Combined morphologic-metabolic biomarkers from [18F]FDG-PET/CT stratify prognostic groups in low-risk NSCLC.

AIM: The aim of this study was to derive prognostic parameters from 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG-PET/CT) in patients with low-risk NSCLC and determine their prognostic value. METHODS: 81 (21 female, mean age 66 a) therapy-naive patients that underwent [18F]FDG-PET/CT before histologic confirmation of NSCLC with stadium I and II between 2008-2016 were included. A mean follow-up time of 58 months (13-176), overall and progression free survival (OS, PFS) were registered. A volume of interest for the primary tumor was defined on PET and CT images. Parameters SUVmax, PET-solidity, PET-circularity, and CT-volume were analyzed. To evaluate the prognostic value of each parameter for OS, a minimum p-value approach was used to define cutoff values, survival analysis, and log-rank tests were performed, including subgroup analysis for combinations of parameters. RESULTS: Mean OS was 58±28 months. Poor OS was associated with a tumor CT-volume >14.3 cm3 (p=0.02, HR=7.0, CI 2.7-17.7), higher SUVmax values >12.2 (p=0.003; HR=3.0, CI 1.3-6.7) and PET-solidity >0.919 (p=0.004; HR=3.0, CI 1.0-8.9). Combined parameter analysis revealed worse prognosis in larger volume/high SUVmax tumors compared to larger volume/lower SUVmax (p=0.028; HR=2.5, CI 1.1-5.5), high PET-solidity/low volume (p=0.01; HR=2.4, CI 0.8-6.6) and low SUVmax/high PET-solidity (p=0.02, HR=4.0, CI 0.8-19.0). CONCLUSION: Even in this group of low-risk NSCLC patients, we identified a subgroup with a significantly worse prognosis by combining morphologic-metabolic biomarkers from [18F]FDG-PET/CT. The combination of SUVmax and CT-volume performed best. Based on these preliminary data, future prospective studies to validate this combined morphologic-metabolic imaging biomarker for potential therapeutic decisions seem promising.

Outcome of infrainguinal prosthetic graft infections depending on the surgical management.

BACKGROUND: To evaluate the outcome of different therapeutic pathways to manage infrainguinal prosthetic graft infections. METHODS: In this study a total of 66 patients treated between 1993 and 2009 (48 males and 18 females) were included. Subgroups were formed according to the following options of surgical management: excision of the grafts with or without arterial reconstruction (including prosthetic grafts and vein grafts), primary amputation, and surgical debridement with negative wound pressure therapy. Additionally, mortality, amputation rate, re-infection rate, and microbiological findings were analyzed. RESULTS: Mean age was 65.64±11.33 y and follow up was 22.21±36.85 mo. Thirty-day survival rate was 89.5%±4.1%, overall limb salvage rate was 82.5%±5.1%. In the group with primary amputation, one patient (20%) died; however, in the group of surgical debridement with negative wound pressure therapy, mortality was nil. In the group with graft excision, seven patients died (14.3%); no difference between the study groups was found (p=0.058). Amputation rate was 10% (n=5), 0% and 20.4% (n=10), respectively, with a higher rate in the primary amputation group (p<0.001). Reinfection rate was 0%, 8.3% (n=1) and 14.2% (n=7) respectively; p=0.822. Also, no difference was found regarding bypass level or revascularization graft material. CONCLUSION: Mortality and amputation rate is still high after infrainguinal prosthetic graft infection. Our strategy to preserve the graft whenever possible showed no difference compared with more aggressive strategies.

Platypnea-orthodeoxia: a rare complication after repair of a contained rupture of an abdominal aortic aneurysm.

After open repair of a contained rupture of a giant abdominal aortic aneurysm, the patient, a 67-year-old man, developed respiratory insufficiency, and his hemoglobin oxygen saturation dramatically decreased when his position was changed from supine to upright. Transesophageal echocardiography revealed platypnea-orthodeoxia syndrome due to a patent foramen ovale and subsequent right-to-left-shunting despite normal intracardiac pressures. After interventional patent foramen ovale closure, the patient could be separated from the respirator without difficulty.

The diabetic patient has a higher benefit from infrapopliteal revascularization than the non-diabetic patient: a 10-year retrospective study.

OBJECTIVE: The objective of this article is to evaluate the limb salvage and patency rates after crural arterial revascularization, differences between graft material and co-morbidities. PATIENTS AND METHODS: All patients with crural artery bypasses were analysed retrospectively in a single centre (Department of Vascular Surgery, Thüringen Kliniken Saalfeld, Rudolstadt, Germany) over a 10-year period (1996-2006); 157 patients with 170 consecutive arterial reconstructions could be included. RESULTS: Follow-up time was 55 months (6-119). Median age of the 56 women and the 101 men at the time of operation was 70 years (45.6-93.6). The five-year secondary patency rates were 71.5 ± 6.22% (vein), 44.3 ± 10.8% (composite; p = 0.0011), 52.6 ± 13.4% (prosthetic graft with distal vein cuff/patch; p = 0.00953) and 42 ± 12% (prosthetic graft without distal vein cuff/patch; p = 0.00443). Limb salvage rates after five years were 79.5 ± 5.8%, 61.6 ± 10.3%, 77.9 ± 11.3% and 70.1 ± 14.7%, respectively. Cumulative limb salvage rate was significantly higher in diabetic patients (78.9 ± 4.9%), than in non-diabetic patients (66.6 ± 6.8); p = 0.023. CONCLUSION: Crural reconstruction is a suitable method for peripheral arterial occlusive disease to prevent amputation, particularly in diabetics.

Endovascular repair of aortic isthmus coarctation with a self-expanding covered stent.

BACKGROUND: Coarctation is one of the most often seen congenital aortal defects. In the majority, diagnosis will be made in newborns. Endovascular repair is critical in children owing to their growth, but in adult patients, it is an interesting alternative. METHODS: A 31-year-old man presenting with hypertension of upper extremities and pulseless lower extremities was admitted to our hospital. Systolic blood pressure was 190 mm Hg, although a triple antihypertensive medication was administered. Computed tomographic angiography showed a nearly total occlusion of the aortic isthmus. Coarctation was treated by an endovascular approach with a self-expanding covered stent-graft (Medtronic Talent; Medtronic World Medical, Sunrise, FL) after predilatation with a Reliant balloon (Medtronic World Medical, Sunrise, FL). RESULTS: After a follow-up of 40 months, the patient is normotensive and antihypertensive medication could be reduced. Lower extremities showed normal pulses and normal ankle-brachial index. Computed tomographic scans showed unchanged stent-graft position, with constant slight waist. DISCUSSION: Endovascular repair of atresia or coarctation of the thoracic aorta is a minimal invasive debatable option. Not only reduction of blood pressure but also reduction of left ventricular mass and prolongation of life expectancy can be achieved by endovascular treatment.

Comparison of clinical and surgical-pathological staging in IIIA non-small cell lung cancer patients.

BACKGROUND: The heterogeneous group of IIIA NSCLC patients requires careful preoperative clinical staging as tumor size and lymph node involvement guide treatment. The purpose of our study was to analyze the correctness of clinical staging in IIIA patients. METHODS: Retrospective analysis of all patients resected due to lung cancer that had been staged IIIA either clinically using invasive and noninvasive techniques or surgical-pathologically after surgical resection. Correctness, sensitivity, specificity, and positive and negative predictive values of clinical staging were calculated. RESULTS: From our tumor database, 49 patients who met the inclusion criteria were identified. The histology of the primary tumor included adenocarcinoma (53%), squamous cell carcinoma (41%), and other (6%). Preoperative clinical staging consisted of computed tomography (CT), integrated positron emission tomography-CT (PET-CT), bronchoscopy, and mediastinoscopy. The predominant surgical procedures performed were lobectomies (57%) and pneumonectomies (29%). Clinical staging for UICC, T and N stage was correct in 36.7, 38.7, and 40.8%, respectively. In terms of T4 stage, sensitivity was 28.5%, specificity was 80.9%, positive predictive value was 20%, and negative predictive value was 87.1%. As for N2 involvement, we found a sensitivity of 66.6% and a specificity of 35.7%. Positive and negative predictive values for N2 involvement were 43.7 and 58.8% in that order. CONCLUSIONS: Despite multimodal preoperative invasive and noninvasive staging techniques, the correctness of clinical staging in IIIA NSCLC patients is low. Hence, in doubt more invasive staging or probatory thoracotomy should be performed not to deny potentially curative surgery in those patients.

Technical and clinical success after endovascular therapy for chronic type B aortic dissections.

OBJECTIVE: To analyze early technical success and late clinical success after endovascular entry sealing for chronic type B dissection with special emphasis on reintervention, false lumen thrombosis, and aortic remodeling. METHODS: Retrospective analysis of a prospective database. From September 1999 to January 2011, 19 patients with chronic type B dissections were treated by endovascular entry sealing. Median age was 60 years. Median time between onset of acute dissection and surgical intervention was 36 (1 to 60) months. Median follow-up was 13 months (1 to 124). RESULTS: The endografts used were: Medtronic Captivia (5), Medtronic Valiant (5), Gore TAG (6), Gore C-TAG (2), and Cook Zenith (1). In four patients, revascularization of the left subclavian artery was performed prior to entry sealing. Primary technical success rate (entry sealing, absence of type I leak) was 18/19 (94.7%). In-hospital mortality was 0%. Spinal cord injury with persistent paraplegia occurred in 1/19 (5.2%) patients. After a maximal follow-up of 124 months, reinterventions in 9/19 (47.3%) were necessary: distal/proximal extension of stent graft (8), replacement of the aortic arch due to retrograde dissection (1), and open infrarenal aneurysm repair (1). During follow-up, none of the patients died due to stent-related complications. CONCLUSION: Endovascular treatment (EVT) in chronic type B dissections has a high technical success rate and low mortality/morbidity. However reintervention rates are not negligible which might reduce the clinical success of EVT. Future investigations should aim at identifying patients who benefit from EVT at better defining the timing of EVT and at determining if entry sealing alone is sufficient.

Fast track management reduces the systemic inflammatory response and organ failure following elective infrarenal aortic aneurysm repair.

OBJECTIVES: Systemic inflammatory response syndrome (SIRS) is common after abdominal aortic aneurysm (AAA) repair. The aim of this study was to analyze the impact of a multimodal fast track (FT) regimen on incidence rates of SIRS after elective infrarenal AAA repair. METHODS: Post hoc analysis of a randomized controlled trial including 99 patients after either traditional (TC) or FT care. Basic FT elements were no bowel preparation, reduced preoperative fasting, patient controlled epidural analgesia, enhanced postoperative feeding and mobilization. The presence of SIRS, organ failure and mortality, length of stay (LOS) on intensive care unit (ICU) were analyzed during the postoperative course. RESULTS: The incidence of SIRS in the FT treatment arm was significantly lower as compared to TC: 28% vs. 50%, P = 0.04. The rate of any organ failure (AOF) and multiple organ failure (MOF) was lower in the FT group: AOF: 16% vs. 36%, P = 0.039; MOF: 2% vs. 12%; P = 0.112. LOS on ICU showed a slight advantage for FT care: 20 hours vs. 32 hours (P = 0.183). CONCLUSION: An optimized patient care program in elective open AAA repair significantly decreases the postoperative incidence of SIRS as well as rates of organ failure.

In vivo study on the expression pattern of resistin in patients with abdominal aortic aneurysm.

OBJECTIVE: To study the expression pattern of resistin in abdominal aortic aneurysms and to correlate its plasma levels to aneurysm size and statin therapy. PATIENTS AND METHODS: From 25 patients on regular and 38 patients without statin therapy tissue specimen and plasma samples were obtained for analysis. RESULTS: Demographic data, past medical history, and body mass index showed no significant differences between the statin and no statin group. Immunohistochemistry showed positive stainings for resistin in all sections and in part colocalization to CD 68 positive cells. Patients with large aneurysms showed significant correlation of C-reactive protein (CRP) and interleukin 10 (IL-10) levels; patients on statin medication had significantly lower plasma levels of resistin and CRP. CONCLUSION: In contrast to IL-10 and CRP plasma levels of resistin are not correlated to aneurysm diameter; yet statin therapy results in decrease of resistin and CRP, suggesting an anti-inflammatory action in patients with abdominal aortic aneurysms (AAAs).

Tyrosine kinase expression in pulmonary metastases and paired primary tumors.

Tyrosine kinase inhibitors against the receptors of vascular endothelial growth factor (VEGFR), epidermal growth factor (EGFR) and the platelet derived growth factor (PDGFR) are increasingly used in the treatment of progressive cancers. However, the expression of these receptors especially in lung metastases has not been examined. Tissue specimen from 35 lung metastases of 33 patients with renal cell carcinoma (n=8), sarcoma (n=10), colorectal carcinoma (n=6), otolaryngologic carcinoma (OLC, n=4), testicular and endometrial cancer (n=1 each), malignant melanoma (n=1), adrenal cancer (n=2), malignant fibrous histiocytoma and malignant peripheral nerve sheath tumor (n=1 each) have been immunohistochemically tested for the expression of PDGFR alpha/beta, VEGFR and EGFR. None of the patients had been pretreated with angiogenic inhibitors prior to metastasectomy. PDGFRalpha was expressed in all metastases; 31% stained negative for PDGFRbeta, 86% negative for VEGFR and 45% negative for EGFR. Primary tumors revealed positive staining for PDGFRalpha in 88%, for PDGFRbeta in 59%, for VEGFR in 0% and for EGFR in 18%. Our investigation of a pilot character represents a 'biomarker-based' analysis of pulmonary metastases of different primary tumors; we conclude that an immediate 'tumor profiling' at initial diagnosis should be considered in order to guide tumor therapy individually.

Hybrid procedures for complex thoracoabdominal aortic aneurysms: early results and secondary interventions.

BACKGROUND: Hybrid procedures for thoracoabdominal aortic aneurysms (TAAA) have been previously described as an attractive alternative to open reconstruction. PATIENTS AND METHODS: Between 1999 and 2009, 16 patients with a median age of 67years underwent hybrid repair of a TAAA (Crawford type I: 3, type II: 3, type III: 1, and type IV: 9). In 94%, 3 and more severe comorbidities were present, with previous aortic surgery in 56% of the patients; elective/urgent repair was done in 10 and emergent surgery in 6 patients. RESULTS: Primary technical success was 100%, with 31 vessels grafted. Elective/urgent mortality was 20% (2 of 10) and emergent mortality 50% (3 of 6). During follow-up time (median: 12 months) 2 patients died and 2 patients had to undergo secondary interventions. CONCLUSION: In high-risk patients especially after prior aortic surgery hybrid repair of TAAA is feasible. However, due to high mortality rates especially in the emergent situation this procedure should be reserved only for decidedly selected patients.

Elective infrarenal abdominal aortic aneurysm repair--transperitoneal, retroperitoneal, endovascular?

We retrospectively analyzed the peri-operative outcome of 210 consecutive patients undergoing elective infrarenal abdominal aortic aneurysm (AAA) repair according to the surgical approach: transperitoneal (TP; 63 patients), retroperitoneal (RP; 81 patients) and endovascular (EV; 66 patients) repair. Concerning gender, AAA diameter and classification of the American Society of Anesthesiologists (ASA score) all groups were comparable; the median age in the EV group was significantly higher (78 years vs. 68 years and 67 years, respectively, P=0.001). Mortality rates were 0% for TP, 1.2% for RP and 3% for EV repair (n.s.). Morbidity rates did not significantly differ between the groups. In specialized centres mortality rates of elective infrarenal aneurysm repair are low - regardless of the surgical approach. In such centres the best treatment options for each patient as to the surgical approach as well as peri-operative management can be provided individually.

A prospective randomized trial comparing traditional and fast-track patient care in elective open infrarenal aneurysm repair.

BACKGROUND: Fast-track recovery programs have led to reduced patient morbidity and mortality after major surgery. In terms of elective open infrarenal aneurysm repair, no evidence is available about such programs. To address this issue, we have conducted a randomized prospective pilot study. METHODS: The study involved prospective randomization of 101 patients with the indication for elective open aneurysm repair in a traditional and a fast-track treatment arm. The basic fast-track elements were no bowel preparation, reduced preoperative fasting, patient-controlled epidural analgesia (PCEA), enhanced postoperative feeding, and postoperative mobilization. Morbidity and mortality, need for postoperative mechanical ventilation, length of stay (LOS) in the intensive care unit (ICU) and total length of postoperative hospital stay were analyzed in terms of an intention to treat. RESULTS: Demographic data for the two groups were similar. In the fast-track group the need for postoperative ventilation was significantly lower (6.1% versus 32%; p = 0.002), the median LOS on ICU did not significantly differ (20 h versus 32 h; p = 0.183), full enteral feeding was achieved significantly earlier (5 versus 7 days; p < 0.0001), and the rate of postoperative medical complications-gastrointestinal, cardiac, pulmonary, renal, and infective-was significantly lower (16% versus 36%; p = 0.039). The postoperative hospital stay was significantly shorter in the fast-track group (10 days versus 11 days; p = 0.016); the mortality rate in both groups was 0%. CONCLUSIONS: An optimized patient care program in open infrarenal aortic aneurysm repair shows favorable results concerning need for postoperative assisted mechanical ventilation, time to full enteral feeding, and incidence of medical complications. Further ranomized multicentric trials are necessary to justify broad implementation (clinical trials. gov identifier NCT 00615888).

The retroperitoneal approach combined with epidural anesthesia reduces morbidity in elective infrarenal aortic aneurysm repair.

In elective open infrarenal aortic aneurysm repair the surgical approach and the use of epidural anesthesia (EDA) may determine patients' outcome. Hence we analyzed our results after elective open aneurysm repair in the light of the surgical approach and the use of EDA. Retrospective analysis of a prospective data base. From December 2005 to April 2008, 125 patients with infrarenal aortic aneurysm underwent elective open repair. Patients were divided into four groups: retro- and transperitoneal approach with and without epidural anesthesia (RP+/-EDA and TP+/-EDA). In terms of age, sex, aneurysm diameter, ASA score and clamping time all groups were comparable. In the retroperitoneal groups significantly more tube grafts were implanted (63 vs. 27; P=0.001). The rate of surgical complications did not differ between the groups. The RP+EDA group had the lowest rate of postoperative assisted mechanical ventilation (5.1% vs. 35.7%; P=0.002) and medical complications (17.9% vs. 42.8%; P=0.032). Concerning frequency of surgical complications, the retroperitoneal incision was comparable to the transperitoneal approach in infrarenal aortic reconstruction. Supplementation with EDA resulted in a decreased rate of postoperative assisted mechanical ventilation and in lower morbidity rates.

Reduction of postoperative pulmonary complications after lung surgery using a fast track clinical pathway.

BACKGROUND: Fast track programs, multimodal therapy strategies, have been introduced in many surgical fields to minimize postoperative morbidity and mortality. In terms of lung resections no randomized controlled trials exist to evaluate such patient care programs. METHODS: In a prospective, randomized controlled pilot study a conservative and fast track treatment regimen in patients undergoing lung resections was compared. Main differences between the two groups consisted in preoperative fasting (6h vs 2h) and analgesia (patient controlled analgesia vs patient controlled epidural analgesia). Study endpoints were pulmonary complications (pneumonia, atelectasis, prolonged air leak), overall morbidity and mortality. Analysis was performed in an intention to treat. RESULTS: Both study groups were similar in terms of age, sex, preoperative forced expiratory volume in one second (FEV(1)), American Society of Anesthesiologists score and operations performed. The rate of postoperative pulmonary complications was 35% in the conservative and 6.6% in the fast track group (p=0.009). A subgroup of patients with reduced preoperative FEV(1) (<75% of predicted value) experienced less pulmonary complications in the fast track group (55% vs 7%, p=0.023). Overall morbidity was not significantly different (46% vs 26%, p=0.172), mortality was comparable in both groups (4% vs 3%). CONCLUSION: We evaluated an optimized patient care program for patients undergoing lung resections in a prospective randomized pilot study. Using this fast track clinical pathway the rate of pulmonary complications could be significantly decreased as compared to a conservative treatment regimen; our results support the implementation of an optimized perioperative treatment in lung surgery in order to reduce pulmonary complications after major lung surgery.

Prospective randomized controlled trial to evaluate "fast-track" elective open infrarenal aneurysm repair.

BACKGROUND AND AIMS: Fast-track programs have been introduced in many surgical fields to minimize postoperative morbidity and mortality. Morbidity after elective open infrarenal aneurysm repair is as high as 30%; mortality ranges up to 10%. In terms of open infrarenal aneurysm repair, no randomized controlled trials exist to introduce and evaluate such patient care programs. MATERIALS AND METHODS: This study involved prospective randomization of 82 patients in a "traditional" and a "fast-track" treatment arm. Main differences consisted in preoperative bowel washout (none vs. 3 l cleaning solution) and analgesia (patient controlled analgesia vs. patient controlled epidural analgesia). Study endpoints were morbidity and mortality, need for postoperative mechanical ventilation, and length of stay (LOS) on intensive care unit (ICU). RESULTS: The need for assisted postoperative ventilation was significantly higher in the traditional group (33.3% vs. 5.4%; p = 0.011). Median LOS on ICU was shorter in the fast-track group, 41 vs. 20 h. The rate of postoperative medical complications was significantly lower in the fast-track group, 16.2% vs. 35.7% (p = 0.045). CONCLUSION: We introduced and evaluated an optimized patient care program for patients undergoing open infrarenal aortic aneurysm repair which showed a significant advantage for "fast-track" patients in terms of postoperative morbidity.

Effect of statin therapy on serum activity of proteinases and cytokines in patients with abdominal aortic aneurysm.

BACKGROUND AND AIMS: Metalloproteinases (MMPs) are considered to be key enzymes in the pathogenesis of abdominal aortic aneurysms (AAA), with elevated levels in diseased aorta and in patient sera. Statins seem to exert an inhibitory effect on MMP activity in the aortic wall. No data exist on the effect of statins on serum activity of MMPs and inflammatory cytokines (interleukins, IL). METHODS: The serum activities of MMP2 and MMP9, osteoprotegerin (OPG), and IL6 and IL10 in 63 patients undergoing elective infrarenal aneurysm repair were measured on the day before surgery. Levels were correlated to statin therapy and aneurysm diameter. RESULTS: There was no significant difference between the two groups in the activity of circulating levels of MMP2/9, OPG, and IL6/10 in patients with infrarenal aortic aneurysm. IL6 levels in patients with AAA larger than 6 cm were significantly elevated; differences in serum activities of MMP2/9, OPG, and IL10 were not related to AAA diameter. CONCLUSION: Serum activities of MMP2/9, OPG, and IL6/10 are not correlated to statin therapy; IL6 levels are higher in patients with large aneurysms. Hence the effect of statin therapy in the treatment of aneurysmal disease remains to be elucidated.

NSC-631570 (Ukrain) in the palliative treatment of pancreatic cancer. Results of a phase II trial.

BACKGROUND: NSC-631570 (Ukrain) is a semisynthetic compound of thiophosphoric acid and the alkaloid chelidonine from the plant Chelidonium majus. It has been used in complementary herbal medicine for more than 20 years for the treatment of benign and malignant tumors. PATIENTS/METHODS: Between August 1999 and June 2001, 90 patients with histologically proven unresectable pancreatic cancer were randomized in a monocentric, controlled, randomized study. Patients in arm A received 1000 mg gemcitabine/m2, those in arm B received 20 mg NSC-631570, and those in arm C received 1000 mg gemcitabine/m2 followed by 20 mg NSC-631570 weekly. End point of the study was overall survival. RESULTS: In all three arms therapy was well tolerated and toxicity was moderate. At the first re-evaluation in arm A 32%, in arm B 75%, and in arm C 82% showed no change or partial remission according to WHO criteria (arm A versus arm B: P<0.01, arm A versus arm C: P<0.001). Median survival according to Kaplan-Meier analysis was in arm A 5.2 months, in arm B 7.9 months, and in arm C 10.4 months (arm A versus arm B: P<0.01, arm A versus arm C: P<0.01). Actuarial survival rates after 6 months were 26%, 65% and 74% in arms A B and C, respectively (arm A versus arm B: P<0.05, arm A versus arm C P<0.01). CONCLUSION: We could show that in unresectable advanced pancreatic cancer, NSC-631570 alone and in combination with gemcitabine nearly doubled the median survival times in patients suffering from advanced pancreatic cancer.