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Background: Insufficient remnant liver volume (RLV) after the resection of hepatic malignancy could lead to liver failure and mortality. Portal vein ligation (PVL) prior to hepatectomy is subsequently introduced to increase the remnant liver volume and improve the outcome of hepatic malignancy. IL-22 has previously been reported to promote liver regeneration, while facilitating tumor development in the liver via Steap4 upregulation. Here we performed PVL in mouse models to study the role of IL-22 in liver regeneration post-PVL., Methods: Liver weight and volume was measured via magnetic resonance imaging (MRI). Immunohistochemistry for Ki67 and hepatocyte growth factor (HGF) was performed. IL-22 was analyzed by flow cytometry and quantitative polymerase chain reaction (qPCR) was used for acquisition of Il-33, Steap4, Fga, Fgb and Cebpd . To analyze signaling pathways, mice with deletion of STAT3 and a neutralizing antibody for IL-22 were used., Results: The remnant liver weight and volume increased over time after PVL. Additionally, we found that liver regenerative molecules, including Ki67 and HGF, were significantly increased in remnant liver at day 3 post-PVL, as well as IL-22. Administration of IL-22 neutralizing antibody could reduce Ki67 expression after PVL. The upregulation of IL-22 after PVL was mainly derived from innate cells. IL-22 blockade resulted in lower levels of IL-33 and Steap4 in the remnant liver, which was also the case in mice with deletion of STAT3, the main downstream signaling molecule of IL-22, in hepatocytes., Conclusion: IL-22 promotes liver regeneration after PVL. Thus, a combination of IL-22 supplementation and Steap4 blockade could potentially be applied as a novel therapeutic approach to boost liver regeneration without facilitating tumor progression after PVL., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background and Aims: Alterations in liver histology influence the liver's capacity to regenerate, but the relevance of each of the different changes in rapid liver growth induction is unknown. This study aimed to analyze the influence of the degree of histological alterations during the first and second stages on the ability of the liver to regenerate., Methods: This cohort study included data obtained from the International ALPPS Registry between November 2011 and October 2020. Only patients with colorectal liver metastases were included in the study. We developed a histological risk score based on histological changes (stages 1 and 2) and a tumor pathology score based on the histological factors associated with poor tumor prognosis., Results: In total, 395 patients were included. The time to reach stage 2 was shorter in patients with a low histological risk stage 1 (13 vs 17 days, P ˂0.01), low histological risk stage 2 (13 vs 15 days, P <0.01), and low pathological tumor risk (13 vs 15 days, P <0.01). Regarding interval stage, there was a higher inverse correlation in high histological risk stage 1 group compared to low histological risk 1 group in relation with future liver remnant body weight ( r =-0.1 and r =-0.08, respectively), and future liver remnant ( r =-0.15 and r =-0.06, respectively)., Conclusions: ALPPS is associated with increased histological alterations in the liver parenchyma. It seems that the more histological alterations present and the higher the number of poor prognostic factors in the tumor histology, the longer the time to reach the second stage., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Metastasis is a cancer-related systemic disease and is responsible for the greatest mortality rate among cancer patients. Interestingly, the interaction between the immune system and cancer cells seems to play a key role in metastasis formation in the target organ. However, this complex network is only partially understood. We previously found that IL-22 produced by tissue resident iNKT17 cells promotes cancer cell extravasation, the early step of metastasis. Based on these data, we aimed here to decipher the role of IL-22 in the last step of metastasis formation. We found that IL-22 levels were increased in established metastatic sites in both human and mouse. We also found that Th22 cells were the key source of IL-22 in established metastasis sites, and that deletion of IL-22 in CD4+ T cells was protective in liver metastasis formation. Accordingly, the administration of a murine IL-22 neutralizing antibody in the establishment of metastasis formation significantly reduced the metastatic burden in a mouse model. Mechanistically, IL-22-producing Th22 cells promoted angiogenesis in established metastasis sites. In conclusion, our findings highlight that IL-22 is equally as important in contributing to metastasis formation at late metastatic stages, and thus, identify it as a novel therapeutic target in established metastasis., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2023 The Author(s). Published with license by Taylor & Francis Group, LLC.)

Background: The immune system plays a pivotal role in cancer progression. Interleukin 22 binding protein (IL-22BP), a natural antagonist of the cytokine interleukin 22 (IL-22) has been shown to control the progression of colorectal cancer (CRC). However, the role of IL-22BP in the process of metastasis formation remains unknown., Methods: We used two different murine in vivo metastasis models using the MC38 and LLC cancer cell lines and studied lung and liver metastasis formation after intracaecal or intrasplenic injection of cancer cells. Furthermore, IL22BP expression was measured in a clinical cohort of CRC patients and correlated with metastatic tumor stages., Results: Our data indicate that low levels of IL-22BP are associated with advanced (metastatic) tumor stages in colorectal cancer. Using two different murine in vivo models we show that IL-22BP indeed controls the progression of liver but not lung metastasis in mice., Conclusions: We here demonstrate a crucial role of IL-22BP in controlling metastasis progression. Thus, IL-22 might represent a future therapeutic target against the progression of metastatic CRC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Giannou, Kempski, Zhang, Lücke, Shiri, Zazara, Belios, Machicote, Seeger, Agalioti, Tintelnot, Sagebiel, Tomczak, Bauditz, Bedke, Kocheise, Mercanoglu, Fard-Aghaie, Giorgakis, Lykoudis, Pikouli, Grass, Wahib, Bardenhagen, Brunswig, Heumann, Ghadban, Duprée, Tachezy, Melling, Arck, Stringa, Gentilini, Gondolesi, Nakano, Thomson, Perez, Li, Mann, Izbicki, Gagliani, Maroulis and Huber.)

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., Competing Interests: Declaration of interests S.K. declares honoraria from GSK, BMS, Novartis, and TCR2, Inc.; license fees from TCR2, Inc. and Carina Biotech; and research support from TCR2, Inc., Plectonic GmbH, Tabby Therapeutics, and Arcus Biosciences., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Repeated liver resections for the recurrence of colorectal liver metastasis (CRLM) are described as safe and have similar oncological outcomes compared to first hepatectomy. Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) is performed in patients with conventionally non-resectable CRLM. Repeated resections after ALPPS has not yet been described., Methods: Patients that underwent repeated liver resection in recurrence of CRLM after ALPPS were included in this study. The primary endpoint was morbidity and secondary endpoints were mortality, resection margin and survival., Results: Thirty patients were included in this study. During ALPPS, most of the patients had classical split (60%, n = 18) and clearance of the FLR (77%, n = 23). Hepatic recurrence was treated with non-anatomical resection (57%, n = 17), resection combined with local ablation (13%, n = 4), open ablation (13%, n = 4), segmentectomy (10%, n = 3) or subtotal segmentectomy (7%, n = 2). Six patients (20%) developed complications (10% minor complications). No post-hepatectomy liver failure or perioperative mortality was observed. One-year patient survival was 87%. Five patients received a third hepatectomy., Conclusion: Repeated resections after ALPPS for CRLM in selected patients are safe and feasible with low morbidity and no mortality. Survival seems to be comparable with repeated resections after conventional hepatectomy., (Copyright © 2021 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Intraoperative fluorescence angiography and cholangiography with indocyanine green (ICG) are increasingly used in routine hepatobiliary surgery. Its usage is manifold. It improves and facilitates navigation especially in minimal invasive and robotic surgery and therefore increases the safety of the surgical intervention. In laparoscopic cholecystectomy for example, the bileduct anatomy can be easily visualized, even in complicated cholecystitis or anatomical variants without being too time consuming. ICG fluorescence also enables the visualization of vascular structures and perfusion. Anatomical liver resections, for example in hepatocellular carcinoma (HCC), can be performed easily as liver segments and territories can be identified. Anatomical resection is becoming more important, e.g. in the treatment of HCC. Another useful application is the intraoperative detection of bile leakages after liver resection. In particular, the intraoperative control of a biliodigestive anastomosis is possible with ICG fluorescence cholangiography and therefore reduces morbidity. Even primary and secondary liver tumors can be detected with ICG fluorescence. Whereas well-differentiated HCCs homogeneously take up ICG, poorly differentiated HCCs and metastases do not: however, in these cases the adjacent liver parenchyma stores ICG more intensively than healthy liver tissue, which creates a ring-like fluorescence pattern. To conclude, the use of ICG fluorescence in hepatobiliary surgery is diverse but in Germany it is still at the beginning compared to other countries.

Purpose: Pancreatic surgery is still thought as a challenging field even for experienced hepatobilliary (HPB) surgeons and high volume tertiary centers. The purpose of this study was to present the results (mortality and morbidity) of pancreatic surgery in a high volume center, in operations performed solely by inexperienced surgeons (two 6th year residents and a HPB fellow) under the supervision of expert surgeons on the field., Methods: Forty-one consecutive patients who underwent curative-intent pancreatic resection with a modified pancreaticojejunostomy between January 2010 and December 2014 at Asklepios Hospital Barmbek, Germany, were identified from our institutional computer-based database. Two 6th year residents and an HPB-fellow performed all pancreatic anastomoses under the instructions of an experienced surgeon. Perioperative outcomes were recorded and analyzed., Results: Median postoperative length of stay for all patients was 15 days (IQR:7-31). In the first 90 postoperative days, the postoperative mortality rate was 0% and morbidity rate reached 39%. Reoperation was required in 1 patient (2.44%). However, no reoperation was performed for pancreatic anastomotic failure. No postoperative hemorrhage requiring interventional procedure or reoperation occurred in any patient., Conclusions: The outcomes of pancreatic surgery performed by less experienced surgeons are satisfactory. The instructions of an expert surgeon in a high volume hospital definitely secures a favorable outcome after pancreatic surgery with lower mortality and morbidity rates compared with current literature trends.

Background: Despite recent advances in multimodality and multidisciplinary treatment of colorectal liver metastases, many patients suffer from extensive bilobar disease, which prevents the performance of a single procedure due to an insufficient future liver remnant (FLR). We present a novel indication for associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) as a "liver-first" approach when inadequate FLR was faced preoperatively, in a patient with extensive bilobar liver metastatic disease of colon cancer origin., Case Presentation: A 51-year-old lady was referred to our center due to a stage IV colon cancer with extensive bilobar liver disease and synchronous colon obstruction. During the multidisciplinary tumor board, it was recommended to proceed first in a palliative loop colostomy (at the level of transverse colon) operation and afterwards to offer her palliative chemotherapy. After seven cycles of chemotherapy, the patient was re-evaluated by CT scans that revealed an excellent response (>30%), but the metastatic liver disease was still considered inoperable. Moreover, with the completion of 12 cycles, the indicated restaging process showed further response. Subsequent to a thorough review by the multidisciplinary team, it was decided to proceed to the ALPPS procedure as a feasible means to perform extensive or bilobar liver resections, combined with a decreased risk of tumor progression in the interim., Conclusions: All in all, ALPPS can offer a feasible but surgically demanding liver-first approach with satisfactory short-term results in selected patients. Larger studies are mandatory to evaluate short- and long-term results of the procedure on survival, morbidity, and mortality.

Background: In 1942, Stout described tumors which derive from Zimmerman's pericytes and suggested the term hemangiopericytoma (HPC). These tumors, which are often highly vascularized, pose difficulties in the surgical management regarding blood loss and complete resection. Therefore, preoperative management seems to be an essential part in dealing with these issues., Case Presentation: We present a 70-year-old female patient with a large HPC in the pelvis. Preoperative embolization of the tumor was performed, and 2 weeks after the intervention, we completely resected the tumor with minimal blood loss., Conclusion: In which cases do we need preoperative treatment, especially emboliziation of hemangiopericytomas/solid fibrous tumors (SFT)? Although preoperative embolizations of tumors are now commonly undertaken, as for now, neither a clear statement nor a standardized approach has been given or developed. The purpose of this article is to provide our experience with preoperative embolization and to start a new discussion concerning a standardized approach.

Pancreatic injury is uncommon, accounting for less than 7% of penetrating and 5% of blunt abdominal trauma. Blunt isolated pancreatic trauma in football has been rarely described in the literature and its diagnosis, detection and treatment still remains a challenge. We report a case of a young adult with an isolated complete rupture of the pancreatic body due to a blunt abdominal trauma during a football game. In order to preserve the pancreas and therefore retain function, we performed a terminolateral pancreaticojejunostomy. The postoperative course of the patient was uneventful. The diagnosis of isolated injuries of the pancreas in blunt abdominal trauma can be difficult and challenging and due to the nature of the game physicians should be highly alerted when dealing with football players sustaining abdominal trauma., (2014 BMJ Publishing Group Ltd.)