Patient-reported outcomes at three months after pancreatic surgery for benign and malignant diseases - A prospective observational study.

BACKGROUND/OBJECTIVES: Pancreatic surgery may have a long-lasting effect on patients' health status and quality of life (QoL). We aim to evaluate patient-reported outcomes (PRO) 3 months after pancreatic surgery. METHODS: Patients scheduled for pancreatic surgery were enrolled in a prospective trial at five German centers. Patients completed PRO questionnaires (EQ-5D-5L, EORTC QLQ-PAN26, patient-reported happiness, and HADS-D), we report the first follow-up 3 months after surgery as an interim analysis. Statistical testing was performed using R software. RESULTS: From 2019 to 2022 203 patients were enrolled, a three-month follow-up questionnaire was available in 135 (65.5 %). 77 (57.9 %) underwent surgery for malignant disease. Patient-reported health status (EQ-5D-5L) was impaired in 4/5 dimensions (mobility, self-care, usual activities, pain, discomfort) for patients with malignant and 3/5 dimensions (mobility, self-care, usual activities) for patients with benign disease 3 months after surgery (p < 0.05). Patients with malignant disease reported an increase in depressive symptoms, patients with benign disease had a decrease in anxiety symptoms (HADS-D; depression: 5.00 vs 6.51, p = 0.002; anxiety: 8.04 vs. 6.34, p = 0.030). Regarding pancreatic-disease-specific symptoms (EORTC-QLQ-PAN26), patients with malignant disease reported increased problems with taste, weight loss, weakness in arms and legs, dry mouth, body image and troubling side effects at three months. Patients with benign disease indicated more weakness in arms and legs, troubling side effects but less future worries at three months. CONCLUSION: Patient-reported outcomes of patients undergoing pancreatic surgery for benign vs. malignant disease show important differences. Patients with malignant tumors report more severely decreased quality of life 3 months postoperatively than patients with benign tumors.

Current Trends and Advancements in the Management of Hepatocellular Carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) remains a significant global health burden with a high mortality rate. Over the past 40 years, significant progress has been achieved in the prevention and management of HCC. SUMMARY: Hepatitis B vaccination programs, the development of direct acting antiviral drugs for Hepatitis C, and effective surveillance strategies provide a profound basis for the prevention of HCC. Advanced surgery and liver transplantation along with local ablation techniques potentially offer cure for the disease. Also, just recently, the introduction of immunotherapy opened a new chapter in systemic treatment. Finally, the introduction of the BCLC classification system for HCC, clearly defining patient groups and assigning reasonable treatment options, has standardized treatment and become the basis of almost all clinical trials for HCC. With this review, we provide a comprehensive overview of the evolving landscape of HCC management and also touch on current challenges. KEY MESSAGE: A comprehensive and multidisciplinary approach is crucial for effective HCC management. Continued research and clinical trials are imperative to further enhance treatment options and will ultimately reduce the global burden of this devastating disease.

Oncological right hemicolectomy in a trimodal comparison: open surgery versus laparoscopic procedures with extra- and intracorporeal anastomosis technique.

PURPOSE: This study aimed to investigate the surgical short- and mid-term outcomes, as well as the impact on quality of life and recovery, following oncological right hemicolectomy. To accomplish this, three patient cohorts were examined, which included laparotomy OA), laparoscopy with intracorporeal anastomosis (LIA), and laparoscopy with extracorporeal anastomosis (LEA). Our hypothesis was that the group undergoing intracorporeal anastomosis would demonstrate superior outcomes compared to the other cohorts. METHODS: The analysis included a total of 135 patients who were enrolled between 2015 and 2020. In addition to retrospectively collected data, we conducted follow-up surveys using a validated Gastrointestinal Quality of Life Index (GIQLI) questionnaire and semi-structured interviews. These surveys were conducted between July and September 2021 to gather comprehensive information regarding the patients' quality of life. RESULTS: The study cohort was divided into OA (n = 67), LEA (n = 14), and LIA (n = 54). The duration of surgery was significantly longer in the laparoscopic groups (median = 200.5 (LEA) and 184.0 (LIA) min vs 170.0 min (OA); p = 0.007), while the length of hospital stay was significantly shorter (median = 6.0 and 7.0 days vs 9.0 days; p = 0.005). The overall postoperative complication rate was significantly higher in the laparotomy group compared to the intracorporeal group (64.2% vs 35.2%; p = 0.006), with the extracorporeal group having a rate of 42.9%. Reoperation within 30 days occurred exclusively in the open surgery group (n = 9; 13.43%; p = 0.007). The overall response rate to the survey was 75%. Overall, the GIQLI score was comparable among the three groups, and there were no significant differences in the questions related to recovery, regained function, and contentment. CONCLUSION: The laparoscopic approaches demonstrated significantly lower complication rates compared to laparotomy, while no significant differences were observed between the two laparoscopic techniques.

Is survival after transanal total mesorectal excision (taTME) worse than that after traditional total mesorectal excision? A retrospective propensity score-adjusted cohort study.

PURPOSE: Transanal total mesorectal excision (taTME) was developed to provide better vision during resection of the mesorectum. Conflicting results have shown an increase in local recurrence and shorter survival after taTME. This study compared the outcomes of taTME and abdominal (open, laparoscopic, robotic) total mesorectal excision (abTME). METHODS: Patients who underwent taTME or abTME for stages I-III rectal cancer and who received an anastomosis were included. A retrospective analysis of a prospectively conducted database was performed. The primary endpoints were overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS). Risk factors were adjusted by propensity score matching (PSM). The secondary endpoints were local recurrence rates and combined poor pathological outcomes. RESULTS: From 2012 to 2020, a total of 189 patients underwent taTME, and 119 underwent abTME; patients were followed up for a mean of 54.7 (SD 24.2) and 78.4 (SD 34.8) months, respectively (p < 0.001). The 5-year survival rates after taTME and abTME were not significantly different after PSM: OS: 78.2% vs. 88.6% (p = 0.073), CSS: 87.4% vs. 92.1% (p = 0.359), and DFS: 69.3% vs. 80.9% (p = 0.104), respectively. No difference in the local recurrence rate was observed (taTME, n = 10 (5.3%); abTME, n = 10 (8.4%); p = 0.280). Combined poor pathological outcomes were more frequent after abTME (n = 36, 34.3%) than after taTME (n = 35, 19.6%) (p = 0.006); this difference was nonsignificant according to multivariate analysis (p = 0.404). CONCLUSION: taTME seems to be a good treatment option for patients with rectal cancer and is unlikely to significantly affect local recurrence or survival. However, further investigations concerning the latter are warranted. TRIAL REGISTRATION: ClinicalTrials.gov (NCT0496910).

Remote ischemic preconditioning versus sham-control for prevention of anastomotic leakage after resection for rectal cancer (RIPAL trial): a pilot randomized controlled, triple-blinded monocenter trial.

PURPOSE: Remote ischemic preconditioning (RIPC) reportedly reduces ischemia‒reperfusion injury (IRI) in various organ systems. In addition to tension and technical factors, ischemia is a common cause of anastomotic leakage (AL) after rectal resection. The aim of this pilot study was to investigate the potentially protective effect of RIPC on anastomotic healing and to determine the effect size to facilitate the development of a subsequent confirmatory trial. MATERIALS AND METHODS: Fifty-four patients with rectal cancer (RC) who underwent anterior resection were enrolled in this prospectively registered (DRKS0001894) pilot randomized controlled triple-blinded monocenter trial at the Department of Surgery, University Medicine Mannheim, Mannheim, Germany, between 10/12/2019 and 19/06/2022. The primary endpoint was AL within 30 days after surgery. The secondary endpoints were perioperative morbidity and mortality, reintervention, hospital stay, readmission and biomarkers of ischemia‒reperfusion injury (vascular endothelial growth factor, VEGF) and cell death (high mobility group box 1 protein, HMGB1). RIPC was induced through three 10-min cycles of alternating ischemia and reperfusion to the upper extremity. RESULTS: Of the 207 patients assessed, 153 were excluded, leaving 54 patients to be randomized to the RIPC or the sham-RIPC arm (27 each per arm). The mean age was 61 years, and the majority of patients were male (37:17 (68.5:31.5%)). Most of the patients underwent surgery after neoadjuvant therapy (29/54 (53.7%)) for adenocarcinoma (52/54 (96.3%)). The primary endpoint, AL, occurred almost equally frequently in both arms (RIPC arm: 4/25 (16%), sham arm: 4/26 (15.4%), p = 1.000). The secondary outcomes were comparable except for a greater rate of reintervention in the sham arm (9 (6-12) vs. 3 (1-5), p = 0.034). The median duration of endoscopic vacuum therapy was shorter in the RIPC arm (10.5 (10-11) vs. 38 (24-39) days, p = 0.083), although the difference was not statistically significant. CONCLUSION: A clinically relevant protective effect of RIPC on anastomotic healing after rectal resection cannot be assumed on the basis of these data.

The role of the multidisciplinary tumor board after endoscopic resection of malignant tumors: is it worth it?

OBJECTIVES: The value of multidisciplinary tumor boards (MTBs) in the treatment of gastrointestinal cancer patients is well known. Most of the current evidence focuses on advanced cancer cases, whereas little is known about the effect of MTBs on early tumors, especially after endoscopic resection. The aim of our study is to evaluate the value of the MTB after endoscopic resection of malignant tumors of the gastrointestinal tract. METHODS: We retrospectively analyzed all endoscopically resected malignant tumors in our department between 2011 and 2019, focusing on the existence of an MDT recommendation after endoscopic resection, the MDT adherence to the current guidelines, and the implementation of the recommendation by the patients. RESULTS: We identified 198 patients fulfilling our inclusion criteria, of whom 168 (85%) were discussed in the MDT after endoscopic resection. In total, 155 of the recommendations (92%) were in accordance with the current guidelines, and 147 (88%) of them were implemented by the patients. The MDT discussion itself did not influence the overall survival, whereas the implementation of the MTB recommendation was associated with a significantly better prognosis. Deviations of the MDT recommendation from the guidelines had no effect on the overall survival. CONCLUSIONS: The discussion of endoscopically resected malignant tumors in the MTB is crucial for the treatment of patients with this type of cancer, since the implementation of the MTB recommendation, even if it deviates from the current guidelines, improves the prognosis.

Robotic or laparoscopic repeat hepatectomy after open hepatectomy: a cohort study.

BACKGROUND: Repeat hepatectomies are technically complex procedures. The evidence of robotic or laparoscopic (= minimally invasive) repeat hepatectomies (MIRH) after previous open hepatectomy is poor. Therefore, we compared postoperative outcomes of MIRH vs open repeat hepatectomies (ORH) in patients with liver tumors after previous open liver resections. METHODS: Consecutive patients who underwent repeat hepatectomies after open liver resections were identified from a prospective database between April 2018 and May 2023. Postoperative complications were graded in line with the Clavien-Dindo classification. We stratified patients by intention to treat into MIRH or ORH and compared outcomes. Logistic regression analysis was performed to define variables associated with the utilization of a minimally invasive approach. RESULTS: Among 46 patients included, 20 (43%) underwent MIRH and 26 (57%) ORH. Twenty-seven patients had advanced or expert repeat hepatectomies (59%) according to the IWATE criteria. Baseline characteristics were comparable between the study groups. The use of a minimally invasive approach was not dependent on preoperative or intraoperative variables. All patients had negative resection margins on final histology. MIRH was associated with less blood loss (450 ml, IQR (interquartile range): 200-600 vs 600 ml, IQR: 400-1500 ml, P = 0.032), and shorter length of stay (5 days, IQR: 4-7 vs 7 days, IQR: 5-9 days, P = 0.041). Postoperative complications were similar between the groups (P = 0.298). CONCLUSIONS: MIRH is feasible after previous open hepatectomy and a safe alternative approach to ORH. (German Clinical Trials Register ID: DRKS00032183).

Influence of motivational interviewing on postoperative mobilization in the enhanced recovery after surgery (ERAS®) pathway in elective colorectal surgery - a randomized patient-blinded pilot study.

PURPOSE: Early mobilization is an essential component of the Enhanced Recovery after Surgery (ERAS®)-pathway. However, a large percentage of patients fail to achieve the ERAS® recommended goal (360 min out of bed from post-operative day 1/POD1). Motivational Interviewing (MI) is an evidence-based type of patient-centered consultation to promote intrinsic motivation. This study aims to evaluate if MI can improve postoperative mobilization. METHODS: This two-arm, patient-blinded pilot randomized controlled trial included ERAS®-patients undergoing elective bowel resections. Conversations were validated by MI Treatment Integrity. Two validated motion sensors (movisens) and self-assessments were used to measure mobilization (POD1-POD3: Time out of bed, time on feet and step count). RESULTS: 97 patients were screened, 60 finally included and randomized. Cumulatively across POD1-3, the intervention group (IG) was longer out of bed than the control group (CG) (median: 685 vs. 420 min; p=0.022). The IG achieved the ERAS®-goal of 360 min/day more frequently across POD1-3 (27.4% vs. 10.61%; p=0.013). Time on feet was 131.5 min/day (median per POD) in IG vs. 95.8 min/day in the CG (p=0.212), step count was 1347 in IG vs. 754 steps/day in CG (p=0.298). CONCLUSION: MI could be conducted low threshold and was well accepted by patients. MI can improve mobilization in the context of ERAS®. Despite better performance, it should be noted that only 27.4% of the IG reached the ERAS®-compliance goal of 360 min/day. The findings of this pilot study stipulate to further test the promising perioperative effects of MI within a multicenter superiority trial. REGISTRATION: This study was registered prospectively in the German Clinical Trials Register on 25.02.2022. Trial registration number is "DRKS00027863".

Treatment in certified cancer centers is related to better survival in patients with colon and rectal cancer: evidence from a large German cohort study.

BACKGROUND: Certified cancer centers aim to ensure high-quality care by establishing structural and procedural standards according to evidence-based guidelines. Despite the high clinical and health policy relevance, evidence from a nation-wide study for the effectiveness of care for colorectal cancer in certified centers vs. other hospitals in Germany is still missing. METHODS: In a retrospective cohort study covering the years 2009-2017, we analyzed patient data using demographic information, diagnoses, and treatments from a nationwide statutory health insurance enriched with information on certification. We investigated whether patients with incident colon or rectal cancer did benefit from primary therapy in a certified cancer center. We used relative survival analysis taking into account mortality data of the German population and adjustment for patient and hospital characteristics via Cox regression with shared frailty for patients in hospitals with and without certification. RESULTS: The cohorts for colon and rectal cancer consisted of 109,518 and 51,417 patients, respectively, treated in a total of 1052 hospitals. 37.2% of patients with colon and 42.9% of patients with rectal cancer were treated in a certified center. Patient age, sex, comorbidities, secondary malignoma, and distant metastases were similar across groups (certified/non-certified) for both colon and rectal cancer. Relative survival analysis showed significantly better survival of patients treated in a certified center, with 68.3% (non-certified hospitals 65.8%) 5-year survival for treatment of colon cancer in certified (p < 0.001) and 65.0% (58.8%) 5-year survival in case of rectal cancer (p < 0.001), respectively. Cox regression with adjustment for relevant covariates yielded a lower hazard of death for patients treated in certified centers for both colon (HR = 0.92, 95% CI = 0.89-0.95) and rectal cancer (HR = 0.92, 95% CI = 0.88-0.95). The results remained robust in a series of sensitivity analyses. CONCLUSIONS: This large cohort study yields new important evidence that patients with colorectal cancer have a better chance of survival if treated in a certified cancer center. Certification thus provides one powerful means to improve the quality of care for colorectal cancer. To decrease the burden of disease, more patients should thus receive cancer care in a certified center.

The Role of Adjuvant Therapy in Duodenal Adenocarcinoma and Intestinal Subtype Ampullary Carcinoma after Curative Resection.

OBJECTIVE: Defining the role of adjuvant therapy in duodenal adenocarcinoma (DAC) and intestinal subtype ampullary carcinoma (iAC). SUMMARY BACKGROUND DATA: DAC and iAC share a similar histological differentiation but the benefit of adjuvant therapy remains unclear. METHODS: Patients undergoing curative-intent surgical resection for DAC and iAC between 2010 and 2021 at five high-volume centers were included. Patient baseline, perioperative and long-term oncological outcomes were evaluated. Statistical testing was performed with SPSS 25 (IBM). RESULTS: A total of 136 patients with DAC and 171 with iAC were identified. Patients with DAC had more advanced tumors than those with iAC. Median overall survival (OS) in DAC patients was 101 months versus 155 months for iAC patients (P=0.098). DAC had a higher rate of local (14.1% vs. 1.2%, P<0.001) and systemic recurrence (30.4% vs. 3.5%, P<0.001). Adjuvant therapy failed to improve overall survival in all patients with DAC and iAC. For DAC, patients with perineural invasion, but not other negative prognostic factors had improved OS rates with adjuvant therapy (72 m vs. 44 m, P=0.044). IAC patients with N+ (190 m vs. 57 m, P=0.003), T3-4 (177 m vs. 59 m, P=0.050) and perineural invasion (150 m vs. 59 m, P=0.019) had improved OS rates with adjuvant therapy. CONCLUSION: While adjuvant therapy fails to improve OS in all patients with DAC and iAC in the current study, it improved overall survival in DAC patients with perineural invasion and in iAC patients with T3-4 tumors, positive lymph nodes, and perineural invasion.

Adherence to fast track measures in colorectal surgery-a survey among German and Austrian surgeons.

PURPOSE: The effectiveness of modern perioperative treatment concepts has been demonstrated in several studies and meta-analyses. Despite good evidence, limited implementation of the fast track (FT) concept is still a widespread concern. To assess the status quo in Austrian and German hospitals, a survey on the implementation of FT measures was conducted among members of the German Society of General and Visceralsurgery (DGAV), the German Society of Coloproctology (DGK) and the Austrian Society of Surgery (OEGCH) to analyze where there is potential for improvement. METHODS: Twenty questions on perioperative care of colorectal surgery patients were sent to the members of the DGAV, DGK and OEGCH using the online survey tool SurveyMonkey®. Descriptive data analysis was performed using Microsoft Excel. RESULTS: While some of the FT measures have already been routinely adopted in clinical practice (e.g. minimally invasive surgical approach, early mobilization and diet buildup), for other components there are discrepancies between current recommendations and present implementation (e.g. the use of local nerve blocks to provide opioid-sparing analgesia or the use of abdominal drains). CONCLUSION: The implementation of the FT concept in Austria and Germany is still in need of improvement. Particularly regarding the use of abdominal drains and postoperative analgesia, there is a tendency to stick to traditional structures. To overcome the issues with FT implementation, the development of an evidence-based S3 guideline for perioperative care, followed by the founding of a surgical working group to conduct a structured education and certification process, may lead to significant improvements in perioperative patient care.

Endoscopic Stricturoplasty with Linear Stapler: An Efficient Alternative for the Refractory Rectal Anastomotic Stricture.

INTRODUCTION: Symptomatic anastomotic stricture is a rare but major complication after left-sided colorectal surgery. Hydraulic balloon dilatation is the first-line treatment in cases where the complication occurs, but 20% of patients present with refractory strictures after multiple sessions. Endoscopic stricturoplasty with the use of a linear stapler is a novel therapeutic alternative for those difficult cases. MATERIALS AND METHODS: We identified all patients in our department who underwent endoscopic stricturoplasty with a linear stapler between 2004 and 2022. The technical, periinterventional, and follow-up data of the patients were retrospectively analyzed. RESULTS: We identified nine patients who fulfilled our inclusion criteria. The procedure was technically possible in eight cases, whereas in one case, the anatomy of the anastomosis did not allow for a correct placement of the stapler. All patients with a technically successful procedure were relieved from their symptoms and could have their ostomy reversed. There was no periprocedural morbidity and mortality. Two patients presented with a recurrent stricture eight and 26 months after the initial stricturoplasty, and the procedure was successfully repeated in both cases. CONCLUSIONS: Endoscopic stricturoplasty is a feasible, safe, and minimally invasive alternative for the treatment of refractory anastomotic strictures in the distal colon and rectum for patients with a suitable anatomy.

Three-year survival and distribution of lymph node metastases in gastric cancer following neoadjuvant chemotherapy: results from a European randomized clinical trial.

BACKGROUND: Adequate lymphadenectomy is an important step in gastrectomy for cancer, with a modified D2 lymphadenectomy being recommended for advanced gastric cancers. When assessing a novel technique for the treatment of gastric cancer, lymphadenectomy should be non-inferior. The aim of this study was to assess completeness of lymphadenectomy and distribution patterns between open total gastrectomy (OTG) and minimally invasive total gastrectomy (MITG) in the era of peri-operative chemotherapy. METHODS: This is a retrospective analysis of the STOMACH trial, a randomized clinical trial in thirteen hospitals in Europe. Patients were randomized between OTG and MITG for advanced gastric cancer after neoadjuvant chemotherapy. Three-year survival, number of resected lymph nodes, completeness of lymphadenectomy, and distribution patterns were examined. RESULTS: A total of 96 patients were included in this trial and randomized between OTG (49 patients) and MITG (47 patients). No difference in 3-year survival was observed, this was 57.1% in OTG group versus 46.8% in MITG group (P = 0.186). The mean number of examined lymph nodes per patient was 44.3 ± 16.7 in the OTG group and 40.7 ± 16.3 in the MITG group (P = 0.209). D2 lymphadenectomy of 71.4% in the OTG group and 74.5% in the MITG group was performed according to the surgeons; according to the pathologist compliance to D2 lymphadenectomy was 30% in the OTG group and 36% in the MITG group. Tier 2 lymph node metastases (stations 7-12) were observed in 19.6% in the OTG group versus 43.5% in the MITG group (P = 0.024). CONCLUSION: No difference in 3-year survival was observed between open and minimally invasive gastrectomy. No differences were observed for lymph node yield and type of lymphadenectomy. Adherence to D2 lymphadenectomy reported by the pathologist was markedly low.

Personalized checkpoint acupuncture can reduce postoperative pain after abdominal surgery-a STRICTA-conform pilot study.

BACKGROUND: Optimal pain management is one of the core elements of Enhanced Recovery After Surgery (ERAS®) protocols and remains a challenge. Acupuncture (AC) is an effective treatment for various pain conditions. Systematic and personalized allocation of acupoints may be decisive for efficacy. METHODS: Based on the predominant pressure sensitivity of six gastrointestinal (GI) checkpoints (G1-G6), we devised a method to detect personalized patterns of pain and a corresponding set of acupoints. We performed a single AC treatment with semi-permanent needles and assessed the visual analogue scale (VAS) score, pain threshold based on pressure algometry (PA), and temperature changes on abdominal skin areas before and 5 min after AC. RESULTS: Between April and June 2021, thirty-eight patients were prospectively included in this pilot study. The mean reduction in subjective pain sensation as assessed by VAS was 86%, paralleled by an augmentation of the pain threshold as measured by PA by 64%. A small but significant increase in the skin temperature was observed above the abdominal surface. These effects were independent of the type of surgery. CONCLUSION: Checkpoint acupuncture may be a complementary tool for postoperative pain management. Further investigations are needed to explore this analgesic effect.

Cognitive and motor skill competence are different: Results from a prospective randomized trial using virtual reality simulator and educational video in laparoscopic cholecystectomy.

BACKGROUND AND PURPOSE: Cognitive transfer represents an important issue in surgical education. It is essential for the acquisition of competence, such as decision making and error avoidance. This randomized study aims to compare the effectivity of cognitive transfer by observing the surgery versus using modern virtual reality simulators for learning a laparoscopic cholecystectomy. METHOD: This was a prospective, randomized, single centre study. 40 medical students from a university hospital, a tertiary care teaching institution, were enrolled. After a short introduction of laparoscopic cholecystectomy, they were randomized into two groups (video group and simulator group). In the video group, participants watched the step-by-step educational video twice. In the simulator group, participants underwent training using the virtual reality simulator, including tutorial procedural tasks of laparoscopic cholecystectomy as well as a complete cholecystectomy on the simulator. After the training, cognitive competence including decision making and error awareness was assessed using a questionnaire. RESULTS: In the most critical step of laparoscopic cholecystectomy, "Dissection in Calot's triangle", as well as in the aspect of planning next step, the video group was superior significantly (P = 0.038 and P = 0.04). No significant differences concerning the recognition of critical anatomical structures, choosing the necessary instruments as well as error awareness were found. CONCLUSIONS: Learning by watching a high-quality educational video is more effective in acquiring the cognitive competence to combine learned single tasks. Traditional learning means as watching educational videos and modern, sophisticated VRS should be deployed complementarily to establish cognitive and motor competencies separately.

Adipose-Derived Mesenchymal Stem Cells Protect Endothelial Cells from Hypoxic Injury by Suppressing Terminal UPR In Vivo and In Vitro.

Adipose-derived stem cells (ASCs) have been used as a therapeutic intervention for peripheral artery disease (PAD) in clinical trials. To further explore the therapeutic mechanism of these mesenchymal multipotent stromal/stem cells in PAD, this study was designed to test the effect of xenogeneic ASCs extracted from human adipose tissue on hypoxic endothelial cells (ECs) and terminal unfolded protein response (UPR) in vitro and in an atherosclerosis-prone apolipoprotein E-deficient mice (ApoE-/- mice) hindlimb ischemia model in vivo. ASCs were added to Cobalt (II) chloride-treated ECs; then, metabolic activity, cell migration, and tube formation were evaluated. Fluorescence-based sensors were used to assess dynamic changes in Ca2+ levels in the cytosolic- and endoplasmic reticulum (ER) as well as changes in reactive oxygen species. Western blotting was used to observe the UPR pathway. To simulate an acute-on-chronic model of PAD, ApoE-/- mice were subjected to a double ligation of the femoral artery (DLFA). An assessment of functional recovery after DFLA was conducted, as well as histology of gastrocnemius. Hypoxia caused ER stress in ECs, but ASCs reduced it, thereby promoting cell survival. Treatment with ASCs ameliorated the effects of ischemia on muscle tissue in the ApoE-/- mice hindlimb ischemia model. Animals showed less muscle necrosis, less inflammation, and lower levels of muscle enzymes after ASC injection. In vitro and in vivo results revealed that all ER stress sensors (BIP, ATF6, CHOP, and XBP1) were activated. We also observed that the expression of these proteins was reduced in the ASCs treatment group. ASCs effectively alleviated endothelial dysfunction under hypoxic conditions by strengthening ATF6 and initiating a transcriptional program to restore ER homeostasis. In general, our data suggest that ASCs may be a meaningful treatment option for patients with PAD who do not have traditional revascularization options.

Comparison of Tumour-Specific Phenotypes in Human Primary and Expandable Pancreatic Cancer Cell Lines.

There is an ongoing need for patient-specific chemotherapy for pancreatic cancer. Tumour cells isolated from human tissues can be used to predict patients' response to chemotherapy. However, the isolation and maintenance of pancreatic cancer cells is challenging because these cells become highly vulnerable after losing the tumour microenvironment. Therefore, we investigated whether the cells retained their original characteristics after lentiviral transfection and expansion. Three human primary pancreatic cancer cell lines were lentivirally transduced to create expandable (Ex) cells which were then compared with primary (Pri) cells. No obvious differences in the morphology or epithelial-mesenchymal transition (EMT) were observed between the primary and expandable cell lines. The two expandable cell lines showed higher proliferation rates in the 2D and 3D models. All three expandable cell lines showed attenuated migratory ability. Differences in gene expression between primary and expandable cell lines were then compared using RNA-Seq data. Potential target drugs were predicted by differentially expressed genes (DEGs), and differentially expressed pathways (DEPs) related to tumour-specific characteristics such as proliferation, migration, EMT, drug resistance, and reactive oxygen species (ROS) were investigated using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. We found that the two expandable cell lines expressed similar chemosensitivity and redox-regulatory capability to gemcitabine and oxaliplatin in the 2D model as compared to their counterparts. In conclusion, we successfully generated expandable primary pancreatic cancer cell lines using lentiviral transduction. These expandable cells not only retain some tumour-specific biological traits of primary cells but also show an ongoing proliferative capacity, thereby yielding sufficient material for drug response assays, which may provide a patient-specific platform for chemotherapy drug screening.

Current Therapy of Cryptoglandular Anal Fistula: Gold Standards and Alternative Methods. / Therapie der kryptograndulären Analfisteln: aktuelle Goldstandards und Alternativen.

Cryptoglandular anal fistulas are one of the most common colorectal diseases and occur with an incidence of about 20/100,000. Anal fistulas are defined as an inflammatory junction between the anal canal and the perianal skin. They develop from an abscess or chronic infection of the anorectum. Surgical treatment of the disease is the method of choice. Even when treating an acute abscess, its cause should be sought at the same time. If there is a connection to the anal canal without affecting relevant parts of the sphincter muscles, primary fistulotomy should be performed. If larger parts of the sphincter muscle are involved, the insertion of a seton drain is usually useful. There are essentially two recommendations for the elective treatment of cryptoglandular anal fistulas. Distal fistulas should be excised, with the proviso that as little sphincter muscle as possible is sacrificed. In the case of highly proximally located and complex fistulas, sphincter-preserving surgical techniques should be used. In this case, the method of choice is the mucosal or advancement flap. Alternatively, clips, fibrin injections, fistula plugs, fistula ligatures, or laser-based procedures are described in the literature. In the case of intermediate fistulas, a fistulectomy with primary sphincter reconstruction can be useful. Every operation is carried out as a compromise between definitive healing of the fistula and a potential risk to the patient's continence. It is often difficult to make a reliable prognosis about the continence function to be expected postoperatively. In addition to the fistula morphology, particular attention should be paid to whether previous proctological operations have already been performed, the gender of the patient, and whether there are pre-existing sphincter dysfunctions. Since the surgeon's expertise plays a decisive role in the success of the treatment, the procedure should be carried out in a specialist proctological centre, especially in the case of complex fistulas or in the case of a condition after previous operations. In addition to the classic procedures, such as fistulectomy or the plastic fistula closure, this article examines alternative methods and their areas of application.

[Robotic Left Hepatectomy Using the Glissonean Pedicle Approach for the Treatment of Caroli's Syndrome]. / Roboter-assistierte Hemihepatektomie links mittels Glissonean pedicle approach bei Caroli Syndrom.

BACKGROUND: Caroli's syndrome is a rare disease characterised by non-obstructive dilation of intrahepatic bile ducts, hepatic fibrosis, and an increased risk of developing cholangiocarcinoma. Minimally invasive liver resection has recently been increasingly adopted for the treatment of patients with localised Caroli's syndrome. However, robot-assisted liver resection for the treatment of Caroli's syndrome has not been published. MATERIALS AND METHODS: We report a case of a 72-year-old Asian female who was referred to our hospital with multifocal cystic dilation of liver segments II, III, and IV. She had no family history of congenital cysts. Her past medical history was uneventful except for an open appendectomy. The liver function tests were normal, with a negative echinococcus serology test. On MRI, the biliary anatomy at the hilum and right liver appeared to be regular. Therefore, a robotic left hepatectomy was carried out for the unilobar involvement of Caroli's syndrome using the Da Vinci Xi-system. RESULTS: We performed a Glissonean pedicle approach while preserving the caudate lobe. After removing surgical adhesions from the anterior abdominal wall using robotic scissors, a routine cholecystectomy was performed. An aberrant left hepatic artery arising from the left gastric artery was clipped and divided. The left portal pedicle was controlled after lowering the hilar plate. The ischemic demarcation line on the liver surface was followed after clamping the left pedicle, and parenchymal dissection was performed using Maryland bipolar forceps. A Pringle manoeuvre was not applied. The left pedicle and the left hepatic vein were transected using a GIA stapling device while the middle hepatic vein was preserved. Indocyanin green fluorescence imaging confirmed adequate perfusion of the remnant liver tissue including the caudate lobe. The specimen was placed in an extraction bag and removed via a Pfannenstiel incision. The total operation time was 239 min, including a total blood loss of 100 ml. The postoperative course was uneventful. The patient was discharged on postoperative day 5. On 6 months follow-up, the patient had normal liver function and no signs of recurrent disease. CONCLUSION: Robotic left hepatectomy using an extrahepatic Glissonean pedicle approach is technically feasible.