RESUMO
INTRODUCTION: The aim of this study was to investigate long-term outcomes in terms of pain, quality of life (QoL), and gastrointestinal symptoms in women following colorectal surgery for deep endometriosis. MATERIAL AND METHODS: In this historical cohort, women who underwent surgical treatment for deep endometriosis by either nerve-sparing full-thickness discoid resection (DR) or colorectal segmental resection (SR) between March 2011 and August 2016 were re-evaluated through telephone interviews about their long-term pain symptoms, subjective overall QoL as rated using a score from 0 (worst) to 10 (optimal), and gastrointestinal outcomes reflected by lower anterior resection syndrome (LARS) following a first postsurgical evaluation (visit 1) published previously and a long-term follow-up evaluation (visit 2). RESULTS: The median long-term follow-up time was 35.4 months at visit 1 and 86 months at visit 2. Of 134 patients, 77 were eligible for final analysis and 57 were lost to follow-up. Compared with presurgical values, QoL scores were significantly increased at both postsurgical evaluation visits in both the SR cohort (scores of 3, 8.5, and 10 at the presurgical visit, visit 1, and visit 2, respectively; p < 0.001) and the DR cohort (scores of 3, 9, and 10, respectively; p < 0.001). Pain scores for dysmenorrhea (SR group scores of 8, 2, and 2, respectively; p < 0.001; DR group scores of 9, 2, and 1, respectively; p < 0.001), dyspareunia (SR group scores of 4, 0, and 0, respectively; p < 0.001; DR group scores of 5, 0, and 1, respectively; p = 0.003), and dyschezia (SR group scores of 8, 2, and 2, respectively; p < 0.001; DR group scores of 9, 2, and 1, respectively; p < 0.001) significantly decreased after surgery and remained stable in both cohorts over the follow-up period. Minor and major LARS, reflecting gastrointestinal function, was observed in 6.5% and 8.1% of the SR group and in 13.3% and 6.7% of the DR group, respectively, at visit 1 and in 3.2% and 3.2% of the SR group and 0% and 0% of the DR group, respectively, at visit 2, without significant differences between the SR and DR groups. CONCLUSIONS: Colorectal surgery for deep endometriosis, either by DR or SR, provides stable and long-term pain relief with low rates of permanent gastrointestinal function impairment.
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Procedimentos Cirúrgicos do Sistema Digestório , Endometriose , Laparoscopia , Doenças Retais , Dismenorreia/cirurgia , Endometriose/cirurgia , Feminino , Humanos , Complicações Pós-Operatórias/cirurgia , Qualidade de Vida , Doenças Retais/cirurgia , Resultado do TratamentoRESUMO
PURPOSE: To assess whether Creactive protein (CRP), white blood cell count (WBC) and body temperature changes are suitable parameters for the early detection of septic complications following resection of colorectal deep endometriosis (DE). METHODS: Retrospective data analysis of CRP, WBC and body temperature courses following colorectal surgery for DE at a tertiary referral center for endometriosis. RESULTS: Out of 183 surgeries performed, 10 major surgical complications were observed, including 4 anastomotic leakages (AL 2%) and 2 rectovaginal fistulae (RVF 1%). In the presence of a lower gastrointestinal tract (GIT)-related septic complication or abdominal wall abscess, serum CRP levels were increased starting at postoperative day 2-3. A cut-off value of 10â¯mg/dl on day 4 for prediction of early septic complications could be verified (area under the curve 0.94, obtained by receiver operating characteristics analysis, sensitivity 88%, specificity 90%, positive predictive value 32%, negative predictive value 99%). Additionally, most patients with early septic complications exhibited increased WBC levels starting mainly from day 3-4; however, increased inflammatory parameters could not be observed in one patient with an RVF. Body temperature did not prove useful for early discrimination between uncomplicated cases and those with early septic complications. CONCLUSION: Relevant elevations of serum CRP and WBC levels were demonstrated in patients with early septic complications following surgery for colorectal DE starting at postoperative day 2-4. The cut-off value of 10â¯mg/dl for CRP levels may serve as an early predictor for lower GIT-related septic complications but should be used with caution in women with suspected RVF development.
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Neoplasias Colorretais , Endometriose , Fístula Anastomótica/diagnóstico , Biomarcadores , Proteína C-Reativa/análise , Endometriose/diagnóstico , Endometriose/cirurgia , Feminino , Humanos , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Valor Preditivo dos Testes , Estudos RetrospectivosRESUMO
INTODUCTION: Choosing the optimal treatment for bowel endometriosis, ie, conservative vs radical surgery, is under debate. We aimed to evaluate the surgical outcomes of segmental resection and disk resection regarding fertility, pain symptoms, and quality of life score of women with colorectal deep infiltrating endometriosis. MATERIAL AND METHODS: From March 2011 to December 2016, 134 consecutive patients with symptomatic deep infiltrating endometriosis of the rectosigmoid up to 25 cm from the anal verge undergoing segmental resection or disk resection were prospectively evaluated regarding reduction in pain symptoms, fertility outcomes, and complication rates according to Clavien-Dindo classification. RESULTS: Of the 134 women included, segmental resection was performed in 102 (76.1%) women and disk resection was performed in 32 (23.9%) women. There was no difference in duration of surgery, complication rates, mean hospital stay, or discrepancy in hemoglobin level comparing the two groups. There was no significant difference regarding reduction of pain symptoms, fertility, and functional outcomes. One hundred and twelve (83.6%) women were followed up long-term. In both cohorts, there was a significant reported decrease in pain symptoms and increase in quality of life scores. Of all the 61 infertile women, 26 (42.6%) became pregnant spontaneously, and 13 (21.3%) by in vitro fertilization with an overall pregnancy rate of 63.4%. The overall complication rate (Clavien-Dindo III-IV) was 8 of 134 (5.9%) without statistically significant difference between the cohorts. CONCLUSIONS: Both conservative surgery with disk resection, and nerve- and vessel-sparing segmental resection reduce pain symptoms with equal morbidity. Fertility is improved with surgery with both techniques.
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Doenças do Colo/cirurgia , Tratamento Conservador , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Endometriose/cirurgia , Infertilidade Feminina/etiologia , Dor Pós-Operatória/etiologia , Doenças Retais/cirurgia , Adulto , Feminino , Seguimentos , Humanos , Infertilidade Feminina/epidemiologia , Dor Pós-Operatória/epidemiologia , Estudos Prospectivos , Qualidade de Vida , Resultado do TratamentoRESUMO
BACKGROUND: Impairment of gastric digestion due to pH elevation increases the risk for food allergy induction. As patients after Roux-en-Y gastric bypass (RYGB) surgery have lower gastric acidity and less gastric gland secretion, we aimed to analyse in a prospective study the effect of limiting gastric digestion capacity by surgical intervention on the immune response towards allergens. METHODS: Nine patients undergoing RYGB surgery for morbid obesity and one control patient having undergone surgery for treatment of an incisional hernia were enrolled in the study. Before and 1, 3, 6, 9 and 12 months after surgery, blood was collected for analysis of specific IgE antibodies, and patients were subjected to skin prick testing with 16 food and 18 aeroallergens. RESULTS: Skin prick test results revealed an increase of positive reactions indicating sensitisations towards the tested food and aeroallergens in 77.8 and 88.9 % of the patients, respectively, after surgical elimination of gastric digestion. These results were in line with elevated titers of food- and aeroallergen-specific IgE antibodies in 7 out of 9 (7/9) and 5/9 patients, respectively, after RYGB surgery. Serum cytokine levels revealed a mixed response for IFN-γ and were mostly beneath detection limit for IL-4. CONCLUSION: A change of IgE reactivity pattern occurred after impairment of gastric digestion due to surgical elimination underlining the important gastric gatekeeping function during oral sensitisation. Even though this study indicates an increased allergy risk for gastric bypass patients, further studies are needed to investigate in-depth the immunological changes associated with RYGB surgery.
Assuntos
Digestão/fisiologia , Hipersensibilidade Alimentar/etiologia , Derivação Gástrica/efeitos adversos , Obesidade Mórbida/cirurgia , Estômago/cirurgia , Adolescente , Adulto , Estudos de Casos e Controles , Feminino , Alimentos , Derivação Gástrica/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Estômago/fisiopatologia , Adulto JovemRESUMO
BACKGROUND: Diverticular disease is increasingly prevalent in Western societies and is associated with significant morbidity. OBJECTIVE: Two-stage endoscopic device development for inversion and secured ligation of colonic diverticula; first, human cadaver studies were performed to measure forces required for diverticular inversion; second, a novel set of devices (elastic spiked O-ring with delivery system) was tested in animals. DESIGN: Prospective, observational study of human cadavers and prospective, interventional study of a porcine model. SETTING: University hospital pathology laboratory and animal facility. INTERVENTION: Full-thickness inversion of the colonic wall with a pipelike delivery instrument to produce an inverted pseudodiverticulum that was secured with a spiked O-ring. MAIN OUTCOME MEASUREMENTS: The forces required for diverticular inversion, the secured closure of inverted pseudodiverticula, and the time until necrotic tissue falls off. RESULTS: A total of 248 of 248 of cadaveric sigmoid diverticula could be inverted by means of vacuum or forceps. The forces required for inversion ranged from 0.28 to 0.47 N (median, 0.37 N). Twenty-four spiked O-rings were delivered in 6 living pigs to produce 24 inverted pseudodiverticula. One animal died the day after the procedure of a pulmonary thromboembolism. In the remaining 5 pigs, all delivered spiked O-rings remained in place for 7 to 22 days. At necropsy, none of the inverted sites showed signs of perforation but rather full-thickness reparative scarring with ingrowth of connective tissue. LIMITATIONS: Animal model, stiff pipelike delivery instrument, variations in diverticular location, diameter, and size. CONCLUSIONS: Endoluminal inversion and securing of colonic diverticula induces tissue necrosis, diverticular sloughing, and full-thickness scarring.
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Divertículo do Colo/cirurgia , Laparoscopia/métodos , Animais , Feminino , Humanos , Laparoscopia/instrumentação , Estudos Prospectivos , Suínos , VácuoRESUMO
BACKGROUND: Megachannel is a newly developed colonic access system allowing rapid and multiple passes of the colonoscope to the right side of the colon. OBJECTIVE: The aim of this study was to evaluate the safety and clinical feasibility of placing a 100 cm Megachannel prototype in the right side of the colon. SETTING: Six centers, international, both surgeons and gastroenterologists performing endoscopy. DESIGN AND INTERVENTION: Patients scheduled for colonoscopy with suspected right-side colonic polypoid lesions were included. The prototype was loaded onto a 160 cm lower GI endoscope and introduced via colonoscopic guidance. MAIN OUTCOME MEASUREMENT: The ability to place this device in the right side of the colon. RESULTS: The Megachannel prototype was introduced in 41 patients (19 female, mean age 54 years) undergoing colonoscopy. The cecum was reached in 27 cases (66%) within 18 minutes (range, 3-35 minutes) and with 73 cm (range, 40-100 cm) of the device being inserted into the colon. Mild tissue bruises and mild pain were observed in 5 and 3 patients, respectively. In 14 patients, the device assisted the removal of multiple polyps (2-12) as tissue was repeatedly retrieved through the channel. The device also allowed delivery of an endoscopic US scope or suction caps to the right side of the colon. LIMITATIONS: Prototype performance may differ from the actual product (80 cm in length, redesigned introducer plugs). Small number of patients, difficult in diverticular disease. CONCLUSIONS: This newly developed colonic access system can be safely placed in the right side of the colon and is useful for a variety of advanced procedures that require repeated insertion of the colonoscope or delivery of bulky instruments. ( CLINICAL TRIAL REGISTRATION NUMBER: NCT00987896.).
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Pólipos do Colo/terapia , Colonoscópios , Colonoscopia/métodos , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reoperação , Gravação em VídeoRESUMO
BACKGROUND: There is increasing interest in natural orifice surgery (NOS). Because the lumen of the appendix is connected to the cecum, a minimally invasive method for removing the appendix by colonoscopy may be feasible. OBJECTIVES: Our purpose was to design, develop, and test new devices for inverting and removing the appendix by colonoscopy. DESIGN: Prospective prototype development program. SETTING: University-based study in 25 colons from adult human cadavers. INTERVENTIONS AND METHODS: Various prototypes were evaluated by inserting them into the appendiceal orifice to its luminal tip, with the intent to invert the appendix in a controlled fashion into the lumen of the cecum. The advantage of using a tubular structure as a counterforce to aid inversion of the appendix was evaluated. When inversion was incomplete, the growing tissue strain was relieved by endoluminal incision of the mesenteric side of the appendix. Closure methods with endoloops or ligating loops were studied. Appendiceal resection was completed by snare diathermy, leaving an inverted intraluminal stump. MAIN OUTCOME MEASUREMENT: Ability to invert the appendix into the cecum. RESULTS: The mean appendix length and luminal diameter were 84 +/- 23 mm and 4.9 +/- 1.2 mm, respectively. It was possible to advance various types of inversion devices to the tip of the appendiceal lumen. Partial inversion of the appendix was successful in 22 of 25 tests. Mesenteric tissue tension, tissue volume, and device slippage were the main reasons for incomplete inversion. The complete inversion was achieved with a combination of vacuum, tip grip, counterforce at the appendix base, and eventually endoluminal incision. CONCLUSIONS: The inversion of the human appendix by colonoscopy seems feasible and may be an alternative approach to conventional appendectomy.
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Apendicectomia/métodos , Colonoscópios , Colonoscopia/métodos , Apendicectomia/instrumentação , Cadáver , Desenho de Equipamento , Segurança de Equipamentos , Humanos , Ligadura/métodos , Sensibilidade e EspecificidadeRESUMO
Despite previous studies suggesting that surgery cause immune suppression, the underlying biologic mechanisms have not been studied using advanced immune function assays. Unilateral nephrectomy was performed in nonhuman primates. Blood was collected before surgery and at different time-points through 14 days after surgery. Lymphocyte proliferation (expression of proliferating cell nuclear antigen in cells in S/G(2)M-phase), production of intracellular cytokines [interleukin (IL)-2, interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha] and expression of surface-activation antigens (CD25, CD71) on T-lymphocytes were assessed in whole blood using flow cytometry. Results were compared with nonoperated control animals. The procedure caused a decrease of 25% in absolute lymphocyte count on postoperative day 3. Inhibition of lymphocyte proliferation was maximal on postoperative day 1 (55% normalized to preoperative values) and was detectable until postoperative day 7, when it was 25%. Expression of T-cell activation antigens was decreased during the first postoperative week with a maximum on postoperative day 1 for CD71 (29%) and on postoperative day 3 for CD25 (49%). Intracellular production of cytokines by T cells was decreased only on postoperative day 1 (50% for IL-2, 29% for IFN-gamma and 22% for TNF-alpha). Immune functions returned to presurgery values by day 14. A major surgical procedure severely inhibits lymphocyte proliferation and various T-cell functions up to 1 week postoperatively.
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Citometria de Fluxo/métodos , Nefrectomia/métodos , Animais , Antígenos CD/biossíntese , Complexo CD3/biossíntese , Proliferação de Células , Tolerância Imunológica , Terapia de Imunossupressão , Interferon gama/metabolismo , Interleucina-2/metabolismo , Fígado/cirurgia , Ativação Linfocitária , Linfócitos/citologia , Macaca fascicularis , Masculino , Primatas , Receptores de Interleucina-2/biossíntese , Receptores da Transferrina/biossíntese , Linfócitos T/citologia , Linfócitos T/imunologia , Linfócitos T/metabolismo , Fatores de Tempo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Ehlers-Danlos syndrome (EDS) is a rare inherited disorder of connective tissue characterized by hyperextensible skin, hypermobile joints, and abnormalities of the cardiovascular system. Most patients are unaware of their disease until a catastrophic event such as arterial rupture or bowel perforation occurs. Aortic disruption accounts for many of the deaths in EDS type IV cases and only two cases of survival after spontaneous aortic rupture have previously been reported. We report on a third case of a survivor of spontaneous abdominal aortic rupture in EDS type IV.
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Ruptura Aórtica/etiologia , Síndrome de Ehlers-Danlos/complicações , Adulto , Aorta Abdominal/diagnóstico por imagem , Aorta Abdominal/patologia , Ruptura Aórtica/diagnóstico por imagem , Ruptura Aórtica/patologia , Síndrome de Ehlers-Danlos/diagnóstico por imagem , Síndrome de Ehlers-Danlos/patologia , Humanos , Masculino , Microscopia Eletrônica/métodos , Tomografia Computadorizada por Raios X/métodosRESUMO
ISA247 is a novel cyclosporine analog. In this study we compare, in vitro, the effects of ISA247 on immune function with those of cyclosporine. Whole blood from cynomolgus monkeys (n = 5) was incubated with different concentrations of ISA247 or cyclosporine and stimulated with different mitogens in culture medium. Lymphocyte proliferation was assessed by [3H]-TdR incorporation assay and by flow cytometry. Flow cytometry was also used to assess production of intracellular cytokines by T cells and expression of T cell activation surface antigens. The concentration of drug necessary to attain 50% of the maximum effect (EC50) was subsequently calculated. EC50 values for ISA247 were lower than for cyclosporine, and the differences were statistically significant for lymphocyte proliferation, T cell cytokine production, and expression of all T cell activation surface antigens but one. We conclude that ISA247 suppresses diverse immune functions more potently than cyclosporine in vitro.
Assuntos
Inibidores de Calcineurina , Ciclosporina/farmacologia , Imunossupressores/farmacologia , Linfócitos T/efeitos dos fármacos , Animais , Calcineurina/metabolismo , Relação Dose-Resposta a Droga , Interferon gama/metabolismo , Interleucina-2/metabolismo , Macaca fascicularis , Linfócitos T/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
BACKGROUND: ISA(TX)247 is a novel calcineurin inhibitor that has shown more potency than cyclosporine in vitro. This is the first in vivo study of the effects of ISA(TX)247 on lymphocyte functions in non-human primates. METHODS: Groups of cynomolgus monkeys were treated orally twice daily for 7 days, each dose consisting of 25 mg/kg cyclosporine (n = 5), 25 mg/kg ISA(TX)247 (n = 6) or 50 mg/kg ISA(TX)247 (n = 6). Levels of cyclosporine and ISA(TX)247 in whole blood were measured by liquid chromatography/mass spectrometry. After mitogen stimulation, lymphocyte proliferation was assessed by tritium-labeled thymidine incorporation and by flow cytometry (expression of proliferating cell nuclear antigen in cells in S/G(2)M phase). Flow cytometry was also used to assess production of intracellular cytokines by T cells (interleukin-2, interferon-gamma, tumor necrosis factor-alpha) and expression of T-cell surface activation antigens (CD25, CD71, CD11a, CD95, CD154). RESULTS: Trough (C(14 hr)) and peak (C(3 hr)) drug levels, as well as area under the concentration-time curve, were significantly higher for cyclosporine than ISA(TX)247 (370 ng/ml vs 70 ng/ml, 877 ng/ml vs 303 ng/ml and 6,262 ng. h/ml vs 1,979 ng. h/ml, respectively). On Day 7 at C(14 hr), lymphocyte proliferation had been suppressed by approximately 50% in all groups compared with proliferation before treatment. Three hours after dosing, lymphocyte proliferation was inhibited significantly more by ISA(TX)247 (approximately 80%, with no differences between the two ISA(TX)247 dose levels) than by cyclosporine (65% inhibition). Similar differences between the immunosuppressive effects of ISA(TX)247 and cyclosporine were found for inhibition of expression of T-cell surface activation antigens. Despite lower ISA(TX)247 exposures compared with cyclosporine, the cyclosporine treatment only rarely suppressed cytokine production more than treatment with ISA(TX)247. CONCLUSIONS: In non-human primates, ISA(TX)247 produces a greater or similar inhibition of lymphocyte proliferation, expression of T-cell activation surface antigens, and cytokine production when compared with cyclosporine, despite ISA(TX)247's lower blood levels and total exposure. We conclude that ISA(TX)247 suppresses diverse T-cell functions more potently than cyclosporine in non-human primates in vivo.
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Inibidores de Calcineurina , Ciclosporina/farmacologia , Imunossupressores/farmacologia , Linfócitos T/efeitos dos fármacos , Animais , Antígenos CD/metabolismo , Citocinas/metabolismo , Macaca fascicularis , Masculino , Modelos Animais , Linfócitos T/fisiologiaRESUMO
BACKGROUND: Co-stimulatory blockade has been shown to prolong allograft survival in different transplant models. We investigated the effect of combining humanized anti-CD80 and anti-CD86 monoclonal antibodies (mAb) with sirolimus in cynomolgus monkey renal transplant recipients. METHODS: After renal transplantation, groups of four animals were treated daily with sirolimus, sirolimus and nine weekly doses of mAb, two weekly doses of mAb, or sirolimus and two weekly doses of mAb. RESULTS: Survival was significantly better in monkeys treated with the combination of sirolimus and mAb when compared with treatment with either agent alone (P=0.0067 by log-rank analysis). When combined with sirolimus, nine weekly doses of mAb did not result in an additional survival benefit compared with only two mAb doses (P=0.74). None of the treatment regimens used in this study resulted in development of transplantation tolerance. CONCLUSIONS: Sirolimus can be successfully combined with humanized mAb against CD80 and CD86. Induction with a short course of mAb is effective in prolonging allograft survival in combination with sirolimus.
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Anticorpos Monoclonais/uso terapêutico , Antígenos CD/imunologia , Antígeno B7-1/imunologia , Sobrevivência de Enxerto/imunologia , Imunossupressores/farmacologia , Transplante de Rim/imunologia , Glicoproteínas de Membrana/imunologia , Sirolimo/farmacologia , Animais , Anticorpos Monoclonais/sangue , Antígeno B7-2 , Biópsia , Sobrevivência de Enxerto/efeitos dos fármacos , Teste de Histocompatibilidade , Humanos , Transplante de Rim/patologia , Macaca fascicularis , Fatores de Tempo , Transplante Homólogo/imunologiaRESUMO
OBJECTIVES: Cyclosporine (INN: ciclosporin) A or tacrolimus have been used mostly in combination with azathioprine as primary immunosuppression after lung transplantation. Benefit or risk deriving from the combination with mycophenolate mofetil are yet unknown. METHODS: In a prospective, 2-center, open randomized trial, the combination of cyclosporine A, mycophenolate mofetil, and steroids was compared with tacrolimus, mycophenolate mofetil, and steroids as primary therapy after primary lung transplantation. All patients underwent induction therapy with rabbit antithymocyte globulin for 3 days. The 2 groups were compared with regard to patient survival, freedom from acute rejection, bronchiolitis obliterans, infectious episodes, and side effects. RESULTS: Between September 1997 and April 1999, 74 lung transplant recipients were randomized to receive either cyclosporine A (n = 37) or tacrolimus (n = 37). Groups were comparable with regard to age, sex, transplant procedure, and cytomegalovirus match. Mean follow-up was 507 +/- 258 and 508 +/- 248 days, respectively. Six- and 12-month survival was similar in both groups (89% vs 84% and 82% vs 71%, respectively; P =.748 at 12 months). Two patients from the cyclosporine A group were retransplanted. Freedom from acute rejection at 6 and 12 months was comparable between groups (46% vs 51% and 35% vs 46%, respectively; P =.774 at 12 months). The mean number of treated acute rejection episodes per 100 patient-days was higher in the cyclosporine A than in the tacrolimus group, but the difference was not statistically significant (0.32 +/- 0.42 vs 0.22 +/- 0.30, respectively; P =.097). Four patients from the cyclosporine A group had to be switched to tacrolimus to control ongoing rejection, whereas no patient from the tacrolimus group had to be switched to cyclosporine A. There was a trend toward more infections (0.7 +/- 0.36 vs 0.55 +/- 0.31, P =.059) in the cyclosporine A group. New-onset diabetes mellitus was observed in the tacrolimus group only (11% vs 0%, P =.151), whereas there was a higher incidence of hypertension (60% vs 11%, P =.03) in the cyclosporine A group. CONCLUSION: This 2-center, prospective randomized study showed high immunosuppressive potency of both cyclosporine A and tacrolimus in combination with mycophenolate mofetil. No significant difference in incidence of acute rejection was observed between the 2 groups. Moreover, survival and incidence of infection were similar. Incidence of drug-related adverse events were similar, yet their spectrum was different.