Surgical ampullectomy: an underestimated operation in the era of endoscopy

AbstractIntroductionBenign neoplastic, inflammatory or functional pathologies of the ampulla of Vater are mainly treated by primary endoscopic interventions. Consequently, transduodenal surgical ampullectomy (TSA) has been abandoned in many centres, although it represents an important tool not only after unsuccessful endoscopic treatment. The aim of the study was to analyse TSA for benign lesions of the ampulla of Vater.Patients and methodsAll patients who underwent TSA between 2001 and 2014 were included. Patients were analysed in terms of indications, postoperative morbidity and mortality as well as long-term success.ResultsEighty-three patients underwent TSA. Indications included adenomas in 44 and inflammatory stenosis in 39 patients. 96% of the patients had undergone endoscopic therapeutic approaches prior to TSA (median no. of interventions n = 3). Postoperative morbidity occurred in 20 patients (24%). There was one procedure-associated death (mortality 1.2%). The mean follow-up was 54 months. Long-term overall success rate for TSA was 83.6%. After TSA for ampullary adenoma, the recurrence rate was 4.5%.ConclusionTSA is an underestimated surgical procedure, which can be performed safely with high long-term efficacy. It can be implemented in clinical algorithms for patients with benign pathologies of the ampulla of Vater, particularly after unsuccessful endoscopic treatment

Surgical ampullectomy: an underestimated operation in the era of endoscopy

AbstractIntroductionBenign neoplastic, inflammatory or functional pathologies of the ampulla of Vater are mainly treated by primary endoscopic interventions. Consequently, transduodenal surgical ampullectomy (TSA) has been abandoned in many centres, although it represents an important tool not only after unsuccessful endoscopic treatment. The aim of the study was to analyse TSA for benign lesions of the ampulla of Vater.Patients and methodsAll patients who underwent TSA between 2001 and 2014 were included. Patients were analysed in terms of indications, postoperative morbidity and mortality as well as long-term success.ResultsEighty-three patients underwent TSA. Indications included adenomas in 44 and inflammatory stenosis in 39 patients. 96% of the patients had undergone endoscopic therapeutic approaches prior to TSA (median no. of interventions n = 3). Postoperative morbidity occurred in 20 patients (24%). There was one procedure-associated death (mortality 1.2%). The mean follow-up was 54 months. Long-term overall success rate for TSA was 83.6%. After TSA for ampullary adenoma, the recurrence rate was 4.5%.ConclusionTSA is an underestimated surgical procedure, which can be performed safely with high long-term efficacy. It can be implemented in clinical algorithms for patients with benign pathologies of the ampulla of Vater, particularly after unsuccessful endoscopic treatment

Does preoperative analysis of intrahepatic venous anastomoses improve the surgeon's intraoperative decision making? Pilot data from a case report

<p>Abstract</p> <p>Background</p> <p>Three-dimensional (3D) visualization is thought to improve the anatomical understanding of clinicians, thus improving patient safety.</p> <p>Case presentation</p> <p>A 58-year-old male was admitted to our hospital in April 2007 with a suspected metastasis of a sigmoid cancer in the Couinaud segment (CS) 7. The anatomical situation of this patient was analyzed using both a CT scan and 3D images. The initial CT scan revealed that the proximal part of the middle hepatic vein was completely missing and the metastasis in the CS 7 was closely attached to the right hepatic vein. After analyzing additional 3D images, it became clear that due to the close proximity of metastasis and right hepatic vein, the resection of the right hepatic vein was inevitable. Based on this 3D analysis, it was decided to perform a right-sided hemihepatectomy. In this case report, 3D visualization resulted in a faster and clearer understanding of the unique anatomical situation in a patient with complicated liver anatomy than transversal CT images.</p> <p>Conclusion</p> <p>The here presented data shows for the first time 3D visualization of intravenous anastomoses in the human liver. The information offered by 3D visualization is not redundant but rather serves as a true source of additional information, indicating the potential benefit of 3D visualization in surgical operation planning.</p

Teres Ligament Patch Reduces Relevant Morbidity After Distal Pancreatectomy (the DISCOVER Randomized Controlled Trial)

Objective:The aim of this study was to analyze the impact of teres ligament covering on pancreatic fistula rate after distal pancreatectomy (DP).Background:Postoperative pancreatic fistula (POPF) represents the most significant complication after DP. Retrospective studies suggested a benefit of covering the resection margin by a teres ligament patch.Methods:This prospective randomized controlled study (DISCOVER trial) included 152 patients undergoing DP, between October 2010 and July 2014. Patients were randomized to undergo closure of the pancreatic cut margin without (control, n = 76) or with teres ligament coverage (teres, n = 76). The primary endpoint was the rate of POPF, and the secondary endpoints included postoperative morbidity and mortality, length of hospital stay, and readmission rate.Results:Both groups were comparable regarding epidemiology (age, sex, body mass index), operative parameters (operation time [OP] time, blood loss, method of pancreas transection, additional operative procedures), and histopathological findings. Overall inhospital mortality was 0.6% (1/152 patients). In the group of patients with teres ligament patch, the rate of reoperations (1.3% vs 13.0%;P = 0.009), and also the rate of readmission (13.1 vs 31.5%;P = 0.011) were significantly lower. Clinically relevant POPF rate (grade B/C) was 32.9% (control) versus 22.4% (teres, P = 0.20). Multivariable analysis showed teres ligament coverage to be a protective factor for clinically relevant POPF (P = 0.0146).Conclusions:Coverage of the pancreatic remnant after DP is associated with less reinterventions, reoperations, and need for readmission. Although the overall fistula rate is not reduced by the coverage procedure, it should be considered as a valid measure for complication prevention due to its clinical benefit

Pylorus Resection Does Not Reduce Delayed Gastric Emptying After Partial Pancreatoduodenectomy A Blinded Randomized Controlled Trial (PROPP Study, DRKS00004191)

Objectives: The aim of this study was to investigate the effect of pylorus resection on postoperative delayed gastric emptying (DGE) after partial pancreatoduodenectomy (PD). Background: PD is the standard treatment for tumors of the pancreatic head. Preservation of the pylorus has been widely accepted as standard procedure. DGE is a common complication causing impaired oral intake, prolonged hospital stay, and postponed further treatment. Recently, pylorus resection has been shown to reduce DGE. Methods:Patients undergoing PD for any indication at the University of Heidelberg were randomized to either PD with pylorus preservation (PP) or PD with pylorus resection and complete stomach preservation (PR). The primary endpoint was DGE within 30 days according to the International Study Group of Pancreatic Surgery definition. Results: Ninety-five patients were randomized to PP and 93 patients to PR. There were no baseline imbalances between the groups. Overall, 53 of 188 patients (28.2%) developed a DGE (grade: A 15.5%;B 8.8%;C 3.3%). In the PP group 24 of 95 patients (25.3%) and in the PR group 29 of 93 patients (31.2%) developed DGE (odds ratio 1.534, 95% confidence interval 0.788 to 2.987;P = 0.208). Higher BMI, indigestion, and intraabdominal major complications were significant risk factors for DGE. Conclusions: In this randomized controlled trial, pylorus resection during PD did not reduce the incidence or severity of DGE. The development of DGE seems to be multifactorial rather than attributable to pyloric dysfunction alone. Pylorus preservation should therefore remain the standard of care in PD.Trial Registration:German Clinical Trials Register DRKS0000419

Abdominal drainage versus no drainage after distal pancreatectomy: study protocol for a randomized controlled trial

Background: The placement of prophylactic intra-abdominal drains has been common practice in abdominal operations including pancreatic surgery. The PANDRA trial showed that the omission of drains following pancreatic head resection was non-inferior to intra-abdominal drainage in terms of postoperative reinterventions and superior in terms of clinically relevant pancreatic fistula rate and fistula-associated complications. The aim of the present PANDRA II trial is to evaluate the clinical outcome with versus without prophylactic drain placement after distal pancreatectomy. Methods: The PANDRA II trial is a mono-center, randomized controlled, non-inferiority trial with two parallel study groups. In the control group at least one passive intra-abdominal drain is placed at the pancreatic resection margin. In the experimental group no drains are placed. The primary endpoint of this trial will be the Comprehensive Complication Index (CCI) measuring all postoperative complications within 90 days. Secondary endpoints are in-hospital mortality and morbidity, including the rates of postoperative pancreatic fistula, chyle leak, postpancreatectomy hemorrhage, delayed gastric emptying, reinterventions and reoperations, surgical site infection, and abdominal fascia dehiscence. Moreover, length of hospital stay, duration of intensive care unit stay, and the rate of readmission after discharge from hospital (up to day 90 after surgery) are assessed. We will need to analyze 252 patients to test the hypothesis that no drainage is non-inferior to drain placement in terms of the CCI (δ 7.5 points) in a one-sided t test with a one-sided level of significance of 2.5% and a power of 80%. Discussion: The results of the PANDRA II trial will help to evaluate the effect of an omission of prophylactic intraperitoneal drainage on the rate of complications after open or minimally invasive distal pancreatectomy. Trial registration: German Clinical Trials Register (DRKS), DRKS00013763. Registered on 6 March 2018

Phase I/II trial evaluating carbon ion radiotherapy for the treatment of recurrent rectal cancer: the PANDORA-01 trial

<p>Abstract</p> <p>Background</p> <p>Treatment standard for patients with rectal cancer depends on the initial staging and includes surgical resection, radiotherapy as well as chemotherapy. For stage II and III tumors, radiochemotherapy should be performed in addition to surgery, preferentially as preoperative radiochemotherapy or as short-course hypofractionated radiation. Advances in surgical approaches, especially the establishment of the total mesorectal excision (TME) in combination with sophisticated radiation and chemotherapy have reduced local recurrence rates to only few percent. However, due to the high incidence of rectal cancer, still a high absolute number of patients present with recurrent rectal carcinomas, and effective treatment is therefore needed.</p> <p>Carbon ions offer physical and biological advantages. Due to their inverted dose profile and the high local dose deposition within the Bragg peak precise dose application and sparing of normal tissue is possible. Moreover, in comparison to photons, carbon ions offer an increase relative biological effectiveness (RBE), which can be calculated between 2 and 5 depending on the cell line as well as the endpoint analyzed.</p> <p>Japanese data on the treatment of patients with recurrent rectal cancer previously not treated with radiation therapy have shown local control rates of carbon ion treatment superior to those of surgery. Therefore, this treatment concept should also be evaluated for recurrences after radiotherapy, when dose application using conventional photons is limited. Moreover, these patients are likely to benefit from the enhanced biological efficacy of carbon ions.</p> <p>Methods and design</p> <p>In the current Phase I/II-PANDORA-01-Study the recommended dose of carbon ion radiotherapy for recurrent rectal cancer will be determined in the Phase I part, and feasibilty and progression-free survival will be assessed in the Phase II part of the study.</p> <p>Within the Phase I part, increasing doses from 12 × 3 Gy E to 18 × 3 Gy E will be applied.</p> <p>The primary endpoint in the Phase I part is toxicity, the primary endpoint in the Phase II part is progression-free survival.</p> <p>Discussion</p> <p>With conventional photon irradiation treatment of recurrent rectal cancer is limited, and the clinical effect is only moderate. With carbon ions, an improved outcome can be expected due to the physical and biological characteristics of the carbon ion beam. However, the optimal dose applicable in this clincial situation as re-irradiation still has to be determined. This, as well as efficacy, is to be evaluated in the present Phase I/II trial.</p> <p>Trial registration</p> <p><a href="http://www.clinicaltrials.gov/ct2/show/NCT01528683">NCT01528683</a></p

The impact of diabetes mellitus on survival following resection and adjuvant chemotherapy for pancreatic cancer

BACKGROUND: Diabetes mellitus is frequently observed in pancreatic cancer patients and is both a risk factor and an early manifestation of the disease. METHODS: We analysed the prognostic impact of diabetes on the outcome of pancreatic cancer following resection and adjuvant chemotherapy using individual patient data from three European Study Group for Pancreatic Cancer randomised controlled trials. Analyses were carried out to assess the association between clinical characteristics and the presence of preoperative diabetes, as well as the effect of diabetic status on overall survival. RESULTS: In total, 1105 patients were included in the analysis, of whom 257 (23%) had confirmed diabetes and 848 (77%) did not. Median (95% confidence interval (CI)) unadjusted overall survival in non-diabetic patients was 22.3 (20.8–24.1) months compared with 18.8 (16.9–22.1) months for diabetic patients (P=0.24). Diabetic patients were older, had increased weight and more co-morbidities. Following adjustment, multivariable analysis demonstrated that diabetic patients had an increased risk of death (hazard ratio: 1.19 (95% CI 1.01, 1.40), P=0.034). Maximum tumour size of diabetic patients was larger at randomisation (33.6 vs 29.7 mm, P=0.026). CONCLUSIONS: Diabetes mellitus was associated with increased tumour size and reduced survival following pancreatic cancer resection and adjuvant chemotherapy

Queen rearing and selection practices and their impact on the genetic diversity and fitness of honey bee colonies

The Apimondia working group on honey bee diversity and fitness (AWG 7) was created on October 25, 2010 as a Scientific Working Group of Apimondia. The aim of this AWG is to collect information on honey bee queen rearing practices, and examine their impact on the genetic variability and general health of honey bee colonies. The AWG consists of 23 members from 16 different countries. The world wide survey being conducted by this AWG is focused on gathering information on how selection methods, instrumental insemination, disease management procedures, introduction of exotic bee lines, queen replacement strategies, and loss of local colony populations due to introduced parasites and pathogens, affect the ability of our bees to survive and reproduce. The information collected will contribute on an international level to our understanding of how apiculture practices affect honey bee genetics, health and productivity

Persister cell phenotypes contribute to poor patient outcomes after neoadjuvant chemotherapy in PDAC

Neoadjuvant chemotherapy can improve the survival of individuals with borderline and unresectable pancreatic ductal adenocarcinoma; however, heterogeneous responses to chemotherapy remain a significant clinical challenge. Here, we performed RNA sequencing (n = 97) and multiplexed immunofluorescence (n = 122) on chemo-naive and postchemotherapy (post-CTX) resected patient samples (chemoradiotherapy excluded) to define the impact of neoadjuvant chemotherapy. Transcriptome analysis combined with high-resolution mapping of whole-tissue sections identified GATA6 (classical), KRT17 (basal-like) and cytochrome P450 3A (CYP3A) coexpressing cells that were preferentially enriched in post-CTX resected samples. The persistence of GATA6hi and KRT17hi cells post-CTX was significantly associated with poor survival after mFOLFIRINOX (mFFX), but not gemcitabine (GEM), treatment. Analysis of organoid models derived from chemo-naive and post-CTX samples demonstrated that CYP3A expression is a predictor of chemotherapy response and that CYP3A-expressing drug detoxification pathways can metabolize the prodrug irinotecan, a constituent of mFFX. These findings identify CYP3A-expressing drug-tolerant cell phenotypes in residual disease that may ultimately inform adjuvant treatment selection