Background The prognosis of patients with liver metastasis is generally considered dismal, and combined resections of the primary tumor and metastasectomies are not recommended. In highly selected ...patients, however, resections are performed. The evidence for this indication is limited. The aim of the current study was to assess the operative and oncologic outcomes of patients with combined pancreatic and liver resections of synchronous liver metastases. Methods In a retrospective analysis of 6 European pancreas centers, we identified 69 patients with pancreatic ductal adenocarcinoma and synchronous liver metastasis who underwent simultaneous pancreas and liver metastasis resections. Patients receiving exploration without tumor resection served as the control group. Results Overall survival (OS) appeared to be prolonged in the group of resected patients (median 14 vs 8 months, P < .001). Subgroup analysis revealed that the survival benefit of the resected patients was driven by pancreatic ductal adenocarcinomas localized in the pancreatic head (median OS 13.6 vs 7 months, P < .001). Body/tail pancreatic ductal adenocarcinomas showed no benefit of resection (median OS 14 vs 15 months, P = .312). In the multivariate analysis, tumor resection was the only independent prognosticator for OS (hazard ratio 2.044, 95% confidence interval 1.342–3.114). Conclusion The data of this retrospective and selective patient cohort suggested a clear survival benefit for patients undergoing synchronous pancreas and liver resections for pancreatic ductal adenocarcinoma, but due to the limitations of this retrospective study and very strong potential for selection bias, a strong conclusion for resection cannot be drawn. Prospective trials must validate these data and investigate the use of combined operative and systemic treatments in case of resectable metastatic pancreatic cancer. Is it time for a multicenter, prospective trial?
Background
Postoperative pancreatic fistulas (POPF) grade C represent a rare but feared complication following pancreaticoduodenectomy (PD). They can contribute significantly to postoperative ...morbidity and mortality.
Methods
We performed a retrospective chart review for all patients who had undergone pancreatic head resection between 2007 and 2016 to identify those who suffered from POPF grade C according to the updated definition of the International Study Group of Pancreatic Surgery (ISGPS).
Results
A total of 722 patients underwent PD. Twenty‐three patients (3.19%) developed a POPF grade C. Cardiovascular diseases, soft pancreatic texture and main pancreatic duct diameter were identified as risk factors (P < .05). Reoperation was necessary in all affected patients on postoperative day 12 ± 9 on average. Mortality was significantly associated with POPF grade C (P < .05) being present in 39.1% (9/23).
Conclusions
POPF grade C after PD remains a serious complication with a high level of morbidity and mortality. Surgical treatment is the sole curative therapy and thus the treatment of choice.
Highlight
Postoperative pancreatic fistulas grade C are a rare complication contributing significantly to postoperative morbidity and mortality. Completion pancreatectomy is the sole curative therapy which must be initiated as quickly as possible.
Intra-abdominal infections (IAIs) are common surgical emergencies and have been reported as major contributors to non-trauma deaths in the emergency departments worldwide. The cornerstones of ...effective treatment of IAIs are early recognition, adequate source control, and appropriate antimicrobial therapy. Prompt resuscitation of patients with ongoing sepsis is of utmost important. In hospitals worldwide, non-acceptance of, or lack of access to, accessible evidence-based practices and guidelines result in overall poorer outcome of patients suffering IAIs. The aim of this paper is to promote global standards of care in IAIs and update the 2013 WSES guidelines for management of intra-abdominal infections.
Introduction: The versatile open modular design of the newly introduced robotic platform HugoTM RAS is expected to allow its rapid spread in general surgery. However, the system is not yet approved ...for use in oesophageal and HPB-surgery and is not licensed worldwide. The aim of this work was to review the current spectrum of general surgical procedures that may be feasibly and safely performed with Hugo. Methods: We retrospectively reviewed our own series and performed a systematic review of all the published reports of general surgical procedures performed with this system in the literature. Results: Seventy patients underwent general surgery with Hugo at our institution, and another 99 patients were reported in the literature. The most common procedures were colorectal (n = 55); cholecystectomy (n = 44); repair of groin, ventral and hiatal hernias (n = 34); upper GI (n = 28); adrenalectomy (n = 6); and spleen cyst deroofing (n = 2). No device-related complications were reported. Arm collisions and technical problems were rare. The docking and console times improved in all series. The port positions and robotic arm configurations varied among authors and depended on the surgical indication, patient characteristics and surgeon’s preference. Conclusions: A wide spectrum of general surgical procedures has been safely and effectively performed with the Hugo RAS, even by robotically inexperienced teams with a limited choice of instruments. Technical improvements to the system and the introduction of robotic energy devices may help Hugo evolve to a vital alternative to established robotic systems.
Chronic pancreatitis (CP) is a fibroinflammatory syndrome leading to organ dysfunction, chronic pain, an increased risk for pancreatic cancer and considerable morbidity. Due to a lack of specific ...biomarkers, diagnosis is based on symptoms and specific but insensitive imaging features, preventing an early diagnosis and appropriate management.
We conducted a type 3 study for multivariable prediction for individual prognosis according to the TRIPOD guidelines. A signature to distinguish CP from controls (n=160) was identified using gas chromatography-mass spectrometry and liquid chromatography-tandem mass spectrometry on ethylenediaminetetraacetic acid (EDTA)-plasma and validated in independent cohorts.
A Naive Bayes algorithm identified eight metabolites of six ontology classes. After algorithm training and computation of optimal cut-offs, classification according to the metabolic signature detected CP with an area under the curve (AUC) of 0.85 ((95% CI 0.79 to 0.91). External validation in two independent cohorts (total n=502) resulted in similar accuracy for detection of CP compared with non-pancreatic controls in EDTA-plasma (AUC 0.85 (95% CI 0.81 to 0.89)) and serum (AUC 0.87 (95% CI 0.81 to 0.95)).
This is the first study that identifies and independently validates a metabolomic signature in plasma and serum for the diagnosis of CP in large, prospective cohorts. The results could provide the basis for the development of the first routine laboratory test for CP.
Background
Procedures suitable for preoperative localization of insulinomas are widely used but it is unclear whether they determine surgical success. We wanted to clarify whether preoperative ...localization or intraoperative ultrasound determines the success of surgically identifying and removing insulinomas.
Methods
We performed a systematic literature search (PubMed) yielding 100 publications with patient‐level data on preoperative localization procedures, intraoperative ultrasound, success of surgical identification and removal or single, benign insulinomas (published until 31 December 2016). The consequences of successful preoperative localization and intraoperative ultrasound for surgical identification and removal of an insulinoma could be analyzed for 863 and 529 patients with single benign insulinomas, respectively. Sensitivities of commonly employed methods to localize biochemically proven insulinomas were calculated for single benign (1,153 patients), multiple benign, and malignant insulinomas, also in relation to diameter and intra‐pancreatic location.
Results
The success of surgery (identification and removal of single benign insulinomas) in patients with a biochemically proven insulinoma was high (approximately 98%) even in the absence of preoperative localization. However, successful preoperative localization or intraoperative ultrasonography slightly, but significantly, increased the probability of surgically identifying/removing single benign insulinomas (by 1.4% and 2.0%, P = 0.012 and 0.0032, respectively). Diagnostic sensitivities of localization procedures varied widely, with GLP‐1 receptor scintigraphy achieving the highest sensitivity despite its non‐invasive nature.
Conclusion
The probability of surgically identifying and removing a single, benign insulinoma is high even in the absence of successful preoperative localization or intraoperative ultrasound. However, both approaches slightly, but significantly, improve the outcome to near 100%.
Highlight
To clarify whether preoperative localization improves the yield of surgery for single benign insulinomas, Burghardt and colleagues conducted a systematic analysis of 100 publications. While the rate at which insulinomas were identified by the surgeon was high, it can be slightly, but significantly, improved by preoperative localization or intraoperative ultrasound.
This study aimed to compare different pancreatic enzyme preparations (PEPs) available in Germany regarding particle geometry and size, and to evaluate enzyme activity under physiologically relevant ...conditions in vitro. Pancreatic endocrine insufficiency is characterized by deficiency of pancreatic enzymes resulting in maldigestion. It is orally treated by pancreatic enzyme replacement therapy. The formulations differ in their physical properties and enzyme release behavior, potentially resulting in inconsistent dosages and poor interchangeability of products. A total of 25 products were analyzed for particle size and number of particles per capsule. Enzyme activities of lipase, amylase, and protease were measured by digestion of olive oil emulsion, starch, and casein, respectively. To analyze enzyme release, gastric environments were simulated by incubating PEPs at pH 1, 4, or 5. Duodenal conditions were simulated by subsequent incubation at pH 6. Regarding physical properties and enzyme release kinetics, considerable differences between different PEPs were found. Furthermore, compared to the label claim, excess lipase activity was observed for most products, reaching up to 148%. These in vitro results suggest poor interchangeability of PEPs, potentially explained by physical and release characteristics. Physicians and patients should be aware of the potential gap between label claims and the real-life performance of different PEPs.
Even clearly resectable pancreatic cancer still has an unfavorable prognosis. Neoadjuvant or perioperative therapies might improve the prognosis of these patients. Thus, evaluation of perioperative ...chemotherapy in resectable pancreatic cancer in a prospective, randomized trial is warranted. A substantial improvement in overall survival of patients with metastatic pancreatic cancer with FOLFIRINOX and nab-paclitaxel/gemcitabine vs standard gemcitabine has been demonstrated in phase III-trials. Indeed nab-paclitaxel/gemcitabine has a more favorable toxicity profile compared to the FOLFIRINOX protocol and appears applicable in a perioperative setting.
NEONAX is an interventional, prospective, randomized, controlled, open label, two sided phase II study with an unconnected analysis of the results in both experimental arms against a fixed survival probability (38% at 18 months with adjuvant gemcitabine), NCT02047513. NEONAX will enroll 166 patients with resectable pancreatic ductal adenocarcinoma (≤ cT3, N0 or N1, cM0) in two arms: Arm A (perioperative arm): 2 cycles nab-paclitaxel (125 mg/m2)/gemcitabine (1000 mg/m2, d1, 8 and 15 of an 28 day-cycle) followed by tumor surgery followed by 4 cycles nab-paclitaxel/gemcitabine, Arm B (adjuvant arm): tumor surgery followed by 6 cycles nab-paclitaxel/gemcitabine. The randomization (1:1) is eminent to avoid allocation bias between the groups. Randomization is stratified for tumor stage (ct1/2 vs. cT3) and lymph node status (cN0 vs. cN1). Primary objective is disease free survival (DFS) at 18 months after randomization. Key secondary objectives are 3-year overall survival (OS) rate and DFS rate, progression during neoadjuvant therapy, R0 and R1 resection rate, quality of life and correlation of DFS, OS and tumor regression with pharmacogenomic markers, tumor biomarkers and molecular analyses (ctDNA, transcriptome, miRNA-arrays). In addition, circulating tumor-DNA will be analyzed in patients with the best and the worst responses to the neoadjuvant treatment. The study was initiated in March 2015 in 26 centers for pancreatic surgery in Germany.
The NEONAX trial is an innovative study on resectable pancreatic cancer and currently one of the largest trials in this field of research. It addresses the question of the role of intensified perioperative treatment with nab-paclitaxel plus gemcitabine in resectable pancreatic cancers to improve disease-free survival and offers a unique potential for translational research.
ClinicalTrials.gov : NCT02047513, 08/13/2014.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Pancreatic ductal adenocarcinoma cancer (PDAC) is a highly lethal malignancy requiring efficient detection when the primary tumor is still resectable. We previously developed the MxPancreasScore ...comprising 9 analytes and serum carbohydrate antigen 19-9 (CA19-9), achieving an accuracy of 90.6%. The necessity for 5 different analytical platforms and multiple analytical runs, however, hindered clinical applicability. We therefore aimed to develop a simpler single-analytical run, single-platform diagnostic signature.
We evaluated 941 patients (PDAC, 356; chronic pancreatitis CP, 304; nonpancreatic disease, 281) in 3 multicenter independent tests, and identification (ID) and validation cohort 1 (VD1) and 2 (VD2) were evaluated. Targeted quantitative plasma metabolite analysis was performed on a liquid chromatography–tandem mass spectrometry platform. A machine learning–aided algorithm identified an improved (i-Metabolic) and minimalistic metabolic (m-Metabolic) signatures, and compared them for performance.
The i-Metabolic Signature, (12 analytes plus CA19-9) distinguished PDAC from CP with area under the curve (95% confidence interval) of 97.2% (97.1%-97.3%), 93.5% (93.4%-93.7%), and 92.2% (92.1%-92.3%) in the ID, VD1, and VD2 cohorts, respectively. In the VD2 cohort, the m-Metabolic signature (4 analytes plus CA19-9) discriminated PDAC from CP with a sensitivity of 77.3% and specificity of 89.6%, with an overall accuracy of 82.4%. For the subset of 45 patients with PDAC with resectable stages IA-IIB tumors, the sensitivity, specificity, and accuracy were 73.2%, 89.6%, and 82.7%, respectively; for those with detectable CA19-9 >2 U/mL, 81.6%, 88.7%, and 84.5%, respectively; and for those with CA19-9 <37 U/mL, 39.7%, 94.1%, and 76.3%, respectively.
The single-platform, single-run, m-Metabolic signature of just 4 metabolites used in combination with serum CA19-9 levels is an innovative accurate diagnostic tool for PDAC at the time of clinical presentation, warranting further large-scale evaluation.
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The m-Metabolic signature, based on just 4 plasma analytes combined with serum carbohydrate antigen 19-9, is highly accurate in diagnosing pancreatic cancer and could contribute to earlier treatment and improved prognosis of patients with pancreatic cancer.
An accurate blood‐based RAS mutation assay to determine eligibility of metastatic colorectal cancer (mCRC) patients for anti‐EGFR therapy would benefit clinical practice by better informing decisions ...to administer treatment independent of tissue availability. The objective of this study was to determine the level of concordance between plasma and tissue RAS mutation status in patients with mCRC to gauge whether blood‐based RAS mutation testing is a viable alternative to standard‐of‐care RAS tumor testing. RAS testing was performed on plasma samples from newly diagnosed metastatic patients, or from recurrent mCRC patients using the highly sensitive digital PCR technology, BEAMing (beads, emulsions, amplification, and magnetics), and compared with DNA sequencing data of respective FFPE (formalin‐fixed paraffin‐embedded) tumor samples. Discordant tissue RAS results were re‐examined by BEAMing, if possible. The prevalence of RAS mutations detected in plasma (51%) vs. tumor (53%) was similar, in accord with the known prevalence of RAS mutations observed in mCRC patient populations. The positive agreement between plasma and tumor RAS results was 90.4% (47/52), the negative agreement was 93.5% (43/46), and the overall agreement (concordance) was 91.8% (90/98). The high concordance of plasma and tissue results demonstrates that blood‐based RAS mutation testing is a viable alternative to tissue‐based RAS testing.
Implementation of circulating tumor DNA testing in clinical practice has been hindered by the variable performance of available methods. Here, we demonstrate that plasma mutation testing using BEAMing as a standardized platform is comparable to tumor tissue testing and can be useful in the clinic to select patients with metastatic colorectal cancer for targeted therapy.
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