiza-se o fechamento eletivo da colostomia com anastomose colorretal, restabelecendo-se o trânsito anterógrado do aparelho digestivo. Relatamos 41 casos de cirurgia de Hartmann, atendidos no Hospital Nossa Senhora da Saúde, em Santo Antônio da Platina, norte pioneiro do estado do Paraná. Em cinco pacientes, a cirurgia inicial foi realizada em outro serviço e nos trinta e seis pacientes restantes realizamos o procedimento inicial. Dos pacientes em que a cirurgia inicial foi realizada em outro serviço conseguimos reconstruir o trânsito em 4 dos 5 pacientes e nos 36 pacientes restantes fizemos a reconstruçäo em 25 deles. No grupo de pacientes nos quais tentamos a reconecçäo a mortalidade foi nula e a morbidade em níveis aceitáveis. Em 17 pacientes a reconstruçäo foi realizada por meio de anastomose manual, em 13 com o uso de anastomose mecânica e dentre esses, um por acesso videolaparoscópico