Influence of Certification Program on Treatment Quality and Survival for Rectal Cancer Patients in Germany: Results of 13 Certified Centers in Collaboration with AN Institute.

INTRODUCTION: The certification of oncological units as colorectal cancer centers (CrCCs) has been proposed to standardize oncological treatment and improve the outcomes for patients with colorectal cancer (CRC). The proportion of patients with CRC in Germany that are treated by a certified center is around 53%. Lately, the effect of certification on the treatment outcomes has been critically discussed. AIM: Our aim was to investigate the treatment outcomes in patients with rectal carcinoma at certified CrCCs, in German hospitals of different medical care levels. METHODS: We performed a retrospective analysis of a prospective, multicentric database (AN Institute) of adult patients who underwent surgery for rectal carcinoma between 2002 and 2016. We included 563 patients from 13 hospitals of different medical care levels (basic, priority, and maximal care) over periods of 5 years before and after certification. RESULTS: The certified CrCCs showed a significant increase in the use of laparoscopic approach for rectal cancer surgery (5% vs. 55%, p < 0.001). However, we observed a significantly prolonged mean duration of surgery in certified CrCCs (161 Min. vs. 192 Min., p < 0.001). The overall morbidity did not improve (32% vs. 38%, p = 0.174), but the appearance of postoperative stool fistulas decreased significantly in certified CrCCs (2% vs. 0%, p = 0.036). Concerning the overall in-hospital mortality, we registered a positive trend in certified centers during the five-year period after the certification (5% vs. 3%, p = 0.190). The length of preoperative hospitalization (preop. LOS) was shortened significantly (4.71 vs. 4.13 days, p < 0.001), while the overall length of in-hospital stays was also shorter in certified CrCCs (20.32 vs. 19.54 days, p = 0.065). We registered a clear advantage in detailed, high-quality histopathological examinations regarding the N, L, V, and M.E.R.C.U.R.Y. statuses. In the performed subgroup analysis, a significantly longer overall survival after certification was registered for maximal medical care units (p = 0.029) and in patients with UICC stage IV disease (p = 0.041). In patients with UICC stage III disease, we registered a slightly non-significant improvement in the disease-free survival (UICC III: p = 0.050). CONCLUSIONS: The results of the present study indicate an improvement in terms of the treatment quality and outcomes in certified CrCCs, which is enforced by certification-specific aspects such as a more differentiated surgical approach, a lower rate of certain postoperative complications, and a multidisciplinary approach. Further prospective clinical trials are necessary to investigate the influence of certification in the treatment of CRC patients.

The Pancreas as a Target of Metastasis from Renal Cell Carcinoma: Is Surgery Feasible and Safe? A Single-Center Experience in a High-Volume and Certified Pancreatic Surgery Center in Germany.

Background: Secondary malignant tumors of the pancreas are rare, representing 2-5% of all pancreatic malignancies. Nevertheless, the pancreas is one of the target organs in cases of metastatic clear cell renal cell carcinoma (CCRCC). Additionally, recurrent metastasis may occur. Surgical resection remains the best and prognostically most favorable therapeutic option in cases of solitary pancreatic metastasis. Aim: To review retrospectively the clinical tumor registry of the University Hospital of Magdeburg, Germany, for this rare entity, performing a clinical systematic single-center observational study (design). Methods: A retrospective cohort analysis of consecutive patients who had undergone pancreatic resection for metastatic CCRC was performed in a single high-volume certified center for pancreatic surgery in Germany from 2010 to 2022. Results: All patients (n = 17) included in this study had a metachronous metastasis from a CCRCC. Surgery was performed at a median time interval of 12 (range, 9-16) years after primary resection for CCRCC. All 17 patients were asymptomatic at the time of diagnosis. Three of those patients (17.6%) presented with recurrent metastasis in a different part of the pancreas during follow-up. In a total of 17 patients, including those with recurrent disease, a surgical resection was performed; Pancreatoduodenectomy was performed in 6 patients (35%); left pancreatectomy with splenectomy was performed in 7 patients (41%). The rest of the patients underwent either a spleen-preserving pancreatic tail resection, local resection of the tumor lesion or a total pancreatectomy. The postoperative mortality rate was 6%. Concerning histopathological findings, seven patients (41%) had multifocal metastasis. An R0 resection could be achieved in all cases. The overall survival at one, three and five years was 85%, 85% and 72%, respectively, during a median follow-up of 43 months. Conclusions: CCRC pancreatic metastases can occur many years after the initial treatment of the primary tumor. Surgery for such a malignancy seems feasible and safe; it offers very good short- and long-term outcomes, as indicated. A repeated pancreatic resection can also be safely performed.

Robotic Complete ALPPS (rALPPS)-First German Experiences.

BACKGROUND: ALPPS leads to fast and effective liver hypertrophy. This enables the resection of extended tumors. Conventional ALPPS is associated with high morbidity and mortality. MILS reduces morbidity and the robot adds technical features that make complex procedures safe. MATERIAL AND METHODS: The MD-MILS was screened for patients who underwent rALPPS. Demographic and perioperative data were evaluated retrospectively. Ninety days postoperative morbidity was scored according to the CD classification. The findings were compared with the literature. RESULTS: Since November 2021, five patients have been identified. The mean age and BMI of the patients were 50.0 years and 22.7 kg/m2. In four cases, patients suffered from colorectal liver metastases and, in one case, intrahepatic cholangiocarcinoma. Prior to the first operation, the mean liver volume of the residual left liver was 380.9 mL with a FLR-BWR of 0.677%. Prior to the second operation, the mean volume of the residual liver was 529.8 mL with a FLR-BWR of 0.947%. This was an increase of 41.9% of the residual liver volume. The first and second operations were carried out within 17.8 days. The mean time of the first and second operations was 341.2 min and 440.6 min. The mean hospital stay was 27.2 days. Histopathology showed the largest tumor size of 39 mm in diameter with a mean amount of 4.7 tumors. The mean tumor-free margin was 12.3 mm. One complication CD > 3a occurred. No patient died during the 90-day follow up. CONCLUSION: In the first German series, we demonstrated that rALPPS can be carried out safely with reduced morbidity and mortality in selected patients.

Integrating a microRNA signature as a liquid biopsy-based tool for the early diagnosis and prediction of potential therapeutic targets in pancreatic cancer.

INTRODUCTION: Pancreatic cancer is a highly aggressive cancer, and early diagnosis significantly improves patient prognosis due to the early implementation of curative-intent surgery. Our study aimed to implement machine-learning algorithms to aid in early pancreatic cancer diagnosis based on minimally invasive liquid biopsies. MATERIALS AND METHODS: The analysis data were derived from nine public pancreatic cancer miRNA datasets and two sequencing datasets from 26 pancreatic cancer patients treated in our medical center, featuring small RNAseq data for patient-matched tumor and non-tumor samples and serum. Upon batch-effect removal, systematic analyses for differences between paired tissue and serum samples were performed. The robust rank aggregation (RRA) algorithm was used to reveal feature markers that were co-expressed by both sample types. The repeatability and real-world significance of the enriched markers were then determined by validating their expression in our patients' serum. The top candidate markers were used to assess the accuracy of predicting pancreatic cancer through four machine learning methods. Notably, these markers were also applied for the identification of pancreatic cancer and pancreatitis. Finally, we explored the clinical prognostic value, candidate targets and predict possible regulatory cell biology mechanisms involved. RESULTS: Our multicenter analysis identified hsa-miR-1246, hsa-miR-205-5p, and hsa-miR-191-5p as promising candidate serum biomarkers to identify pancreatic cancer. In the test dataset, the accuracy values of the prediction model applied via four methods were 94.4%, 84.9%, 82.3%, and 83.3%, respectively. In the real-world study, the accuracy values of this miRNA signatures were 82.3%, 83.5%, 79.0%, and 82.2. Moreover, elevated levels of these miRNAs were significant indicators of advanced disease stage and allowed the discrimination of pancreatitis from pancreatic cancer with an accuracy rate of 91.5%. Elevated expression of hsa-miR-205-5p, a previously undescribed blood marker for pancreatic cancer, is associated with negative clinical outcomes in patients. CONCLUSION: A panel of three miRNAs was developed with satisfactory statistical and computational performance in real-world data. Circulating hsa-miRNA 205-5p serum levels serve as a minimally invasive, early detection tool for pancreatic cancer diagnosis and disease staging and might help monitor therapy success.

Management of acute appendicitis during COVID-19 pandemic. Single center data from a tertiary care hospital in Germany.

Objectives: The unexpected global overload of the health system during COVID-19 pandemic has caused changes in management of acute appendicitis worldwide. Whereas conservative treatment was widely recommended, the appendicectomy remained standard therapy in Germany. We aimed to investigate the impact of COVID-19 pandemic on treatment routine for acute appendicitis at University Hospital of Magdeburg. Methods: Adult patients with clinical and/or radiological diagnosis of acute appendicitis were included in the single center retrospective study. Data was collected to patient demographics, treatment modality and outcomes including morbidity and length of stay. The patient data related to COVID-19 period from March 22, 2020 to December 31, 2021 (649 days) were compared to the Non-COVID-19 period from June 12, 2018 to March 21, 2020 (649 days). Subgroup analysis related to conservative or surgical treatment has been performed. Results: A total of 385 patients was included in the study, 203 (52.73 %) during Non-COVID-19 period and 182 (47.27 %) during COVID-19 period. Mean age of entire collective was 43.28 years, containing 43.9 % female patients (p=0.095). Conservative treatment was accomplished in 49 patients (12.7 % of entire collective), increasing from 9.9 % to 15.9 % during COVID-19 period (p=0.074). Laparoscopic appendicectomy was performed in 99.3 % (n=152) of operated patients during COVID-19 period (p=0.013), followed by less postoperative complications compared to reference period (23.5 % vs. 13.1 %, p=0.015). The initiation of antibiotic therapy after the diagnosis increased from 37.9 % to 53.3 % (p=0.002) during COVID-19 period regardless the following treatment modality. Antibiotic treatment showed shorter duration during pandemic period (5.57 days vs. 3.16 days, p<0.001) and it was given longer in the conservative treatment group (5.63 days vs. 4.26 days, p=0.02). The overall length of stay was shorter during COVID-19 period (4.67 days vs. 4.12 days, p=0.052) and in the conservative treatment group (3.08 days vs. 4.47 days, p<0.001). However, the overall morbidity was lower during the COVID-19 period than before (17.2 % vs. 7.7 %, p=0.005) and for conservative therapy compared to appendicectomy (2 % vs. 14.3 %, p=0.016). There was no mortality documented. Conclusions: According to our findings the COVID-19 pandemic had a relevant impact on treatment of acute appendicitis, but it was possible to maintain the traditional diagnostic and treatment pathway. Although laparoscopic appendicectomy remains a recommended procedure, the conservative treatment of uncomplicated appendicitis with excellent short-term outcome can be a safe alternative to surgery during potential new wave of COVID-19 pandemic and in the daily routine.

Concept of a fully-implantable system to monitor tumor recurrence.

Current treatment for glioblastoma includes tumor resection followed by radiation, chemotherapy, and periodic post-operative examinations. Despite combination therapies, patients face a poor prognosis and eventual recurrence, which often occurs at the resection site. With standard MRI imaging surveillance, histologic changes may be overlooked or misinterpreted, leading to erroneous conclusions about the course of adjuvant therapy and subsequent interventions. To address these challenges, we propose an implantable system for accurate continuous recurrence monitoring that employs optical sensing of fluorescently labeled cancer cells and is implanted in the resection cavity during the final stage of tumor resection. We demonstrate the feasibility of the sensing principle using miniaturized system components, optical tissue phantoms, and porcine brain tissue in a series of experimental trials. Subsequently, the system electronics are extended to include circuitry for wireless energy transfer and power management and verified through electromagnetic field, circuit simulations and test of an evaluation board. Finally, a holistic conceptual system design is presented and visualized. This novel approach to monitor glioblastoma patients is intended to early detect recurrent cancerous tissue and enable personalization and optimization of therapy thus potentially improving overall prognosis.

RoCS: Robotic Curriculum for young Surgeons.

Robotic-assisted procedures gain increasing acceptance for daily surgical routine. However, structured training programs are designed for surgeons with high expertise. Hence, a comprehensive training curriculum was established to ensure a basic competence in robotic abdominal surgery for young surgeons during their residency. The aim of the current work is to propose a feasible and effective training concept. The development process of this training curriculum is based on a comprehensive literature review which led to the concept of "robotic curriculum for young surgeons" (RoCS). It was implemented in the daily routine of a German university hospital starting in 2020. The robotic assessment questionnaire (RAQ) was used for electronic data collection. After the initial phase adjustments, it led to an improvement of the initial version of the curriculum. RoCS is a multimodal training program containing basic training through assistance at the operation table during robotic-assisted operations and basic console training. Key elements are the robotic team time-out (rTTO), perioperative process standardization including feasible personnel scheduling and useful procedure clustering into organ systems, procedural steps and procedural step complexity. Evaluation of standardized communication, performance assessment, patient factors and individual overall workload using NASA Task Load Index is realizable. Flexibility and adaptability to internal organization processes of surgical departments are the main advantages of the concept. RoCS is a strong training tool to meet the specific needs of young surgeons and evaluate their learning success of robotic procedural training. Furthermore, comparison within the different robotic systems should be considered. Further studies are needed to validate a multicenter concept design.

Transient receptor potential channels as predictive marker and potential indicator of chemoresistance in colon cancer.

Transient receptor potential (TRP) channels are strongly associated with colon cancer development and progression. This study leveraged a multivariate Cox regression model on publicly available datasets to construct a TRP channels-associated gene signature, with further validation of signature in real world samples from our hospital treated patient samples. Kaplan-Meier (K-M) survival analysis and receiver operating characteristic (ROC) curves were employed to evaluate this gene signature's predictive accuracy and robustness in both training and testing cohorts, respectively. Additionally, the study utilized the CIBERSORT algorithm and single-sample gene set enrichment analysis to explore the signature's immune infiltration landscape and underlying functional implications. The support vector machine algorithm was applied to evaluate the signature's potential in predicting chemotherapy outcomes. The findings unveiled a novel three TRP channels-related gene signature (MCOLN1, TRPM5, and TRPV4) in colon adenocarcinoma (COAD). The ROC and K-M survival curves in the training dataset (AUC = 0.761; p = 1.58e-05) and testing dataset (AUC = 0.699; p = 0.004) showed the signature's robust predictive capability for the overall survival of COAD patients. Analysis of the immune infiltration landscape associated with the signature revealed higher immune infiltration, especially an increased presence of M2 macrophages, in high-risk group patients compared to their low-risk counterparts. High-risk score patients also exhibited potential responsiveness to immune checkpoint inhibitor therapy, evident through increased CD86 and PD-1 expression profiles. Moreover, the TRPM5 gene within the signature was highly expressed in the chemoresistance group (p = 0.00095) and associated with poor prognosis (p = 0.036) in COAD patients, highlighting its role as a hub gene of chemoresistance. Ultimately, this signature emerged as an independent prognosis factor for COAD patients (p = 6.48e-06) and expression of model gene are validated by public data and real-world patients. Overall, this bioinformatics study provides valuable insights into the prognostic implications and potential chemotherapy resistance mechanisms associated with TRPs-related genes in colon cancer.

COL10A1 allows stratification of invasiveness of colon cancer and associates to extracellular matrix and immune cell enrichment in the tumor parenchyma.

Background: Treatment options for metastatic colorectal cancer (CRC) are mostly ineffective. We present new evidence that tumor tissue collagen type X alpha 1 (COL10A1) is a relevant candidate biomarker to improve this dilemma. Methods: Several public databases had been screened to observe COL10A1 expression in transcriptome levels with cell lines and tissues. Protein interactions and alignment to changes in clinical parameters and immune cell invasion were performed, too. We also used algorithms to build a novel COL10A1-related immunomodulator signature. Various wet-lab experiments were conducted to quantify COL10A1 protein and transcript expression levels in disease and control cell models. Results: COL10A1 mRNA levels in tumor material is clinical and molecular prognostic, featuring upregulation compared to non-cancer tissue, increase with histomorphological malignancy grading of the tumor, elevation in tumors that invade perineural areas, or lymph node invasion. Transcriptomic alignment noted a strong positive correlation of COL10A1 with transcriptomic signature of cancer-associated fibroblasts (CAFs) and populations of the immune compartment, namely, B cells and macrophages. We verified those findings in functional assays showing that COL10A1 are decreased in CRC cells compared to fibroblasts, with strongest signal in the cell supernatant of the cells. Conclusion: COL10A1 abundance in CRC tissue predicts metastatic and immunogenic properties of the disease. COL10A1 transcription may mediate tumor cell interaction with its stromal microenvironment.

Does Robotic Liver Surgery Enhance R0 Results in Liver Malignancies during Minimally Invasive Liver Surgery?-A Systematic Review and Meta-Analysis.

BACKGROUND: Robotic procedures are an integral part of modern liver surgery. However, the advantages of a robotic approach in comparison to the conventional laparoscopic approach are the subject of controversial debate. The aim of this systematic review and meta-analysis is to compare robotic and laparoscopic liver resection with particular attention to the resection margin status in malignant cases. METHODS: A systematic literature search was performed using PubMed and Cochrane Library in accordance with the PRISMA guidelines. Only studies comparing robotic and laparoscopic liver resections were considered for this meta-analysis. Furthermore, the rate of the positive resection margin or R0 rate in malignant cases had to be clearly identifiable. We used fixed or random effects models according to heterogeneity. RESULTS: Fourteen studies with a total number of 1530 cases were included in qualitative and quantitative synthesis. Malignancies were identified in 71.1% (n = 1088) of these cases. These included hepatocellular carcinoma, cholangiocarcinoma, colorectal liver metastases and other malignancies of the liver. Positive resection margins were noted in 24 cases (5.3%) in the robotic group and in 54 cases (8.6%) in the laparoscopic group (OR = 0.71; 95% CI (0.42-1.18); p = 0.18). Tumor size was significantly larger in the robotic group (MD = 6.92; 95% CI (2.93-10.91); p = 0.0007). The operation time was significantly longer in the robotic procedure (MD = 28.12; 95% CI (3.66-52.57); p = 0.02). There were no significant differences between the robotic and laparoscopic approaches regarding the intra-operative blood loss, length of hospital stay, overall and severe complications and conversion rate. CONCLUSION: Our meta-analysis showed no significant difference between the robotic and laparoscopic procedures regarding the resection margin status. Tumor size was significantly larger in the robotic group. However, randomized controlled trials with long-term follow-up are needed to demonstrate the benefits of robotics in liver surgery.

[Influence of the COVID-19 pandemic on robotic visceral surgery in Germany]. / Auswirkungen der COVID-19-Pandemie auf die robotische Viszeralchirurgie in Deutschland.

BACKGROUND: Robotic procedures are gaining more and more importance in visceral surgery and seem to develop into an indispensable tool in minimally invasive visceral surgery. In 2020 the COVID-19 pandemic caused unexpected changes in daily surgical routines with still ongoing challenges. We evaluated the impact of the COVID-19 pandemic on robotic visceral procedures and the associated training provided in Germany. MATERIAL AND METHODS: We performed a thorough evaluation of German hospitals and identified 89 surgical departments performing robotic visceral procedures. After extensive topic-related literature search an online questionnaire was developed. It included 35 questions referring to all relevant topics on robotic surgery, such as training programs and influence of the COVID-19 pandemic. The survey was sent via email three times to each department. Descriptive and subgroup analysis were performed. RESULTS: We reported a response to our questionnaire from 22 (24.7%) surgical departments and17 questionnaires were analyzable. The vast majority of them weresurgical departments of university hospitals (58.8%), 17.6% maximum care clinics and 23.5% main care clinics. Robotic procedures were performed for the upper gastrointestinal tract (UGI 88.2%), the hepatopancreaticobiliary system (HPB 82.4%), in the colorectal region (94.1%) and for hernias (35.3%). The relative proportion of robotic operations in comparison to all visceral procedures was between 0.3% and 15.4%. The average conversion rate was 4.6 ± 3.2% referring to 2020. All participating clinics used the robotic DaVinci® system (Intuitive Surgical Inc., CA, USA). In summary 22 robotic systems were used mainly in an interdisciplinary setting (82.4%). For teaching purposes, 7 departments (41.2%) provided a second robotic console. On average 13.2 ± 6.5% of surgeons per clinic were involved in robotic procedures. Defined operating room (OR) teams (82.4%) consisted of consultants, specialists and residents. Team training for surgeons and OR nurses was mainly (52.9%) based on clinic-specific programs. Due to the COVID-19 pandemic the number of robotic procedures decreased in 70.0% of the participating departments compared to 2019 with the highest decline reported during the second quarter of 2020 (64.7%). Referring to this, staff shortage of non-surgical disciplines (anesthesiologists 35.3%, OR nurses 35.3%, intensive care medics 17.6%), COVID-19-specific regulations (58.8%) and limited capacities of intensive and intermediate care (47.1%) were specified as underlying causes. Due to the COVID-19 pandemic, caused by a decline in numbers of robotic procedures, robotic training was paused completely in assistance at the operating table in 23.5% and at the second console in 42.9%. CONCLUSION: Robotic visceral surgery is already implemented with a broad spectrum of operations in many German clinics of different care levels; however, the relative proportion of robotic procedures is low, when compared to the overall caseload of each clinic. Training concepts are heterogeneous and focused on experts. In surgeons with growing experience in robotic surgery, conversion rates are recorded to be very low. There was a negative impact on robotic case numbers and training provided in 2020 caused by the COVID-19 pandemic. Therefore, a further endorsement of robotic training programs and an improvement of training designs seem to be essential tools in order to enforce robotic procedures in visceral surgery.

The LiMAx Test as Selection Criteria in Minimally Invasive Liver Surgery.

BACKGROUND: Liver failure is a crucial predictor for relevant morbidity and mortality after hepatic surgery. Hence, a good patient selection is mandatory. We use the LiMAx test for patient selection for major or minor liver resections in robotic and laparoscopic liver surgery and share our experience here. PATIENTS AND METHODS: We identified patients in the Magdeburg registry of minimally invasive liver surgery (MD-MILS) who underwent robotic or laparoscopic minor or major liver surgery and received a LiMAx test for preoperative evaluation of the liver function. This cohort was divided in two groups: patients with normal (LiMAx normal) and decreased (LiMAx decreased) liver function measured by the LiMAx test. RESULTS: Forty patients were selected from the MD-MILS regarding the selection criteria (LiMAx normal, n = 22 and LiMAx decreased, n = 18). Significantly more major liver resections were performed in the LiMAx normal vs. the LiMAx decreased group (13 vs. 2; p = 0.003). Hence, the mean operation time was significantly longer in the LiMAx normal vs. the LiMAx decreased group (356.6 vs. 228.1 min; p = 0.003) and the intraoperative blood transfusion significantly higher in the LiMAx normal vs. the LiMAx decreased group (8 vs. 1; p = 0.027). There was no significant difference between the LiMAx groups regarding the length of hospital stay, intraoperative blood loss, liver surgery related morbidity or mortality, and resection margin status. CONCLUSION: The LiMAx test is a helpful and reliable tool to precisely determine the liver function capacity. It aids in accurate patient selection for major or minor liver resections in minimally invasive liver surgery, which consequently serves to improve patients' safety. In this way, liver resections can be performed safely, even in patients with reduced liver function, without negatively affecting morbidity, mortality and the resection margin status, which is an important predictive oncological factor.

Laparoscopic cholecystectomy during the COVID-19 pandemic in a tertiary care hospital in Germany: higher rates of acute and gangrenous cholecystitis in elderly patients.

BACKGROUND: The COVID-19 pandemic caused a global health crisis in 2020. This pandemic also had a negative impact on standard procedures in general surgery. Surgeons were challenged to find the best treatment plans for patients with acute cholecystitis. The aim of this study is to investigate the impact of the COVID-19 pandemic on the outcomes of laparoscopic cholecystectomies performed in a tertiary care hospital in Germany. PATIENTS AND METHODS: We examined perioperative outcomes of patients who underwent laparoscopic cholecystectomy during the pandemic from March 22, 2020 (first national lockdown in Germany) to December 31, 2020. We then compared these to perioperative outcomes from the same time frame of the previous year. RESULTS: A total of 182 patients who underwent laparoscopic cholecystectomy during the above-mentioned periods were enrolled. The pandemic group consisted of 100 and the control group of 82 patients. Subgroup analysis of elderly patients (> 65 years old) revealed significantly higher rates of acute [5 (17.9%) vs. 20 (58.8%); p = 0.001] and gangrenous cholecystitis [0 (0.0%) vs. 7 (20.6%); p = 0.013] in the "pandemic subgroup". Furthermore, significantly more early cholecystectomies were performed in this subgroup [5 (17.9%) vs. 20 (58.8%); p = 0.001]. There were no significant differences between the groups both in the overall and subgroup analysis regarding the operation time, intraoperative blood loss, length of hospitalization, morbidity and mortality. CONCLUSION: Elderly patients showed particularly higher rates of acute and gangrenous cholecystitis during the pandemic. Laparoscopic cholecystectomy can be performed safely in the COVID-19 era without negative impact on perioperative results. Therefore, we would assume that laparoscopic cholecystectomy can be recommended for any patient with acute cholecystitis, including the elderly.

Low skeletal muscle mass and post-operative complications after surgery for liver malignancies: a meta-analysis.

PURPOSE: To assess the influence of low skeletal muscle mass (LSMM) on post-operative complications in patients with hepatic malignancies grade (Clavien Dindo ≥ 3) undergoing resection. METHODS: MEDLINE, Cochrane, and SCOPUS databases were screened for associations between sarcopenia and major post-operative complications (≥ grade 3 according to Clavien-Dindo classification) after resection of different malignant liver tumors. RevMan 5.3 software was used to perform the meta-analysis. The methodological quality of the included studies was assessed according to the QUIPS instrument. RESULTS: The analysis included 17 studies comprising 3157 patients. Subgroup analyses were performed for cholangiocarcinoma (CCC), colorectal cancer (CRC) liver metastases, and hepatocellular carcinoma (HCC). LSMM as identified on CT was present in 1260 patients (39.9%). Analysis of the overall sample showed that LSMM was associated with higher post-operative complications grade Clavien Dindo ≥ 3 (OR 1.56, 95% CI 1.25-1.95, p < 0.001). In the subgroup analysis, LSMM was associated with post-operative complications in CRC metastases (OR 1.60, 95% CI 1.11-2.32, p = 0.01). In HCC and CCC sub-analyses, LSMM was not associated with post-operative complications in simple regression analysis. CONCLUSION: LSMM is associated with major post-operative complications in patients undergoing surgery for hepatic metastases and it does not influence major post-operative complications in patients with HCC and CCC.

Sensory Ion Channel Candidates Inform on the Clinical Course of Pancreatic Cancer and Present Potential Targets for Repurposing of FDA-Approved Agents.

Background: Transient receptor potential channels (TRPs) have been demonstrated to take on functions in pancreatic adenocarcinoma (PAAD) biology. However, little data are available that validate the potential of TRP in a clinical translational setting. Methods: A TRPs-related gene signature was constructed based on the Cox regression using a TCGA-PAAD cohort and receiver operating characteristic (ROC) was used to evaluate the predictive ability of this model. Core genes of the signature were screened by a protein-to-protein interaction (PPI) network, and expression validated by two independent datasets. The mutation analysis and gene set enrichment analysis (GSEA) were conducted. Virtual interventions screening was performed to discover substance candidates for the identified target genes. Results: A four TRPs-related gene signature, which contained MCOLN1, PKD1, TRPC3, and TRPC7, was developed and the area under the curve (AUC) was 0.758. Kaplan−Meier analysis revealed that patients with elevated signature score classify as a high-risk group featuring significantly shorter recurrence free survival (RFS) time, compared to the low-risk patients (p < 0.001). The gene prediction model also had a good predictive capability for predicting shortened overall survival (OS) and disease-specific survival (DSS) (AUC = 0.680 and AUC = 0.739, respectively). GSEA enrichment revealed the core genes of the signature, TRPC3 and TRPC7, were involved in several cancer-related pathways. TRPC3 mRNA is elevated in cancer tissue compared to control tissue and augmented in tumors with lymph node invasion compared to tumors without signs of lymph node invasion. Virtual substance screening of FDA approved compounds indicates that four small molecular compounds might be potentially selective not only for TRPC3 protein but also as a potential binding partner to TRPC7 protein. Conclusions: Our computational pipeline constructed a four TRP-related gene signature that enables us to predict clinical prognostic value of hitherto unrecognized biomarkers for PAAD. Sensory ion channels TRPC3 and TRPC7 could be the potential therapeutic targets in pancreatic cancer and TRPC3 might be involved in dysregulating mitochondrial functions during PAAD genesis.

Low skeletal muscle mass in cholangiocarcinoma treated by surgical resection. A meta-analysis.

BACKGROUND: To date, the role of low skeletal muscle mass (LSMM) in cholangiocarcinoma (CC) is unclear. Our purpose was to analyze the influence of LSMM on survival in patients with CC treated by surgical resection. METHODS: MEDLINE, Cochrane, and SCOPUS databases were screened for associations between LSMM and survival in CC up to June 2021. Overall, 16 studies met the inclusion criteria. The methodological quality of the involved studies was analyzed using the QUADAS instrument. The meta-analysis was undertaken using RevMan 5.4 software. RESULTS: The prevalence of LSMM was 48.40%. LSMM was associated with lower overall survival (OS): HR = 2.44, 95%CI = (2.01-2.96) (simple regression); HR = 2.39, 95%CI = (1.83-3.13) (multiple regression). In extrahepatic CC, sarcopenic patients had lower OS, simple regression: HR = 2.11, 95%CI = (1.39-3.20); multiple regression: HR = 2.28, 95%CI = (1.41-3.70). In intrahepatic CC, LSMM predicted recurrence free survival: HR = 2.33, 95%CI = (1.93-2.81) (simple regression); HR = 2.23, 95%CI = (1.73-2.88) (multiple regression). LSMM predicted OS in intrahepatic CC, simple regression: HR = 2.69, 95%CI = (2.24-3.24); multiple regression: HR = 2.43, 95%CI = (1.73-3.41). CONCLUSION: LSMM is a risk factor for OS in patients with CC treated by surgical resection. LSMM is a predictor of RFS in patients with intrahepatic CC.

Three-Device (3D) Technique for Liver Parenchyma Dissection in Robotic Liver Surgery.

BACKGROUND: The implementation of robotics in liver surgery offers several advantages compared to conventional open and laparoscopic techniques. One major advantage is the enhanced degree of freedom at the tip of the robotic tools compared to laparoscopic instruments. This enables excellent vessel control during inflow and outflow dissection of the liver. Parenchymal transection remains the most challenging part during robotic liver resection because currently available robotic instruments for parenchymal transection have several limitations and there is no standardized technique as of yet. We established a new strategy and share our experience. METHODS: We present a novel technique for the transection of liver parenchyma during robotic surgery, using three devices (3D) simultaneously: monopolar scissors and bipolar Maryland forceps of the robot and laparoscopic-guided waterjet. We collected the perioperative data of twenty-eight patients who underwent this procedure for minor and major liver resections between February 2019 and December 2020 from the Magdeburg Registry of minimally invasive liver surgery (MD-MILS). RESULTS: Twenty-eight patients underwent robotic-assisted 3D parenchyma dissection within the investigation period. Twelve cases of major and sixteen cases of minor hepatectomy for malignant and non-malignant cases were performed. Operative time for major liver resections (≥ 3 liver segments) was 381.7 (SD 80.6) min vs. 252.0 (70.4) min for minor resections (p < 0.01). Intraoperative measured blood loss was 495.8 (SD 508.8) ml for major and 256.3 (170.2) ml for minor liver resections (p = 0.090). The mean postoperative stay was 13.3 (SD 11.1) days for all cases. Liver surgery-related morbidity was 10.7%, no mortalities occurred. We achieved an R0 resection in all malignant cases. CONCLUSIONS: The 3D technique for parenchyma dissection in robotic liver surgery is a safe and feasible procedure. This novel method offers an advanced locally controlled preparation of intrahepatic vessels and bile ducts. The combination of precise extrahepatic vessel handling with the 3D technique of parenchyma dissection is a fundamental step forward to the standardization of robotic liver surgery for teaching purposing and the wider adoption of robotic hepatectomy into routine patient care.

Surgical Approaches and Oncological Outcomes in the Management of Duodenal Gastrointestinal Stromal Tumors (GIST).

BACKGROUND: Duodenal gastrointestinal stromal tumors (GIST) are a rare subset of GIST. Their surgical management in this anatomically complex region consists of varied approaches, and the administration of imatinib mesylate (IM) has not been clarified. METHODS: We retrospectively reviewed patients with duodenal GIST treated during a 10-year-period. We analysed the clinicopathological characteristics and survival factors and evaluated the perioperative and long-term outcomes based on the extent of resection ((ocal-resection (LR) versus pancreaticoduodenectomy (PD)) and the IM-administration. The median follow-up period was 60 months (range, 12-140). RESULTS: A total of thirteen patients (M:F = 7:6) with median age of 64 years (range, 42-77) underwent resection of duodenal GIST. Median tumor size was 5.2 cm (range, 1.5-13.3). Eight patients (61.5%) underwent LR and five patients (38.5%) PD. R0-resection was achieved in 92.5%. Neoadjuvant IM-therapy was administered in five patients leading to tumor downsizing and in 40% to less-extended resection. The PD group consisted of larger tumors with higher mitotic count, mostly located in D2 (p = 0.031). The PD group had longer operative time (p = 0.026), longer hospital stay (p = 0.016), and higher rate of postoperative complications (p = 0.128). The actuarial 1-, 3-, and 5-year overall survival were 92.5%, 84%, and 73.5%, respectively, whereas the disease-free survival rates at 1, 3, and 5 years were 91.5%, 83%, and 72%, respectively. A tendency towards increased risk of disease recurrence was demonstrated for patients with tumor >5 cm and high-risk potential. There was not statistic survival benefit for one or the other surgical approach. CONCLUSION: The type of resection depends on duodenal site of origin and tumor size. LR can be the treatment of choice for duodenal GIST whenever technically feasible. Recurrence of duodenal GIST is dependent on tumor biology rather than surgical approach. Administration of IM in neaodjuvant setting should be considered in cases with high-risk GIST scheduled for PD since it might facilitate less-extended resection.

Tumor visualization and fluorescence angiography with indocyanine green (ICG) in laparoscopic and robotic hepatobiliary surgery - valuation of early adopters from Germany.

OBJECTIVES: Indocyanine green (ICG) is a fluorescent dye which was initially used for liver functional assessment. Moreover, it is of value for intraoperative visualization of liver segments and bile ducts or primary and secondary liver tumors. Especially in minimally invasive liver surgery, this is essential to enhance the precision of anatomical guided surgery and oncological quality. As early adopters of ICG implementation into laparoscopic and robotic-assisted liver surgery in Germany, we summarize the current recommendations and share our experiences. METHODS: Actual strategies for ICG application in minimally invasive liver surgery were evaluated and summarized during a review of the literature. Experiences in patients who underwent laparoscopic or robotic-assisted liver surgery with intraoperative ICG staining between 2018 and 2020 from the Magdeburg registry for minimally invasive liver surgery (MD-MILS) were evaluated and the data were analyzed retrospectively. RESULTS: ICG can be used to identify anatomical liver segments by fluorescence angiography via direct or indirect tissue staining. Fluorescence cholangiography visualizes the intra- and extrahepatic bile ducts. Primary and secondary liver tumors can be identified with a sensitivity of 69-100%. For this 0.5 mg/kg body weight ICG must be applicated intravenously 2-14 days prior to surgery. Within the MD-MILS we identified 18 patients which received ICG for intraoperative tumor staining of hepatocellular carcinoma (HCC), cholangiocarcinoma, peritoneal HCC metastases, adenoma, or colorectal liver metastases. The sensitivity for tumor staining was 100%. In 27.8% additional liver tumors were identified by ICG fluorescence. In 39% a false positive signal could be detected. This occurred mainly in cirrhotic livers. CONCLUSIONS: ICG staining is a simple and useful tool to assess individual hepatic anatomy or to detect tumors during minimally invasive liver surgery. It may enhance surgical precision and improve oncological quality. False-positive detection rates of liver tumors can be reduced by respecting the tumor entity and liver functional impairments.

Diffuse Neuromatosis of Intrahepatic and Extrahepatic Bile Ducts as a Rare Cause of Jaundice.

BACKGROUND: Neuroma of the biliary tree is extremely rare with no more than 100 cases reported so far. They mostly present with obstructive jaundice and have been commonly described after surgery or abdominal trauma. Although involvement of the extrahepatic bile duct is far more common, occurrence in the intrahepatic ducts has not so far been reported. CASE REPORT: We describe 3 cases of diffuse biliary tree neuroma affecting 3 females aged 53-68 years. None had a history of neurofibromatosis type1. All presented with progressive obstructive jaundice with no evidence of gallstones. A history of previous surgery was noted in 2 patients. Initial impression on clinical and imaging examination was highly suspicious for bile duct carcinoma in 2 patients. Histology showed diffuse neuromatous proliferation replacing and thickening the bile duct walls. The third patient had concurrent neuroma and recurrent cholangiocarcinoma causing great clinical confusion as initial biopsy showed only benign neuroma, but CA 19-9 was steadily increasing, necessitating a second biopsy which then confirmed recurrent carcinoma. CONCLUSION: This uncommon cause of long-distance bile duct stenosis and progressive jaundice should be included in the differential diagnosis of bile duct neoplasms, in particular when there is a previous surgical history in this abdominal region.