Comparison of preoperative short-course radiotherapy and long-course radiochemotherapy for locally advanced rectal cancer.

BACKGROUND: The purpose of this work was to perform a single institution comparison between preoperative short-course radiotherapy (SC-RT) and long-course radiochemotherapy (LC-RCHT) for locally advanced rectal cancer. METHODS: A total of 225 patients with clinical stage UICC II-III rectal cancer were treated with SC-RT (29 Gy in 10 twice daily fractions followed by immediate surgery; n = 108) or LC-RCHT (54 Gy in 28 fractions with simultaneous 5-fluorouracil (5-FU) ± oxaliplatin chemotherapy followed by delayed surgery; n = 117). All patients in the LC-RCHT cohort and patients in the SC-RT with pathological UICC stage ≥ II received adjuvant chemotherapy. Before 2004, the standard of care was SC-RT with LC-RCHT reserved for patients where downstaging was considered as required for sphincter preservation or curative resection. In the later period, SC-RT was practiced only for patients unfit for radiochemotherapy. RESULTS: Patients in the LC-RCHT cohort had a significantly higher proportion of cT4 tumors, clinical node positivity, and lower tumor location. The 5-year local control (LC) and overall survival (OS) were 91% and 66% without differences between the SC-RT and LC-RCHT groups. Acute toxicity was increased during LC-RCHT (grade ≥ II 1% vs. 33%) and there were no differences in postoperative complications. Severe late toxicity grade ≥ III was increased after SC-RT (12% vs. 3%). Of patients aged > 80 years, 7 of 7 patients and 4 of 9 patients received curative surgery after SC-RT and LC-RCHT, respectively. CONCLUSION: Despite the fact that patients with worse prognostic factors were treated with LC-RCHT, there were no significant differences in LC and OS between the SC-RT and LC-RCHT group. Age > 80 years was identified as a significant risk factor for LC-RCHT and these patients could be treated preferably with SC-RT.

[Comment on the article "Operative Techniques and Outcomes in Metabolic Surgery: Sleeve Gastrectomy"]. / Kommentar zum Artikel "Operative Techniken und deren Outcome in der metabolischen Chirurgie: Sleeve-Gastrektomie" von T.P.Hüttl et al.

The review article "Operative Techniques and Outcomes in Metabolic Surgery: Sleeve Gastrectomy" by Hüttl et al. is concerned with laparoscopic sleeve stomach operations ("sleeve gastrectomy") for the surgical treatment of morbid obesity (Zentralblatt für Chirurgie 2009; 134: 24-31). After an analysis of the available literature and own results, the authors concluded that the laparoscopic sleeve operation is established today as an effective standard procedure in the therapy for obesity.We would like to comment on the content of this article.

Tumor cell dissemination in a human colon cancer animal model: orthotopic implantation or intraportal injection?

BACKGROUND: The development of therapeutic strategies for treatment of metastasized colorectal carcinoma requires biologically relevant and adequate animal models generating both metastases and the dissemination of tumor cells. METHODS: To prove the efficiency of orthotopic implantation concerning induction of minimal residual disease (MRD) colorectal cancer tissue from 10 patients was transplanted orthotopically into nude mice. In the intraportal injection model 1 x 10(6) HT-29 human colon cancer cells were injected. We investigated by histological studies and CK-20 RT-PCR the occurrence of hematogenous metastases and the dissemination of human colon cancer cells in bone marrow. RESULTS: Following orthotopic implantation of human colon cancer tissue the lymph node and hepatic metastasis rates were low. MRD as reflected by CK-20 positivity of the bone marrow was present in 22.2%. The intraportal injection of 1 x 10(6) HT-29 human colon cancer cells produced hepatic metastases in up to 89% of all animals. The intraportal injection of 1 x 10(6) cells also generated MRD in the bone marrow in 63% of animals. CONCLUSIONS: The intraportal injection model represents a biologically relevant and adequate animal model for the induction of both reproducible hepatic metastasis and MRD in the bone marrow. In this regard it seems to be superior to the orthotopic implantation model.

[Less reflux recurrence following Nissen fundoplication : results of laparoscopic antireflux surgery after 10 years]. / Weniger Refluxrezidive nach Nissen-Fundoplikation : 10-Jahres-Ergebnisse der laparoskopischen Antirefluxoperation.

BACKGROUND: Reflux recurrence is the most common long-term complication following fundoplication. Results for different techniques of laparoscopic antireflux surgery were retrospectively compared after 10 years. METHODS: From 1992 to 1997, the 120 patients studied had laparoscopic fundoplication with 'tailored' approaches: 88 Nissen, 22 anterior, and ten Toupet fundoplications. Follow-up of 87% of these patients included disease-related questions and the gastrointestinal quality of life index (GIQLI). RESULTS: Of the patients, 89% would select surgery again. Regurgitations after fundoplication were noted from 15% of patients after Nissen, 44% after anterior, and 10% after Toupet types (P=0.04). Twenty-eight percent were on acid suppression therapy. Proton pump inhibitors were used less frequently following Nissen fundoplication (P=0.01). The GIQLI score was 110+/-24 without significant differences for type of fundoplication. DISCUSSION: Overall results are satisfactory after 10 years of experience with fundoplication. Total fundoplication appears to control reflux better than partial fundoplication.

abiliti Closed-Loop Gastric Electrical Stimulation System for Treatment of Obesity: Clinical Results with a 27-Month Follow-Up.

BACKGROUND: The aim of the study was to evaluate the safety and effectiveness of a novel closed-loop gastric electric stimulation device (abiliti system) featuring a transgastric sensor to detect food intake and an accelerometer to record physical activity to induce and maintain lifestyle changes to treat obesity. METHODS: In a prospective, multi-center study, 34 obese subjects (BMI of 42.1 ± 5.3 kg/m(2)) who passed an eligibility evaluation were implanted with the abiliti system. Safety evaluation included an endoscopic exam to assess the intragastric electrode healing. Efficacy evaluation at 1 year of therapy included weight loss, improvements in eating, and exercise behavior and quality of life. RESULTS: The transgastric implant controlled by endoscopy was stable for all participants. At 12 months (12 M) the mean excess weight loss (EWL) was 28.7% (95%CI, 34.5 to 22.5%), and mean reduction in BMI was 4.8 ± 3.2 kg/m(2). At 27 months (27 M), the EWL was 27.5% (95% CI, 21.3% to 33.7%). Eating behavior, evaluated by the "Three Factor Eating Questionnaire", showed a significant increase in the cognition factor and decrease in the disinhibition and hunger factors at 12 M in comparison to baseline (p < 0.001). Participants significantly increased their weekly physical activity (p < 0.001). Quality of life was improved in 55.2% of the patients. CONCLUSIONS: Gastric electrical stimulation with abiliti system in obese participants is well tolerated and leads to significant 12 M weight loss, which was stable to 27 M. We suggest that weight loss is achieved due to the assessed alteration of eating behavior in particular the reduction in disinhibition and hunger, and the measured increase in physical activity.

[Gastrointestinal stromal tumor of the abdominal wall. An unusual localization of a rare tumor]. / Gastrointestinaler Stromatumor der Bauchwand. Ungewöhnliche Lokalisation eines seltenen Tumors.

Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal tract. We describe here for the first time a patient with a huge GIST of the abdominal wall without any relation to the gastrointestinal tract, omentum, or mesentery. With regard to the size of 24 cm and a low mitotic index, this GIST is considered an intermediate risk for metastasis. Radical surgical resection was performed with negative pathologic resection margins. The classic immunohistochemical phenotype of the tumor described facilitates the differential diagnosis to exclude abdominal desmoid tumor and solitary fibrous tumor (SFT). In the case of metastasis, therapeutic nihilism no longer seems justified with the availability of imatinib, a tyrosine kinase inhibitor, which shows encouraging results in the therapy of metastatic GIST.

[Metabolic surgery]. / Metabolische Chirurgie.

The prevalence of obesity and diabetes mellitus type 2 is constantly rising worldwide and is one of the most threatening global health and health economic problems. Whereas bariatric surgery is well established in the treatment of morbid obesity, the surgical treatment options for type 2 diabetes mellitus alone are still under discussion (metabolic surgery). Bariatric procedures differ considering weight loss and influencing associated comorbidities. Detailed knowledge of available surgical treatment options for morbid obesity, the risks and requirements of laparoscopic skills, effectiveness and, as far as already known, mechanisms of action are crucial for appropriate implementation.

Improvement of type 2 diabetes mellitus (T2DM) after bariatric surgery--who fails in the early postoperative course?

BACKGROUND: Diabetes surgery in nonobese or moderately obese patients is an emerging topic. The identification of preoperative factors predicting diabetes outcome following bariatric surgery, especially for metabolic nonresponders, is imperative. METHODS: Between 2005 and 2011, 235 patients underwent bariatric surgery for morbid obesity. Eighty-two of 235 patients had type 2 diabetes mellitus (T2DM). Data from this subgroup were investigated with univariate and multivariate analyses to identify predictors for metabolic nonresponse after surgery. RESULTS: Diabetes did not improve in 17/82 patients within 3 months after surgery. No correlation between excess body weight loss and metabolic response was detected. In univariate analysis, preoperative duration of diabetes was significantly longer in the nonresponder group (9.146 vs. 6.270 years; *p = 0.016), preoperative HbA1c levels were significantly higher among the nonresponders than among the responders (8.341 vs. 7.781 %; *p = 0.033), and more patients in the nonresponder group were reliant on a multi-drug approach preoperatively (*p = 0.045). In multivariate analysis, age, preoperative doses of insulin, and preoperative oral antidiabetics showed positive correlation to metabolic nonresponse after surgery (*p = 0.04; *p = 0.021; *p = 0.021). Metabolic failure rate was lower after Roux-en-Y gastric bypass compared to other bariatric procedures (**p = 0.008). CONCLUSIONS: A long history of preoperative T2DM, high preoperative HbA1c levels, and a preoperative therapy consisting of diverse approaches to diabetes treatment may be factors predicting failure of diabetes improvement in the early postoperative course after bariatric surgery. Age, preoperative insulin, and oral antidiabetic medication can be regarded as independent, significant predictors for metabolic outcome after bariatric surgery.

Concordance of KRAS/BRAF Mutation Status in Metastatic Colorectal Cancer before and after Anti-EGFR Therapy.

Anti-EGFR targeted therapy is a potent strategy in the treatment of metastatic colorectal cancer (mCRC) but activating mutations in the KRAS gene are associated with poor response to this treatment. Therefore, KRAS mutation analysis is employed in the selection of patients for EGFR-targeted therapy and various studies have shown a high concordance between the mutation status in primary CRC and corresponding metastases. However, although development of therapy related resistance occurs also in the context of novel drugs such as tyrosine kinase-inhibitors the effect of the anti-EGFR treatment on the KRAS/BRAF mutation status itself in recurrent mCRC has not yet been clarified. Therefore, we analyzed 21 mCRCs before/after anti-EGFR therapy and found a pre-/posttherapeutic concordance of the KRAS/BRAF mutation status in 20 of the 21 cases examined. In the one discordant case, further analyses revealed that a tumor mosaicism or multiple primary tumors were present, indicating that anti-EGFR therapy has no influence on KRAS/BRAF mutation status in mCRC. Moreover, as the preselection of patients with a KRAS(wt) genotype for anti-EGFR therapy has become a standard procedure, sample sets such ours might be the basis for future studies addressing the identification of potential anti-EGFR therapy induced genetic alterations apart from KRAS/BRAF mutations.

Ten-year outcome of laparoscopic antireflux surgery.

BACKGROUND: Reflux recurrence is the most common long-term complication of fundoplication. Its frequency was independent from the type of fundoplication in randomized studies. Results for different techniques of laparoscopic antireflux surgery were retrospectively evaluated after 10 years. METHODS: From 1992 to 1997, 120 patients had primary laparoscopic fundoplication with a "tailored approach" (type of wrap chosen according to esophageal peristalsis): 88 received a Nissen, 22 an anterior, and 10 a Toupet fundoplication. Follow-up of 87% of the patients included disease-related questions and the gastrointestinal quality-of-life index (GIQLI). RESULTS: Of the patients, 89% would select surgery again. Heartburn was reported by 30% of the patients. Regurgitations were noted from 15% of patients after a Nissen, 44% after anterior fundoplication, and 10% after a Toupet (p = 0.04). Twenty-eight percent were on acid-suppressive drugs again. Following Nissen fundoplication, proton pump inhibitors were less frequently used (p = 0.01) and on postoperative pH-metry reflux recurrence rate was lower (p = 0.04). The GIQLI was 110 +/- 24 without significant differences for the type of fundoplication. DISCUSSION: Ten years after laparoscopic fundoplication, overall outcome is good. A quarter of the patients are on acid-suppressive drugs. Nissen fundoplication appears to control reflux better than a partial fundoplication.

[Antibody treatment in colorectal cancer--what the surgeon needs to know]. / Antikörpertherapie beim metastasierten kolorektalen Karzinom--was der Chirurg wissen sollte.

Advances in the medical treatment of colorectal cancer patients have resulted in considerable improvements through the introduction of new cytotoxic drugs. The significant progress in molecular and tumour biology has produced a great number of targeted, tumour-specific, monoclonal antibodies that are now in various stages of clinical development. Two of these antibodies, cetuximab (Erbitux) und bevacizumab (Avastin), directed against the epidermal growth factor receptor (EGFR) and the vascular epithelial growth factor (VEGF), respectively, have recently been approved for use in metastatic colorectal cancer. The combination of well-known and newly developed cytotoxic agents with monoclonal antibodies makes the medical treatment of colorectal cancer patients considerably more complex, but also provides additional therapeutic strategies for patients in advanced stages of disease.