Descending necrotizing mediastinitis caused by a minor whiplash injury.

We describe a case of descending necrotizing mediastinitis from a very unusual origin, caused by cervical oesophageal perforation by osteophytes after an apparently minor whiplash injury. Diagnosis was delayed by atypical and predominantly neurological clinical presentation. Despite late presentation, minimally invasive access surgical debridement of mediastinum and cervical injury site lead to full recovery.

Intrapericardial liver herniation after coronary artery bypass grafting: a case report of minimally invasive repair with 20-year follow-up.

BACKGROUND: Transdiaphragmatic intrapericardial herniation (DIPH) of intra-abdominal organs is a rare but potentially life-threatening phenomenon often requiring urgent repair. There are currently no guidelines on the preferred repair technique in this situation. METHODS: Retrospective case report with long-term follow-up. We describe a case in which the left liver herniated into the pericardium after coronary artery bypass grafting (CABG) using the right gastroepiploic artery (RGEA). RESULTS: Urgent laparoscopic reduction of the liver herniation and repair of the large diaphragmatic defect was performed using an expanded polytetrafluoroethylene (ePTFE) mesh in a 50 year old male patient. Hemodynamic instability normalized after the hernia reduction. The postoperative course was uneventful. CT-scan evaluation after 9 and 20 years of follow-up showed perfect integrity of the mesh. CONCLUSION: A laparoscopic approach for DIPH is feasible in emergency situations provided sufficient hemodynamic stability of the patient. On-lay ePTFE mesh repair is a valid option for such repairs. We illustrate the long-term durability and safety of ePTFE for DIPH repair in what seems to be by far the longest documented follow-up after laparoscopic ePTFE mesh repair for DIPH.

Comparison of uniportal robotic-assisted thoracic surgery pulmonary anatomic resections with multiport robotic-assisted thoracic surgery: a multicenter study of the European experience.

Background: Robotic-assisted thoracic surgery (RATS) has seen increasing interest in the last few years, with most procedures primarily being performed in the conventional multiport manner. Our team has developed a new approach that has the potential to convert surgeons from uniportal video-assisted thoracic surgery (VATS) or open surgery to robotic-assisted surgery, uniportal-RATS (U-RATS). We aimed to evaluate the outcomes of one single incision, uniportal robotic-assisted thoracic surgery (U-RATS) against standard multiport RATS (M-RATS) with regards to safety, feasibility, surgical technique, immediate oncological result, postoperative recovery, and 30-day follow-up morbidity and mortality. Methods: We performed a large retrospective multi-institutional review of our prospectively curated database, including 101 consecutive U-RATS procedures performed from September 2021 to October 2022, in the European centers that our main surgeon operates in. We compared these cases to 101 consecutive M-RATS cases done by our colleagues in Barcelona between 2019 to 2022. Results: Both patient groups were similar with respect to demographics, smoking status and tumor size, but were significantly younger in the U-RATS group [M-RATS =69 (range, 39-81) years; U-RATS =63 years (range, 19-82) years; P<0.0001]. Most patients in both operative groups underwent resection of a primary non-small cell lung cancer (NSCLC) [M-RATS 96/101 (95%); U-RATS =60/101 (59%); P<0.0001]. The main type of anatomic resection was lobectomy for the multiport group, and segmentectomy for the U-RATS group. In the M-RATS group, only one anatomical segmentectomy was performed, while the U-RATS group had twenty-four (24%) segmentectomies (P=0.0006). All M-RATS and U-RATS surgical specimens had negative resection margins (R0) and contained an equivalent median number of lymph nodes available for pathologic analysis [M-RATS =11 (range, 5-54); U-RATS =15 (range, 0-41); P=0.87]. Conversion rate to thoracotomy was zero in the U-RATS group and low in M-RATS [M-RATS =2/101 (2%); U-RATS =0/101; P=0.19]. Median operative time was also statistically different [M-RATS =150 (range, 60-300) minutes; U-RATS =136 (range, 30-308) minutes; P=0.0001]. Median length of stay was significantly lower in U-RATS group at four days [M-RATS =5 (range, 2-31) days; U-RATS =4 (range, 1-18) days; P<0.0001]. Rate of complications and 30-day mortality was low in both groups. Conclusions: U-RATS is feasible and safe for anatomic lung resections and comparable to the multiport conventional approach regarding surgical outcomes. Given the similarity of the technique to uniportal VATS, it presents the potential to convert minimally invasive thoracic surgeons to a robotic-assisted approach.

Glue Embolization of Gastroesophageal Varices during Transjugular Intrahepatic Portosystemic Shunt (TIPS) Improves Survival Compared to Coil-only Embolization-A Single-Center Retrospective Study.

PURPOSE: To compare the safety and effectiveness of coil versus glue embolization of gastroesophageal varices during transjugular intrahepatic portosystemic shunt (TIPS) creation. MATERIALS AND METHODS: In this monocentric retrospective study 104 (males: 67 (64%)) patients receiving TIPS with concomitant embolization of GEV and a minimum follow-up of one year (2008-2017) were included. Primary outcome parameter was overall survival (6 week; 1 year). Six-week overall survival was assessed as a surrogate for treatment failure as proposed by the international Baveno working group. Secondary outcome parameters were development of acute-on-chronic liver failure (ACLF), variceal rebleeding and hepatic encephalopathy (HE). Survival analysis was performed using Kaplan-Meier with log-rank test and adjusted Cox regression analysis. RESULTS: Indications for TIPS were refractory ascites (n = 33) or variceal bleeding (n = 71). Embolization was performed using glue with or without coils (n = 40) (Group G) or coil-only (n = 64) (Group NG). Overall survival was significantly better in group G (p = 0.022; HR = -3.333). Six-week survival was significantly lower in group NG (p = 0.014; HR = 6.945). Rates of development of ACLF were significantly higher in group NG after 6 months (NG = 14; G = 6; p = 0.039; HR = 3.243). Rebleeding rates (NG = 6; G = 3; p = 0.74) and development of HE (NG = 22; G = 15; p = 0.75) did not differ significantly between groups. CONCLUSION: Usage of glue in embolization of GEV may improve overall survival, reduce treatment failure and may be preferable over coil embolization alone.

Combined one-stage esophagectomy and duodeno-pancreatectomy for synchronous cancers of the esophagus and pancreatic ampulla in an elderly patient.

BACKGROUND: We report the case of a 77-year-old patient, who underwent multi-modality treatment including single-stage radical oesophagectomy and duodeno-pancreatectomy for a synchronous adenocarcinoma of the distal oesophagus and adenocarcinoma of the ampulla of Vater. METHODS: The ampulloma was diagnosed incidentally during the work-up of the symptomatic esophageal cancer. After induction chemo-radiation of the oesophageal cancer (CROSS regimen), a single-stage radical resection of the esophagus, total gastrectomy and a cephalic duodeno-pancreatectomy was performed. Intestinal reconstruction was done by a right coloplasty with esophago-colic anastomosis in the upper chest and distally to the Roux-en-Y (Child) used for reconstruction of the hepato-biliary tract. Adjuvant chemotherapy was proposed due to the unexpectedly advanced stage of the ampullary cancer (pT4N1M0) and was completed uneventfully despite the magnitude of the preceding surgery. RESULTS: According to our literature review, this is the first report of a successfully completed tri-modality treatment with combined single-stage oesophagectomy and Whipple procedure in an elderly (>75 years). Functional and metabolic outcome was satisfactory until cancer recurrence due to liver metastasis of bilio-pancreatic origin. The patient is alive 2 years post-operatively. CONCLUSION: Single-stage radical resection of the oesophagus and a cephalic duodeno-pancreatectomy can be more considered for synchronous cancers even in elderly patient.

Identification of a Blood-Based Protein Biomarker Panel for Lung Cancer Detection.

Lung cancer is the deadliest cancer worldwide, mainly due to its advanced stage at the time of diagnosis. A non-invasive method for its early detection remains mandatory to improve patients' survival. Plasma levels of 351 proteins were quantified by Liquid Chromatography-Parallel Reaction Monitoring (LC-PRM)-based mass spectrometry in 128 lung cancer patients and 93 healthy donors. Bootstrap sampling and least absolute shrinkage and selection operator (LASSO) penalization were used to find the best protein combination for outcome prediction. The PanelomiX platform was used to select the optimal biomarker thresholds. The panel was validated in 48 patients and 49 healthy volunteers. A 6-protein panel clearly distinguished lung cancer from healthy individuals. The panel displayed excellent performance: area under the receiver operating characteristic curve (AUC) = 0.999, positive predictive value (PPV) = 0.992, negative predictive value (NPV) = 0.989, specificity = 0.989 and sensitivity = 0.992. The panel detected lung cancer independently of the disease stage. The 6-protein panel and other sub-combinations displayed excellent results in the validation dataset. In conclusion, we identified a blood-based 6-protein panel as a diagnostic tool in lung cancer. Used as a routine test for high- and average-risk individuals, it may complement currently adopted techniques in lung cancer screening.

The impact of rheolytic percutaneous mechanical thrombectomy on glomerular filtration rate levels.

OBJECTIVE: Rheolytic percutaneous mechanical thrombectomy (PMT) has been established as an endovascular technique for thrombus removal. Initial studies reporting on postinterventional kidney dysfunction have surfaced. The aim of this study was to investigate glomerular filtration rate (GFR) changes after PMT. METHODS: A total of 45 interventions were included; 21 were performed in the venous system and 24 in the arterial system. Renal function was evaluated through assessment of GFR value changes from baseline to a minimum of two postinterventional values, and RIFLE criteria (Risk, Injury, Failure, Loss of kidney function, End-stage kidney disease) were applied. RESULTS: The univariate analysis of variance revealed a significant association of GFR increase between time points and the type of intervention (arterious or venous; P = .002), whereas there was no significant association of intervention duration (P = .382), quantity of administered contrast medium (P = .544), or use of urokinase (P = .377). Repeated measures analysis of variance revealed a significant difference in GFR values between the four time points for venous interventions (P = .008) but not for arterial interventions (P = .908). In venous interventions, postinterventional GFR values were significantly lower compared with preinterventional values (P = .008) and the two measurements after intervention (P = .017 and P = .014, respectively). According to the RIFLE criteria, 1 of the 21 patients in the venous group had a complete loss of kidney function and 2 patients progressed to the risk group (GFR decreases >25%). CONCLUSIONS: PMT in the venous system has a significant impact on GFR levels, although there is only a low risk for clinically important renal dysfunction. The occurrence of renal impairment should be taken into account in evaluating PMT treatment, especially because of the associated morbidity.

Interventional Treatment of Acute Portal Vein Thrombosis.

BACKGROUND: Acute portal vein thrombosis is a potentially fatal condition. In symptomatic patients not responding to systemic anticoagulation, interventional procedures have emerged as an alternative to surgery. This study sought to retrospectively evaluate initial results of interventional treatment of acute portal vein thrombosis (aPVT) using a transjugular interventional approach. MATERIALS AND METHODS: Between 2014 and 2016, 11 patients were treated because of aPVT (male: 7; female: 4; mean age: 41.06 years). All patients presented a rapid onset of symptoms without collateralization of portal flow as assessed by a CT scan at the time of admittance. The patients showed thrombotic occlusion of the main portal vein (11/11), the lienal vein (10/11) and the superior mesenteric vein (10/11). Different techniques for recanalization were employed: catheter thromboaspiration (1/9), AngioJet device (7/9), local-lysis-only (1/9) and TIPSS (7/9). Local lysis was administered using a dual (4/9) or single (5/9) catheter technique. The mean follow-up was 24.32 months. RESULTS: In 9 patients transhepatic access was successful. Initially reduction of thrombus load and recanalization were achieved in all 9 cases with residual thrombi in PV (n = 3), SMV (n = 7), and IL (n = 5). In the collective undergoing interventional procedures (n = 9) rethrombosis and continuous abdominal pain were seen in one patient, and thrombus progression after successful recanalization was seen in another. Freedom from symptoms could be achieved in 6 patients. One patient developed peritoneal and pleural effusion, respiratory insufficiency and portosystemic collaterals. Both patients who could not undergo an interventional procedure developed a cavernous transformation of the portal vein. One of them also had continuous intermittent abdominal pain. CONCLUSION: Interventional percutaneous approaches are able to improve patient outcome in patients with aPVT. It appears to be of utmost importance to not only remove/reduce the thrombotic material but to establish sufficient inflow and outflow by TIPS and simultaneous multi-catheter thrombolysis. KEY POINTS: · Pharmacomechanic thrombectomy in combination with local thrombolysis is a feasible approach. · The transjugular transhepatic approach seems to be a safe procedure. · TIPSS and dual catheter lysis may support flow management. CITATION FORMAT: · Wolter K, Decker G, Kuetting D et al. Interventional Treatment of Acute Portal Vein Thrombosis. Fortschr Röntgenstr 2018; 190: 740 - 746.

In-bore transrectal MRI-guided prostate biopsies: Are there risk factors for complications?

PURPOSE: To systematically analyze risk factors for complications of in-bore transrectal MRI-guided prostate biopsies (MRGB). MATERIALS AND METHODS: 90 patients, who were scheduled for MRGB were included for this study. Exclusion criteria were coagulation disorders, therapy with anticoagulant drugs, and acute infections of the urinary and the lower gastrointestinal tract. Directly after, one week and one year after the biopsy, we assessed biopsy related complications (e.g. hemorrhages or signs of prostatitis). Differences between patients with and without complications were analyzed regarding possible risk factors: age, prostate volume, number of taken samples, biopsy duration, biopsy of more than one lesion, diabetes, arterial hypertension, hemorrhoids, benign prostate hyperplasia, carcinoma or prostatitis (according to histopathological analysis), and lesion localization. Complications were classified according to the Clavien-Dindo classification. RESULTS: We observed 15 grade I complications in 90 biopsies (16.7%) with slight hematuria in 9 cases (10%), minor vasovagal reactions in 4 cases (4.4%), and urinary retention and positioning-related facial dysesthesia in 1 case each (1.1%). One patient showed acute prostatitis requiring antibiotics as the only grade II complication (1.1%). There were no adverse events that occurred later than one week. Complications grade III or higher such as pelvic abscesses, urosepsis or severe hemorrhages were not seen. There were no significant associations between the assessed risk factors and biopsy-related complications. CONCLUSION: In-bore transrectal MRI-guided prostate biopsies can be considered safe procedures in the diagnosis of prostate cancer with very low complication rates. There seem to be no risk factors for complications.

Differentiation of prostatitis and prostate cancer using the Prostate Imaging-Reporting and Data System (PI-RADS).

PURPOSE: To determine if prostate cancer (PCa) and prostatitis can be differentiated by using PI-RADS. MATERIALS AND METHODS: 3T MR images of 68 patients with 85 cancer suspicious lesions were analyzed. The findings were correlated with histopathology. T2w imaging (T2WI), diffusion weighted imaging (DWI), dynamic contrast enhancement (DCE), and MR-Spectroscopy (MRS) were acquired. Every lesion was given a single PI-RADS score for each parameter, as well as a sum score and a PI-RADS v2 score. Furthermore, T2-morphology, ADC-value, perfusion type, citrate/choline-level, and localization were evaluated. RESULTS: 44 of 85 lesions showed PCa (51.8%), 21 chronic prostatitis (24.7%), and 20 other benign tissue such as hyperplasia or fibromuscular tissue (23.5%). The single PI-RADS score for T2WI, DWI, DCE, as well as the aggregated score including and not including MRS, and the PI-RADS v2-score were all significantly higher for PCa than for prostatitis or other tissue (p<0.001). The single PI-RADS score for MRS and the PI-RADS sum score including MRS were significantly higher for prostatitis than for other tissue (p=0.029 and p=0.020), whereas the other parameters were not different. Prostatitis usually presented borderline pathological PI-RADS scores, showed restricted diffusion with ADC≥900mm(2)/s in 100% of cases, was more often indistinctly hypointense on T2WI (66.7%), and localized in the transitional zone (57.1%). An ADC≥900mm(2)/s achieved the highest predictive value for prostatitis (AUC=0.859). CONCLUSION: Prostatitis can be differentiated from PCa using PI-RADS, since all available parameters are more distinct in cases of cancer. However, there is significant overlap between prostatitis and other benign findings, thus PI-RADS is only suitable to a limited extent for the primary assessment of prostatitis. Restricted diffusion with ADC≥900mm(2)/s is believed to be a good indicator for prostatitis. MRS can help to distinguish between prostatitis and other tissue.

Intensity-modulated radiotherapy of the prostate: dynamic ADC monitoring by DWI at 3.0 T.

BACKGROUND AND PURPOSE: Diffusion weighted imaging (DWI) as a functional MR technique allows for both qualitative and quantitative assessment of tumour cellularity and changes during therapy. The objective of this study was to evaluate changes of apparent diffusion coefficient (ADC) in biopsy proven prostate cancer (PCa) under intensity modulated radiotherapy (IMRT) at 3T. MATERIAL & METHODS: Thirteen patients with biopsy proven PCa treated with intensity modulated external beam radiotherapy (IMRT) underwent four standardized MR examinations after approval of the local institutional review board. These included DWI at 3T on a strict time table: before, in between, directly after (between 1 and 4 days after the last radiation), as well as 3 months after IMRT. Quantitative analysis of two different ADCs, - the ADC(0,800) and the ADC(50,800), was performed dynamically over 4 time points in PCa, gluteal muscle and healthy prostate tissue. RESULTS: In PCa, a significant increase of ADC(0,800)/ADC(50,800) values was measured under IMRT by about 16%/15% (P=0.00008/0.00017), 21%/21% (P=0.00006/0.00030), and 33%/34% (P=0.00004/0.00002) at the three time points compared to initial value. Healthy prostate tissue did not show any significant increase. CONCLUSION: DWI is suitable as a biomarker for radiation therapy response of PCa by allowing the dynamic monitoring of treatment effectiveness.

Can extracapsular lymph node involvement be a tool to fine-tune pN1 for adenocarcinoma of the oesophagus and gastro-oesophageal junction in the Union Internationale contre le Cancer (UICC) TNM 7th edition?†.

OBJECTIVES: The current (7th) International Union Against Cancer (UICC) pN staging system is based on the number of positive lymph nodes but does not take into consideration the characteristics of the metastatic lymph nodes itself. In particular, it has been suggested that tumour penetration beyond the lymph node capsule in metastatic lymph nodes, which is also called extracapsular lymph node involvement, has a prognostic impact. The aim of the current study was to assess the prognostic value of extracapsular (EC) and intracapsular (IC) lymph node involvement (LNI) in adenocarcinoma of the oesophagus and gastro-oesophageal junction (GOJ) and to assess its potential impact on the 7th edition of the UICC TNM manual. METHODS: From 2000 to 2010, all consecutive adenocarcinoma patients with primary R0-resection (n = 499) were prospectively included for analysis. The number of resected lymph nodes, number of positive lymph nodes and number of EC-LNI/IC-LNI were determined. Extracapsular spread was defined as infiltration of cancer cells beyond the capsule of the positive lymph node. RESULTS: Two hundred and eighteen (43%) patients had positive lymph nodes. Cancer-specific 5-year survival in lymph node-positive patients was significantly (P < 0.0001) worse compared with lymph node-negative patients, being 88.3 vs 28.7%, respectively. In 128 (58.7%) cases EC-LNI was detected. EC-LNI showed significantly worse cancer-specific 5-year survival compared with IC-LNI, 19.6 vs 44.0% (P < 0.0001). In the pN1 category (1 or 2 positive LN's-UICC stages IIB and IIIA), this was 30.4% vs 58%; (P = 0.029). In higher pN categories, this effect was no longer noticed. Integrating these findings into an adapted TNM classification resulted in improved homogeneity, monotonicity of gradients and discriminatory ability indicating an improved performance of the staging system. CONCLUSIONS: EC-LNI is associated with worse survival compared with IC-LNI. EC-LNI patients show survival rates that are more closely associated with the current TNM stage IIIB, while IC-LNI patients have a survival more similar to TNM stage IIB. Incorporating the EC-IC factor in the TNM classification results in an increased performance of the TNM model. Further confirmation from other centres is required within the context of future adaptations of the UICC/AJCC (American Joint Committee on Cancer) staging system for oesophageal cancer.

Improving immunotherapy of hepatocellular carcinoma (HCC) using dendritic cells (DC) engineered to express IL-12 in vivo.

BACKGROUND: Interleukin 12 (IL-12), one of the most potent Th1-cytokines, has been used to improve dendritic cells (DC)-based immunotherapy of cancer. However, it failed to achieve clinical response in patients with hepatocellular carcinoma (HCC). In this study, improved conditions of immunotherapy with DC engineered to express IL-12 were studied in murine subcutaneous HCC. METHODS: Tumour-lysate pulsed DC were transduced with IL-12-encoding adenoviruses or cultivated with recombinant (r)IL-12. DC were injected intratumourally, subcutaneously or intravenously at different stages of tumour-development. RESULTS: Dendritic cell overexpressing IL-12 by adenoviruses showed enhanced expression of costimulatory molecules and stronger priming of HCC-specific effector cells than DC cultured with rIL-12. Intratumoural but not systemic injections of IL-12-DC induced the strongest antitumoural effects reaching complete regressions in 75% of early-staged tumours and in 33% of advanced tumours. Importantly, antitumoural effects could be further enhanced through combination with sorafenib. Analysing the tumour-environment, IL-12-DC increased the levels of Th1-cytokines/chemokines and of CD4(+) -, CD8(+) -T- and NK-cells. Induced immunity was tumour-specific and sustained since all tumour-free animals were protected towards hepatic tumour-cell rechallenge. However, IL-12-DC also enhanced immunosuppressive cytokines, regulatory T cells and even myeloid-derived suppressor cells within the tumours. CONCLUSIONS: Induced IL-12-overexpression by adenoviral vectors can effectively immunostimulate DC. Intratumoural but not systemic injection of activated IL-12-DC was crucial for effective tumour regression. The mechanism of this approach seems to be the induction of a sufficient Th1 tumour-environment allowing the recruitment of effector cells rather than the inhibition of tumour immunosuppression. Thus, improved immunotherapy with IL-12-DC represents a promising approach towards HCC.

Assessing the relationships between health-related quality of life and postoperative length of hospital stay after oesophagectomy for cancer of the oesophagus and the gastro-oesophageal junction.

OBJECTIVES: To evaluate baseline health-related quality of life (HRQL) factors that influence short-term outcome after oesophagectomy for cancer of the oesophagus and gastro-oesophageal junction and the effects of postoperative length of hospital stay on postoperative HRQL, as perceived by the patients themselves. METHODS: Four hundred and fifty-five patients operated on with curative intent between January 2005 and December 2009 were analysed. HRQL scores were obtained by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ)-C30 and oesophageal-specific symptoms (OES-18) questionnaires at baseline (=day before surgery) and 3-monthly post-surgery for the first year. RESULTS: There were 372 males and 83 females, with a mean age of 63.1 years. Hospital mortality was 3.7% (17 patients). When analysing postoperative length of stay (LOS), a median of 10 days was found. In a multivariable analysis, using a binary logistic regression model, independent prognosticators for a longer LOS (>10 days) were: medical [hazard ratio, HR, 6.2 (3.62-10.56); P < 0.0001] and surgical [HR 2.79 (1.70-4.59); P < 0.0001] morbidity, readmittance to intensive care unit [HR 33.82 (4.55-251.21); P = 0.001] and poor physical functioning [HR 1.89 (1.14-3.14); P = 0.014]. Postoperatively, patients with early discharge (LOS <10 days) indicated, at 3 and 12 months postoperatively, significant better HRQL scores in the functional scales (physical, emotional, social and role functioning) and in symptoms scales (fatigue, nausea, dyspnoea appetite loss and dry mouth) when compared with LOS >10 days. Return to the level of the reference population scores was achieved at 1 year in the LOS ≤10 days for almost all the scales, but not in the LOS >10 days group. CONCLUSIONS: A better perception of preoperative physical functioning might have a beneficial effect on LOS. Our data, furthermore, suggest that early discharge correlates with improved postoperative HRQL outcomes. A clear decrease of the HRQL is seen at 3 months after the surgery, particularly in the LOS >10 days group. Generally, return to the level of the reference population scores is achieved at 1 year in the LOS ≤10 days, but not in the LOS >10 days group.

Combination of hypoxia and RNA-interference targeting VEGF induces apoptosis in hepatoma cells via autocrine mechanisms.

Control of VEGF signaling is an intense objective of pre-clinical and clinical studies in HCC disease with steadily increasing clinical application. Despite its emerging role, several aspects of anti-VEGF based treatments are poorly investigated, like the impact on tumor cells themselves, such as the effect on intracellular signaling and apoptosis induction in hepatoma cells. Effects of siRNA-VEGF on VEGF, VEGF-receptor expression and VEGF-A signaling such as AKT and JNK phosphorylation were determined under normoxic or hypoxic conditions in murine hepatoma cells. Apoptosis induction was analyzed by SubG1-fraction, JC1-staining and caspase-8 activation. VEGF receptor expression was analysed by semiquantitative real time PCR. Independent of oxygen status, siRNA-VEGF reduced VEGF levels resulting in decreased AKT and increased JNK phosphorylation in Hepa129 cells. The VEGF-receptors neuropilin-1 (Nrp1) and neuropilin-2 (Nrp2) were downregulated following siRNA-VEGF treatment or hypoxia induction respectively. Functionally, hypoxia significantly increased the apoptosis rate (as analyzed by SubG1-fraction, JC1-staining and JNKphosphorylation) which was further stimulated by siRNA-VEGF treatment. Our data indicate that antitumoral efficacy of an anti-VEGF based treatment with siRNA is partly based on negative autocrine feedback mechanisms which are even enhanced under hypoxic conditions. This observation helps to understand why antitumoral efficacy can be maintained despite of counteracting stimulation of tumoral VEGF secretion due to hypoxia. The direct impact on tumor cells further underscores the attractiveness of an anti-VEGF based siRNA treatment.

Minimally invasive oesophagectomy: a valuable alternative to open oesophagectomy for the treatment of early oesophageal and gastro-oesophageal junction carcinoma.

OBJECTIVE: The aim was to conduct a comparative analysis of outcome after minimally invasive oesophagectomy (MIO) versus open oesophagectomy (OO) for early oesophageal and gastro-oesophageal junction (GOJ) carcinoma. METHODS: Inclusion criteria for MIO and a matched group of OO were pT<2 and N0. Surgical outcome, complications, survival and health-related quality of life (HRQL) were assessed. RESULTS: Between January 2005 and January 2010, 175 patients (101 OOs, 65 MIOs and nine MIOs converted to OO) fulfilled the abovementioned criteria. Histology was predominantly adenocarcinoma (75%), equally distributed between both groups as were preoperative co-morbidities (p = 0.43), pathologic staging (pT: p = 0.56) and mean number of resected lymph nodes in pTIS/1a (p = 0.23) and pT1b (p = 0.13). Blood loss was less (p = 0.01) and duration of operation longer (p = 0.001) in MIO. Hospital mortality (p = 0.66) and postoperative complications (p = 0.34) were comparable. However, respiratory complications (p = 0.008) and intensive care unit (ICU) admission (p = 0.02) were higher in OO. Gastrointestinal complications (p = 0.005), that is, gastroparesis (p = 0.004) were more frequent in MIO. At 3 months, postoperative fatigue, pain (general) and gastrointestinal pain were less in MIO (p = 0.09, 0.05 and 0.01, respectively). Five-year cancer-specific and recurrence-free survival stratified to the pathologic T-stage were not statistically different between MIO and OO. CONCLUSION: MIO is a valuable alternative to OO for the treatment of early oesophageal and GOJ carcinoma. This study underscores the need for large-scale, preferably multicentric studies to assess the real value of MIO versus OO.

Quality indicators of surgery for adenocarcinoma of the esophagus and gastroesophageal junction.

Surgical treatment of adenocarcinoma of the esophagus and gastroesophageal junction is complex and challenging. Huge variation exist in the immediate and long term outcomes of such interventions and it is generally accepted that this is a direct consequence of the experience of the surgical team. However beside surgical quality many other indicators of quality management may influence outcome. Definition of the gastroesophageal junction remains controversial and the performance of staging procedures i.e. CT scan, endoscopy and fine needle aspiration, PET scan still suboptimal. As a result there is disagreement on the selection of patients for surgery, type of surgical approach in particular in relation to the extent of lymph node dissection as well as the extent of esophageal and/or gastric resection. In the design of randomized controlled trials comparing primary surgery versus multimodality treatment surgical quality criteria are notoriously lacking. It therefore remains a matter of debate which patients eventually will benefit from primary surgery versus those who will benefit from induction therapy. A lack of surgical quality indicators is also very prominent when assessing the value of new surgical technologies such as minimally invasive surgery or robotic surgery. Improvements in this wide spectrum of aspects is mandatory and will certainly be of great value to further improve both short and long term outcome after surgery for these complex cancers.

Postoperative complications after transthoracic esophagectomy for cancer of the esophagus and gastroesophageal junction are correlated with early cancer recurrence: role of systematic grading of complications using the modified Clavien classification.

OBJECTIVES: To assess the impact of postoperative complications after transthoracic esophagectomy, using the modified Clavien classification, on recurrence and on its timing in patients with cancer of the esophagus or gastroesophageal junction. BACKGROUND DATA: It is hypothesized that complications after esophagectomy for cancer may have a negative effect on recurrence and its timing because of negative interference with the immune system. METHODS: Out of 150 consecutive patients operated with curative intent between January 2005 and May 2006, the data of 138 patients with macroscopically complete resection and no synchronous other malignancy were graded according to the modified Clavien classification. Uni- and multivariable analyses were performed to study the impact of postoperative complications on tumor recurrence and its timing. RESULTS: Mean age was 63.1 years, male-female ratio was 4:1; 76.1% of the patients underwent primary surgery, 23.9% received induction therapy, R0-resection rate was 92.8%. Adenocarcinoma was found in 75%. Complication rates according to the modified Clavien classification were grade 0: 29.7%, grade 2: 35.5%, grade 3: 17.4%, grade 4: 15.9%, and grade 5 (postoperative mortality): 1.4%. Ten patients developed recurrence within 6 months, 29 within 12 months, 39 within 18 months, 42 within 24 months, totaling up to 47 at 3 years. Univariable analysis retained complications, LN-status, number of positive nodes, extracapsular lymph node involvement (EC LNI), pStage, pT, and R1-status as factors significantly influencing occurrence of recurrence. In the multivariable model, presence of complications, EC LNI, and R1-status were independent negative factors. Cox-regression analysis also identified these same 3 factors as significant determinators for the timing of recurrence. CONCLUSIONS: This study indicates a correlation between complications and early recurrence and its timing. Modified Clavien classification, beside R1-status and EC LNI, appears to be a useful prognostic indicator of early recurrence and its timing. Achieving esophagectomy without postoperative complications is of utmost importance also for oncologic reasons given its negative potential on early oncologic outcome.

Lung donor selection and management.

Lung transplantation is still limited by the shortage of suitable donor organs. This results in long waiting times for listed patients with a substantial risk (10-15%) of dying before transplantation. All efforts to increase donor awareness through legislation, public campaigns, and training of transplant coordinators and medical ICU staff should be encouraged. Only a minority of cadaveric donors meets the preset ideal lung donor criteria, leaving many transplantable lungs untouched. Donor lung utilization can be further improved by careful selection of extended criteria donors, by active participation of transplant teams in donor management, and by verifying as often as possible the quality of lungs in the donor hospital by a member of the transplant team. This article aims to update the current evidence from the literature to identify and select potential lung donors and to manage cadaveric donors to maximally increase the organ yield for lung transplantation.

Minimally invasive esophagectomy for cancer.

Since 1992, various combinations of thoracoscopy (VATS), laparoscopy or hand-assisted thoracolaparoscopy have been used for 'minimally invasive' cancer esophagectomy (MIE). Despite widespread current use, indications and potential benefits of the many technical approaches remain controversial. A systematic literature search was conducted until June 2007. Out of 128 publications, 46 original series (1932 patients) met the inclusion criteria and were analyzed for surgical and oncological outcome. No prospective controlled study has compared any MIE technique to another or to open surgery. Most publications are retrospective series of highly selected patients, mostly excluding high-risk patients and locally advanced (T3) tumors. Altogether, the overall conversion rate was 5.9%, mortality 2.9% and morbidity 46%, many papers reporting only major complications. Overall, rates for pulmonary complications were 22%, leakage 8.8% and vocal cord palsy 7.1%. Fifteen tracheo-bronchial injuries or fistulas (1% of all VATS cases) were reported. Laparoscopy and VATS were combined in 11 series (609 patients, 4.7% conversions, 2.4% mortality). VATS combined with (mini)-laparotomy was reported in 14 papers (743 patients, 6.3% conversions, 2.4% mortality). Laparoscopy combined with right thoracotomy was reported in four papers (147 patients, 5.4% conversions, 2% mortality). Laparoscopic transhiatal resections were reported in 17 papers (433 patients, 7% conversions, 4.6% mortality). Overall morbidity rates for these four approaches were 43%, 47.6%, 51.6% and 46%, respectively. Data on oncological outcome are scarce. Lymph node retrieval (median of all series: 14 nodes, range 5-62) was mostly inferior to open surgery standards and follow-up too short to draw definitive conclusions regarding long-term survival. Based on the available literature, the morbidity and mortality of MIE is substantial and not inferior to radical open esophagectomy in experienced centers. Many different operative techniques for MIE have been reported without obvious superiority for any of them. The term 'minimally invasive' is not supported by hitherto reported results. Selection bias and huge variability in extent of resection and lymphadenectomy impair comparisons of different MIE techniques. Oncological outcome of MIE remains largely unknown by lack of good quality data and selection bias. MIE remains an investigational and still evolving treatment for invasive cancer.