RESUMO
Novel direct-acting oral anticoagulants (NOAC) represent an effective new familiy of drugs and an interesting alternative to optimise and simplify anticoagulation. Rates of bleeding complications by NOAC are comparabel to those of warfarin but a previously assumed increase in gastrointestinal bleeding complications was meanwhile confirmed. Therefore, indications and contraindications concerning the use of NOAC should be closely considered. The endoscopic approach of gastrointestinal bleeding is conform to the recommended management of gastrointestinal bleeding complications under conventional anticoagulants or inhibitors of platelet aggregation. There are no specific antidotes to the anticoagulant effects of NOAC in case of bleeding. The recommendation concerning elective endoscopic procedures with high risk of bleeding more or less reflects expert oppinion. There are no recommendations on the basis of randomised studies. However, because of the short plasmatic half-life time of NOAC, their utilisation seems to be well controllable even in cases of high risk endoscopic interventions. More evidence based data about the periinterventional use of NOAC in endoscopic routine, in cases of endoscopic interventions with high bleeding risk or bleeding complications, bridging and the possibility of specific antidots in case of bleeding would be desirable.
Assuntos
Anticoagulantes/administração & dosagem , Endoscopia Gastrointestinal/efeitos adversos , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/prevenção & controle , Pré-Medicação/métodos , Administração Oral , Medicina Baseada em Evidências , Humanos , Resultado do TratamentoRESUMO
UNLABELLED: HISTORY UND CLINICAL FINDINGS: Within a few weeks, two patients aged 16 and 75 years with fever of unknown origin were referred to the emergency unit. INVESTIGATIONS: Laboratory tests revealed increased aminotransferase levels, progressive cytopenia and an increase of inflammatory markers. In the older patient a rapid clinical detoriation with multi organ failure was observed. Progressively increasing levels of ferritin and soluble-interleukin-2-receptor levels led to the diagnosis of hemophagocytic lymphohistiocytosis, which was confirmed by bone marrow examination in the case of the younger patient. TREATMENT AND COURSE: Immunsuppressive treatment induced a clear improvement of clinical and laboratory findings and in the case of the older patient finally led to convalescence. CONCLUSION: Hemophagocytic lymphohistiocytosis is a rare but potentially fatal differential diagnosis, which should be considered in patients with fever and cytopenia.
Assuntos
Artrite Juvenil/sangue , Artrite Juvenil/diagnóstico , Ferritinas/sangue , Febre de Causa Desconhecida/sangue , Febre de Causa Desconhecida/etiologia , Linfo-Histiocitose Hemofagocítica/sangue , Linfo-Histiocitose Hemofagocítica/diagnóstico , Receptores de Interleucina-2/sangue , Adolescente , Idoso , Exame de Medula Óssea , Diagnóstico Diferencial , Serviço Hospitalar de Emergência , Feminino , Humanos , Valor Preditivo dos TestesAssuntos
Emigrantes e Imigrantes , Pancreatopatias/diagnóstico , Pancreatopatias/cirurgia , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/cirurgia , Doenças Raras , Tuberculose/diagnóstico , Tuberculose/cirurgia , Adulto , Antituberculosos/uso terapêutico , Biópsia , Diagnóstico Diferencial , Alemanha , Artéria Hepática/patologia , Humanos , Laparoscopia , Fígado/patologia , Masculino , Invasividade Neoplásica , Paquistão/etnologia , Pâncreas/patologia , Pâncreas/cirurgia , Pancreatopatias/patologia , Neoplasias Pancreáticas/patologia , Veia Porta/patologia , Tomografia Computadorizada por Raios X , Tuberculose/patologia , UltrassonografiaRESUMO
BACKGROUND AND STUDY AIMS: Colon capsule endoscopy (CCE) offers an alternative approach for endoscopic visualization of the colon. Some of the current CCE bowel cleansing regimens use sodium phosphate, which has raised safety concerns. Therefore, the aim of the current study was to test the feasibility and efficacy of a new low-volume, sodium phosphate-free polyethylene glycol (PEG) bowel preparation. METHODS: The first 26 patients (original cleansing procedure) received a colon cleansing regimen of PEG plus ascorbic acid: patients drank 1 L in the evening and 0.75 L in the morning before capsule ingestion. Patients also drank an additional 0.5 L PEG boost and an optional 0.25 L PEG boost during the capsule procedure. Following an interim analysis, the cleansing procedure of the subsequent 24 patients was modified, with the morning intake before capsule ingestion being increased to 1 L, as well as the second boost (0.25 L) being administered 1 - 2 hours earlier (modified cleansing procedure). RESULTS: The overall colon cleanliness was considered to be good or excellent in 83 % (original cleansing procedure) and 82 % (modified cleansing procedure) of patients, without any significant difference between regimens (P > 0.05). In 37 /49 (76 %) of the CCE procedures, the hemorrhoidal plexus was identified and thus the examination was considered complete, with no significant differences between the two CCE cleansing procedures. The capsule sensitivity and specificity for detecting colonic polyps ≥ 6 mm were 91 % (95 %CI 70 % - 98 %) and 94 % (95 %CI 87 % - 97 %), respectively, compared with standard optical colonoscopy. CONCLUSION: A colon cleansing procedure using PEG + ascorbic acid for capsule colonoscopy yielded an adequate cleansing level in > 80 % of patients, a completion rate of 76 %, and good accuracy for detecting polyps. This procedure may be considered as an alternative, particularly for patients in whom sodium phosphate-based preparations are contraindicated.
Assuntos
Endoscopia por Cápsula , Catárticos/administração & dosagem , Pólipos do Colo/diagnóstico , Enema/métodos , Polietilenoglicóis/administração & dosagem , Adulto , Idoso , Ácido Ascórbico/administração & dosagem , Colonoscopia , Feminino , Trânsito Gastrointestinal , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Sensibilidade e EspecificidadeRESUMO
BACKGROUND AND AIM: Natural-orifice transluminal endoscopic surgery (NOTES) is an emerging transluminal technique in which interventions are carried out by entering the abdominal cavity via a natural orifice such as the stomach. Infection is a potential risk of the procedure, and the potential pathogens are different from those encountered with skin incisions. Currently, available data regarding prophylactic anti-infective treatment are limited. We compared the effectiveness of topical antimicrobial lavage of mouth and stomach and proton pump inhibitor therapy with gastric cleansing with sterile saline solution in preventing NOTES-related contamination and infection. METHODS: A randomized survival swine study was performed. Eight pigs underwent preparation with intravenously administered proton pump inhibitors, mouth and gastric lavage (chlorhexidine), and gastric irrigation (diluted neomycin), plus single-shot intravenous antibiotics. Control group (n = 8) underwent gastric cleansing with sterile saline solution. Peritoneal biopsy, multiple smears, and dilutions for cultures were taken and incubated. The swine were sacrificed after 14 days. Bacterial load was expressed in colony-forming units (CFU). RESULTS: One pig died due to gallbladder perforation after 3 days, 2/15 swine presented minor clinical signs of infection in the 14-day follow-up (all 3 pigs were in the control group). Mean C-reactive protein levels were 5.7 +/- 2.4 g/dL (therapy group) and 12.2 +/- 3.8 g/dL (control) ( P = 0.17). Bacterial growth was seen in 1/8 swine (therapy group) and 6/8 swine (control group) ( P = 0.002). Bacterial load was 282 CFU/mL (therapy) vs. 3.2 x 10 (5) CFU/mL (control) ( P = 0.023) in the follow-up. CONCLUSION: The use of intravenous antibiotics in addition to topical antimicrobial lavage of mouth and stomach and treatment with proton pump inhibitors decreased the peritoneal bacterial load to almost zero and this was associated with a significantly lower peritoneal infection rate compared with saline-only lavage.
Assuntos
Antibioticoprofilaxia , Infecções Bacterianas/etiologia , Infecções Bacterianas/prevenção & controle , Procedimentos Cirúrgicos do Sistema Biliar/métodos , Endoscopia/métodos , Gastrostomia/efeitos adversos , Peritônio/microbiologia , Cuidados Pré-Operatórios/métodos , Infecção da Ferida Cirúrgica/prevenção & controle , Animais , Contagem de Colônia Microbiana , Feminino , Lavagem Gástrica , Gastrostomia/métodos , Modelos Animais , Cavidade Peritoneal/cirurgia , Estudos Prospectivos , SuínosRESUMO
BACKGROUND: Today, endoscopic resection is a standard procedure for the resection of colonic polyps. Before the establishment of endoscopic techniques, the surgical approach was a clearly preferred method for removal of polyps with a size larger than three centimeters. The safety and effectiveness concerning endoscopic resections of colorectal polyps also with a size of more than 3 cm have been demonstrated in numerous studies. PATIENTS AND METHODS: Data from 165 patients (age: 68 +/- 10.4 years) harboring 167 polyps with a minimum diameter of 3 cm were retrospectively evaluated. Objects of interest were macroscopic morphology and histopathology of the polyps, their localization in the colon, the modality of endoscopic resection and follow-up. In those cases with macroscopic signs of malignancy the patients were excluded. RESULTS: Successful endoscopic resections were obtained in 72.5 %. Therefrom, resection in the piecemeal-technique was necessary in 73.6 %. Recurrence polyps after endoscopic complete resections occurred in 26.3 % after a mean follow-up of 16 +/- 12.5 months. We registered a complication rate of 19.2 %. Relevant bleeding and perforation were registered as early complications in 18.6 %. We observed no intervention-related mortality. CONCLUSION: Endoscopic mucosal resection is a safe and efficient method even for removing giant colorectal polyps. Controls are recommended at defined intervals for detecting polyp recurrence.
Assuntos
Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Endoscopia Gastrointestinal/métodos , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/prevenção & controle , Idoso , Feminino , Humanos , Masculino , Resultado do TratamentoRESUMO
BACKGROUND AND OBJECTIVE: Benign non-peptic esophageal stricture (BNES) is a rare condition in routine clinical practice. The distribution of different diseases causing BNES is not known and the efficacy and safety of endoscopic treatment in this setting has not been established. PATIENTS AND METHODS: All patients with BNES undergoing endoscopic treatment at our hospital between 2000 and 2006 were assessed retrospectively and questioned by telephone. RESULTS: A total of 26 patients with BNES had been treated at our institution (median age 65 years, range 15-90) during this period. Common causes were esophageal intramural pseudodiverticulosis (n=11), caustic ingestion (n=4) and eosinophilic esophagitis (n=3). Other causes were Schatzki (-Gary) ring, incomplete esophageal atresia, heterotopic gastric mucosa, mucosal pemphigoid, spondylotic caused stenosis, epiphrenic diverticulum, unspecified stenosis. Median time until definitive diagnosis was five-and-a-half years. 20 patients were treated by bougienage, 3 were treated by balloon dilatation, 2 by medication alone and one patient did not require treatment. Lasting successful treatment was achieved in all There were no treatment-related complications. CONCLUSIONS: Benign, non-peptic esophageal stricture is a rare condition in routine clinical practice and can be caused by various diseases. Time to exact diagnosis is often very long. When the underlying diagnosis is clear, excellent results of symptomatic endoscopic therapy can be achieved in a gastroenterological center.
Assuntos
Estenose Esofágica/etiologia , Estenose Esofágica/terapia , Esofagoscopia , Adolescente , Corticosteroides/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Dilatação , Estenose Esofágica/diagnóstico , Feminino , Seguimentos , Humanos , Terapia a Laser , Masculino , Pessoa de Meia-Idade , Recidiva , Retratamento , Estudos Retrospectivos , Adulto JovemAssuntos
Cateteres de Demora , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Assepsia/métodos , Cateteres de Demora/efeitos adversos , Infecção Hospitalar/prevenção & controle , Infecção Hospitalar/transmissão , Desenho de Equipamento , Análise de Falha de Equipamento , Humanos , Infusões IntravenosasRESUMO
Since the introduction of capsule endoscopy and later balloon enteroscopy in clinical practice, endoscopic examination of the small bowel has dramatically improved. For the first time, it is possible to diagnose the whole small bowel without the necessity of laparotomy and intraoperative enteroscopy. The methods revolutionized the field of small bowel diagnostic and therapy and become part of daily clinical practice. This article provides a review of small bowel enteroscopic methods.
Assuntos
Endoscopia Gastrointestinal/métodos , Endoscopia Gastrointestinal/tendências , Aumento da Imagem/métodos , Enteropatias/patologia , Intestino Delgado/patologia , HumanosRESUMO
We report a case of a 43 year old male patient, who was admitted with recurring esophageal bolus impactions. Since his childhood he has been complaining about dysphagia and was unable to swallow medication. He also complained about heartburn. The last esophageal bolus impaction was some weeks ago. After elimination of the bolus impaction with a rigid endoscope we found a high grade stenosis in the proximal esophagus that could not even be passed with a children's endoscope. An initial treatment of eosinophil esophagitis would be the therapy with a local corticoid for 6-9 month. In patients with typical rings or stenosis a dilation therapy might be necessary.
Assuntos
Transtornos de Deglutição/etiologia , Eosinofilia/diagnóstico , Estenose Esofágica/etiologia , Esofagite/diagnóstico , Azia/etiologia , Administração Oral , Adulto , Androstadienos/administração & dosagem , Cateterismo , Terapia Combinada , Transtornos de Deglutição/terapia , Diagnóstico Diferencial , Endoscopia do Sistema Digestório , Eosinofilia/terapia , Estenose Esofágica/terapia , Esofagite/terapia , Fluticasona , Azia/terapia , Humanos , Masculino , Prednisolona/administração & dosagem , RecidivaRESUMO
A 61-year-old man was admitted to hospital due to recurrent upper gastrointestinal bleeding. Four weeks ago, he had been treated with epinephrine and endoclips by endoscopy due to an arterial gastrointestinal bleeding. The patient had a history of coronary and peripheral artery disease, diabetes, and an abdominal aortic aneurysm. Urgent endoscopy suggested the presence of an ulcus Dieulafoy but no definitive bleeding source could be seen. Due to ongoing melena an abdominal computer tomography was performed and a primary aortoduodenal fistula was suspected caused by the infrarenal abdominal aortic aneurysm. Laparatomy was undertaken emergently and an aortoduodenal fistula was found in the descending part of the duodenum. Repair of the duodenal rent was performed and the aortic aneurysm was replaced by a Dacron prosthesis. The patient was transferred to the intensive care unit. 4 days after initial admission, he died due to septic shock.
Assuntos
Aneurisma da Aorta Abdominal/complicações , Doenças da Aorta/diagnóstico , Duodenopatias/diagnóstico , Úlcera Duodenal/complicações , Hemorragia Gastrointestinal/etiologia , Fístula Intestinal/diagnóstico , Fístula Vascular/diagnóstico , Diagnóstico Diferencial , Duodenoscopia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Tomografia Computadorizada por Raios X , UltrassonografiaRESUMO
BACKGROUND AND STUDY AIM: Argon plasma coagulation (APC) has become an established noncontact method of tumor palliation in a variety of locations. The present prospective study evaluated a new APC system (APC-2) using amplified power settings and different application modes, such as intermittent energy delivery (pulsed APC) in comparison with the conventional technique (forced APC). PATIENTS AND METHODS: A total of 100 patients with esophageal, gastric, or rectal tumors were alternately (but not randomized) enrolled and treated with either pulsed APC (n = 46) or forced APC (n = 54). Parameters to assess the palliative effect were: amount of lumen restoration ((1/3), (2/3), complete), objective planimetry, stenosis length, treatment time, and number of APC sessions. RESULTS: Overall response rate was similar in both groups (pulsed 83 %, forced 87 %), the same was found in the subgroups with different amounts of lumen restoration and for the other objective parameters. However, the tumor debulking effect was achieved in a significantly shorter median treatment time with forced compared with pulsed APC (13.6 vs. 18.2 minutes, P = 0.03), with a similar number of treatment sessions in both groups. Complications also occurred with similar frequency in both groups. CONCLUSIONS: There was no significant difference in overall local tumor response between the two modes of APC application. However, data from this nonrandomized study suggest a faster achievement of response with forced APC. A combination of both modes may be superior.
Assuntos
Endoscopia Gastrointestinal/métodos , Estenose Esofágica/cirurgia , Obstrução da Saída Gástrica/cirurgia , Obstrução Intestinal/cirurgia , Fotocoagulação a Laser/instrumentação , Cuidados Paliativos/métodos , Idoso , Desenho de Equipamento , Neoplasias Esofágicas/complicações , Neoplasias Esofágicas/cirurgia , Estenose Esofágica/etiologia , Feminino , Seguimentos , Obstrução da Saída Gástrica/etiologia , Humanos , Obstrução Intestinal/etiologia , Masculino , Estudos Prospectivos , Neoplasias Retais/complicações , Neoplasias Retais/cirurgia , Neoplasias Gástricas/complicações , Neoplasias Gástricas/cirurgia , Resultado do TratamentoRESUMO
BACKGROUND AND OBJECTIVE: The diagnostic approach to newly detected space-occupying lesions in the liver can be difficult and a histogenetic classification of the primary tumor is impossible in some cases. Such cases of metastatic disease without a detectable primary tumor are classified as cancer of unknown primary site (CUP). The incidence of this diagnosis depends on the clinical and histochemical methods used. It was the main aim of this study to analyze the true incidence of adenocarcinoma metastases of the liver with an unknown primary cancer after application of a standardized protocol of clinical and immunhistochemical diagnostic tests and a long-term follow-up. PATIENTS AND METHODS: Between January 2000 and January 2003 127 consecutive patients underwent diagnostic ultrasound-guided biopsy of a space-occupying lesion in the liver. Based on the histopathology and immunochemistry a well defined and individually adapted diagnostic algorithm was employed (endoscopy, imaging). RESULTS: 44 females and 83 males, median age 66.8 years, were enrolled into the study. Primary tumors of the liver were found in 21 cases and non-hepatocellular tumors (metastases) were documented in 106 patients, 82 of the latter (77%) had metastases of an adenocarcinoma. The further diagnostic approach was based on histochemistry, immunhistochemistry and imaging techniques, making possible a full diagnosis of primary tumor in a further 59 (72%) cases. Thus the incidence of an adenocarcinoma of the liver of unknown primary site was 23 of 127 cases (18%). CONCLUSIONS: Although there is a wide variety of modern diagnostic methods today, the histogenetic classification of hepatic metastases is not always possible. However, in the last few years diagnostic advances have occurred based on modern immunhistochemical methods. This immunhistochemical definition has made it possible to avoid an oppressive "overdiagnosis" and offer patients early and appropriate therapeutic options.
Assuntos
Adenocarcinoma/secundário , Neoplasias Hepáticas/secundário , Neoplasias Primárias Desconhecidas/diagnóstico , Adenocarcinoma/diagnóstico , Adenocarcinoma/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Diagnóstico Diferencial , Feminino , Humanos , Imuno-Histoquímica , Incidência , Avaliação de Estado de Karnofsky , Fígado/diagnóstico por imagem , Fígado/patologia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/epidemiologia , Masculino , Pessoa de Meia-Idade , Neoplasias Primárias Desconhecidas/epidemiologia , Neoplasias Primárias Desconhecidas/patologia , Prognóstico , UltrassonografiaRESUMO
BACKGROUND: The NeoGuide Endoscopy System (NES) utilizes a fully articulated, computer-controlled insertion tube that allows proximal segments of the colonoscope to follow the path taken by the tip as it is manually advanced through the colon. The system was designed to eliminate looping and scope displacement during colonoscopy. MATERIAL AND METHODS: Using in vitro testing, an inanimate flexible model of the colon incorporating four force transducers located at the key flexure points was employed to measure the axial forces on the colon wall during colonoscopy. In the second part of the study, 10 gastroenterologists performed colonoscopies, using a training latex-based simulator, with the NES and with a standard colonoscope. Colonic displacement was independently assessed by six gastroenterologists, with each evaluating endoscopist assigning a score between 0 and 5 corresponding to the maximum colonic displacement observed at any location. RESULTS: The average measured forces (in lbs) at three of the four flexure points were significantly lower ( P < 0.05) when the NES was used. The mean colonic displacement was significantly lower for procedures performed with the NES compared with the standard colonoscope (2.36 vs. 4.26, P < 0.001). Interobserver agreement regarding the degree of colonic displacement due to looping was moderate (weighted kappa = 0.45, P < 0.01). CONCLUSIONS: Colonoscopy with the NES was associated with significantly less looping and lateral force required for advancement than procedures with a standard colonoscope. The reduced amount of looping suggests that use of the NES in patients might be associated with less discomfort and thus require less sedation.
Assuntos
Colonoscópios , Colonoscopia/métodos , Fenômenos BiomecânicosRESUMO
BACKGROUND: Endoscopic screening for Barrett's esophagus is an accepted base for surveillance strategies of Barrett's esophagus; data on the natural history of erosive gastroesophageal reflux disease (ERD) are sparse. Therefore, we performed a prospective long-term follow-up examination of the course of ERD to confirm the recommendation of a once-in-lifetime endoscopy as a screening programme for Barrett's esophagus. METHODS: Patients not older than 60 years with reflux symptoms and a first time diagnosis of ERD or Barrett's esophagus at the time of inclusion were identified. Patients were followed up by a further upper GI endoscopy after at least 5 years. They were interviewed about clinical symptoms and medication use. RESULTS: One hundred and thirty-five patients were included. Follow-up data were obtained for 115 patients. Seventy-one patients (22 female, 49 male, average age: 48.3 years; range: 22-60 years) remained in the programme, 37 patients died from unrelated diseases within the follow-up period (mostly due to cardiovascluar diseases). Seven patients were excluded because of missing videoendoscopy. The average follow-up period was 78.3 (range: 60-85) months. During this time, 76 % of the patients received medical therapy. Only three patients (4.5 %) showed progression of erosive lesions, whereas two patients developed a short-segment Barrett's esophagus without intraepithealial neoplasia. These 5 patients received no medical therapy. CONCLUSIONS: Progression of ERD is an unlikely event. Once-in-lifetime endoscopy is an adequate screening tool that may serve as a basis for a Barrett's esophagus surveillance program.
Assuntos
Esôfago de Barrett/diagnóstico , Endoscopia Gastrointestinal , Refluxo Gastroesofágico/diagnóstico , Programas de Rastreamento/métodos , Medição de Risco/métodos , Adulto , Progressão da Doença , Seguimentos , Humanos , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Reprodutibilidade dos Testes , Fatores de Risco , Sensibilidade e EspecificidadeRESUMO
Photodynamic therapy (PDT) is an established treatment for the ablation of dysplastic Barrett's epithelium and early esophageal carcinoma, but no data have been published on curative 5-aminolevulinic acid (5-ALA)-PDT for long-segment early esophageal cancer with infiltration of the upper sphincter. We describe successful curative treatment of an unusual early long-segment squamous cell carcinoma (uT1a,N0) of the proximal esophagus (18 - 28 cm aborally), with three sessions of 5-ALA-PDT. Endoscopic and endosonographic follow-up macroscopically showed a complete remission of the tumor, proven by biopsy showing total histological ablation. After a follow-up period of 23 months, there has been no indication of tumor recurrence. Early superficial (< 3 mm) squamous cell carcinomas of the esophagus can be ablated completely by 5-ALA-PDT. However, long-term follow-up is required in order to prove the effectiveness of endoscopic ablation therapy for early esophageal cancer.
Assuntos
Ácido Aminolevulínico/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias Esofágicas/tratamento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Biópsia , Carcinoma de Células Escamosas/patologia , Intervalo Livre de Doença , Endoscopia Gastrointestinal , Neoplasias Esofágicas/patologia , Seguimentos , Humanos , Pessoa de Meia-Idade , Fatores de TempoRESUMO
Potential synergistic interaction between gemcitabine (GEM) and epirubicin (EPI) in pancreatic cancer have been described previously. The maximum-tolerated dose in this trial was GEM 1000 mg m(-2) and EPI 45 mg m(-2). Median time to progression was 5.1 months and median survival time 7.4 months. This combination appears well tolerated and shows promising clinical activity.