Matthias Schwarzbach

Evaluation of F18-deoxyglucose positron emission tomography (FDG-PET) to assess the nature of neurogenic tumours

AIMS Benign neurofibromas and malignant peripheral nerve sheath tumours (MPNST) commonly develop in patients with neurofibromatosis. Differentiation of benign from malignant tumours by conventional preoperative imaging is unreliable. FDG-PET is a non-invasive technique for biological tumour evaluation. The aim of this study was to assess the value of FDG-PET in patients with neurogenic tumours suspicious for MPNST. METHODS Benign and malignant neurogenic soft tissue tumours were prospectively evaluated by computed tomography or magnetic resonance imaging. Three-dimensional qualitative and quantitative FDG-PET was performed. Standard uptake value (SUV) was analyzed with respect to histological diagnosis and follow-up data. RESULTS Twenty-five neurogenic soft tissue tumours were included. FDG-PET identified all primary (n=6) and recurrent MPNST (n=7). Benign lesions (n=12) did not demonstrate high FDG uptake. The SUV was significantly higher in MPNST (median 2.9; range 1.8-12.3), than in benign tumours (median 1.1; range 0.5-1.8) (p<0.001). At a cut-off value of 1.8 SUV measured 1 h post-injection FDG-PET distinguished between MPNST and benign neurogenic tumours with 100% sensitivity and 83% specificity. CONCLUSIONS FDG-PET allows discrimination of benign from malignant neurogenic tumours. This should be particularly useful in patients with neurofibromatosis as FDG-PET may help to avoid multiple surgical procedures for benign tumours.

Preoperative chemo(radio)therapy versus primary surgery for gastroesophageal adenocarcinoma: Systematic review with meta-analysis combining individual patient and aggregate data

BACKGROUND The prognosis of patients with gastroesophageal adenocarcinoma is poor. There is conflicting evidence regarding effects of preoperative chemotherapy on survival and other outcomes. METHODS We conducted a meta-analysis with aggregate and individual patient data (IPD) to assess the effect of preoperative chemotherapy for gastroesophageal adenocarcinoma on survival and other outcomes. Two independent reviewers identified eligible randomised controlled trials (RCTs) comparing chemotherapy+/-radiotherapy followed by surgery with surgery alone for gastroesophageal adenocarcinoma. IPD was solicited from all trials. Meta-analyses were performed using the two stage method. RESULTS We identified 14 RCTs (2422 patients). For eight RCTs (1049 patients; 43.3%) we obtained IPD. Preoperative chemotherapy was associated with longer overall survival (hazard ratio [HR] 0.81; 95% confidence interval [CI] 0.73-0.89; p<0.0001). There were larger treatment effects in tumours of the gastroesophageal junction and for chemoradiotherapy compared to chemotherapy, but the tests for subgroup differences were not statistically significant. Preoperative chemotherapy was associated with longer disease-free survival, higher likelihood of R0 resection and more favourable post-treatment tumour stage, but not perioperative complications. CONCLUSION Preoperative chemotherapy for locoregional gastroesophageal adenocarcinoma increases survival compared to surgery alone. It should be offered to all eligible patients. There appear to be larger survival advantages in tumours of the gastroesophageal junction and for chemoradiotherapy, but these findings require prospective confirmation.

Clinical Pathways in surgery—should we introduce them into clinical routine? A review article

Background and aimsIn modern health care systems, care providers face ever new challenges with regard to quality and cost of care, as well as to satisfaction and training of staff. Due to the intensiveness of the subject, these challenges are particularly pronounced in surgery. Clinical Pathways, i.e. detailed care plans defining the desired measures to be performed for each treatment period, are thought to be a tool to improve care in surgery with regard to these issues.MethodsWe performed a literature review to identify studies reporting effects of the implementation of Clinical Pathways into clinical care for the most common surgical interventions. We subdivided findings into Clinical Pathways’ effects on economic aspects, quality of care, treatment transparency, staff satisfaction and staff training.ResultsOur search identified 30 studies. Twenty four studies were trials with a before–after design. Four trials had only an intervention group, one trial was a non-randomised controlled trial and one was a randomised controlled trial. Study sizes ranged from six to 1,200 patients. The mean number of patients was 119 in the treatment group and 120 in the comparison group (where existent). Clinical Pathway implementation in surgery has manifold advantages. They improve objective and subjective quality of care, decrease hospitals’ costs, increase staff satisfaction and are valuable tools for training. Their effect seems to be most pronounced for high-volume or particularly complex treatments.ConclusionThere is substantial evidence that Clinical Pathways lead to various improvements in clinical care in surgery. Their widespread use should therefore be encouraged. However, more research encompassing all facets of Clinical Pathway usage and implying sound methods is strongly required.

Frequent amplifications and abundant expression of TRIO, NKD2, and IRX2 in soft tissue sarcomas

Copy number gains and high‐level amplifications of the short arm of chromosome 5 are frequently observed in soft tissue sarcomas. To identify genes from this region possibly involved in tumor progression, we analyzed 34 soft tissue sarcomas (10 pleomorphic and 8 dedifferentiated liposarcomas, 6 malignant fibrous histiocytomas, and 10 malignant peripheral nerve sheath tumors (MPNST)) using a DNA microarray including 418 BAC clones representing 99% of chromosome arm 5p. In seven tumors, distinct high‐level amplifications were identified affecting four different subregions. From these regions, genes TERT, TRIO, SKP2, FBXO32, NKD2, SLC6A3, IRX2, POLS, FYB, PTGER4, and FGF10 were selected for detailed quantitative expression analysis (RQ‐PCR) based on their potential tumorigenic function. Of these, TRIO, coding for a guanidine nucleotide exchange factor, was consistently overexpressed in all cases, while IRX2 and NKD2, both involved in the regulation of developmental processes via the WNT pathway, showed a characteristic expression only in MPNSTs. Detailed nonparametric multidimensional scaling analysis further showed that the expression of TRIO, IRX2, and NKD2 strongly correlated with the gene copy number. In conclusion, we found TRIO, IRX2, and NKD2 frequently affected by high‐level amplifications as well as up‐regulated in a gene‐dosage dependent manner. Thus, these genes represent candidate targets of 5p amplifications in soft tissue sarcomas and might play a crucial role during the progression of this disease.

Endoluminal Stent-Graft Repair of Aortobronchial Fistulas: Bridging or Definitive Long-Term Solution?

PURPOSE To describe our experience with endoluminal stent-graft repair of aortobronchial fistulas (ABF) and to analyze midterm results focusing on late chronic graft infections, secondary conversion, and survival. METHODS The records of 8 patients (6 men; mean age 69 years, range 28-88) treated between March 1997 and October 2003 for traumatic and postsurgical ABFs were reviewed. Seven presented with hemoptysis and 1 with hemorrhagic shock. According to the severity of emergency, patients underwent computed tomography, angiography, bronchoscopy, and transesophageal echocardiography. Preoperatively, no clinical signs of infection were evident. Two different stent-graft models (Talent and Excluder) were implanted using standard endovascular techniques. RESULTS Procedural and clinical success was achieved in all patients. Paraplegia, secondary intervention, conversion, or procedure-related death was not observed. Mean follow-up was 30 months (range 0.6-77). One patient with a postsurgical ABF (Dacron tube graft) successfully treated with an Excluder stent-graft died 13 months later from hemorrhage secondary to aortoesophageal fistula repair procedures. A second patient died from pneumonia after 42 months. A third patient, in whom 2 Talent stent-grafts had been implanted to treat an ABF from the false lumen of a type B dissection, died 7 months later from massive hemorrhage. CONCLUSIONS Endoluminal stent-grafting of ABF is feasible and the preferred method of treatment. Secondary conversion due to endograft infection is not absolutely mandatory, but close surveillance is necessary.

Early surgical outcome after failed primary stenting for lower limb occlusive disease.

Purpose: To evaluate the early results of revascularization after failed primary stent placement for lower limb occlusive disease. Methods: A retrospective review was conducted of 25 consecutive patients (16 men; mean age 65 years, range 32–89) treated between January 2001 to October 2003 for infrainguinal stent failure at a median 6.6 months (range 3–60) after primary stent implantation (27 femoropopliteal and 20 popliteal-crural) at referring hospitals. All surgical procedures for stent failure were performed at tertiary centers. The results of bypass grafting for failed stenting were compared to a contemporaneous cohort of patients undergoing primary bypass surgery performed by the same surgeons. Results: At the time of admission, 22 stents were thrombosed, and 3 patent stents presented with >50% in-stent stenosis. Twenty patients had 7 femoropopliteal or 9 femorodistal vein bypasses and 4 reconstructions of the common femoral or profunda femoris artery. Four patients had 3 primary amputations and 1 lumbar sympathectomy. One patient with claudication was treated conservatively. Procedure-related complications were observed in 40%; 30-day mortality was 4% (1/25). Early (30-day) graft thrombosis occurred in 6 (30%) of 20 arterial reconstructions, necessitating 8 secondary amputations (44% [11/25] overall amputation rate). A total of 47 surgical procedures were performed in the 24 surviving patients (median 2 operations per patient, range 1–9) over an 11-month period (range 1–57). Primary patency rates at 30 days and at 6 and 12 months were 67%, 44%, and 33%, respectively, in the poststent bypass cohort versus 98%, 96%, and 88%, respectively, in a contemporaneous group of patients treated with primary bypass grafting. Conclusions: Failed stents in lower limb arteries often require distal reconstructive bypass surgery, which is associated with high complication rates and poor outcome, including major amputations. There is no scientific evidence to support stenting below the inguinal ligament.

Late surgical conversion after thoracic endograft failure due to fracture of the longitudinal support wire.

Purpose: To report complications from a thoracic endograft wire fracture and early experience with elective conversion after thoracic endografting. Case Report: A 43-year-old man underwent urgent endovascular repair of a symptomatic post-traumatic thoracic aneurysm in 1999. The patient had been involved in a car accident 14 years before. He developed clinical and radiological signs of graft infection 46 months after stent-graft implantation. Multidetector computed tomography confirmed a fracture of the longitudinal support wire in the Excluder thoracic stent-graft. Additionally, radiological signs of suspected endograft infection were described. Due to concerns over a potential chronic infection, the stent-graft was successfully excised, and a polyester graft was implanted 50 months after primary endovascular repair. Conclusions: Recognition or strong suspicion of endograft infection requires conversion with removal of the device. Long-term follow-up after endografting is necessary to assess material fatigue that undermines the durability of these implants.

Perioperative and Oncological Outcome of Laparoscopic Resection of Gastrointestinal Stromal Tumour (GIST) of the Stomach

Background. Surgery remains the only curative treatment for gastrointestinal stromal tumour (GIST). Resection needs to ensure tumour-free margins while lymphadenectomy is not required. Thus, partial gastric resection is the treatment of choice for small gastric GISTs. Evidence on whether performing resection laparoscopically compromises outcome is limited. Methods. We compiled patients undergoing laparoscopic resection of suspected gastric GIST between 2003 and 2007. Follow-up was performed to obtain information on tumour recurrence. Results. Laparoscopic resection with free margins was performed in 21/22 patients. Histology confirmed GIST in 17 cases, 4 tumours were benign neoplasms. Median operation time and postoperative stay for GIST patients were 130 (range 80–201) mins and 7 (range 5–95) days. Two patients experienced stapler line leakage necessitating surgical revision. After median follow-up of 18 (range 1–53) months, no recurrence occurred. Conclusions. Laparoscopic resection of gastric GISTs yields good perioperative outcomes. Oncologic outcome needs to be assessed with longer follow-up. For posterior lesions, special precaution is needed. Laparoscopic resection could become standard for circumscribed gastric GISTs if necessary precautions for oncological procedures are observed.

Stomach cancer mortality in two large cohorts of migrants from the Former Soviet Union to Israel and Germany: are there implications for prevention?

Objectives Prevention and early detection are key elements for the reduction of stomach cancer mortality. To apply pertinent measures effectively, high-risk groups need to be identified. With this aim, we assessed stomach cancer mortality among migrants from the Former Soviet Union (FSU), a high-risk area, to Germany and Israel. Methods We calculated standardized mortality ratios (SMRs) comparing stomach cancer mortality in two retrospective migrant cohorts from the FSU to Germany (n=34 393) and Israel (n=589 388) to that in the FSU and the host country. The study period ranges from 1990 to 2005 in Germany and from 1990 to 2003 in Israel. Vital status and cause of death were retrieved from municipal and state registries. To assess secular mortality trends, we calculated annual age-standardized mortality rates in the cohorts, the FSU, and the two host countries and conducted Poisson regression modeling. Results SMRs (95% confidence intervals) for men in the German migrant cohort were 0.51 (0.36–0.70) compared with the FSU population and 1.44 (1.04–1.99) compared with the German population, respectively. For women, SMRs were 0.73 (0.49–1.03) compared with the FSU population and 1.40 (0.98–1.99) compared with the German population. SMRs for men in the Israeli migrant cohort were 0.49 (0.45–0.53) compared with the FSU population and 1.79 (1.65–1.94) compared with the Israeli population. SMRs for women in the Israeli cohort were 0.65 (0.59–0.72) compared with the FSU population and 1.82 (1.66–1.99) compared with the Israeli population. Poisson modeling showed a secular decrease in all populations with a time lag of 4–5 years between migrants and ‘natives’ in Germany and converging rates between migrants and the general population in Israel. Conclusion Stomach cancer mortality in migrants from the FSU remains elevated after migration to Germany and Israel but is much lower than in the FSU. Due to a secular decline, it can be expected that mortality among migrants from the FSU reaches within a few years levels similar to those of the host countries today. Therefore, migrant-specific prevention and early detection measures cannot be recommended. Detailed risk factor profiles, however, need to be obtained through further studies.

Which factors are important for the successful development and implementation of clinical pathways? A qualitative study

Introduction Clinical pathways (CPs) are detailed longitudinal care plans delineating measures to be conducted during a patients treatment. Although positive effects on resource consumption and quality of care have been shown, CPs are still underutilised in many clinical settings because their development and implementation are difficult. Evidence underpinning successful development and implementation is sparse. Methods The authors conducted semistructured face-to-face interviews with key staff members involved in the design and implementation of CPs in a large surgery department. Interviewees were asked to provide opinions on various issues, which were previously identified as potentially important in CP development and implementation. The transcribed text was read and coded independently by two researchers. Results Respondents highlighted the importance of a multidisciplinary participatory approach for CP design and implementation. There was a strong initial fear of losing individual freedom of treatment, which subsided after people worked with CPs in clinical everyday life. It was appreciated that the project originated from people at different levels of the departments hierarchy. Likewise, it was felt that CP implementation granted more autonomy to lower-level staff. Conclusion The structured qualitative approach of this study provides information on what issues are considered important by staff members for CP design and implementation. Whereas some concepts such as the importance of a multidisciplinary approach or continuous feedback of results are known from theories, others such as strengthening the authority especially of lower-level health professionals through CPs have not been described so far. Many of the findings point towards strong interactions between factors important for CP implementation and a departments organisational structure.