Cachexia causes time-dependent activation of the inflammasome in the liver.

BACKGROUND: Cachexia is a wasting syndrome associated with systemic inflammation and metabolic disruption. Detection of the early signs of the disease may contribute to the effective attenuation of associated symptoms. Despite playing a central role in the control of metabolism and inflammation, the liver has received little attention in cachexia. We previously described relevant disruption of metabolic pathways in the organ in an animal model of cachexia, and herein, we adopt the same model to investigate temporal onset of inflammation in the liver. The aim was thus to study inflammation in rodent liver in the well-characterized cachexia model of Walker 256 carcinosarcoma and, in addition, to describe inflammatory alterations in the liver of one cachectic colon cancer patient, as compared to one control and one weight-stable cancer patient. METHODS: Colon cancer patients (one weight stable [WSC] and one cachectic [CC]) and one patient undergoing surgery for cholelithiasis (control, n = 1) were enrolled in the study, after obtainment of fully informed consent. Eight-week-old male rats were subcutaneously inoculated with a Walker 256 carcinosarcoma cell suspension (2 × 107 cells in 1.0 mL; tumour-bearing [T]; or phosphate-buffered saline-controls [C]). The liver was excised on Days 0 (n = 5), 7 (n = 5) and 14 (n = 5) after tumour cell injection. RESULTS: In rodent cachexia, we found progressively higher numbers of CD68+ myeloid cells in the liver along cancer-cachexia development. Similar findings are described for CC, whose liver showed infiltration of the same cell type, compared with both WSC and control patient organs. In advanced rodent cachexia, hepatic phosphorylated c-Jun N-terminal kinase protein content and the inflammasome pathway protein expression were increased in relation to baseline (P < 0.05). These changes were accompanied by augmented expression of the active interleukin-1ß (IL-1ß) form (P < 0.05 for both circulating and hepatic content). CONCLUSIONS: The results show that cancer cachexia is associated with an increase in the number of myeloid cells in rodent and human liver and with modulation of hepatic inflammasome pathway. The latter contributes to the aggravation of systemic inflammation, through increased release of IL-1ß.

The learning curve of bilateral laparoscopic varicocelectomy: a prospective study.

Varicocele occurs in 15% of general male population and in 35% of infertile men. Since 1992, surgical correction with laparoscopic varicocelectomy is the gold standard for treatment of symptomatic patients or patients with abnormal seminal analysis. The learning curve for this frequently performed procedure has not yet been described. In the present study, we investigated the learning curve of a single urologist in training performing his first 21 laparoscopic varicocelectomies using qualitative and quantitative tools to evaluate his performance during the process. Our results show that 14 bilateral laparoscopic varicocelectomies are enough to achieve the plateau of the learning curve.

Bilateral inguinal transabdominal pre-peritoneal laparoscopic hernioplasty associated to bilateral laparoscopic varicocelectomy in the same intervention: a feasibility study.

INTRODUCTION: Inguinal hernia and varicocele are common conditions in male population. Laparoscopy brings the opportunity to treat them simultaneously, through the same incision. However, there are different opinions about the risks for testicular perfusion of multiple procedures in the inguinal region. In this study, we assessed the feasibility of simultaneous laparoscopic procedures by studying clinical and surgical outcomes of patients undergoing bilateral inguinal hernioplasty using the transabdominal preperitoneal (TAPP) technique with and without concomitant bilateral laparoscopic varicocelectomy (VLB). METHODS: a sample of 20 patients from the University Hospital of USP-SP with indirect inguinal hernia and varicocele with indication for surgical correction was selected. Patients were randomized into two groups, 10 undergoing TAPP (Group I) and 10 undergoing simultaneous TAPP and VLB (Group II). Data regarding total operative time, complications and postoperative pain was gathered and analyzed. RESULTS: there was no statistical difference between groups regarding total operative time and postoperative pain. Only one complication (spermatic cord hematoma) was observed in Group I and no complications were observed in Group II. CONCLUSIONS: simultaneous TAPP and VLB in was shown to be effective and safe, which provides a basis for conducting studies on larger scales.

The learning curve of bilateral laparoscopic varicocelectomy: a prospective study / A curva de aprendizado da varicocelectomia laparoscópica bilateral: um estudo prospectivo

ABSTRACT Varicocele occurs in 15% of general male population and in 35% of infertile men. Since 1992, surgical correction with laparoscopic varicocelectomy is the gold standard for treatment of symptomatic patients or patients with abnormal seminal analysis. The learning curve for this frequently performed procedure has not yet been described. In the present study, we investigated the learning curve of a single urologist in training performing his first 21 laparoscopic varicocelectomies using qualitative and quantitative tools to evaluate his performance during the process. Our results show that 14 bilateral laparoscopic varicocelectomies are enough to achieve the plateau of the learning curve.

RESUMO Varicocele ocorre em 15% dos homens e em 35% dos homens inférteis. Desde 1992, a correção cirúrgica com varicocelectomia laparoscópica é o padrão ouro para o tratamento de pacientes sintomáticos ou com análise seminal anormal. A curva de aprendizado para esse procedimento frequentemente realizado ainda não foi descrita. No presente estudo, investigamos a curva de aprendizado de um único urologista em treinamento realizando suas primeiras 21 varicocelectomias laparoscópicas usando ferramentas qualitativas e quantitativas para avaliar seu desempenho durante o processo. Nossos resultados mostram que 14 varicocelectomias laparoscópicas bilaterais são suficientes para atingir o platô da curva de aprendizado.

Bilateral inguinal transabdominal pre-peritoneal laparoscopic hernioplasty associated to bilateral laparoscopic varicocelectomy in the same intervention: a feasibility study / Hernioplastia inguinal pré-peritoneal transabdominal bilateral e varicocelectomia laparoscópica bilateral na mesma intervenção: um estudo de viabilidade

ABSTRACT Introduction: Inguinal hernia and varicocele are common conditions in male population. Laparoscopy brings the opportunity to treat them simultaneously, through the same incision. However, there are different opinions about the risks for testicular perfusion of multiple procedures in the inguinal region. In this study, we assessed the feasibility of simultaneous laparoscopic procedures by studying clinical and surgical outcomes of patients undergoing bilateral inguinal hernioplasty using the transabdominal preperitoneal (TAPP) technique with and without concomitant bilateral laparoscopic varicocelectomy (VLB). Methods: a sample of 20 patients from the University Hospital of USP-SP with indirect inguinal hernia and varicocele with indication for surgical correction was selected. Patients were randomized into two groups, 10 undergoing TAPP (Group I) and 10 undergoing simultaneous TAPP and VLB (Group II). Data regarding total operative time, complications and postoperative pain was gathered and analyzed. Results: there was no statistical difference between groups regarding total operative time and postoperative pain. Only one complication (spermatic cord hematoma) was observed in Group I and no complications were observed in Group II. Conclusions: simultaneous TAPP and VLB in was shown to be effective and safe, which provides a basis for conducting studies on larger scales.

RESUMO Introdução: hérnia inguinal e varicocele são doenças comuns na população masculina. O advento da laparoscopia traz a oportunidade de tratá-las simultaneamente, pelo mesmo acesso. Entretanto, existem divergências sobre os riscos para a perfusão testicular de múltiplos procedimentos na região inguinal. Neste estudo, avaliamos a viabilidade de procedimentos laparoscópicos simultâneos estudando resultados clínicos e cirúrgicos de pacientes submetidos à hernioplastia inguinal bilateral pela técnica transabdominal préperitoneal (TAPP) com e sem varicocelectomia laparoscópica bilateral (VLB) concomitante. Métodos: uma amostra de 20 pacientes do Hospital Universitário da USP-SP com hérnia inguinal indireta e varicocele com indicação de correção cirúrgica foi selecionada. Os pacientes foram randomizados em dois grupos, sendo 10 submetidos à TAPP (Grupo I) e 10 submetidos à TAPP e VLB simultâneas (Grupo II). O tempo operatório total, complicações e dor pós-operatória foram coletados e analisados. Resultados: não houve diferença estatística entre os grupos com relação ao tempo operatório total e à dor pós-operatória. Apenas uma complicação (hematoma do cordão espermático) foi observada no Grupo I e não foram observadas complicações no Grupo II. Conclusões: no mesmo procedimento, submeter pacientes à TAPP e à VLB no mesmo procedimento se mostrou eficaz e seguro, o que fornece embasamento para a realização de estudos em maiores escalas.

Learning curve of semi-rigid ureteroscopy for small calculi: how many cases are necessary?

INTRODUCTION: semi-rigid ureteroscopy is the procedure of choice for the treatment of ureterolithiasis, but it requires a learning curve to be performed safely. OBJECTIVE: To describe an estimate of the learning curve for performing semi-rigid ureterorenolithotripsy in patients with small-sized ureterolithiasis and to estimate the minimum number of procedures necessary to safely perform the surgical procedure. METHODS: this is a prospective study evaluating the learning curve of a resident of urology in the first 60 semirigid ureteroscopies in patients with ureterolithiasis up to 1cm. The patients were divided into three groups: Group I one to twenty surgeries, Group II twenty one to forty surgeries and Group III forty one to sixty surgeries. The surgeries were recorded and analyzed by two urologists experienced in endourology. A qualitative analysis was performed based on a previously validated tool and a quantitative analysis. RESULTS: all qualitative variables had significant variation between Groups I and II (p<0.001), and between Groups I and III (p<0.001). There was a difference in time to access the ureter, passage of a double J catheter and total operative time between Groups I and II (p<0.001) and Groups I and III (p<0.001). CONCLUSION: after 40 cases there seems to be little increase in both quantitative as well as qualitative evaluation in surgical performance for performing semi-rigid ureterolithotripsy safely in calculations up to 1cm.

The learning curve for retrograde intrarenal surgery: A prospective analysis.

INTRODUCTION: retrograde intrarenal surgery (CRIR) is an evolving tool. Its learning curve is not well established, despite the common use of flexible ureteroscopes today. Our aim is to estimate the number of procedures needed for one to perform RIRS consistently. MATERIAL AND METHODS: a urology resident had his first 80 RIRS for nephrolithiasis analyzed quantitatively and qualitatively. The procedures were divided into 4 groups containing 20 surgeries each (I to IV), according to their order, for comparison. RESULTS: there was no difference in stone sizes between groups. All qualitative variables varied significantly between groups (p<0.001), except between III and IV. In the quantitative analysis, there was a difference between groups I and IV in time for double-J catheter placement (p=0.012). There was an increasing difference in sheath placement time (p<0.001) and in total operative time (p=0.004). The time fot stone treatment (p=0.011) was significant only between groups I, II and III. There was difference in total sheath time only between groups I and III (p=0.023). Stone free status did not change between groups. DISCUSSION: the differences between the qualitative and quantitative variables show the relation between number of surgeries performed and proficiency in the procedure. Intergroup comparisons show sequential optimization of parameters. CONCLUSIONS: we found that 60 is a reasonable number of surgeries to be performed in order to reach the plateau of RIRSs learning curve.

Learning curve of semi-rigid ureteroscopy for small calculi: how many cases are necessary? / Curva de aprendizado em ureteroscopia semi-rígida em cálculos de pequenas dimensões: quantos casos são necessários?

ABSTRACT Introduction: semi-rigid ureteroscopy is the procedure of choice for the treatment of ureterolithiasis, but it requires a learning curve to be performed safely. Objective: To describe an estimate of the learning curve for performing semi-rigid ureterorenolithotripsy in patients with small-sized ureterolithiasis and to estimate the minimum number of procedures necessary to safely perform the surgical procedure. Methods: this is a prospective study evaluating the learning curve of a resident of urology in the first 60 semirigid ureteroscopies in patients with ureterolithiasis up to 1cm. The patients were divided into three groups: Group I one to twenty surgeries, Group II twenty one to forty surgeries and Group III forty one to sixty surgeries. The surgeries were recorded and analyzed by two urologists experienced in endourology. A qualitative analysis was performed based on a previously validated tool and a quantitative analysis. Results: all qualitative variables had significant variation between Groups I and II (p<0.001), and between Groups I and III (p<0.001). There was a difference in time to access the ureter, passage of a double J catheter and total operative time between Groups I and II (p<0.001) and Groups I and III (p<0.001). Conclusion: after 40 cases there seems to be little increase in both quantitative as well as qualitative evaluation in surgical performance for performing semi-rigid ureterolithotripsy safely in calculations up to 1cm.

RESUMO Introdução: ureteroscopia semi-rígida é o procedimento de escolha para o tratamento da ureterolitíase, mas necessita de uma curva de aprendizado para ser executada com segurança. Objetivo: descrever uma estimativa da curva de aprendizado para realização da ureterorrenolitotripsia semi-rígida em pacientes com ureterolitíase de pequena dimensão e estimar o número mínimo de procedimentos necessários para realizar o procedimento cirúrgico com segurança. Métodos: trata-se de um estudo prospectivo avaliando a curva de aprendizado de um residente de urologia nas primeiras 60 ureteroscopias semi-rígidas em pacientes com ureterolitíase até 1cm. Os pacientes foram divididos em três grupos: Grupo I uma a vinte cirurgias, Grupo II vinte e uma a quarenta cirurgias e Grupo III quarenta e uma a sessenta cirurgias. As cirurgias foram gravadas e analisadas por dois urologistas experientes em endourologia. Foi feita uma análise qualitativa baseada em uma ferramenta previamente validada e uma análise quantitativa. Resultados: todas as variáveis qualitativas tiveram variação significativa entre os Grupos I e II (p<0.001), e entre os Grupos I e III (p<0.001). Houve diferença no tempo para acesso ao ureter, passagem de cateter duplo J e tempo operatório total entre os Grupos I e II (p<0.001) e nos Grupos I e III (p<0.001). Conclusão: após 40 casos parece haver pouco incremento tanto na avaliação quantitativa bem como na avaliação qualitativa em performance cirúrgica para a realização de ureterolitotripsia semi-rígida com segurança em cálculos de até 1cm.

The learning curve for retrograde intrarenal surgery: A prospective analysis / A curva de aprendizado em cirurgia retrógrada intrarrenal: Uma análise prospectiva

ABSTRACT Introduction: retrograde intrarenal surgery (CRIR) is an evolving tool. Its learning curve is not well established, despite the common use of flexible ureteroscopes today. Our aim is to estimate the number of procedures needed for one to perform RIRS consistently. Material and Methods: a urology resident had his first 80 RIRS for nephrolithiasis analyzed quantitatively and qualitatively. The procedures were divided into 4 groups containing 20 surgeries each (I to IV), according to their order, for comparison. Results: there was no difference in stone sizes between groups. All qualitative variables varied significantly between groups (p<0.001), except between III and IV. In the quantitative analysis, there was a difference between groups I and IV in time for double-J catheter placement (p=0.012). There was an increasing difference in sheath placement time (p<0.001) and in total operative time (p=0.004). The time fot stone treatment (p=0.011) was significant only between groups I, II and III. There was difference in total sheath time only between groups I and III (p=0.023). Stone free status did not change between groups. Discussion: the differences between the qualitative and quantitative variables show the relation between number of surgeries performed and proficiency in the procedure. Intergroup comparisons show sequential optimization of parameters. Conclusions: we found that 60 is a reasonable number of surgeries to be performed in order to reach the plateau of RIRSs learning curve.

RESUMO Introdução: a cirurgia retrógrada intrarrenal (CRIR) é ferramenta em evolução. Sua curva de aprendizado não está bem estabelecida, apesar do uso comum dos ureteroscópios flexíveis atualmente. O objetivo é estimar o número de procedimentos necessários para se realizar CRIR consistentemente. Material e Métodos: Um residente de urologia teve suas primeiras 80 CRIR para tratamento de nefrolitíase analisadas quantitativa e qualitativamente. Os procedimentos foram divididos em 4 grupos contendo 20 cirurgias cada (I a IV), de acordo com sua ordem, para comparação. Resultados: Não houve diferença nos tamanhos dos cálculos entre grupos. Todas as variáveis qualitativas apresentaram variação significativa entre os grupos (p<0,001), exceto entre III e IV. Na análise quantitativa houve diferença entre os grupos I e IV no tempo de colocação do cateter duplo J (p=0,012). Houve uma diferença crescente no tempo de colocação da bainha (p<0,001) e no tempo operatório total (p=0,004). O tempo para o tratamento do cálculo (p=0,011) foi significativo apenas entre os grupos I, II e III. Houve diferença no tempo total de bainha apenas entre os grupos I e III (p=0,023). Taxa livre de cálculos não se alterou entre os grupos. Discussão: as diferenças observadas entres as variáveis qualitativas e quantitativas evidenciam a relação entre o número de cirurgias realizadas e a proficiência no procedimento. As comparações intergrupo mostram otimização sequencial dos parâmetros. Conclusões: estima-se que 60 é um número razoável de cirurgias para que se atinja o platô da curva de aprendizado.

Activation of the Adipose Tissue NLRP3 Inflammasome Pathway in Cancer Cachexia.

Background: Cachexia is a paraneoplastic syndrome that accompanies and compromises cancer treatment, especially in advanced stages, affecting the metabolism and function of several organs. The adipose tissue is the first to respond to the presence of the tumor, contributing to the secretion of factors which drive the systemic inflammation, a hallmark of the syndrome. While inflammation is a defensive innate response, the control mechanisms have been reported to be disrupted in cachexia. On the other hand, little is known about the role of NLRP3 inflammasome in this scenario, a multiprotein complex involved in caspase-1 activation and the processing of the cytokines IL-1ß and IL-18. Aim: based on the evidence from our previous study with a rodent model of cachexia, we examined the activation of the NLRP3 inflammasome pathway in two adipose tissue depots obtained from patients with colorectal cancer and compared with that another inflammatory pathway, NF-κB. Results: For CC we found opposite modulation in ScAT and PtAT for the gene expression of TLR4, Caspase-1 (cachectic group) and for NF-κB p50, NF-κB p65, IL-1ß. CD36, expression was decreased in both depots while that of NLRP3 and IL-18 was higher in both tissues, as compared with controls and weight stable patients (WSC). Caspase-1 basal protein levels in the ScAT culture supernatant were higher in WSC and (weight stable patients) CC, when compared to controls. Basal ScAT explant culture medium IL-1ß and IL-18 protein content in ScAT supernatant was decreased in the WSC and CC as compared to CTL explants. Conclusions: The results demonstrate heterogeneous responses in the activation of genes of the NLRP3 inflammasome pathway in the adipose tissue of patients with cancer cachexia, rendering this pathway a potential target for therapy aiming at decreasing chronic inflammation in cancer.

Plasma Lipid Profile and Systemic Inflammation in Patients With Cancer Cachexia.

Cancer cachexia affects about 80% of advanced cancer patients, it is linked to poor prognosis and to date, there is no efficient treatment or cure. The syndrome leads to progressive involuntary loss of muscle and fat mass induced by systemic inflammatory processes. The role of the white adipose tissue (WAT) in the onset and manifestation of cancer cachexia gained importance during the last decade. WAT wasting is not only characterized by increased lipolysis and release of free fatty acids (FFA), but in addition, owing to its high capacity to produce a variety of inflammatory factors. The aim of this study was to characterize plasma lipid profile of cachectic patients and to correlate the FA composition with circulating inflammatory markers; finally, we sought to establish whether the fatty acids released by adipocytes trigger and/or contribute to local and systemic inflammation in cachexia. The study selected 65 patients further divided into 3 groups: control (N); weight stable cancer (WSC); and cachectic cancer (CC). The plasma FA profile was significantly different among the groups and was positively correlated with pro-inflammatory cytokines expression in the CC patients. Therefore, we propose that saturated to unsaturated FFA ratio may serve as a means of detecting cachexia.

Cancer cachexia induces morphological and inflammatory changes in the intestinal mucosa.

BACKGROUND: Cachexia is a multifactorial and multiorgan syndrome associated with cancer and other chronic diseases and characterized by severe involuntary body weight loss, disrupted metabolism, inflammation, anorexia, fatigue, and diminished quality of life. This syndrome affects around 50% of patients with colon cancer and is directly responsible for the death of at least 20% of all cancer patients. Systemic inflammation has been recently proposed to underline most of cachexia-related symptoms. Nevertheless, the exact mechanisms leading to the initiation of systemic inflammation have not yet been unveiled, as patients bearing the same tumour and disease stage may or may not present cachexia. We hypothesize a role for gut barrier disruption, which may elicit persistent immune activation in the host. To address this hypothesis, we analysed the healthy colon tissue, adjacent to the tumour. METHODS: Blood and rectosigmoid colon samples (20 cm distal to tumour margin) obtained during surgery, from cachectic (CC = 25) or weight stable (WSC = 20) colon cancer patients, who signed the informed consent form, were submitted to morphological (light microscopy), immunological (immunohistochemistry and flow cytometry), and molecular (quantification of inflammatory factors by Luminex® xMAP) analyses. RESULTS: There was no statistical difference in gender and age between groups. The content of plasma interleukin 6 (IL-6) and IL-8 was augmented in cachectic patients relative to those with stable weight (P = 0.047 and P = 0.009, respectively). The number of lymphocytic aggregates/field in the gut mucosa was higher in CC than in WSC (P = 0.019), in addition to those of the lamina propria (LP) eosinophils (P < 0.001) and fibroblasts (P < 0.001). The area occupied by goblet cells in the colon mucosa was decreased in CC (P = 0.016). The M1M2 macrophages percentage was increased in the colon of CC, in relation to WSC (P = 0.042). Protein expression of IL-7, IL-13, and transforming growth factor beta 3 in the colon was significantly increased in CC, compared with WSC (P = 0.02, P = 0.048, and P = 0.048, respectively), and a trend towards a higher content of granulocyte-colony stimulating factor in CC was also observed (P = 0.061). The results suggest an increased recruitment of immune cells to the colonic mucosa in CC, as compared with WSC, in a fashion that resembles repair response following injury, with higher tissue content of IL-13 and transforming growth factor beta 3. CONCLUSIONS: The changes in the intestinal mucosa cellularity, along with modified cytokine expression in cachexia, indicate that gut barrier alterations are associated with the syndrome.

Tracheal stenosis due to endotracheal tube cuff hyperinflation: a preventable complication.

Endotracheal intubation injuries are rare, but may be devastating-mostly among the pediatric patients or when these occur in the distal trachea. Such complications typify a therapeutic challenge, which, besides requiring intellectual and technical resources, takes a long time to reach a resolution. The authors present the case of a 15-year-old girl admitted with an abnormal state of consciousness due to diabetic ketoacidosis. She was submitted to endotracheal intubation with hyperinflation of the tube cuff, which rendered tracheal necrosis and detachment of the tracheal mucosa, and consequent obstruction. Later, she developed scarring retraction and stenosis. The patient was successfully treated with an endotracheal prosthesis insertion. The aim of this report is to illustrate a preventable complication.

Tracheal stenosis due to endotracheal tube cuff hyperinflation: a preventable complication

Endotracheal intubation injuries are rare, but may be devastating­mostly among the pediatric patients or when these occur in the distal trachea. Such complications typify a therapeutic challenge, which, besides requiring intellectual and technical resources, takes a long time to reach a resolution. The authors present the case of a 15-year-old girl admitted with an abnormal state of consciousness due to diabetic ketoacidosis. She was submitted to endotracheal intubation with hyperinflation of the tube cuff, which rendered tracheal necrosis and detachment of the tracheal mucosa, and consequent obstruction. Later, she developed scarring retraction and stenosis. The patient was successfully treated with an endotracheal prosthesis insertion. The aim of this report is to illustrate a preventable complication.

Madelung disease (multiple symmetric lipomatosis)

Madelung disease or multiple symmetric lipomatosis (MSL) is a rare entity among the overgrowth syndromes. It is characterized by painless non-encapsulated and symmetric fatty deposits in the neck, torso, mammary, and abdominal areas, and in the upper and lower limbs. The etiology of the disease is still unknown. Chronic alcohol consumption may play a role in adipocyte hyperplasia in genetically susceptible individuals. Besides the overgrowth of adipose tissue, patients with MSL present features of metabolic syndrome. Patients seek medical attention usually for esthetic reasons. We present the case of a middle-aged man who sought the outpatient clinic complaining of bulging masses in the posterior upper part of the thorax, the occipital area, and the neck. The masses grew over a period of 2 years. The physical examination and imaging study revealed the presence of symmetric lipomatosis. A two-step surgical treatment was undertaken for the excision of the lipomatous tissue. The postoperative outcome was uneventful with satisfactory esthetic results.

Madelung disease (multiple symmetric lipomatosis).

Madelung disease or multiple symmetric lipomatosis (MSL) is a rare entity among the overgrowth syndromes. It is characterized by painless non-encapsulated and symmetric fatty deposits in the neck, torso, mammary, and abdominal areas, and in the upper and lower limbs. The etiology of the disease is still unknown. Chronic alcohol consumption may play a role in adipocyte hyperplasia in genetically susceptible individuals. Besides the overgrowth of adipose tissue, patients with MSL present features of metabolic syndrome. Patients seek medical attention usually for esthetic reasons. We present the case of a middle-aged man who sought the outpatient clinic complaining of bulging masses in the posterior upper part of the thorax, the occipital area, and the neck. The masses grew over a period of 2 years. The physical examination and imaging study revealed the presence of symmetric lipomatosis. A two-step surgical treatment was undertaken for the excision of the lipomatous tissue. The postoperative outcome was uneventful with satisfactory esthetic results.

Abdominal and pelvic actinomycosis due to longstanding intrauterine device: a slow and devastating infection.

Actinomycosis is a chronic or subacute bacterial infection characterized by large abscess formation, caused mainly by the gram-positive non-acid-fast, anaerobic, or microaerophilic/capnophilic, obligate parasites bacteria from the Actinomyces genus. Although pelvic inflammatory disease is an entity associated with the longstanding use of intrauterine devices (IUDs), actinomycosis is not one of the most frequent infections associated with IUDs. We present the case of a 43-year-old female patient who was referred to the emergency facility because of a 20-day history of abdominal pain with signs of peritoneal irritation. Imaging exams revealed collections confined to the pelvis, plus the presence of an IUD and evidence of sepsis, which was consistent with diffuse peritonitis. An exploratory laparotomy was undertaken, and a ruptured left tubal abscess was found along with peritonitis, and a huge amount of purulent secretion in the pelvis and abdominal cavity. Extensive lavage of the cavities with saline, a left salpingo-oophorectomy, and drainage of the cavities were performed. The histopathological examination of the surgical specimen revealed an acute salpingitis with abscesses containing sulfur granules. Therefore, the diagnosis of abdominal and pelvic actinomycosis was made. The postoperative outcome was troublesome and complicated with a colocutaneous fistula, which drained through the surgical wound. A second surgical approach was needed, requiring another extensive lavage and drainage of the recto-uterine pouch, plus the performance of a colostomy. Broad-spectrum antibiotics added to ampicillin were the first antimicrobial regimen followed by 4 weeks of amoxicillin during the outpatient follow-up. The patient satisfactorily recovered and is already scheduled for the intestinal transit reconstitution.

Abdominal and pelvic actinomycosis due to longstanding intrauterine device: a slow and devastating infection

Actinomycosis is a chronic or subacute bacterial infection characterized by large abscess formation, caused mainly by the gram-positive non-acid-fast, anaerobic, or microaerophilic/capnophilic, obligate parasites bacteria from the genus. Although pelvic inflammatory disease is an entity associated with the longstanding use of intrauterine devices (IUDs), actinomycosis is not one of the most frequent infections associated with IUDs. We present the case of a 43-year-old female patient who was referred to the emergency facility because of a 20-day history of abdominal pain with signs of peritoneal irritation. Imaging exams revealed collections confined to the pelvis, plus the presence of an IUD and evidence of sepsis, which was consistent with diffuse peritonitis. An exploratory laparotomy was undertaken, and a ruptured left tubal abscess was found along with peritonitis, and a huge amount of purulent secretion in the pelvis and abdominal cavity. Extensive lavage of the cavities with saline, a left salpingo-oophorectomy, and drainage of the cavities were performed. The histopathological examination of the surgical specimen revealed an acute salpingitis with abscesses containing sulfur granules. Therefore, the diagnosis of abdominal and pelvic actinomycosis was made. The postoperative outcome was troublesome and complicated with a colocutaneous fistula, which drained through the surgical wound. A second surgical approach was needed, requiring another extensive lavage and drainage of the recto-uterine pouch, plus the performance of a colostomy. Broad-spectrum antibiotics added to ampicillin were the first antimicrobial regimen followed by 4 weeks of amoxicillin during the outpatient follow-up. The patient satisfactorily recovered and is already scheduled for the intestinal transit reconstitution.

Cachexia-associated adipose tissue morphological rearrangement in gastrointestinal cancer patients.

BACKGROUND AND AIMS: Cachexia is a syndrome characterized by marked involuntary loss of body weight. Recently, adipose tissue (AT) wasting has been shown to occur before the appearance of other classical cachexia markers. We investigated the composition and rearrangement of the extracellular matrix, adipocyte morphology and inflammation in the subcutaneous AT (scAT) pad of gastrointestinal cancer patients. METHODS: Surgical biopsies for scAT were obtained from gastrointestinal cancer patients, who were signed up into the following groups: cancer cachexia (CC, n = 11), weight-stable cancer (WSC, n = 9) and weight-stable control (non-cancer) (control, n = 7). The stable weight groups were considered as those with no important weight change during the last year and body mass index <25 kg/m(2). Subcutaneous AT fibrosis was quantified and characterized by quantitative PCR, histological analysis and immunohistochemistry. RESULTS: The degree of fibrosis and the distribution and collagen types (I and III) were different in WSC and CC patients. CC patients showed more pronounced fibrosis in comparison with WSC. Infiltrating macrophages surrounding adipocytes and CD3 Ly were found in the fibrotic areas of scAT. Subcutaneous AT fibrotic areas demonstrated increased monocyte chemotactic protein 1 (MCP-1) and Cluster of Differentiation (CD)68 gene expression in cancer patients. CONCLUSIONS: Our data indicate architectural modification consisting of fibrosis and inflammatory cell infiltration in scAT as induced by cachexia in gastrointestinal cancer patients. The latter was characterized by the presence of macrophages and lymphocytes, more evident in the fibrotic areas. In addition, increased MCP-1 and CD68 gene expression in scAT from cancer patients may indicate an important role of these markers in the early phases of cancer.

NF-κBp65 and Expression of Its Pro-Inflammatory Target Genes Are Upregulated in the Subcutaneous Adipose Tissue of Cachectic Cancer Patients.

Cancer cachexia, of which the most notable symptom is severe and rapid weight loss, is present in the majority of patients with advanced cancer. Inflammatory mediators play an important role in the development of cachexia, envisaged as a chronic inflammatory syndrome. The white adipose tissue (WAT) is one of the first compartments affected in cancer cachexia and suffers a high rate of lipolysis. It secretes several cytokines capable of directly regulating intermediate metabolism. A common pathway in the regulation of the expression of pro-inflammatory cytokines in WAT is the activation of the nuclear transcription factor kappa-B (NF-κB). We have examined the gene expression of the subunits NF-κBp65 and NF-κBp50, as well as NF-κBp65 and NF-κBp50 binding, the gene expression of pro-inflammatory mediators under NF-κB control (IL-1ß, IL-6, INF-γ, TNF-α, MCP-1), and its inhibitory protein, nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκB-α). The observational study involved 35 patients (control group, n = 12 and cancer group, n = 23, further divided into cachectic and non-cachectic). NF-κBp65 and its target genes expression (TNF-α, IL-1ß, MCP-1 and IκB-α) were significantly higher in cachectic cancer patients. Moreover, NF-κBp65 gene expression correlated positively with the expression of its target genes. The results strongly suggest that the NF-κB pathway plays a role in the promotion of WAT inflammation during cachexia.