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In most cases, myasthenia gravis (MG) and thymoma require complete removal of the thymus gland and resection of the pericardial fatty tissue. There is some debate however, over which surgical approach is best for thymectomy. We have developed a new technique for complete thoracoscopic thymectomy. Between October 1994 and February 1998, we performed a prospective observational study of thoracoscopic thymectomy in 19 patients. The results were analyzed with special reference to perioperative morbidity, short- and intermediate-term improvement of MG, and quality of life. This study showed the feasibility of complete thoracoscopic thymectomy. The procedure was successfully applied in 19 of 20 cases. Thoracoscopic thymectomy was accomplished with zero mortality and a very low perioperative morbidity. While the short-term improvement of MG after this procedure was comparable to that seen with conventional surgery, the short- and intermediate-term quality of life was much better. The preliminary results of thoracoscopic thymectomy appear to be excellent for both patients and neurologists. A prospective randomized trial has been designed to compare thoracoscopic thymectomy with the gold standard of median sternotomy for thymectomy. [ABSTRACT FROM AUTHOR]

CONKO-006 was designed for patients with pancreatic adenocarcinoma with postsurgical R1 residual status to evaluate the efficacy and safety of the combination of gemcitabine and sorafenib (GemSorafenib) compared with those of gemcitabine + placebo (GemP) for 12 cycles. This randomised, double-blind, placebo-controlled, multicenter study was planned to detect an improvement in recurrence-free survival (RFS) from 42% to 60% after 18 months. Secondary objectives were overall survival (OS), safety and duration of treatment. 122 patients were included between 02/2008 and 09/2013; 57 were randomised to GemSorafenib and 65 to GemP. Patient characteristics were wellbalanced (GemSorafenib/GemP) in terms of median age (63/63 years), tumour size (T3/T4: 97/97%), and nodal positivity (86/85%). Grade 3/4 toxicities comprised diarrhoea (GemSorafenib: 12%; GemP: 2%), elevated gamma-glutamyl transferase (GGT) (19%; 9%), fatigue (5%; 2%) and hypertension (5%; 2%), as well as neutropenia (18%; 25%) and thrombocytopenia (9%; 2%). By August 2017, 118 (97%) RFS event had occurred. There were no difference in RFS (median GemSorafenib: 8.5 versus GemP: 9.4 months; p = 0.730) nor OS (median GemSorafenib: 17.6 versus GemP: 17.5 months; p = 0.481). Landmark analyses suggest that patients who received more than six cycles of postoperative chemotherapy had significantly longer OS (p = 0.021). CONKO-006 is the first randomised clinical trial to include exclusively patients with PDAC with postsurgical R1 status thus far. Sorafenib added to gemcitabine did neither improve RFS nor OS. However, postoperative treatment exceeding six months seemed to prolong survival and should be further investigated in these high-risk patients. German Tumor Study Registry (Deutsches Krebsstudienregister), DRKS00000242. • Patients with R1 resection of pancreatic ductal adenocarcinoma (PDAC) relapsed in more than 90%. • Gemcitabine + sorafenib is not effective in the postoperative treatment of PDAC. • Adjuvant gemcitabine exceeding 6 months may be beneficial in R1-resected PDAC not suitable for mFOLFIRINOX. [ABSTRACT FROM AUTHOR]

Background: Transvaginal cholecystectomy (TVC) is regarded as a model operation in the newly developed field of natural orifice transluminal endoscopic surgery (NOTES). Randomized, controlled trials to assess TVC as a surgical strategy are largely missing. Materials and methods: The study was a double blind, randomized, controlled, single center trial in female patients > 18 years with symptomatic cholecystolithiasis comparing laparoscopic cholecystectomy (CLC) and TVC. The study investigated pain reduction of ≥ 1 point on a visual-numeric rating scale with a follow-up after 7 days. Secondary endpoints were complications and patient reported outcome. Groups were established using computer-generated randomization and sealed envelopes in the operating theatre. At the end of the surgical procedure all patients received a standard 4-trocar dressing as for CLC and a vaginal tamponade. Results: A total of 426 patients were asked to participate, of which 97 were randomized, 51 in the CLC, 41 in the TVC groups and 5 were excluded from the study. Patients were comparable regarding age, body mass index (BMI) and American Society of Anesthesiologists (ASA) grade. Surgical and anesthesia times were significantly different. There was no difference in postoperative pain. The majority of patients were satisfied with both procedures and TVC was recommended to other patients by 93 % of patients in the TVC group. Conclusion: The results did not show superiority of TVC over CLC with regards to postoperative pain. With no differences in postoperative pain and high patient satisfaction, TVC can be recommended to future patients as an alternative method. For confirmation of this evaluation of TVC further randomized trials are needed. [ABSTRACT FROM AUTHOR]

Abstract: Little is known about pathogenesis – and especially about involvement of CD8+ T-cells – in late-onset myasthenia gravis (LOMG). Remarkably, outstanding CD8+ TCRVβ-subset expansions were found in 64% and 72% of recent onset LOMG or thymoma-associated MG (vs. 16% with early-onset MG (p <0.0002); 21% in older controls (p <0.001)). In LOMG, ~25% of the expanded cells initially showed a naïve CD62L+hi/CD45RA+ recent thymic emigrant (RTE)-like phenotype. These expansions associated significantly with IgG antibodies against cytomegalovirus (p <0.036), IL-12 and/ or IFN-α2 (p <0.03). The CD8+ TCRVβ expansions were stable over 5years, but RTE markers declined. [Copyright &y& Elsevier]

Context: The role of adjuvant therapy in resectable pancreatic cancer is still uncertain, and no recommended standard exists.Objective: To test the hypothesis that adjuvant chemotherapy with gemcitabine administered after complete resection of pancreatic cancer improves disease-free survival by 6 months or more.Design, Setting, and Patients: Open, multicenter, randomized controlled phase 3 trial with stratification for resection, tumor, and node status. Conducted from July 1998 to December 2004 in the outpatient setting at 88 academic and community-based oncology centers in Germany and Austria. A total of 368 patients with gross complete (R0 or R1) resection of pancreatic cancer and no prior radiation or chemotherapy were enrolled into 2 groups.Intervention: Patients received adjuvant chemotherapy with 6 cycles of gemcitabine on days 1, 8, and 15 every 4 weeks (n = 179), or observation ([control] n = 175).Main Outcome Measures: Primary end point was disease-free survival, and secondary end points were overall survival, toxicity, and quality of life. Survival analysis was based on all eligible patients (intention-to-treat).Results: More than 80% of patients had R0 resection. The median number of chemotherapy cycles in the gemcitabine group was 6 (range, 0-6). Grade 3 or 4 toxicities rarely occurred with no difference in quality of life (by Spitzer index) between groups. During median follow-up of 53 months, 133 patients (74%) in the gemcitabine group and 161 patients (92%) in the control group developed recurrent disease. Median disease-free survival was 13.4 months in the gemcitabine group (95% confidence interval, 11.4-15.3) and 6.9 months in the control group (95% confidence interval, 6.1-7.8; P<.001, log-rank). Estimated disease-free survival at 3 and 5 years was 23.5% and 16.5% in the gemcitabine group, and 7.5% and 5.5% in the control group, respectively. Subgroup analyses showed that the effect of gemcitabine on disease-free survival was significant in patients with either R0 or R1 resection. There was no difference in overall survival between the gemcitabine group (median, 22.1 months; 95% confidence interval, 18.4-25.8; estimated survival, 34% at 3 years and 22.5% at 5 years) and the control group (median, 20.2 months; 95% confidence interval, 17-23.4; estimated survival, 20.5% at 3 years and 11.5% at 5 years; P = .06, log-rank).Conclusions: Postoperative gemcitabine significantly delayed the development of recurrent disease after complete resection of pancreatic cancer compared with observation alone. These results support the use of gemcitabine as adjuvant chemotherapy in resectable carcinoma of the pancreas.Trial Registration: isrctn.org Identifier: ISRCTN34802808. [ABSTRACT FROM AUTHOR]

Objectives: Clinical prognosis and treatment schedules of non-small cell lung cancer (NSCLC) are dependent on tumor stage. This explains the importance of an exact pretreatment staging of the primary tumor and lymph nodes especially in locally advanced NSCLC, to differentiate between resectable and non-resectable disease. To assess the lymph node status of the upper mediastinum, the diagnostic value of mediastinoscopy is accepted to be superior to radiological methods. In contrast, thoracoscopy is not yet established as a standard staging tool. Patients and methods: Seventy-three consecutive patients with CT-based suspicion of advanced NSCLC have been investigated as part of a phase II study on neoadjuvant treatment of NSCLC. All patients underwent mediastinoscopy and mediastinal lymph node sampling. In the case of a negative result we performed additional thoracoscopy. Results: In 52.1% (n=38) of the patients the invasive diagnostic methods led to results that were effectively different from those of the radiological findings. In 11 patients (15.1%) CT-assessed lymph node metastases could invasively not be confirmed, whereas nine patients (12.3%) had positive mediastinal lymph nodes but no corresponding CT signs (diameter <1 cm). The results were achieved by mediastinoscopy in 15 (20.5%) and by thoracoscopy in five (6.8.%) patients. A radiologically unexpected T4 stage has been found in four (5.5%) and a M1 stage in four (5.5%) patients by thoracoscopy. On the contrary, in seven patients a suspected infiltration of mediastinum or parietal pleura could be thoracoscopically excluded. Four patients have been in an unexpected high stage of tumor progression at the moment of diagnostic procedures and therefore have been included in palliative therapy schedules. Ten patients have been ‘overstaged’ by radiological methods and benefited from a primarily curative resection after invasive staging. Conclusions: Of the 73 prospectively studied patients with locally advanced NSCLC, 12 (16.4%) have been staged too low and 13 (17.8%) too high. If exclusively staged by radiological methods, about 34% of lung cancers have been classified incorrectly. Therefore, these tools are not a sufficient basis for diagnosis of stage III NSCLC disease. Mediastinoscopy with consecutive thoracoscopy is an essential part of the therapeutic planning in locally advanced NSCLC, and results are significantly superior to clinical staging. [Copyright &y& Elsevier]

Comparative genomic hybridization (CGH) was applied to squamous cell carcinomas (SCC) of the lung to define chromosomal imbalances that are associated with the metastatic phenotype. In total, 64 lung SCC from 50 patients were investigated, 25 each with or without evidence of metastasis formation. The chromosomal imbalances summarized by a CGH histogram of the 50 cases revealed deletions most frequently on chromosomes 1p21-p31, 2q34-q36, 3p, 4p, 4q, 5q, 6q14-q24, 8p, 9p, 10q, 11p12-p14, 13q13-qter, 18q12-qter and 21q21. DNA over-representations were most pronounced for chromosomes 1q11-q25, 1q32-q41, 3q, 5p, 8q22-qter, 11q13, 12p, 17q21-q22, 17q24-q25, 19, 20q and 22q. In ten cases, paired samples of primaries and at least one metastasis were analysed. The comparison revealed a considerable chromosomal instability and genetic heterogeneity; however, the CGH pattern indicated a clonal relationship in each case. The difference in histograms from the metastatic and non-metastatic tumour groups was most useful in pinpointing chromosomal imbalances associated with the metastatic phenotype, indicating that the deletions at 3p12-p14, 3p21, 4p15-p16, 6q24-qter, 8p22-p23, 10q21-qter and 21q22, as well as the over-representations at 1q21-q25, 8q, 9q34, 14q12 and 15q12-q15, occurred significantly more often in the metastatic tumour group. The comparison of the paired samples confirmed these findings in individual cases and suggested distinct genetic changes, in particular the extension of small interstitial deletions, during tumour progression. Importantly, metastasis-associated lesions were frequently detectable in the primary tumour providing a method of identifying patients at risk for tumour dissemination. Individual profiles and histograms are accessible at our web site http://amba.charite.de/cgh. [ABSTRACT FROM AUTHOR]