The impact of intra- and postoperative fluid balance in pancreatic surgery - A retrospective cohort study.

BACKGROUND/OBJECTIVES: The aim of this study was to evaluate the impact of perioperative fluid administration in pancreatic surgery. METHODS: Patients who underwent pancreatic resections were identified from our institution's prospectively maintained database. Fluid balances were recorded intraoperatively and at 24hr postoperatively. Patients were stratified into tertiles of fluid administration (low, medium, high). Adjusted multivariable analysis was performed and outcome measures were postoperative complications. RESULTS: A total of 211 patients were included from 2012 to 2017. Complication rates were POPF(B/C) 19.4%, DGE(B/C) 14.7%, PPH(C) 10.0% and CDC ≥ IIIb 26.1%. In multivariable analysis, high perioperative fluid balance was an independent risk factor associated with POPF (OR = 10.5, 95%CI 2.7-40.7, p = .001), CDC (OR = 2.5, 95%CI 1.2-5.3, p < .002), DGE (OR = 2.3, 95%CI 1.0-5.2, p = .017), PPH (OR = 6.7 95%CI 2.2-20.0, p = .038) and reoperation (OR = 3.1, 95%CI 1.6-6.2, p = .006). In multivariable analysis with intraoperative and postoperative fluid balances as separate predictors, intraoperative (OR = 2,5, 95%CI 1.2-5.5, p = .04) and postoperative fluid balance (OR = 2.5, 95%CI 1.2-5.5, p = .02) were predictors of POPF. Postoperative fluid balance was the only predictor for mortality (OR = 4.5, 95%CI 1.0-18.9, p = .041) and predictor for CDC (OR = 2.0, 95%CI 1.0-4.0, p = .043) and OHS days (OR = 6.9, 95%CI 0.03-13.7, p = .038). CONCLUSIONS: High postoperative fluid balance in particular is associated with postoperative morbidity. Maintaining a fluid-restrictive strategy postoperatively should be recommended for patients undergoing pancreatic surgery.

[Robotic-assisted Enucleation of a Cystic Neoplasm in the Head of the Pancreas]. / Robotisch gestützte Enukleation einer zystischen Neoplasie des Pankreaskopfes.

According to current revised Fukuoka guidelines, there is an indication for resection of BD-IPMN of the pancreas with "worrisome features", as there is a risk of malignant degeneration of up to 30%. This can be performed as a non-anatomical local excision in the absence of clinical, radiological and laboratory signs of malignancy.Robotic enucleation for benign tumours of the pancreas is a very good alternative to resecting procedures, especially those using open techniques. This surgical treatment option is recommended by the "International consensus statement on robotic pancreatic surgery" in a case of a minimum distance to the main pancreatic duct of at least 2 mm.In addition to the known advantages of minimally invasive surgery, this parenchyma-sparing approach results in preservation of endo- and exocrine function (ca. 90%) and 10-year progression-free survival of ca. 75% with slightly increased morbidity (ca. 60%) compared with resecting procedures.The following video article presents the surgical video of a robotic cyst enucleation (for suspected BD-IPMN with "worrisome features") in the pancreatic head and uncinate process in a 62-year-old female patient with special emphasis on the most important vascular landmarks, special features of the approach and advantages of the robotic technique.

Risk Stratification for the Intensive Care Unit Following Pancreaticoduodenectomy. / Risikostratifizierung für intensivmedizinische Betreuung nach Pankreatoduodenektomie.

INTRODUCTION: In view of the limited capacities in intensive care units and the increasing economic burden, identification of risk factors could allow better and more efficient planning. Therefore, the aim of this study was to assess independent risk factors for the duration of intensive care unit stay after pancreatoduodenectomy (PD). METHODS: 147 patients who underwent pancreatoduodenectomy in the time period from 2013 to 2015 were identified from a prospective database and a retrospective analysis was performed. The primary endpoint was length of time spent in the ICU. A retrograde analysis was performed using univariate and multivariate regression analysis. All pre-, intra- and postoperative parameters were considered in the analysis. RESULTS: The median time spent in the intensive care unit (ICU) is one day. The univariate analysis demonstrated increased pack years, cerebrovascular events, anticoagulation, elevated creatinine and CA 19-9 as preoperative risk factors. In multivariate analysis, antihypertensive medication (AHT; OR 2.46; 95% CI 1.57 - 3.87; p = 0.05), operation time (OR 1.01; 95% CI 1.00 - 1.01; p = 0.03), extended LAD (OR 5.46; 95% CI 2.77 - 10.75; p = 0.01) and severe PPH (OR 4.01; 95% CI 2.07 - 7.76; p = 0.04) are significant risk factors for longer ICU stay. DISCUSSION: Patients with cardiovascular risk factors and elevated preoperative creatinine level are at greater risk for a prolonged ICU stay. Risk and benefit of an extended LAD should be weighed during the operation. Median duration on ICU/IMC after PD is one day or less for patients without risk factors. Whether routine monitoring in the ICU/IMC after PD is necessary must be clarified in further studies.

[Incidence, Treatment and Survival in Pancreatic Cancer- Data of the Nationwide Oncological Quality Conference from a Surgical Perspective]. / Inzidenz, Behandlung und Überleben beim Pankreaskarzinom ­ Daten der bundesweiten onkologischen Qualitätskonferenz aus chirurgischer Perspektive.

BACKGROUND: In recent years, there have been changes in the treatment of ductal pancreatic carcinoma with regard to multimodal therapy and also surgical therapy. These changes have not yet been explored in large nationwide studies in Germany. The present work gives an initial overview from a surgical perspective of the developments in diagnosis, therapy and survival of pancreatic cancer within the last 19 years in Germany. METHODS: In this cohort of 18 clinical cancer registries in Germany, patients with a diagnosis of ductal pancreatic cancer from 2000-2018 were included. The patients were categorised according to the years of diagnosis (2000-2009 vs. 2010-2018) and treatment modalities and compared. RESULTS: In the cohort of approx. 48000 patients with ductal pancreatic cancer, the number of newly diagnosed cases increased from approx. 18000 to 30000 patients in the two ten-year periods. The median overall survival increased slightly but statistically significantly from 7.1 to 7.9 months (p < 0.001). The resection rate increased from 25% to 32%, with the proportion of patients for whom no specific therapy was reported decreased by 11%. The rate of palliative chemotherapy and neoadjuvant chemotherapy also increased from 16% to 20% of the patients and from less than 1% to 2% of the patients, respectively. The median survival in the curatively treated subgroups was up to 24 months. SUMMARY: The cancer registry data appear to confirm the known increase in the incidence of pancreatic cancer in the western world. Resection rates and the rates of treatment with neoadjuvant and palliative intent also increased. The overall survival of all patients with ductal pancreatic cancer only increased marginally. In the subgroups of patients who were treated with curative intent, however, significantly longer survival times were found.

[Robot-assisted Distal Pancreatectomy with En Bloc Celiac Axis Resection (Modified Appleby Procedure) after Neoadjuvant Therapy]. / Robotisch assistierte Resektion eines zentralen neoadjuvant behandelten Pankreaskarzinoms mit En-bloc-Resektion des Truncus coeliacus (modifizierte Appleby-Operation).

Pancreatic carcinoma in the body and on the left side of the mesentericoportal axis is often only detected in late stages owing to unspecific or even missing clinical symptoms. In approximately 20% of the cases, there is already infiltration of the tumour into the surrounding arteries or veins. Despite locally advanced growth, 30% of patients do not have distant metastases and would potentially qualify for local resection. Arterial resections and vascular reconstruction are associated with an almost 9-fold increase in postoperative mortality compared with resections without vascular reconstruction. The Appleby procedure is a complex surgical technique originally developed for advanced gastric cancer. The technique has been further developed for patients with advanced pancreatic body and tail tumours with infiltration of the coeliac trunk (modified Appleby procedure). The advantage of the procedure is that technically, no reconstruction of the resected arteries is required. This is because a natural internal anastomosis in the pancreatic head between the A. mesenterica superior and the A. hepatica via branches of the A. gastroduodenalis is used to maintain liver perfusion and gastric blood flow. However, the surgical procedure is also associated with high morbidity and mortality, with comparably poor oncological results (R0 rates of approximately 60%). Therefore, the procedure was not recommended until a few years ago, and patients were considered inoperable. With developments in neoadjuvant therapy for pancreatic carcinoma, the Appleby procedure is being performed more frequently, with the goal of improving oncological outcomes in the context of multimodal treatment. With developments in robotics in visceral surgery, the previous limitations of minimally invasive pancreatic surgery can be overcome, and significantly more patients may benefit from the advantages of this minimally invasive surgery, such as faster convalescence. The use of robotic surgical techniques allows the extension of minimally invasive techniques into the field of complex vessel resection and reconstruction. In this video contribution, we describe a robot-assisted modified Appleby procedure using the Da Vinci Xi Surgical System in a patient with advanced pancreatic carcinoma of the pancreatic body, after neoadjuvant therapy.

[Robot-assisted Pancreatic Surgery]. / Robotergestützte Bauchspeicheldrüsenchirurgie.

INTRODUCTION: The use of robots in minimally invasive surgery has become increasingly common in recent years. Robot-assisted pancreatoduodenectomy is more frequent than the laparoscopic procedure especially due to the greater flexibility of instruments and therefore better handling and better angulation. Furthermore, there are benefits from enhanced 3D visibility, software-based tremor control and reduction in the physical exertion of the surgeon. METHODS AND RESULTS: This review delivers a point-by-point approach to the setup of a robotic pancreatic programme and a detailed approach to robot-assisted pancreatoduodenectomy. RESULTS: In our standardised SOP approach, we use 5 trocars, 4 robotic trocars and one assist trocar. We prefer the position of the robot ports to be in a straight horizontal line with a distance of 20 cm away from the operational field. The operation is dissected in 11 standardised procedural steps, namely 1. Access to the pancreas and visualisation, 2. extended Kocher manoeuvre, 3. lower rim and mesenterico-portal axis, 4. upper rim and hepato-duodenal ligament, 5. dissection of the pancreatic neck, 6. mesenteric root and pars IV duodeni, 7. mesopancreas, 8. pancreatic anastomosis reconstruction, 9. bilio-enteric anastomosis, 10. dudenojejunal anastomosis, 11. drainage and closure. The set up of the pancreas program and the structured approach to complex pancreatic resections are elucidated. SUMMARY: In summary, this review describes the approach to robotic pancreatic surgery in a high-volume pancreas centre at a structural and procedural level, in order to support establishment of such programs at other locations.

[Robot-Assisted Upper Gastrointestinal and Hepato-Pancreato-Biliary Surgery: Implementation Using a Stepwise Approach and Analyses of the First 100 Surgical Procedures]. / Robotisch assistierte obere gastrointestinale und hepatopankreatobiliäre Chirurgie: Etablierung durch einen Stepwise Approach und eine Analyse der ersten 100 Operationen.

INTRODUCTION: Robot-assisted surgery is a promising technique for overcoming the limitations of laparoscopic surgery, especially for complex and advanced surgical procedures. We now describe the implementation of our robotic upper GI and HPB surgery program in our centre of excellence for minimally invasive surgery and the results of our first 100 surgical procedures. METHOD: Robot-assisted surgery was performed using the Da Vinci® Xi Surgical System™. Robot-assisted surgical procedures were performed by two surgeons specialising in minimally invasive surgery. Our robotic surgery program for upper GI and HPB surgery was established in three steps. Step 1: firstly, relatively easy surgical procedures were performed robotically, including cholecystectomies, minor gastric resections and fundoplications. Step 2: secondly, pancreatic left sided resections, adrenalectomies and small liver resection were performed, as procedures with moderate degree of difficulty. Step 3: finally, advanced and highly complex procedures were performed, including right hemihepatectomy, complex pancreatic resections, total gastrectomies and oesophagectomies. Data collected from July 2017 till October 2018 were analysed retrospectively with regard to conversion rate, morbidity (Clavien Dindo > 2) and 90-d-mortality. RESULTS: The first step of establishing our robotic surgical program included 26 procedures. Here, conversion rate, morbidity and mortality were 0%. In the second step of implementation, 23 procedures were performed. Conversion rate, morbidity and mortality were 28, 8 and 0% respectively. The last step included 51 advanced and highly complex procedures. These procedures had a morbidity of 41%, a mortality of 4% and a conversion rate of 43%. CONCLUSION: Our stepwise approach enables safe implementation of a robotic surgical program for upper GI and HPB surgery with comparable morbidity and mortality even for highly complex procedures. However, highly complex procedures in the learning curve required a high conversion rate.

[Indications for Surgical Therapy in Chronic Pancreatitis]. / Operationsindikationen bei der chronischen Pankreatitis.

Chronic pancreatitis is a recurrent disease with repeating exacerbations of inflammation of the pancreatic gland - associated with belt-like back pain. Without treatment, recurrent chronic pancreatitis leads to development of opioid-dependent pain. The chronic pancreatitis leads to recurrent hospital stays for the affected patient and socioeconomic challenges. In progress it can lead to local complications of chronic pancreatitis, such as formation of pseudocysts, biliary duct obstruction, duodenal obstruction or portal hypertension. The aim of this article is a detailed description of the indication for surgical therapy in chronic pancreatitis. The underlying analysis was a systematic literature research and evaluation, the formulation of key questions according to the PICO system and the evaluation of indications and key statements and questions, as implemented in a three level Delphi process among the members of the pancreas research group and the indications for the surgery group of the German Society of General and Visceral Surgery (DGAV). Surgical resection of the inflammatory pancreatic head pseudotumour, after initial conservative therapy, is a highly efficient therapy for the control of pain and the avoidance of complications in chronic pancreatitis. For this purpose, well evaluated surgical strategies are available. Delay in surgical therapy can lead to chronic pain, kachexia and malnutrition and increase complications of surgical therapy.

[Indications for Surgical and Interventional Therapy of Acute Pancreatitis]. / Indikationen zur chirurgischen und interventionellen Behandlung der akuten Pankreatitis.

BACKGROUND: 15 to 20% of patients with acute pancreatitis develop necrosis of the pancreatic parenchyma or extrapancreatic tissue. The disease is associated with a mortality rate of up to 20%. The mainstays of treatment consist of intensive medical care and surgical and interventional therapy. METHODS: A systematic literature search focused on indications for surgical and interventional therapy of necrotising pancreatitis. 85 articles were analysed for this review. By using the Delphi method, the results were presented to the quality committee for pancreas diseases of the German Society for General and Visceral Surgery and to expert pancreatologists in an interactive conference using plenary voting during the visceral medicine congress 2019 in Wiesbaden. For the finalised recommendations, an agreement of 84% of participants was achieved. RESULTS: Documented or clinical suspicion of infected, necrotising pancreatitis are indications for surgical and interventional therapy (recommendation grade: strong; evidence grade; low). Sterile necrosis is a less common indication for intervention due to late complications or persistent severe pancreatitis. Invasive interventions should be delayed when possible until four weeks after onset of pancreatitis. Optimal treatment strategy consists of a "step-up approach" (evidence grade: high; recommendation grade: strong). The first step is catheter drainage, followed, if necessary, by minimally invasive surgical or interventional necrosectomy. If minimally invasive techniques do not result in clinical improvement, open necrosectomy is necessary. 35 to 50% of patients are successfully treated with drainage alone. Indications for emergency intervention are bowel perforation, bowel ischemia and bleeding. Surgical decompression of abdominal compartment syndrome is indicated if the patient is refractory to medical treatment and percutaneous drainage. Abscesses and symptomatic pseudocysts are indications for interventional drainage. Early cholecystectomy during index admission is recommended for patients with mild biliary pancreatitis. Cholecystectomy should be delayed after severe, biliary pancreatitis. CONCLUSION: The recommendations for surgical an interventional therapy of necrotising pancreatitis address the basis of current indications in literature. They should serve in daily practice as a reference standard for decision making in multidisciplinary teams.

[Indications for the Surgical Management of Pancreatic Cystic Lesions]. / Operationsindikationen bei zystischen Tumoren des Pankreas.

A steady improvement in modern imaging as well as increasing age in society have led to an increasing number of cystic pancreatic tumours being detected. Pancreatic cysts are a clinically challenging entity because they span a broad biological spectrum and their differentiation is often difficult, especially in small tumours. Therefore, they require a differentiated indication for indication of surgery. To determine recommendations for the surgical indication in cystic tumours of the pancreas, a quality committee for pancreatic diseases of the German Society for General and Visceral Surgery performed a systematic literature search and created this review. Based on the current evidence, signs of malignancy and high-risk criteria (icterus due to cystic pancreatic duct obstruction in the bile duct, enhancing mural nodules ≥ 5 mm or solid components in the cyst or pancreatic duct ≥ 10 mm), as well as symptoms, are a surgical indication, independently of the cyst entity (except pseudocysts). If the entity of the pancreatic cyst is detectable by diagnostic imaging, all main duct IPMN and IPMN of the mixed type, all MCN > 4 cm and all SPN should be resected. SCN and branch-duct IPMN without worrisome features do not constitute an indication for surgery. The indication of operation in branch-duct IPMN with relative risk criteria and MCN < 4 cm is the subject of current discussions and should be individualised. By defining indication recommendations, the present work aims to improve the indication quality in cystic pancreatic tumours. However, the surgical indication should always be individualised, taking into account age, comorbidities and the patient's wishes.

[Indications for Surgery in Pancreatic Ductal Adenocarcinoma - Consensus Recommendations by the German Society for General and Visceral Surgery]. / Von der Deutschen Gesellschaft für Allgemein- und Viszeralchirurgie konsentierte Operationsindikationen beim duktalen Pankreasadenokarzinom.

BACKGROUND: Surgery for pancreatic cancer in Germany is increasing due to the climbing incidence of this cancer in the population. This review presents a summary of modern evidence-based indications for surgery in patients with pancreatic ductal adenocarcinoma (PDAC). METHODS: The German Society for General and Visceral Surgery (DGAV) authorised a task force to define evidence based indications for surgery in patients with PDAC. A systematic literature search in Medline and Cochrane Library databases (1989 - 2019) was performed. Recommendations were summarised on the basis of the most relevant and recent guidelines and clinical studies and then voted by members of the Working Group on Hepato-Biliary and Pancreatic Diseases (CALGP) in a Delphi procedure. RESULTS: Indications for surgery in patients with PDAC should be set by experienced pancreatic surgeons within a tumour board. Decisions should consider the guidelines as well as the individual patient characteristics. Large vessel infiltration, metastatic disease and severe comorbidities are the most common contraindications for surgery. Borderline-resectable, primary resectable oligometastatic and secondary resectable PDAC should be preferably managed at high-volume centres as a part of clinical studies. Centralisation of pancreatic surgery reduces mortality and improves survival. Palliative bypass surgery as well as staging laparoscopy are still indicated in a large proportion of patients with PDAC. CONCLUSION: Irrespective of the recent development of multimodal therapeutic concepts, surgical resection remains the sole chance of long-term cure for patients with PDAC. Due to the significant proportion of patients in advanced stages of the disease, palliative surgery still plays an important role in the complex management of this cancer.

Perioperative and Long-term Oncological Results of Minimally Invasive Pancreatoduodenectomy as Hybrid Technique - A Matched Pair Analysis of 120 Cases.

BACKGROUND: Laparoscopic pancreatoduodenectomy is a highly challenging procedure. The aim of this study was to analyse post-operative morbidity and mortality as well as long term overall survival in patients undergoing hybrid LPD, as compared to open pancreaticoduodenecomy (OPD) in a single surgeon series. METHODS: Patients undergoing pancreatoduodenectomy (PD) in the period from 2000 to 2015 were identified from a prospectively maintained database. All LPD procedures were performed by one specialised pancreatic surgeon (TK). Patients were matched 1 : 1 for age, sex, BMI, ASA, histological diagnosis, pancreatic texture and portal venous resection (PVR). All LPD procedures were performed as hybrid LPD - combining laparoscopic resection and open reconstruction via mini laparotomy. RESULTS: A total of 549 patients were identified, including 489 patients in the OPD group and 60 patients in the LPD group. 60 patients were identified who underwent LPD between 2010 and 2015 versus 60 OPD patients operated in the same period. Median overall operation time was shorter in the LPD group than with OPD patients (LPD 352 vs. OPD 397 min; p = 0.002). Overall transfusion units were lower in the LPD group (LPD range 0 - 4 vs. OPD range 0 - 11; p = 0.032). Intensive care unit stay (LPD 1 vs. OPD 6 d; p = 0.008) and overall hospital stay (OHS: LPD 14 vs. OPD 18 d; p = 0.012) were shorter in the LPD groups than in the OPD group. As regards postoperative complications, LPD was associated with reduced rates of clinically relevant grade B/C postoperative pancreatic fistula (LPD 15 vs. OPD 36%; p = 0.036) and grade B/C delayed gastric emptying (LPD 8 vs. OPD 20%; p = 0.049). A total of 56 patients were diagnosed with malignant disease. The number of harvested lymph nodes and R0-resection rates were equal for LPD and OPD patients. LPD patients showed a trend to improved median overall survival (LPD mean 56 months vs. OPD mean 48 months; p = 0.056). CONCLUSION: Hybrid LPD is a safe procedure associated with a reduction in clinically relevant postoperative complications and allows faster recovery. Long term oncological outcome of hybrid LPD for malignant disease is equal to that with the standard open approach.

Form follows function: Morphological and immunohistological insights into epithelial-mesenchymal transition characteristics of tumor buds.

In cancer biology, the architectural concept "form follows function" is reflected by cell morphology, migration, and epithelial-mesenchymal transition protein pattern. In vivo, features of epithelial-mesenchymal transition have been associated with tumor budding, which correlates significantly with patient outcome. Hereby, the majority of tumor buds are not truly detached but still connected to a major tumor mass. For detailed insights into the different tumor bud types and the process of tumor budding, we quantified tumor cells according to histomorphological and immunohistological epithelial-mesenchymal transition characteristics. Three-dimensional reconstruction from adenocarcinomas (pancreatic, colorectal, lung, and ductal breast cancers) was performed as published. Tumor cell morphology and epithelial-mesenchymal transition characteristics (represented by zinc finger E-box-binding homeobox 1 and E-Cadherin) were analyzed qualitatively and quantitatively in a three-dimensional context. Tumor buds were classified into main tumor mass, connected tumor bud, and isolated tumor bud. Cell morphology and epithelial-mesenchymal transition marker expression were assessed for each tumor cell. Epithelial-mesenchymal transition characteristics between isolated tumor bud and connected tumor bud demonstrated no significant differences or trends. Tumor cell count correlated significantly with epithelial-mesenchymal transition and histomorphological characteristics. Regression curve analysis revealed initially a loss of membranous E-Cadherin, followed by expression of cytoplasmic E-Cadherin and subsequent expression of nuclear zinc finger E-box-binding homeobox 1. Morphologic changes followed later in this sequence. Our data demonstrate that connected and isolated tumor buds are equal concerning immunohistochemical epithelial-mesenchymal transition characteristics and histomorphology. Our data also give an insight in the process of tumor budding. While there is a notion that the epithelial-mesenchymal transition zinc finger E-box-binding homeobox 1-E-Cadherin cascade is initiated by zinc finger E-box-binding homeobox 1, our results are contrary and outline other possible pathways influencing the regulation of E-Cadherin.

Sensitivity of Helicobacter pylori detection by Giemsa staining is poor in comparison with immunohistochemistry and fluorescent in situ hybridization and strongly depends on inflammatory activity.

BACKGROUND: Conventional stainings (including H&E and special stains like Giemsa) are the most widely applied histopathologic detection methods of Helicobacter pylori (HP). MATERIALS AND METHODS: We aimed to compare the diagnostic performance of Giemsa staining with immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) on a monocentric cohort of 2896 gastric biopsies and relate results to histologic alterations in order to find such histopathologic subgroups in which these methods underperform. All cases were categorized regarding presence or absence of chronic gastritis, inflammatory activity, and mucosal structural alterations. RESULTS: Giemsa revealed 687 cases (23.7%), IHC 795 cases (27.5%), and FISH 788 cases (27.2%) as being HP positive. Giemsa showed significantly lower overall sensitivity (83.3%) compared to IHC (98.8%) and FISH (98.0%). Moreover, the sensitivity of Giemsa dramatically dropped to 33.6% in the nonactive cases. We found that sensitivity of Giemsa strongly depends on HP density and, accordingly, on the presence of activity. Structural alterations (intestinal metaplasia, atrophy, etc.) had only no or weak effect on sensitivity of the three stainings. Both IHC and FISH proved to be equally reliable HP detecting techniques whose diagnostic performance is minimally influenced by mucosal inflammatory and structural alterations contrary to conventional stainings. CONCLUSIONS: We highly recommend immunohistochemistry for clinically susceptible, nonactive chronic gastritis cases, if the conventional stain-based HP detection is negative. Moreover, we recommend to use IHC more widely as basic HP stain. Helicobacter pylori FISH technique is primarily recommended to determine bacterial clarithromycin resistance. Furthermore, it is another accurate diagnostic tool for HP.

Laparoscopic versus open distal pancreatectomy-a propensity score-matched analysis from the German StuDoQ|Pancreas registry.

PURPOSE: The aim of this study was to assess intraoperative, postoperative, and oncologic outcome in patients undergoing laparoscopic distal pancreatectomy (LDP) versus open distal pancreatectomy (ODP) for benign and malignant lesions of the pancreas. METHODS: Data from patients undergoing distal pancreatic resection were extracted from the StuDoQ|Pancreas registry of the German Society for General and Visceral Surgery. After propensity score case matching, groups of LDP and ODP were compared regarding demography, comorbidities, operative details, histopathology, and perioperative outcome. RESULTS: At the time of data extraction, the StuDoQ|Pancreas registry included over 3000 pancreatic resections from over 50 surgical departments in Germany. Data from 353 patients undergoing ODP (n = 254) or LDP (n = 99) from September 2013 to February 2016 at 29 institutions were included in the analysis. Baseline data showed a strong selection bias in LDP patients, which disappeared after 1:1 propensity score matching. A comparison of the matched groups disclosed a significantly longer operation time, higher rate of spleen preservation, more grade A pancreatic fistula, shorter hospital stay, and increased readmissions for LDP. In the small group of patients operated for pancreatic cancer, a lower lymph node yield with a lower lymph node ratio was apparent in LDP. CONCLUSIONS: LDP needed more time but potential advantages include increased spleen preservation and shorter hospital stay, as well as a trend for less transfusion, ventilation, and mortality. LDP for pancreatic cancer was performed rarely and will need critical evaluation in the future. Data from a prospective randomized registry trial is needed to confirm these results.

Characterization of various cell lines from different ampullary cancer subtypes and cancer associated fibroblast-mediated responses.

BACKGROUND: Ampullary cancer is a relatively rare form of cancer and usually treated by pancreatoduodenectomy, followed by adjuvant therapy. The intestinal subtype is associated with markedly improved prognosis after resection. At present, only few cell lines are available for in vitro studies of ampullary cancer and they have not been collectively characterized. METHODS: We characterize five ampullary cancer cell lines by subtype maker expression, epithelial-mesenchymal transition (EMT) features, growth and invasion, drug sensitivity and response to cancer-associated fibroblast conditioned medium (CAF-CM). RESULTS: On the basis of EMT features, subtype marker expression, growth, invasion and drug sensitivity three types of cell lines could be distinguished: mesenchymal-like, pancreatobiliary-like and intestinal-like. Heterogeneous effects from the cell lines in response to CAF-CM, such as different growth rates, induction of EMT markers as well as suppression of intestinal differentiation markers were observed. In addition, proteomic analysis showed a clear difference in intestinal-like cell line from other cell lines. CONCLUSION: Most of the available AMPAC cell lines seem to reflect a poorly differentiated pancreatobiliary or mesenchymal-like phenotype, which is consistent to their origin. We suggest that the most appropriate cell line model for intestinal-like AMPAC is the SNU869, while others seem to reflect aggressive AMPAC subtypes.

Detailed analysis of epithelial-mesenchymal transition and tumor budding identifies predictors of long-term survival in pancreatic ductal adenocarcinoma.

BACKGROUND AND AIM: Pancreatic ductal adenocarcinoma (PDAC) is characterized by aggressive biology and poor prognosis even after resection. Long-term survival is very rare and cannot be reliably predicted. Experimental data suggest an important role of epithelial-mesenchymal transition (EMT) in invasion and metastasis of PDAC. Tumor budding is regarded as the morphological correlate of local invasion and cancer cell dissemination. The aim of this study was to evaluate the biological and prognostic implications of EMT and tumor budding in PDAC of the pancreatic head. METHODS: Patients were identified from a prospectively maintained database, and baseline, operative, histopathological, and follow-up data were extracted. Serial tissue slices stained for Pan-Cytokeratin served for analysis of tumor budding, and E-Cadherin, Beta-Catenin, and Vimentin staining for analysis of EMT. Baseline, operative, standard pathology, and immunohistochemical parameters were evaluated for prediction of long-term survival (≥ 30 months) in uni- and multivariate analysis. RESULTS: Intra- and intertumoral patterns of EMT marker expression and tumor budding provide evidence of partial EMT induction at the tumor-host interface. Lymph node ratio and E-Cadherin expression in tumor buds were independent predictors of long-term survival in multivariate analysis. CONCLUSIONS: Detailed immunohistochemical assessment confirms a relationship between EMT and tumor budding at the tumor-host interface. A small group of patients with favorable prognosis can be identified by combined assessment of lymph node ratio and EMT in tumor buds.

Regulation mechanisms of the hedgehog pathway in pancreatic cancer: a review.

Pancreatic ductal adenocarcinoma (PDAC) is the fourth most common cause of death from cancer. Its 5-year survival rate is less than 5%. This poor prognosis is mostly due to the cancer's early invasion and metastasis formation, leading to an initial diagnosis at an advanced incurable stage in the majority of patients. The only potentially curative treatment is radical surgical resection. The effect of current chemotherapeutics or radiotherapy is limited. Novel therapeutic strategies are therefore much needed. One of the hallmarks of PDAC is its abundant desmoplastic (stromal) reaction. The Hedgehog (Hh) signaling pathway is critical for embryologic development of the pancreas. Aberrant Hh signaling promotes pancreatic carcinogenesis, the maintenance of the tumor microenvironment and stromal growth. The canonical Hh-pathway in the tumor stroma has been targeted widely but has not yet lead to hopeful clinical results. Targeting both the tumor and its surrounding stroma through Hh pathway inhibition by also targeting non-canonical pathways as apparent in the tumor cell may therefore be a novel treatment strategy for PDAC.

Hybrid laparoscopic versus open pylorus-preserving pancreatoduodenectomy: retrospective matched case comparison in 80 patients.

PURPOSE: We compared the outcome of hybrid laparoscopic pylorus-preserving pancreatoduodenectomy (lapPPPD) and open PPPD (oPPPD) in a retrospective case-matched study. METHODS: Patients operated from 2010 to 2013 by lapPPPD were matched 1:1 for age, sex, histopathology, American Society of Anesthesiologists category and body mass index to oPPPD patients operated from 1996 to 2013. RESULTS: Patients eligible for lapPPPD are a risk group due to a high rate of soft pancreata. Complication rate and mortality were comparable to oPPPD. There was a significantly reduced transfusion requirement and a trend towards shorter operation time, less delayed gastric emptying, and reduced hospital stay. The main reason for conversion was portal venous tumor adhesion. Patient selection changed and operation time and hospital stay decreased with the surgeons' experience. CONCLUSION: In selected patients, a hybrid laparoscopic technique of pancreatoduodenectomy is feasible with complication rates comparable to the open procedure. There seem to be advantages in terms of transfusion requirement, operation time, and hospital stay.

When Should Lymphadenectomy Be Performed in Non-Metastatic Pancreatic Neuroendocrine Tumors? A Population-Based Analysis of the German Clinical Cancer Registry Group.

BACKGROUND: Patient selection for lymphadenectomy remains a controversial aspect in the treatment of pancreatic neuroendocrine tumors (pNETs), given the growing importance of parenchyma-sparing resections and minimally invasive procedures. METHODS: This population-based analysis was derived from the German Cancer Registry Group during the period from 2000 to 2021. Patients with upfront resected non-functional non-metastatic pNETs were included. RESULTS: Out of 5520 patients with pNET, 1006 patients met the inclusion criteria. Fifty-three percent of the patients were male. The median age was 64 ± 17 years. G1, G2, and G3 pNETs were found in 57%, 37%, and 7% of the patients, respectively. Lymph node metastasis (LNM) was present in 253 (24%) of all patients. LNM was an independent prognostic factor (HR 1.79, CI 95% 1.21-2.64, p = 0.001) for disease-free survival (DFS). The 3-, 5-, and 10-year disease-free survival in nodal negative tumors compared to nodal positive was 82% vs. 53%, 75% vs. 38%, and 48% vs. 16%. LNM was present in 5% of T1 tumors, 25% of T2 tumors, and 49% of T3-T4 tumors. In T1 tumors, G1 was the most predominant tumor grade (80%). However, in T2 tumors, G2 and G3 represented 44% and 5% of all tumors. LNM was associated with tumors located in the pancreatic head (p < 0.001), positive resection margin (p < 0.001), tumors larger than 2 cm (p < 0.001), and higher tumor grade (p < 0.001). The multivariable analysis showed that tumor size, tumor grade, and location were independent prognostic factors associated with LNM that could potentially be used to predict LNM preoperatively. CONCLUSION: LNM is an independent negative prognostic factor for DFS in pNETs. Due to the low incidence of LNM in T1 tumors (5%), parenchyma-sparing surgery seems oncologically adequate in small G1 pNETs, while regional lymphadenectomy should be recommended in T2 or G2/G3 pNETs.