RESUMO
One of the most common reasons to consult a coloproctologist is symptomatic haemorrhoids. Typical signs and symptoms as well as a specialised examination, including proctoscopy, are essential for the correct diagnosis. The vast majority of patients can be treated conservatively with excellent results in terms of quality of life. Sclerotherapy provides good control of symptoms at any stage of haemorrhoidal disease. If conservative treatment fails, there are various surgical options. A tailored approach is mandatory. Besides well-known procedures such as Fergusson, Milligan-Morgan procedure or haemorrhoidopexy (Longo) there are less invasive options such as HAL-RAR, IRT, LT and RFA. Postoperative bleeding, pain and faecal incontinence are rare complications after surgery.
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Incontinência Fecal , Hemorroidas , Humanos , Qualidade de Vida , Ligadura/efeitos adversos , Ligadura/métodos , Hemorroidas/diagnóstico , Hemorroidas/cirurgia , Resultado do TratamentoRESUMO
BACKGROUND: Patients with peritoneal metastases of gastric cancer have a poor prognosis with a median survival of 7 months. A benefit of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) could be shown in several selected patient cohorts but remains controversial. The aim of this study was, to reflect the results of a national German HIPEC registry initiated by the German Society of General and Visceral Surgery (DGAV). METHODS: The DGAV HIPEC registry StuDoQ|Peritoneum documents patients with peritoneal malignancy contributed from 52 hospitals. All consecutive documented patients from 2011 until 2016 (n = 3078) were treated with CRS and HIPEC and were analysed. A total of 315 (10%) suffered from gastric cancer and were analysed. RESULTS: A complete data set of 235 patients was available for this study, including 113 male (48.1%) and 122 female (51.9%) patients with a median age of 53.4 years (SD ± 11.9). The median PCI was 8.0 (range 1-30). A complete cytoreduction was achieved in 121 patients (71.6%). Postoperative complications (Clavien-Dindo grades 3-4) occurred in 40 patients (17%). The median overall survival (OS) time was 13 months. The 5-year survival rate was 6%. According to the PCI from 0-6 (n = 74); 7-15 (n = 70) and 16-39 (n = 24) the median OS differs significantly (18 months vs. 12 months vs. 5 months; p = 0.002). CONCLUSIONS: CRS and HIPEC in selected patients with gastric cancer and peritoneal spread can improve survival when they are treated in centers. An accurate staging and patient selection are of major importance to achieve long-term survival.
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Neoplasias Peritoneais/secundário , Neoplasias Peritoneais/terapia , Neoplasias Gástricas/patologia , Neoplasias Gástricas/terapia , Adulto , Antineoplásicos/uso terapêutico , Procedimentos Cirúrgicos de Citorredução , Bases de Dados Factuais , Feminino , Alemanha , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Neoplasias Peritoneais/mortalidade , Complicações Pós-Operatórias , Neoplasias Gástricas/mortalidade , Taxa de SobrevidaRESUMO
BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are performed for well-selected patients with peritoneal surface malignancies. This combined treatment is potentially associated with an increased rate of complications. OBJECTIVE: The aim of this paper was to analyze the morbidity and mortality of CRS and HIPEC in the German national registry. METHODS: We present a retrospective analysis of 2149 consecutive patients from 52 hospitals. The data were prospectively documented in the DGAV StuDoQ Registry between February 2011 and December 2016. RESULTS: Almost two-thirds of all patients had a colorectal malignancy; therefore, the most frequently performed resections were colectomies (54%) and rectal resections (30%). Only 36.2% of all patients had no anastomosis, and fewer than 20% of all patients were older than 70 years of age (16.4%). Enteric fistula and anastomotic leaks occurred in 10.5% of all cases. The reoperation rate was 14.6% (95% confidence interval [CI] 11.51-18.1). Major grade 3 and 4 complications (Clavien-Dindo classification) occurred in 19.3% of all patients, half of which were due to surgical complications. The overall 30-day postoperative hospital mortality was 2.3% (95% CI 1.02-3.85). Multivariate analysis showed an increased risk for morbidity associated with pancreatic resections (odds ratio [OR] 2.4), rectal resection (OR 1.5), or at least one anastomosis (OR 1.35), and mortality with reoperation (OR 8.7) or age > 70 years (OR 3.35). CONCLUSIONS: CRS and HIPEC are associated with acceptable morbidity and low mortality. These results show that CRS and HIPEC can be safely performed nationwide when close mentoring by experienced centers is provided.
Assuntos
Quimioterapia do Câncer por Perfusão Regional/mortalidade , Procedimentos Cirúrgicos de Citorredução/mortalidade , Mortalidade Hospitalar/tendências , Hipertermia Induzida/mortalidade , Morbidade , Neoplasias Peritoneais/mortalidade , Idoso , Terapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Neoplasias Peritoneais/patologia , Neoplasias Peritoneais/terapia , Prognóstico , Sistema de Registros , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) as parts of an interdisciplinary treatment concept including systemic chemotherapy can improve survival of selected patients with peritoneal metastatic colorectal cancer (pmCRC). Nevertheless, the sequence of the therapeutic options is still a matter of debate. Thus, the COMBATAC (COMBined Anticancer Treatment of Advanced Colorectal cancer) trial was conducted to evaluate a combined treatment regimen consisting of preoperative systemic polychemotherapy + cetuximab followed by CRS + HIPEC and postoperative systemic polychemotherapy + cetuximab. PATIENTS AND METHODS: The COMBATAC trial is a prospective, multicenter, open-label, single-arm, single-stage phase 2 trial. Twenty-six patients with synchronous or metachronous colorectal or appendiceal peritoneal carcinomatosis were included. Enrollment was terminated prematurely by the sponsor because of slow recruitment. Progression-free survival as primary end point and overall survival were estimated by the Kaplan-Meier method. Also evaluated were morbidity according to Common Terminology Criteria for Adverse Events v4.0 and feasibility of the combined treatment concept. RESULTS: Median progression-free survival for the intention-to-treat population (n = 25) was 14.9 months. Median overall survival was not reached during the study duration. Ninety-two adverse events were documented in 16 patients, including 14 serious adverse events in 9 patients. The overall morbidity rate was 64%, and the grade 3/4 morbidity rate was 44%. Of all grade 3/4 morbidity events, 36.4% were related to systemic chemotherapy and 22.7% to surgery, whereas 40.9% were not directly related. There was no treatment-related mortality. CONCLUSION: The results of the COMBATAC trial show that the multimodal treatment concept consisting of perioperative systemic chemotherapy and CRS + HIPEC is safe and feasible. Progression-free survival in selected patients with colorectal or appendiceal peritoneal metastasis might be improved.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/terapia , Procedimentos Cirúrgicos de Citorredução/métodos , Hipertermia Induzida/métodos , Neoplasias Peritoneais/terapia , Adulto , Idoso , Neoplasias Colorretais/patologia , Terapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Peritoneais/secundário , Prognóstico , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
BACKGROUND: In recent years, there has been a significant change in the treatment recommendations for acute diverticulitis. In order to provide the right treatment to the individual patient, it is therefore important to classify the stage of the disease accurately, after taking various aspects into consideration. METHODS: Patients treated for acute diverticulitis in Würzburg University Hospital during 2010 to 2014 were included. Inclusion criteria were the presence of a computer tomography for disease classification. RESULTS: More than half of the patients examined (n = 135, 52.9%) had acute uncomplicated diverticulitis on admission; 112 (43.2%) had a covered perforation (small paracolic abscess n = 63, 24,3%; large abscess n = 49, 18,9%) and 12 (4.6%) a free perforation. In a total of 150 (57.9%) patients, this was the first episode of diverticulitis, with a covered (66.1%) or a free perforation (75.0%) occurring at a higher than average rate as the first manifestation. Nearly two-thirds (66.4%, n = 168) of patients underwent sigmoid resection during follow-up. DISCUSSION AND CONCLUSION: Despite current trends towards more conservative therapy of acute diverticulitis, sigmoid resection remains a corner stone of successful therapy throughout all types of acute diverticulitis. The indication of sigmoid resection nowadays requires profound knowledge of the individual prognosis for recurrent diverticulitis and quality of life.
Assuntos
Diverticulite , Doença Aguda , Estudos de Coortes , Diverticulite/classificação , Diverticulite/diagnóstico , Diverticulite/epidemiologia , Diverticulite/terapia , Feminino , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de DoençaRESUMO
AIM: The aim of this official guideline published by the German Society of Gynecology and Obstetrics (DGGG) and coordinated with the German Society of Urology (DGU) and the German Society of Reproductive Medicine (DGRM) is to provide consensus-based recommendations, obtained by evaluating the relevant literature, on counseling and fertility preservation for prepubertal girls and boys as well as patients of reproductive age. Statements and recommendations for girls and women are presented below. Statements or recommendations for boys and men are not the focus of this guideline. METHODS: This S2k guideline was developed at the suggestion of the guideline commission of the DGGG, DGU and DGRM and represents the structured consensus of representative members from various professional associations (n = 40). RECOMMENDATIONS: The guideline provides recommendations on counseling and fertility preservation for women and girls which take account of the patient's personal circumstances, the planned oncologic therapy and the individual risk profile as well as the preferred approach for selected tumor entities.
RESUMO
BACKGROUND: The treatment strategies for colorectal cancer located in the right side of the colon have changed dramatically during the last decade. Due to the introduction of complete mesocolic excision (CME) with central ligation of the vessels and systematic lymph node dissection, the long-term survival of affected patients has increased significantly. It has also been proposed that right-sided colon resection can be performed laparoscopically with the same extent of resection and equal long-term results. METHODS: A retrospective evaluation of a prospectively expanded database on right-sided colorectal cancer or adenoma treated at the University Hospital of Wuerzburg between 2009 and 2016 was performed. All patients underwent CME. This data was analyzed alone and in comparison to the published data describing laparoscopic right-sided colon resection for colon cancer. RESULTS: The database contains 279 patients, who underwent right-sided colon resection due to colorectal cancer or colorectal adenoma (255 open; 24 laparoscopic). Operation data (time, length of stay, time on ICU) was equal or superior to laparoscopy, which is comparable to the published results. Surprisingly, the surrogate parameter for correct CME (the number of removed lymph nodes) was significantly higher in the open group. In a subgroup analysis only including patients who were feasible for laparoscopic resection and had been operated with an open procedure by an experienced surgeon, operation time was significantly shorter and the number of removed lymph nodes is significantly higher in the open group. CONCLUSION: So far, several studies demonstrate that laparoscopic right-sided colon resection is comparable to open resection. Our data suggests that a consequent CME during an open operation leads to significantly more removed lymph nodes than in laparoscopically resected patients and in several so far published data of open control groups from Europe. Further prospective randomized trials comparing the long-term outcome are urgently needed before laparoscopy for right-sided colon resection can be recommended ubiquitously.
Assuntos
Adenocarcinoma/cirurgia , Adenoma/cirurgia , Colectomia/métodos , Neoplasias do Colo/cirurgia , Mesocolo/cirurgia , Adenocarcinoma/patologia , Adenoma/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Colo/patologia , Grupos Controle , Bases de Dados Factuais , Feminino , Humanos , Laparoscopia , Excisão de Linfonodo , Linfonodos/patologia , Linfonodos/cirurgia , Metástase Linfática , Masculino , Mesocolo/irrigação sanguínea , Mesocolo/patologia , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
Introdurction: Current guidelines for malignant melanoma do not set a concrete cutoff limit for the number of lymph nodes to be resected during regional lymph node dissection (LND). Here, we investigate if extended LND (ext-LND) has an impact on surgical morbidity and oncological outcome in melanoma patients. MATERIAL AND METHODS: A total of 245 melanoma patients receiving axillary or inguinal LND in curative intention were investigated retrospectively. Ext-LND was defined as axillary LND with 20 or more and inguinal LND with 10 or more resected lymph nodes. Surgical morbidity and regional recurrence-free survival were investigated. RESULTS: Ext-LND did not lead to increased surgical morbidity in the overall study collective. After ext-LND, 55.4% of the patients experienced one of the investigated complications compared to 46.2% in the limited LND group (p = .2113). There was no difference in the occurrence of lymphatic fistula, wound infection, severe bleeding or neurological complications. In addition, patients with positive lymph node status showed improved regional recurrence-free survival following ext-LND (p = .0425). CONCLUSION: Ext-LND can be considered a quality marker of LND in melanoma patients.
Assuntos
Excisão de Linfonodo , Linfonodos/cirurgia , Melanoma/mortalidade , Adulto , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Excisão de Linfonodo/efeitos adversos , Linfonodos/patologia , Masculino , Melanoma/cirurgia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Complicações Pós-Operatórias , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
The use of problem-based learning (PBL) in the Charité Berlin Human Medicine model curriculum requires the annual training of 80 to 100 new PBL tutors using PBL tutor training (PTT). Therefore, the following three measures were taken: The existing traditional PTT (Trad-PTT) was further developed into an interactive PTT (Inter-PTT), which is using more interactive teaching tools. Both PTT concepts ran for 12 months, respectively. The review of the Inter-PTT was significantly better, as the PBL tutors understood their tasks within the PBL process better and felt more motivated. A follow-up survey after the initial experience with PBL confirmed almost all the positive aspects of the Inter-PTT. In addition, the Inter-PTT was also offered to non-clinicians and other scientific staff to make the training interdisciplinary. PTT made it possible to communicate beyond specialist boundaries; however, the interdisciplinary idea was no longer detectable in the follow-up survey. In order to increase the number of available PBL tutors, a self-commitment was introduced for the departments. This increased the number of "involuntary" participants for PTT, but reduced the amount of necessary training courses. The fulfilment of self-commitment succeeded in almost all departments. A PTT tailored to the needs of the tutors is a basic prerequisite in order to excite teachers about PBL and to familiarise them with their role as learning facilitators. The increase of interactive teaching forms led to a joint interdisciplinary learning process within PTT. The excellent review of Inter-PTT makes it a solid basis for further training concepts.
Assuntos
Currículo , Educação Médica , Aprendizagem Baseada em Problemas , Berlim , Humanos , Aprendizagem , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Due to its primarily extraperitoneal location, potential affection of the anorectal continence and different metastatic behavior the rectal carcinoma (RC) is classified and treated as an independent disease. Over the past few decades various trials have led to improved multimodal therapies (including radiation, chemotherapy and surgery) for locally advanced rectal cancer and significant changes in the management of this disease whereas the benefit of adjuvant chemotherapy remains unclear. METHODS: Based on a prospective tumor register of the University Hospital of Wuerzburg data of 263 patients having undergone neoadjuvant therapy and surgical resection for locally advanced rectal cancer were retrieved from the Wuerzburg International database (WID) between October 1992 and September 2013 analyzing the overall survival according to the application of an adjuvant therapy. RESULTS: The cohort consisted of 263 patients with a median age of 65 years (27-89 years), mostly male gender (n = 191; 72.6%) and an ASA performance score of II or III. 143 patients (54.3%) received an adjuvant therapy. Those patients have been significant younger (median 10 years; p < 0.05) and in a better general condition (ASA-score; p < 0.05). The tumor specific overall survival of adjuvant treated patients was significant better (5-years overall-survival 87.4%; p = 0.025) than the surveillance group. In the performed subgroup analysis no significant differences in overall survival according to the kind of neoadjuvant therapy (radiation vs. radiochemotherapy) have been found whereas patients in lower UICC-stages (ypUICC 0 + I) had a significant benefit by receiving a postoperative chemotherapy (p = 0.035). CONCLUSION: We considered patients with locally advanced rectal cancer have a significant benefit in overall survival by receiving an adjuvant chemotherapy especially in lower pathological tumor stage (ypUICC 0 + I). Especially because of the heterogeneity of our study population prospective randomized trials are necessary to determine the impact of adjuvant chemotherapy for locally advanced rectal cancer.
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Adenocarcinoma/mortalidade , Quimiorradioterapia/mortalidade , Quimioterapia Adjuvante/mortalidade , Terapia Neoadjuvante/mortalidade , Neoplasias Retais/mortalidade , Adenocarcinoma/patologia , Adenocarcinoma/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Prospectivos , Neoplasias Retais/patologia , Neoplasias Retais/terapia , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
AIM: The treatment of peritoneal surface malignancies ranges from palliative care to full cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy, HIPEC. Ongoing monitoring of patient recruitment and volume is usually carried out through dedicated registries. With multiple registries available worldwide, we sought to investigate the nature, extent and value of existing worldwide CRS and HIPEC registries. METHODS: A questionnaire was sent out to all known major treatment centres. The questionnaire covers: general purpose of the registry; inclusion criteria in the registry; the date the registry was first established; volume of patients in the registry and description of the data fields in the registries. Finally, the population size of the catchment area of the registry was collected. RESULTS: Twenty-seven questionnaires where returned. National databases are established in northwest European countries. There are five international general databases. Most database collect data on patients who have undergone an attempt to CRS and HIPEC. Two registries collect data on all patients with peritoneal carcinomatosis regardless the treatment. Most registries are primarily used for tracking outcomes and complications. When correlating the number of cases of CRS and HIPEC that are performed to the catchment area of the various registry, a large variation in the number of performed procedures related to the overall population was noted, ranging from 1.3 to 57 patients/million year with an average of 15 patients/1 million year. CONCLUSIONS: CRS and HIPEC is a well-established treatment for peritoneal surface malignancies worldwide. However, the coverage as well as the registration of treatment procedures differs widely. The most striking difference is the proportion of HIPEC procedures per capita which ranges from 1.3 to 57 patients per million. This suggests either a difference in patient selection, lack of access to HIPEC centres or lack of appropriate data collection.
Assuntos
Neoplasias Peritoneais/diagnóstico , Feminino , Humanos , Masculino , Neoplasias Peritoneais/terapia , Sistema de RegistrosRESUMO
BACKGROUND: Inguinal lymph node dissection (LND) is a surgical procedure with a high morbidity rate. Variations in surgical procedure, such as sparing of the saphenous vein, have been proposed to reduce surgical morbidity. While sparing of the saphenous vein has shown promising results in earlier studies, data for this procedure in melanoma patients are rare. In this retrospective study, we report 10-year findings on the effects of saphenous vein-sparing LND on surgical morbidity and oncologic outcomes in melanoma patients. METHODS: A retrospective analysis of melanoma patients receiving inguinal LND in our facility between 2003 and 2013 was performed. Patients were divided into two groups: the saphenous vein resection group and the vein sparing group. Surgical morbidity, including wound infection, lymphatic fistula, severe bleeding, neurological complications, and chronic lymphedema, as well as regional recurrence-free survival were investigated. RESULTS: A total of 106 patients were included in this study; of these, the saphenous vein was spared in 41 patients (38.7%). The rate of lymphatic fistula was 51.6 vs. 48.8%, wound infection occurred in 31.3 vs. 24.4%, and patients suffered from chronic lymphedema in 30.0 vs. 26.5% in V. saphena magna resection vs. sparing group. Differences observed, however, were not significant. No difference in regional recurrence-free survival between the two study groups was detected. CONCLUSIONS: The results of our retrospective analysis could not confirm the promising results reported in earlier studies. Thus, sparing of the saphenous vein appears to be optional.
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Canal Inguinal/patologia , Excisão de Linfonodo/mortalidade , Melanoma/mortalidade , Recidiva Local de Neoplasia/mortalidade , Complicações Pós-Operatórias , Veia Safena/patologia , Feminino , Seguimentos , Humanos , Canal Inguinal/cirurgia , Masculino , Melanoma/patologia , Melanoma/cirurgia , Pessoa de Meia-Idade , Morbidade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Veia Safena/cirurgia , Taxa de SobrevidaRESUMO
BACKGROUND: Comprehensive evidence on the incidence, time course and independent risk factors of metachronous peritoneal carcinomatosis (metaPC) in gastric cancer patients treated with curative intent in the context of available systemic combination chemotherapies is lacking. METHODS: Data from a prospectively collected single-institutional Center Cancer Registry with 1108 consecutive patients with gastric adenocarcinoma (GC), clinical, histological and survival data were analyzed for independent risk factors and prognosis with focus on the development of metaPC. Findings were then stratified to the time periods of treatment with surgery alone, 5-Fluorouracil-only and contemporary combined systemic perioperative chemotherapy strategies, respectively. RESULTS: Despite R0 D2 gastrectomy (n = 560), 49.6% (±5.4%) of the patients were diagnosed with tumour recurrence and 15.5% (±1.8%) developed metaPC after a median time of 17.7 (15.1-20.3) months after surgery resulting in a tumour related mortality of 100% with a median survival of 3.0 months (2.1 - 4.0). Independent risk factors for the development of metaPC were serosa positive T-category, nodal positive-status, signet cell and undifferentiated gradings (G3/G4). Contemporary systemic combination chemotherapy did not improve the incidence and prognosis of metaPC (p = 0.54). CONCLUSIONS: Despite significant improvements in the overall survival for the complete cohort with gastric cancer over time, those patients with metaPC did not experience the same benefits. The lack of change in the incidence, and persistent poor prognosis of metaPC after curative surgery expose the need for further prevention and/or improved treatment options for this devastating condition.
Assuntos
Segunda Neoplasia Primária/epidemiologia , Neoplasias Peritoneais/epidemiologia , Neoplasias Gástricas/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Bases de Dados Factuais , Feminino , Humanos , Incidência , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Mortalidade , Estadiamento de Neoplasias , Sistema de Registros , Fatores de Risco , Neoplasias Gástricas/terapia , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
Tumor involvement of the peritoneum-peritoneal carcinomatosis-is a heterogeneous form of cancer that had been generally regarded as a sign of systemic tumor disease and as a terminal condition. The multimodal treatment approach for patients with peritoneal carcinomatosis, which had been conceived and developed, consists of what is known as cytoreductive surgery, followed by hyperthermic intraperitoneal chemotherapy (HIPEC). Depending on the tumor mass as assessed intraoperatively and the histopathological differentiation, patients who undergo cytoreductive surgery and HIPEC have a significant survival benefit. Mean increases in the survival period ranging from six months to up to four years have now been reported. In view of the substantial logistic effort and the extent of the surgery involved, this treatment approach represents a major challenge both for patients and for surgical oncologists, as well as for the members of the overall interdisciplinary structure required, which includes oncology, anesthesiology and intensive care, psycho-oncology, and patient management. The surgical procedures alone may take 8-14 hr. The present paper provides an overview of the basis for the approach and the use of specialized classifications and quantitative prognostic indicators.
Assuntos
Antineoplásicos/administração & dosagem , Hipertermia Induzida/métodos , Neoplasias Peritoneais/terapia , Peritônio/cirurgia , Terapia Combinada , Humanos , Injeções Intraperitoneais , Laparoscopia , Neoplasias Peritoneais/mortalidade , PrognósticoRESUMO
PURPOSE: To investigate a potential mode of noninvasive screening for colorectal cancer, we evaluated the hypermethylation of the secreted frizzled-related protein-1 gene promoter in human stool DNA. METHODS: In stool samples from 36 patients with colorectal neoplasia (7 adenoma, 29 colorectal cancer) and 17 healthy control subjects, isolated DNA was treated with sodium bisulfite and analyzed by methylation-specific polymerase chain reaction with primers specific for methylated or unmethylated promoter sequences of the secreted frizzled-related protein-1 gene. RESULTS: Hypermethylation of the secreted frizzled-related protein-1 promoter was present in the stool DNA of patients with adenoma and colorectal cancer. A sensitivity of 89 percent and specificity of 86 percent were achieved in the detection of colorectal neoplasia. The difference in hypermethylation status of the secreted frizzled-related protein-1 promoter between the patients with colorectal neoplasia and the control group was statistically highly significant (P < 0.001). Adenoma and early tumor Stage I (International Union Against Cancer) displayed both unmethylated and methylated secreted frizzled-related protein-1 promoter sequences, whereas advanced tumor stages showed only methylated secreted frizzled-related protein-1 (P = 0.05). CONCLUSIONS: The results indicate that this DNA stool test of hypermethylation of the secreted frizzled-related protein-1 promoter is a sensitive and specific method. It has the potential of a clinically useful test for the early detection of colorectal cancer.
Assuntos
Adenoma/metabolismo , Carcinoma/metabolismo , Neoplasias Colorretais/metabolismo , Metilação de DNA , Fezes , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Proteínas de Membrana/metabolismo , Adenoma/diagnóstico , Adenoma/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma/diagnóstico , Carcinoma/genética , Estudos de Casos e Controles , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , Estudos de Viabilidade , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/genética , Masculino , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Regiões Promotoras Genéticas/fisiologiaRESUMO
Dyggve-Melchior-Clausen syndrome (DMC) (MIM 223800) and Smith-McCort dysplasia (SMC) (MIM 607326) are rare allelic autosomal recessive spondylo-epi-metaphyseal dysplasias (SEMDs) characterized by similar skeletal manifestations. Both phenotypes have been mapped to chromosome 18q21.1 and mutations in the DYM (dymeclin) gene were identified in 13 families with DMC and in two families with SMC. Most mutations identified in DMC predict a loss of function, while those identified in SMC are mainly missense mutations, presumably associated with residual DYM activity and a less severe phenotype. We studied three consanguineous families from Turkey, Lebanon, and Georgia, one with SMC and two with DMC and identified different homozygous DYM mutations (IVS3 194-1G > A, 938_942delTGTCT) in the DMC families. No mutation was identified in the SMC family, possibly suggesting genetic heterogeneity of this disorder.