CONKO-006: A randomised double-blinded phase IIb-study of additive therapy with gemcitabine + sorafenib/placebo in patients with R1 resection of pancreatic cancer - Final results.

BACKGROUND: 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. PATIENTS AND METHODS: 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. RESULTS: 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). CONCLUSION: 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. CLINICAL TRIAL INFORMATION: German Tumor Study Registry (Deutsches Krebsstudienregister), DRKS00000242.

[What do general, abdominal and vascular surgeons need to know on plastic surgery - aspects of plastic surgery in the field of general, abdominal and vascular surgery]. / Was der Allgemein-, Viszeral- & Gefäßchirurg über plastische Chirurgie wissen sollte - plastisch-chirurgische Aspekte in der Allgemein- & Viszeralchirurgie.

There is overlap between general, abdominal and vascular surgery on one hand and plastic surgery on the other hand, e.g., in hernia surgery, in particular, recurrent hernia, reconstruction of the abdominal wall or defect closure after abdominal or vascular surgery. Bariatric operations involve both special fields too. Plastic surgeons sometimes use skin and muscle compartments of the abdominal wall for reconstruction at other regions of the body. This article aims to i) give an overview about functional, anatomic and clinical aspects as well as the potential of surgical interventions in plastic surgery. General/abdominal/vascular surgeons can benefit from this in their surgical planning and competent execution of their own surgical interventions with limited morbidity/lethality and an optimal, in particular, functional as well as aesthetic outcome, ii) support the interdisciplinary work of general/abdominal/vascular and plastic surgery, and iii) provide a better understanding of plastic surgery and its profile of surgical interventions and options.

[Evidence base for minimally invasive esophagectomy for esophageal cancer]. / Evidenzlage zur minimalinvasiven Chirurgie beim Ösophaguskarzinom.

Surgery remains the mainstay of potentially curative treatment of esophageal cancer; however, esophageal resection is still associated with a relevant morbidity and mortality. Furthermore, patients frequently suffer from concomitant comorbidities and present in a reduced nutritional status. The rationale of minimally invasive surgery is the reduction of surgical trauma with subsequent minimization of (pulmonary) complications and mortality without compromising oncological quality. Minimally invasive esophageal resection was established nearly two decades ago and since then some centers worldwide have adopted this approach as the preferred option for surgical treatment of esophageal cancer. Minimally invasive esophageal resection can be safely performed and provides excellent results in experienced hands. Currently, there is only one randomized trial available comparing open and minimally invasive resection. It was demonstrated that the latter significantly reduced pulmonary complications with comparable mortality and oncological outcome. However, in the majority of studies these convincing results could not be confirmed. Reduced blood loss and a shortened hospital stay were shown to be the main advantages of the minimally invasive approach. Due to technical modifications, patient selection and a remarkable heterogeneity of current studies, a final conclusion on the value of minimally invasive esophagectomy is difficult to be drawn. Based on the current evidence, a noncritical use of minimally invasive resection for esophageal cancer cannot be recommended; however, in selected patients and with appropriate expertise this approach is at least comparable to open esophagectomy.

Factors influencing the quality of total mesorectal excision.

BACKGROUND: Total mesorectal excision (TME) has become the standard of care for rectal cancer. Incomplete TME may lead to local recurrence. METHODS: Data from the multicentre observational German Quality Assurance in Rectal Cancer Trial were used. Patients undergoing low anterior resection for rectal cancer between 1 January 2005 and 31 December 2009 were included. Multivariable analysis using a stepwise logistic regression model was performed to identify predictors of suboptimal TME. RESULTS: From a total of 6179 patients, complete data sets for 4606 patients were available for analysis. Pathological tumour category higher than T2 (pT3 versus pT1/2: odds ratio (OR) 1.22, 95 per cent confidence interval 1.01 to 1.47), tumour distance from the anal verge less than 8 cm (OR 1.27, 1.05 to 1.53), advanced age (65-80 years: OR 1.25, 1.03 to 1.52; over 80 years: OR 1.60, 1.15 to 2.22), presence of intraoperative complications (OR 1.63, 1.15 to 2.30), monopolar dissection technique (OR 1.43, 1.14 to 1.79) and low case volume (fewer than 20 procedures per year) of the operating surgeon (OR 1.20, 1.06 to 1.36) were independently associated with moderate or poor TME quality. CONCLUSION: TME quality was influenced by patient- and treatment-related factors.

[Palliative chemotherapy for colorectal cancer--current state, significance, trends]. / Palliative Chemotherapie beim kolorektalen Karzinom--Stand, Wertigkeit, Tendenzen.

BACKGROUND: There are a number of effective substances available for palliative treatment of colorectal cancer, contributing to a considerable extension of the median survival time either purely medically or by increasing the chance of secondary resectability through improved effectiveness of the administered drugs. PATIENTS / MATERIAL: Defining treatment depending on predominant patient characteristics remains crucial for any therapeutic success. This requires interdisciplinary co-ordination within tumour boards. METHODS: In aggressive tumours a therapeutic approach inducing high response rates is favoured, usually including a triple or quadruple combination incl. antibodies. In cases of slow tumour progress and limited patient profile, a sequence of chemotherapy is chosen. Implementing and integrating locally ablative modes of therapy into the treatment strategy can increase the effectiveness additionally. In a best case scenario additional systemic side effects can be avoided resulting in a not insignificant benefit in quality of life. RESULTS: Further genotyping beyond the K-RAS state is necessary to make predictive and prognostic statements concerning the drugs applied and to avoid ineffectiveness. CONCLUSION: Considerable progress has been achieved in the medical therapy for metastasised colorectal cancer. The targeted application of already available as well as recently developed substances requires further evaluation by appropriate studies.

Surgical practices for malignant left colonic obstruction in Germany.

AIM: Data from the multicentric observation study Kolon/Rektum-Karzinome (Primärtumor) (primary colorectal carcinoma) are adduced to assess the status of surgical treatment of this condition in Germany and to compare different operative approaches in the emergency treatment of obstructive left-sided colon cancer, especially diversion (Hartmann's procedure) and primary anastomosis. PATIENTS AND METHODS: Out of 15,911 patients with cancer of the left colon, recorded between 01.01.2000 and 31.12.2004, a total of 743 patients underwent emergency surgery for an obstructive tumour, performed as a radical resection. These patients were compared in respect of their risk profile and postoperative result. RESULTS: In 57.9% (n=430) a one-stage operation (Group I), in 11.7% (n=87) a primary anastomosis with protective stoma (Group II), and in 30.4% (n=226), Hartmann's procedure (Group III) was performed. In Group III more patients were male, overweight and multimorbid, and more had advanced-stage tumours. The morbidity and hospital mortality (overall hospital mortality, 7.7%; n=57) did not differ significantly between the groups. The insertion of a protective stoma did not affect the rate of anastomotic insufficiency (Group I, 7%; Group II, 8.0%). CONCLUSIONS: Primary anastomosis for emergency left colon carcinoma obstruction should only be regarded as indicated in cases where the risk profile is favourable. Our results suggest that in advanced obstruction and in high-risk cases Hartmann's procedure should be used. A protective stoma did not appear to confer any advantage.

[Multimodal treatment of colon cancer?]. / Multimodale Therapie beim Kolonkarzinom?

Surgical therapy is still the basis of therapy of patients with colon carcinoma. Multimodal therapeutical concepts are presently applied as a therapeutical standard in the adjuvant therapy and increasingly in the systemic therapy of patients with primarily inoperable metastases of the liver to reach a secondary operability. Interdisciplinary multimodal therapeutical concepts are even accepted within the therapy of metastasized colon carcinomas. There are still unanswered questions regarding sequences of palliative systemic therapies and their combinations with local ablative methods.