Tissue resident iNKT17 cells facilitate cancer cell extravasation in liver metastasis via interleukin-22.

During metastasis, cancer cells invade, intravasate, enter the circulation, extravasate, and colonize target organs. Here, we examined the role of interleukin (IL)-22 in metastasis. Immune cell-derived IL-22 acts on epithelial tissues, promoting regeneration and healing upon tissue damage, but it is also associated with malignancy. Il22-deficient mice and mice treated with an IL-22 antibody were protected from colon-cancer-derived liver and lung metastasis formation, while overexpression of IL-22 promoted metastasis. Mechanistically, IL-22 acted on endothelial cells, promoting endothelial permeability and cancer cell transmigration via induction of endothelial aminopeptidase N. Multi-parameter flow cytometry and single-cell sequencing of immune cells isolated during cancer cell extravasation into the liver revealed iNKT17 cells as source of IL-22. iNKT-cell-deficient mice exhibited reduced metastases, which was reversed by injection of wild type, but not Il22-deficient, invariant natural killer T (iNKT) cells. IL-22-producing iNKT cells promoting metastasis were tissue resident, as demonstrated by parabiosis. Thus, IL-22 may present a therapeutic target for prevention of metastasis.

Perioperative management of pancreatic exocrine insufficiency-evidence-based proposal for a paradigm shift in pancreatic surgery.

BACKGROUND: Despite exocrine pancreatic insufficiency (EPI) being a significant consequence of pancreatic surgery, there is still no consensus on its perioperative management. This study aimed to evaluate unselective pancreatic enzyme replacement therapy (PERT). METHODS: A prospective, observational study of patients undergoing partial pancreatectomy was conducted. EPI status was assessed pre- and postoperatively, based on three fecal-elastase measurements each. Characteristic symptoms were evaluated by questionnaire. In 85 post-surgical patients, the subjective burden of PERT was measured. RESULTS: 101 patients were followed prospectively. Preoperative EPI screening was available for 83 patients, of which 48% were diagnosed with preexisting EPI. Of those patients with regular exocrine function, 54% developed EPI de novo; this rate being higher following pancreatic head resections (72%) compared to left-sided pancreatectomies (LP) (20%) (p = 0.016). Overall postoperative EPI prevalence was significantly greater following pancreatic head resections (86%) than LP (33%) (p < 0.001). Only young and female patients described a significant burden related to PERT. CONCLUSION: For all patients undergoing pancreatic head resection PERT should be considered beginning prior to surgery, due to the subgroup's high EPI rate and the comparatively low burden of PERT. Patients with LP are at lower risk and should be pre- and postoperatively screened and supplemented accordingly.

Robotic-assisted repair of incisional hernia-early experiences of a university robotic hernia program and comparison with open and minimally invasive sublay technique (eMILOS).

PURPOSE: With robotic surgical devices, an innovative tool has stepped into the arena of minimally invasive hernia surgery. It combines the advantages of open (low recurrence rates and ability to perform complex procedure such as transverse abdominis release) and laparoscopic surgery (low rate of wound and mesh infections, less pain). However, a superiority to standard minimally invasive procedures has not yet been proven. We present our first experiences of robotic mesh repair of incisional hernias and a comparison of our results with open and minimally invasive sublay techniques. METHODS: A retrospective analysis of all patients who underwent robotic-assisted mesh repair (RAHR) for incisional hernia between April and November 2022 (RAHR group) and patients who underwent open sublay (Sublay group) or eMILOS hernia repair (eMILOS group) between January 2018 and November 2022 was carried out. Patients in the RAHR group were matched 1:2 to patients in the Sublay group by propensity score matching. Patient demographics, preoperative hernia characteristics and cause of hernia, intraoperative variables, and postoperative outcomes were evaluated. Furthermore, a subgroup analysis of only midline hernia was performed. RESULTS: A total of 21 patients received robotic-assisted incisional hernia repair. Procedures performed included robotic retro-muscular hernia repair (r-RMHR, 76%), with transverse abdominis release in 56% of the cases. In one patient, r-RHMR was combined with robotic inguinal hernia repair. Two patients (10%) were operated with total extraperitoneal technique (eTEP). Robotic-assisted transabdominal preperitoneal hernia repair (r-TAPP) was performed in three patients (14%). Median (range) operating time in the RAHR group was significantly longer than in the sublay and eMILOS group (291 (122-311) vs. 109.5 (48-270) min vs. 123 (100-192) min, respectively, p < 0.001). The meshes applied in the RAHR group were significantly compared to the sublay (mean (SD) 529 ± 311 cm2 vs. 356 ± 231, p = 0.037), but without a difference compared to the eMILOS group (mean (SD) 596 ± 266 cm2). Median (range) length of hospital stay in the RAHR group was significantly shorter compared to the Sublay group (3 (2-7) vs. 5 (1-9) days, p = 0.032), but not significantly different to the eMILOS group. In short term follow-up, no hernia recurrence was observed in the RAHR and eMILOS group, with 9% in the Sublay group. The subgroup analysis of midline hernia revealed very similar results. CONCLUSION: Our data show a promising outcome after robotic-assisted incisional hernia repair, but no superiority compared to the eMILOS technique. However, RAHR is a promising technique especially for complex hernia in patients with relevant risk factors, especially immunosuppression. Longer follow-up times are needed to accurately assess recurrence rates, and large prospective trials are needed to show superiority of robotic compared to standard open and minimally invasive hernia repair.

Liver surgery-specific complications are an independent factor influencing long-term survival following major hepatectomy.

BACKGROUND: A severity grading system for liver surgery-specific complications, given the acronym FABIB, has been standardized to increase the feasibility and comparability of academic reports in liver surgery. Whether the FABIB score is associated with long-term survival following major hepatectomy has not been previously investigated. METHODS: 297 consecutive patients who had undergone major hepatectomy between 2012 and 2019 were recruited. The postoperative complications were documented according to the FABIB system and, for comparison purposes, Clavien-Dindo classification. Their influence on 90-day mortality and long-term survival was analyzed retrospectively. RESULTS: Taking the relevant confounders into account, the FABIB score was a robust factor associated with long-term survival after major hepatectomy: patients with high FABIB scores (≥6) had a 2.415-fold higher risk of death compared to patients with low FABIB scores (≤2) (P = 0.002). In contrast to that, the Clavien-Dindo Classification (grade III + IV vs. grade I + II) was not associated with survival in our cohort (P = 0.873). CONCLUSION: Liver surgery-specific complications, measured by the FABIB system, impact long-term survival after major hepatectomy independent of relevant confounders. We propose the FABIB score as a composite endpoint for randomized controlled trials and a quality assessment tool in liver surgery.

ALPPS for Locally Advanced Intrahepatic Cholangiocarcinoma: Did Aggressive Surgery Lead to the Oncological Benefit? An International Multi-center Study.

BACKGROUND: ALPPS is found to increase the resectability of primary and secondary liver malignancy at the advanced stage. The aim of the study was to verify the surgical and oncological outcome of ALPPS for intrahepatic cholangiocarcinoma (ICC). METHODS: The study cohort was based on the ALPPS registry with patients from 31 international centers between August 2009 and January 2018. Propensity score matched patients receiving chemotherapy only were selected from the SEER database as controls for the survival analysis. RESULTS: One hundred and two patients undergoing ALPPS were recruited, 99 completed the second stage with median inter-stage duration of 11 days. The median kinetic growth rate was 23 ml/day. R0 resection was achieved in 87 (85%). Initially high rates of morbidity and mortality decreased steadily to a 29% severe complication rate and 7% 90-day morbidity in the last 2 years. Post-hepatectomy liver failure remained the main cause of 90-day mortality. Multivariate analysis revealed insufficient future liver remnant at the stage-2 operation (FLR2) to be the only risk factor for severe complications (OR 2.91, p = 0.02). The propensity score matching analysis showed a superior overall survival in the ALPPS group compared to palliative chemotherapy (median overall survival: 26.4 months vs 14 months; 1-, 2-, and 3-year survival rates: 82.4%, 70.5% and 39.6% vs 51.2%, 21.4% and 11.3%, respectively, p < 0.01). The survival benefit, however, was not confirmed in the subgroup analysis for patients with insufficient FLR2 or multifocal ICC. CONCLUSION: ALPPS showed high efficacy in achieving R0 resections in locally advanced ICC. To get the most oncological benefit from this aggressive surgery, ALPPS would be restricted to patients with single lesions and sufficient FLR2.

The decrease of BMI and albumin levels influences the rate of anastomotic leaks in patients following reconstruction after emergency diverting esophagectomy.

OBJECTIVES: Diverting esophagectomies in cases of benign esophageal perforations remain rare but potentially life saving procedures. Usually, an esophagostoma and a feeding jejunostomy or gastrostomy are created, and patients are given time to recover from the emergency situation. However, little is known about morbidity and mortality as well as the optimal timing for a staged reconstruction. METHODS: Patients with benign esophageal perforations were selected from our retrospective database. Perforations in esophageal malignancies were excluded to avoid bias on patients' general outcome. Clinical parameters and especially, the influence of the nutritional status indicated by the BMI (Body Mass Index) as well as serum albumin levels (g/l) were analyzed. RESULTS: A total of 24 patients with diverting esophagectomies were identified. Of these, 13 (54.2%) patients received a staged reconstruction after a median of 143.0 days. Patients presenting for their staged reconstruction demonstrated a significantly decreased level of their BMI (p = 0.026) as compared to their prior hospitalization. Interestingly, the relative decrease of BMI (8.5 kg/m2 vs. 4.3 kg/m2) and albumin levels (6.5 g/l vs. 0.0 g/l) was significantly different in patients with or without anastomotic leaks between both surgeries (p = 0.021; p = 0.034, respectively). In addition, higher rates of overall complications were associated with an increased rate of malnutrition. CONCLUSIONS: The relative amount of malnutrition indicated by BMI or serum albumin levels influences the rate of anastomotic leaks and general complications in patients with staged reconstruction after diverting esophagectomy for non-malignant esophageal perforations. Hence, reconstruction should be done as fast as possible to reduce the amount of malnutrition and a frequent assessment of the nutritional status must be done during recovery from the emergency surgery.

AI-based digital histopathology for perihilar cholangiocarcinoma: A step, not a jump.

Introduction: Perihilar cholangiocarcinoma (PHCC) is a rare malignancy with limited survival prediction accuracy. Artificial intelligence (AI) and digital pathology advancements have shown promise in predicting outcomes in cancer. We aimed to improve prognosis prediction for PHCC by combining AI-based histopathological slide analysis with clinical factors. Methods: We retrospectively analyzed 317 surgically treated PHCC patients (January 2009-December 2018) at the University Hospital of Essen. Clinical data, surgical details, pathology, and outcomes were collected. Convolutional neural networks (CNN) analyzed whole-slide images. Survival models incorporated clinical and histological features. Results: Among 142 eligible patients, independent survival predictors were tumor grade (G), tumor size (T), and intraoperative transfusion requirement. The CNN-based model combining clinical and histopathological features demonstrates proof of concept in prognosis prediction, limited by histopathological complexity and feature extraction challenges. However, the CNN-based model generated heatmaps assisting pathologists in identifying areas of interest. Conclusion: AI-based digital pathology showed potential in PHCC prognosis prediction, though refinement is necessary for clinical relevance. Future research should focus on enhancing AI models and exploring novel approaches to improve PHCC patient prognosis prediction.

Risk Factor Analysis for Developing Major Complications Following Esophageal Surgery-A Two-Center Study.

BACKGROUND: Esophagectomy carries a high risk of morbidity and mortality compared to other major surgeries. With the aim of creating an easy-to-use clinical preoperative risk assessment tool and to validate previously described risk factors for major complications following surgery, esophagectomies at two tertiary medical centers were analyzed. METHODS: A total of 450 patients who underwent esophagectomy for esophageal carcinoma at the University Medical Centre, Hamburg, or at the Medical Center University Duisburg-Essen, Germany (January 2008 to January 2020) were retrospectively analyzed. Epidemiological and perioperative data were analyzed to identify the risk factors that impact major complication rates. The primary endpoint of this study was to determine the incidence of major complications. RESULTS: The mean age of the patients was 63 years with a bimodal distribution. There was a male predominance across the cohort (81% vs. 19%, respectively). Alcohol abuse (p = 0.0341), chronic obstructive pulmonary disease (p = 0.0264), and cardiac comorbidity (p = 0.0367) were associated with a significantly higher risk of major complications in the multivariate analysis. Neoadjuvant chemotherapy significantly reduced the risk of major postoperative complications (p < 0.0001). CONCLUSIONS: Various patient-related risk factors increased the rate of major complications following esophagectomy. Patient-tailored prehabilitation programs before esophagectomy that focus on minimizing these risk factors may lead to better surgical outcomes and should be analyzed in further studies.

Minimally invasive intrathoracic negative-pressure therapy and flexible thoracoscopy (FlexVATS) for patients with pleural empyema.

To determine whether a new surgical method using a flexible endoscope (FlexVATS) to perform sparing debridement and apply negative-pressure therapy without extensive decortication may be an alternative treatment option for empyema. Surgical treatment of pleural empyema is associated with considerable postoperative complications and mortality rates, and alternative treatment options are being explored to improve patient outcomes. This was a prospective case series. Seventeen consecutive patients treated with FlexVATS between February 2021 and August 2022 were included in the study. Only patients for whom FlexVATS was the first therapeutic intervention for pleural empyema were included. Treatment success, defined as infection resolution, was the primary endpoint of the study. The secondary endpoints were length of hospital stay, 90-day mortality, and empyema cavity volume reduction. Patients who had previously been treated for pleural empyema by either drainage or surgery were excluded. The trial was performed as a single-centre study at a tertiary medical centre in Germany. In total, 17 patients with pleural empyema were included in the study. The median (IQR) duration of vacuum treatment was 15 days (8-35 days). Twelve of the 17 (71%) patients were successfully treated, and a significant reduction in the empyema cavity volume was observed. 41% of the dressing changes were performed outside the operating room. Compared with a historic cohort of conventionally treated patients (decortication via VATS or thoracotomy), the 90-day mortality rates tended to be lower without reaching statistical significance. Three patients (18%) died in hospital during treatment. No negative pressure-therapy-related complications were observed. FlexVATS therapy is a promising alternative therapy for both healthy and debilitated patients with pleural empyema. Larger randomised trials are required to validate this treatment option.

Intrathoracic vacuum therapy for the therapy of pleural empyema-a systematic review and analysis of the literature.

Background: Pleural empyema is a serious and potentially deadly disease leading to a significant burden on health care systems. Conservative and surgical treatment results remain poor, with high morbidity and mortality rates. Patients with pleural empyema are often multimorbid and poor candidates for surgery. Therefore, it appears sensible to explore alternative, less invasive treatment options. Recently, the well-established vacuum sponge therapy has been adopted in the treatment of pleural infections. The goal of this systematic review was to identify the existing literature and reported results of vacuum therapy for pleural empyema. Methods: A systematic search of MEDLINE and the Cochrane Database was performed independently by two reviewers using predefined criteria according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. In addition, abstracts from selected conference proceedings were screened and reference scanning of the search results was performed. Single case reports were excluded. Results: Fourteen studies met the selection criteria and were reviewed. A total of 165 patients were treated with vacuum therapy in the studies reviewed. 61.2% of the patients had pleural empyema secondary to thoracic surgery. In 71.5% of the patients, vacuum therapy was applied following open window thoracostomy (OWT). Mortality rates of 0-33% were reported for vacuum therapy after OWT and 0-9.3% for vacuum therapy without OWT. Length of hospital stay (LOHS) ranged from 44-217 days for patients after OWT and could not be analysed for vacuum therapy without OWT due to lacking data. Median treatment time was 7-14 days. Treatment related complications were rare overall. Success rates defined as infection resolution were high irrespective of previous treatment and cause of empyema. Conclusions: The current literature shows that pleural vacuum therapy is a promising, safe, and feasible treatment alternative to existing treatment modalities for pleural empyema. However, the evidence for vacuum therapy without OWT is poor, and further data, optimally prospective or randomised control trials comparing the conventional surgical approach of video-assisted thoracoscopic surgery (VATS) decortication and minimally invasive vacuum therapy, are needed.

Transplantation for Primary Sclerosing Cholangitis: Outcomes and Recurrence.

Primary sclerosing cholangitis (PSC) is characterized by inflammation of the whole bile duct system. Liver transplantation is only approved as a curative treatment when it comes to end-stage liver disease. The aim of our study was to assess morbidity, survival rates and PSC recurrence and the impact of donor characteristics in long-term follow-up. This was an IRB-approved retrospective study. A total of 82 patients were identified who were transplanted between January 2010 and December 2021 for PSC. Among these patients, 76 adult liver transplant PSC patients and their corresponding donors were analyzed. Three pediatric cases and three adult patients with a follow-up within <1 year were excluded from further analysis. Median (range) age was 47 years (18-70) with a median (range) lab-MELD of 16 (7-40). Median (range) ICU and hospital stays were 4.6 days (0-147) and 21 days (1-176), respectively. The majority of patients suffered from Crohn's disease or ulcerative colitis as a concomitant comorbidity (65.8%). The ten-year survival rate was 74.6%. A significantly lower lab-MELD score was identified in patients surviving for > 10 years (15 vs. 22, p = 0.004). Most patients (65%) passed in the first year following transplantation, with primary non-function (PNF), sepsis and arterial thrombosis being the most common causes of death. Donor characteristics did not affect patient survival. Patients with PSC show excellent 10-year survival rates. While the lab-MELD score significantly affected long term outcomes, donor characteristics did not affect survival rates.

Completion of FLOT Therapy, Regardless of Tumor Regression, Significantly Improves Overall Survival in Patients with Esophageal Adenocarcinoma.

Esophageal cancer is the eighth most common cancer worldwide, with poor prognosis and high mortality. The combination of surgery and systemic therapy provide the best chances for long-term survival. The purpose of this study was to analyze the impact of the FLOT protocol on the overall survival of patients following surgery for esophageal adenocarcinoma, with a focus on the patients who did not benefit in terms of pathological remission from the neoadjuvant therapy. A retrospective analysis of all the patients who underwent esophagectomies from 2012 to 2017 for locally advanced adenocarcinomas of the esophagus at a tertiary medical center was performed. The results show that the completion of systemic therapy, regardless of the tumor regression grading, had a significant positive impact on the overall survival. The patients with complete regression and complete systemic therapy showed the best outcomes. Anastomotic insufficiency did not negatively impact the long-term survival, while complications of the systemic therapy led to significantly reduced overall survival. We conclude that adjuvant systemic therapy should, when possible, always be completed, regardless of the tumor regression, following an esophagectomy.

Advanced Robotic Surgery: Liver, Pancreas, and Esophagus - The State of the Art?

BACKGROUND: The trend in performing robotic-assisted operations in visceral surgery has been increasing in the last decade, also reaching the challenging field of hepatic, pancreatic, and esophageal surgery. Nevertheless, solid data about advantages and disadvantages of the robotic approach are still missing. The aim of this review is to analyze the benefit and impact of robotic surgery in the field of hepatic, pancreatic, and esophageal surgery, focusing on the comparison with the conventional laparoscopic or open approach. SUMMARY: The well-known advantages of laparoscopic surgery in comparison to the open approach are also valid for robotic surgery, with the addition of a 3D-view camera, wristed instrumentation, and an ergonomic console. On the other hand, the use of a robotic system leads to longer operating time and higher costs. Randomized controlled trials comparing the robotic approach with the laparoscopic one are still missing. KEY MESSAGE: Recent meta-analyses show promising results of the usage of robotic systems in advanced surgical procedures, like hepatic, pancreatic, and esophageal resections. Further randomized studies are needed to validate the postulated benefit.

Oesophageal Adenocarcinomas: Where Do We Stand Today?

Oesophageal cancers (oesophageal squamous cell carcinomas and adenocarcinomas) haven been responsible for more than one million deaths worldwide in 2018 [...].

Successful Use of the Recanalized Remnant Umbilical Vein as a Patch Graft for Venous Reconstruction in Abdominal Surgery.

Various approaches have been described for the reconstruction of the portal vein (PV), superior mesenteric vein (SMV), and the inferior vena cava (IVC). We present the use of the recanalized remnant umbilical vein in various settings including transplantation, major liver resection, and pancreatic surgery. We retrospectively analyzed four cases, in which a recanalized remnant umbilical vein was used for vascular reconstruction. The graft harvesting, size of the graft, technique of application, and short-term results of vascular patency were studied. A recanalized umbilical vein was successfully harvested from the ligamentum teres hepatis in all patients with 5 cm (median, range 3-7 cm) in length and 1.3 cm (median, range 1.0-1.8 cm) in width. The preparation of the vein was technically feasible and took no more than 5 min in each patient. All grafts were used as a patch for venous reconstruction. In three cases, the graft was used for the reconstruction of the PV or SMV. In one patient, the graft was used to repair a large defect of the IVC. All vascular reconstructions were considered as successful as no bleeding or thrombosis was observed postoperatively. The remnant umbilical vein is a reliable native autologous graft. We found that it is feasible to use this graft as a patch for the reconstruction of the IVC, PV, and SMV.

Unobtrusive Nocturnal Heartbeat Monitoring by a Ballistocardiographic Sensor in Patients with Sleep Disordered Breathing.

Sleep disordered breathing (SDB) is known for fluctuating heart rates and an increased risk of developing arrhythmias. The current reference for heartbeat analysis is an electrocardiogram (ECG). As an unobtrusive alternative, we tested a sensor foil for mechanical vibrations to perform a ballistocardiography (BCG) and applied a novel algorithm for beat-to-beat cycle length detection. The aim of this study was to assess the correlation between beat-to-beat cycle length detection by the BCG algorithm and simultaneously recorded ECG. In 21 patients suspected for SDB undergoing polysomnography, we compared ECG to simultaneously recorded BCG data analysed by our algorithm. We analysed 362.040 heartbeats during a total of 93 hours of recording. The baseline beat-to-beat cycle length correlation between BCG and ECG was r s = 0.77 (n = 362040) with a mean absolute difference of 15 ± 162 ms (mean cycle length: ECG 923 ± 220 ms; BCG 908 ± 203 ms). After filtering artefacts and improving signal quality by our algorithm, the correlation increased to r s = 0.95 (n = 235367) with a mean absolute difference in cycle length of 4 ± 72 ms (ECG 920 ± 196 ms; BCG 916 ± 194 ms). We conclude that our algorithm, coupled with a BCG sensor foil provides good correlation of beat-to-beat cycle length detection with simultaneously recorded ECG.