Surgical treatment of locally advanced thyroid cancer.

Operations in this area are demanding and require special experience in endocrine, thoracic and vascular surgery, an experienced anaesthesiologist, as well as the interdisciplinary cooperation with other medical specialists (nuclear medicine, oncology, radiology, otolaryngology). A reliable system of surgical guidelines has been developed from a few individual publications with special impact.

• Pancho trial (p53-adapted neoadjuvant chemotherapy for resectable esophageal cancer) completed-mutation rate of the marker higher than expected.

BACKGROUND: In operable esophageal cancer patients, neoadjuvant therapy benefits only those who respond to the treatment. The • Pancho trial represents the first prospective randomized trial evaluating the relevance of the mark53 status for predicting the effect of two different neoadjuvant chemotherapies. METHOD: Biomarker analysis was conducted using the mark53 analysis. Calculation of patient number needed was based on a 60% rate of marker positivity, deduced from the results of a phase II pilot study. RESULTS: From 2007-2012, the • Pancho trial recruited 235 patients with operable esophageal cancer in Austria. A total of 181 patients were eligible and could be subjected to mark53 analysis and randomization. After randomizing 74 patients, the overall TP53 mutation rate was 79%. However, due to the high prevalence of marker positivity, the number of projected patients was increased to 181 patients in order to ensure a sufficient number of marker-negative patients. After completion of the trial, the overall TP53 mutation rate was 77.9%. CONCLUSION: Due to high medical need, the recruitment for the academic trial was excellent. Mark53 analysis clearly detected more mutations in the TP53 gene as compared to the cancer-specific p53 literature. Final analysis examining the interaction between the mark53 status and the effect of chemotherapies applied in the • Pancho trial is now awaited.

Cetuximab, gemcitabine, and oxaliplatin in patients with unresectable advanced or metastatic biliary tract cancer: a phase 2 study.

BACKGROUND: Patients with biliary tract cancer have a poor prognosis, and, until recently, no standard palliative chemotherapy has been defined. We aimed to investigate the efficacy and safety of cetuximab in combination with gemcitabine and oxaliplatin (GEMOX) for first-line treatment of biliary tract cancer. METHODS: From Oct 1, 2006, to July 26, 2008, patients with unresectable locally advanced or metastatic biliary tract cancer were sequentially enrolled and treated at one centre in Austria. All patients received intravenous infusions of 500 mg/m(2) cetuximab on day 1, 1000 mg/m(2) gemcitabine on day 1, and 100 mg/m(2) oxaliplatin on day 2, every 2 weeks for 12 cycles. The primary outcome was overall response rate. Analysis was by intention to treat. Adverse reactions were assessed according to National Cancer Institute Common Toxicity Criteria. The study is completed and registered with ClinicalTrials.gov, number NCT01216345. FINDINGS: 30 patients with median age of 68 years (IQR 62-73) were enrolled and included in the analysis. Objective response occurred in 19 patients (63%; 95% CI 56·2-69·8), of whom three (10%; 3·2-16·8) achieved complete response, and 16 (53%; 46·2-59·8) achieved partial response. Nine patients underwent potentially curative secondary resection after major response to therapy. Grade 3 adverse events were recorded in 13 patients: skin rash (n=4), peripheral neuropathy (n=4), thrombocytopenia (n=3), nausea (n=1), diarrhoea (n=1), and neutropenia (n=1); no grade 4 adverse events were recorded. INTERPRETATION: Cetuximab plus GEMOX was well tolerated and had encouraging antitumour activity, leading to secondary resection in a third of patients. These findings warrant further study of cetuximab plus GEMOX in a large randomised trial.

Differential diagnosis of benign and malign pancreatic masses with 18F-fluordeoxyglucose-positron emission tomography recorded with a dual-head coincidence gamma camera.

INTRODUCTION: Metabolic imaging using 18F-fluordeoxyglucose and a ring-positron emission tomography camera is an established method in the differential diagnosis of pancreatic masses. Ring-positron emission tomography cameras, however, are expensive and available in only few specialized centres. The aim of this study was to investigate how far 18F-fluordeoxyglucose scan with a conventional dual-head gamma-camera could differentiate between benign and malign pancreatic masses. MATERIAL AND METHODS: Forty-one patients (male/female: 25/16; mean age: 64.0 years; range: 41-86 years) with a pancreatic mass detected by ultrasound, computed tomography or MRI were included. In all patients 18F-fluordeoxyglucose scan was performed after overnight fasting and injection of 4 mCi 18F-fluordeoxyglucose using an ADAC Vertex MCD dual head gamma-camera (ADAC; Milpitas, California, USA), equipped with a 5/8-inch NaI-crystal. Images were acquired through a 180 degrees grade rotation in the three dimensional mode. The chosen matrix was 128 x 128 x 16, a Butterworthfilter (ADAC) was used and data were transferred into visible sinograms via Fourier-Rebinning. Coronar, sagittal and transversal slices of 3.9 mm thickness each were acquired. Focal tracer enhancement was suspicious for a malignoma and therefore regarded as positive, diffuse or no tracer uptake was suspicious for a benign process and was regarded as negative for cancer. DEFINITION OF GOLD STANDARDS: A diagnosis of cancer had to be confirmed histologically by specimens obtained by 18G-needle biopsy, surgical resection or at autopsy. A diagnosis of an inflammatory mass was considered proven, if no carcinoma could be found histologically in the surgically resected mass or at autopsy, or if there was no progression of the disease during a follow-up of at least 12 months. RESULTS: In 22 patients carcinoma was diagnosed (pancreatic cancer: n=17; endocrine tumour: n=3; carcinoma of the common bile duct: n=2). 18F-fluordeoxyglucose scan showed a focal tracer enhancement in 19 of these 22 patients (sensitivity: 86.4%). False negative results were acquired in two patients with cancer of the common bile duct and in one patient with poorly controlled insulin-dependent diabetes mellitus. In 19 patients the final diagnosis was an inflammatory pancreatic mass. 18F-fluordeoxyglucose scan showed a diffuse tracer enhancement in 15 of these 19 patients (specificity: 78.9%). False positive results were acquired in three patients whose blood tests showed signs of an acute episode of chronic pancreatitis. Positive and negative predictive values of 18F-fluordeoxyglucose scan were 82.6% and 83.3%, respectively. CONCLUSION: 18F-fluordeoxyglucose scan with a conventional dual-head gamma-camera is a highly sensitive and specific method in the differential diagnosis of benign and malign pancreatic masses.

Treatment of gastro-jejunal leakage and fistulization after gastric bypass with coated self-expanding stents.

Leakage and fistulization of the gastro-jejunostomy have been the major drawback of Roux-en-Y gastric bypass (RYGBP) surgery. Most authors agree that operative treatment is the mainstay of therapy in patients with signs of sepsis. However, intestinal contents causing localized infection may impede healing of sutured leaks in some patients, and fistulas develop. Because the anastomosis cannot be disconnected or exteriorized for anatomical reasons, other forms of treatment have to be applied. The following case-reports describe a technique with implantation of coated self-expanding stents. Leakage of the gastro-jejunostomy occurred in one patient 3 days after RYGBP and resulted in formation of a fistula. A fistula developed in a second patient 63 days after RYGBP. Coated self-extending stents were implanted endoscopically in both patients on postoperative days 19 and 67. Enteral nutrition could be started 6 days later. Stents were removed 2 months after implantation without problems. Weight loss and quality of life 7 and 21 months after stent removal have been excellent in both patients. Implantation of coated self-expanding stents was an effective and minimally invasive option for gastro-jejunal anastomotic fistulas after RYGBP where surgical repair was not possible. In these cases, application of stents allows septic source control without any other intervention.

Band slippage--a potentially life-threatening complication after laparoscopic adjustable gastric banding.

BACKGROUND: Although gastric bands are safe and effective devices, severe late complications may develop in rare cases. PATIENTS: 3 patients were treated for complete dysphagia after slippage of gastric bands. 2 of the patients were admitted for severe dehydration, 1 of whom developed cerebral venous infarction. Ischemia of the gastric pouch occurred in 1 patient. RESULTS: All 3 patients survived after successful medical therapy and surgical removal of the bands. Bariatric reoperations were performed in 2 patients (gastric sleeve resection, gastric bypass). CONCLUSION: Complete dysphagia on the basis of band slippage represents a life-threatening acute event, which may occur even years after implantation. Patients and doctors should be informed about this long-term risk of gastric banding.

Weight loss reduces tissue factor in morbidly obese patients.

OBJECTIVE: To investigate the tissue factor (TF) pathway in clinical obesity and associated metabolic syndrome. RESEARCH METHODS AND PROCEDURES: Thirty-seven morbidly obese patients (4 men; BMI, 48 +/- 7 kg/m(2); range, 42 to 53 kg/m(2)), undergoing elective gastroplasty for the induction of weight loss, were examined for hemostatic, metabolic, and inflammatory parameters at baseline and 14 +/- 5 months postoperatively. RESULTS: Weight loss significantly reduced circulating plasma TF (314 +/- 181 vs. 235 +/- 113 pg/mL, p = 0.04), coagulation factor VII (130 +/- 22% vs. 113 +/- 19%, p = 0.023), and prothrombin fragment F1.2 (2.4 +/- 3.4 vs. 1.14 +/- 1.1 nM, p = 0.04) and normalized glucose metabolism in 50% of obese patients preoperatively classified as diabetic or of impaired glucose tolerance. The postoperative decrease in plasma TF correlated with the decrease of F1.2 (r = 0.56; p = 0.005), a marker of in vivo thrombin formation. In subgroup analysis stratified by preoperative glucose tolerance, baseline circulating TF (402.6 +/- 141.6 vs. 176.2 +/- 58.2, p < 0.001) and TF decrease after gastroplasty (DeltaTF: 164.7 +/- 51.4 vs. -81 +/- 31 pg/mL, p = 0.02) were significantly higher in obese patients with impaired glucose tolerance than in patients with normal glucose tolerance. DISCUSSION: Procoagulant TF is significantly reduced with weight loss and may contribute to a reduction in cardiovascular risk associated with obesity.

Laryngeal recurrent nerve injury in surgery for benign thyroid diseases: effect of nerve dissection and impact of individual surgeon in more than 27,000 nerves at risk.

OBJECTIVE: To evaluate the effect of recurrent nerve dissection on the incidence of recurrent laryngeal nerve injury (RLNI) and to analyze the performance of individual surgeons. SUMMARY BACKGROUND DATA: Dissection of the recurrent nerve is mandatory in total thyroidectomy, but its relative merit in less extensive resections is not clear. The reported rates of RLNI differ widely; this may reflect a variation in the performance of individual surgeons. METHODS: The authors studied the incidence of RLNI in primary surgery for benign thyroid disease during three periods in a single center. In period 1 (1979-1990; 9,385 consecutive patients, 15,865 nerves at risk), the recurrent nerve was not exposed. In period 2 (1991-1998; 6,128 patients, 10,548 nerves at risk), dissection of the recurrent nerve was the standard procedure. Global outcome and individual performance in these two periods were compared and presented to the surgeons. The effect of this quality control procedure was tested in 1999 (period 3; 930 patients, 1,561 nerves at risk). RESULTS: Exposure of the recurrent nerve significantly reduced the global rate of postoperative and permanent RLNI. Some but not all surgeons improved their results by recurrent nerve dissection (e.g., permanent RLNI rates ranged from 0% to 1.1%). The documented significant differences in individual performances did not affect the outcome in period 3. The extent of nerve dissection was a source of variability; the rate of permanent RLNI averaged 0.9%, 0.3%, and 0.1% for surgeons who only localized, partially exposed, and completely dissected the recurrent nerve, respectively. CONCLUSIONS: Recurrent nerve dissection significantly reduces the risk of RLNI. Extensive dissection facilitates visual control of nerve integrity during resection and is therefore superior to a more limited exposure of the nerve. Quality control can improve the global outcome and identify the variability in individual performance. This cannot be eliminated by merely confronting surgeons with comparative data; hence, it is important to search for the underlying causes.