Safety and Feasibility of Cholecystectomy with the HugoTM RAS: Proof of Setup Guides and First-In-Human German Experience.

Introduction: The Hugo RAS robotic platform by Medtronic was recently certified for human use in Europe. Several centers have gained initial experience with this system in urology and gynecology. However, few data about its feasibility and safety in general surgery have been published. Methods: The first-in-human surgical procedures with the Hugo RAS in Germany were performed at our hospital in February 2023. We report our early experience with robotic cholecystectomy using this new platform. The primary aim was to test the setup guides of the manufacturer and to evaluate the safety and feasibility of Hugo RAS for this procedure. Results: A modified setup with two 11-mm ports and two 8-mm ports without an assistant port was used in 14 consecutive cases. A 30° or a 0° camera, a bipolar grasper or a Maryland on the left arm, a monopolar scissors on the right arm, and a double-fenestrated grasper on the additional arm were mounted. Clip application and gallbladder extraction were performed by the bedside assistant through the right arm 11-mm port. There were no complications, no adverse events, and no conversions. Arm collisions were reduced through slight corrections in trocar positions. Conclusion: Robotic-assisted cholecystectomy with the Hugo RAS was safe and feasible. The modularity of robotic arms allows individual setup modifications which may be of advantage for patients and surgeons.

The article presents technical details and results of the first 14 robotically assisted gallbladder removals performed in Germany with the use of a new-generation surgical robot named Hugo RAS. Setup and configurations of the platform for this type of surgical procedure recommended by the manufacturer were modified by the authors to achieve optimal results. The procedures were performed safely and without complications. Advantages and disadvantages of the Hugo RAS robotic platform for its use in visceral surgery are discussed.

Treatment characteristics and outcomes of pure Acinar cell carcinoma of the pancreas - A multicentric European study on radically resected patients.

BACKGROUND: Acinar cell carcinomas (ACC) belong to the exocrine pancreatic malignancies. Due to their rarity, there is no consensus regarding treatment strategies for resectable ACC. METHODS: This is a retrospective multicentric study of radically resected pure pancreatic ACC. Primary endpoints were overall survival (OS) and disease-free survival (DFS). Further endpoints were oncologic outcomes related to tumor stage and therapeutic protocols. RESULTS: 59 patients (44 men) with a median age of 64 years were included. The median tumor size was 45.0 mm. 61.0% were pT3 (n = 36), nodal positivity rate was 37.3% (n = 22), and synchronous distant metastases were present in 10.1% of the patients (n = 6). 5-Years OS was 60.9% and median DFS 30 months. 24 out of 31 recurred systemically (n = 18 only systemic, n = 6 local and systemic). Regarding TNM-staging, only the N2-stage negatively influenced OS and DFS (p = 0.004, p = 0.001). Adjuvant treatment protocols (performed in 62.7%) did neither improve OS (p = 0.542) nor DFS (p = 0.159). In 9 cases, radical resection was achieved following neoadjuvant therapy. DISCUSSION: Radical surgery is currently the mainstay for resectable ACC, even for limited metastatic disease. Novel (neo)adjuvant treatment strategies are needed, since current systemic therapies do not result in a clear survival benefit in the perioperative setting.

Applicability of the surgical risk calculator by the American College of Surgeons in the setting of German patients undergoing complete pancreatectomy: multicentre study using data from the StuDoQ|Pancreas registry.

INTRODUCTION: Surgical risk calculators can estimate risk probabilities for postoperative outcomes utilizing patient-specific risk factors. They provide meaningful information for obtaining informed consent. The aim of the present paper was to evaluate the predictive value of the surgical risk calculators by the American College of Surgeons in German patients undergoing total pancreatectomy. METHODS: Data for patients who underwent total pancreatectomy between 2014 and 2018 were acquired from the Study, Documentation, and Quality Center of the German Society for General and Visceral Surgery. Risk factors were entered manually into the surgical risk calculators and calculated risks were compared with actual outcomes. RESULTS: Of the 408 patients analysed, predicted risk was higher in patients with complications except for the prediction of re-admission (P = 0.127), delayed gastric emptying (P = 0.243), and thrombosis (P = 0.256). In contrast, classification of patients into below, above, or average risk by the surgical risk calculators only produced meaningful results for discharge to nursing facility (P < 0.001), renal failure (P = 0.003), pneumonia (P = 0.001), serious complications, and overall morbidity (both P < 0.001). Assessment of discrimination and calibration showed poor results (scaled Brier scores 8.46 per cent or less). CONCLUSION: Overall surgical risk calculator performance was poor. This finding promotes the development of a specific surgical risk calculator applicable to the German healthcare system.

Risk Factor Identification for Delayed Gastric Emptying after Distal Pancreatectomy-An Evaluation of 1688 Patients Based on the German StuDoQ|Pancreas Registry.

Delayed gastric emptying (DGE) ranks as one of the most frequent complications in pancreatic surgery. It leads to increased costs for healthcare systems, lengthened hospital stays and reduced quality of life. Data about DGE after distal pancreatectomy (DP) are scarce. The StuDoQ|Pancreas registry of the German Society of General and Visceral Surgery provided data of patients who underwent distal pancreatectomy from 1 January 2014 to 31 December 2018. The retrospective evaluation included comprehensive data: 1688 patients were enrolled; DGE occurred 160 times (9.5%); grade "A" was reported for 98 (61.3%), grade "B" for 41 (25.6%) and grade "C" for 21 (13.1%) patients. In univariate analysis pancreatic fistulas were associated with higher frequencies of intraabdominal abscesses (9.1% vs. 2%, p > 0.001), postpancreatectomy haemorrhage (8.1% vs. 3.7%, >0.001) and DGE (14.5% vs. 6%, p < 0.001). According to multivariate analysis, "abscesses with invasive therapy" (p < 0.001), "other surgical complications" (p < 0.001), prolonged "stays in ICU" (p < 0.001), lengthened duration of surgery (p < 0.001) and conventional surgery (p = 0.007) were identified as independent risk factors for DGE. Perioperative and postoperative factors were identified as risk factors for DGE. Following research should examine this highly relevant topic in a prospective, register-based manner. As there is no causal therapy for DGE, its avoidance is of major importance.

Independent Validation and Assay Standardization of Improved Metabolic Biomarker Signature to Differentiate Pancreatic Ductal Adenocarcinoma From Chronic Pancreatitis.

BACKGROUND & AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Impact of pylorus preservation on delayed gastric emptying after pancreaticoduodenectomy-analysis of 5,000 patients based on the German StuDoQ|Pancreas-Registry.

BACKGROUND: Delayed gastric emptying (DGE) is one of the most common complications after pancreatic head resection. It leads to increased length of hospital stay, high costs for healthcare systems and reduced quality of life. The primary aim of the study was to assess the impact of pylorus preservation, respectively resection on the occurrence of DGE in patients undergoing pancreaticoduodenectomy (PD). METHODS: All cases of pylorus-resecting PD (PRPD) and pylorus-preserving PD (PPPD) entered in the StuDoQ|Pancreas nationwide registry of the German Society of General and Visceral Surgery from 01/01/2014 until 31/12/2018 including demographics, surgical techniques, histopathological and perioperative data were retrospectively analyzed. This study was approved by the ethics committee of the Ruhr-University Bochum, Germany. RESULTS: Data of 5,080 patients were enrolled. PPPD was the method of choice (70.4%). Pylorus preservation had no impact on the occurrence of DGE (20.3% vs. 21.5%, P=0.33), but further risk factors could be identified. The comparison of PPPD and PRPD groups showed statistically significant differences in the surgical approach (primary open approach, 94.8% vs. 98.0%, P<0.001), duration of surgery (326.4 vs. 352.1 minutes, P<0.001), technique of pancreatic anastomosis (pancreaticojejunostomy vs. pancreaticojejunostomy), 78.6% vs. 85.2%, P<0.001). CONCLUSIONS: Patient factors, intraoperative factors, duration of surgery and postoperative factors (postoperative pancreatic fistula, biliary leakage and other surgical complications) were identified as risk factors for DGE. Future research should focus on register-based, prospective, randomised-controlled studies such as the currently recruiting "PyloResPres trial".

Plasma Metabolome Profiling Identifies Metabolic Subtypes of Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers. Developing biomarkers for early detection and chemotherapeutic response prediction is crucial to improve the dismal prognosis of PDAC patients. However, molecular cancer signatures based on transcriptome analysis do not reflect intratumoral heterogeneity. To explore a more accurate stratification of PDAC phenotypes in an easily accessible matrix, plasma metabolome analysis using MxP® Global Profiling and MxP® Lipidomics was performed in 361 PDAC patients. We identified three metabolic PDAC subtypes associated with distinct complex lipid patterns. Subtype 1 was associated with reduced ceramide levels and a strong enrichment of triacylglycerols. Subtype 2 demonstrated increased abundance of ceramides, sphingomyelin and other complex sphingolipids, whereas subtype 3 showed decreased levels of sphingolipid metabolites in plasma. Pathway enrichment analysis revealed that sphingolipid-related pathways differ most among subtypes. Weighted correlation network analysis (WGCNA) implied PDAC subtypes differed in their metabolic programs. Interestingly, a reduced expression among related pathway genes in tumor tissue was associated with the lowest survival rate. However, our metabolic PDAC subtypes did not show any correlation to the described molecular PDAC subtypes. Our findings pave the way for further studies investigating sphingolipids metabolisms in PDAC.

Is surgery for serous cystic neoplasms of the pancreas still indicated? Sixteen years of experience at a high-volume center.

BACKGROUND: Current guidelines discourage surgery for serous cystic neoplasms (SCN) of the pancreas, because of their benign character, slow growth, and excellent prognosis. Nevertheless, SCN continue to contribute up to 30% of resected cystic pancreatic lesions worldwide. METHODS: Spectrum of indications and outcomes of surgery were analysed in a retrospective series of 133 SCN at a single high-volume center in Germany between 2004 and 2019. RESULTS: Relevant symptoms justified surgery in 60% of patients with SCN, while 40% underwent surgery because of preoperative diagnostic uncertainty about suspected malignancy. There were 4 malignant SCN (3%). Ninety-day mortality was 0.75%, major morbidity - 15%, 10-year survival - 95%. Risks of malignant transformation and of postoperative mortality were similarly low. CONCLUSIONS: Surgery is reasonable and safe for symptomatic patients with SCN. Preoperative diagnostic uncertainty is the main reason for futile resections of benign asymptomatic SCN. Conservative management with close initial surveillance should be the first choice for this population. Surgery for supposed SCN without symptoms is justified only in carefully selected patients with suspected malignancy.

Identification and validation of a multivariable prediction model based on blood plasma and serum metabolomics for the distinction of chronic pancreatitis subjects from non-pancreas disease control subjects.

OBJECTIVE: 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. DESIGN: 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. RESULTS: 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)). CONCLUSIONS: 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.

Facing the surgeon's nightmare: Incidence and management of postoperative pancreatic fistulas grade C after pancreaticoduodenectomy based on the updated definition of the International Study Group of Pancreatic Surgery (ISGPS).

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.

The Unusual Suspects of the Pancreas-Understanding Pancreatic Acinar Cell Carcinomas and Adenomas.

PURPOSE: Acinar cell carcinomas (ACC) and adenomas (ACA) of the pancreas are rare entities. Sufficient knowledge about occurrence and prognosis is scarce. METHODS: A retrospective chart review of our database was performed for all patients who had undergone pancreatic surgery between 2006 and 2018. Results were compared to recent literature findings. RESULTS: Nine patients were diagnosed with ACC and four patients with ACA of the pancreas in the study period. ACC patients were older and more often male than patients of the ACA group. ACC were mainly localized in the pancreatic head, whereas ACA were more often found in the distal pancreas. Tumor markers are not necessarily elevated, even in case of malignancy. CONCLUSIONS: ACC and ACA are very rare pancreatic tumors. Both entities account for less than 1% of all pancreatic neoplasms. Diagnosis is challenging due to unspecific radiologic features and clinical symptoms. Nevertheless, a patient complaining of abdominal discomfort and an unclear hypodense pancreatic lesion should undergo surgical exploration.

Tuberculosis Mimicking Disseminated Peritoneal Carcinomatosis of a Sigmoid Carcinoma.

BACKGROUND: A 76-year-old Moroccan patient with a medical history of sigmoid carcinoma suffered from weight loss of 15 kg and abdominal pain. Laparoscopy showed disseminated miliary peritoneal lesions, prima vista suspicious for disseminated peritoneal cancer spread. METHODS: Patient's medical history was reprocessed and compared to recent literature via PubMed. RESULTS: Pathological evaluation revealed granulomas and an infection with miliary intraabdominal tuberculosis (TB) was proven. CONCLUSION: Symptoms of TB may vary and findings can be misleading. An interdisciplinary approach is needed for diagnosis and treatment.

Acinar Cell Cystadenoma - a Rarity in Advanced von Hippel-Lindau Disease: A Case Report.

BACKGROUND: Von Hippel-Lindau (VHL) disease may occur at various localisations which can be both intra- and extrapancreatic as well as challenging to diagnose by medical imaging. CASE REPORT: A positron emission tomography/magnetic resonance imaging in a 40-year-old woman was performed to monitor a haemangioblastoma. Additionally, it showed findings which were considered to be a pancreatic neuroendocrine tumour (pNET) and retroumbilical metastasis. The suspected metastasis was laparoscopically resected; however, pathological evaluation did not lead to a clear categorisation. Consequently, the pancreatic head was resected in which a pNET and various acinar cell cystadenomas were found. CONCLUSION: Diagnostic and therapy of advanced VHL disease can be difficult; if in doubt, a surgical approach may establish clarity.