Quantification of Indocyanine Green Fluorescence Imaging in General, Visceral and Transplant Surgery.

Near-infrared (NIR) imaging with indocyanine green (ICG) has proven to be useful in general, visceral, and transplant surgery. However, most studies have performed only qualitative assessments. Therefore, a systematic overview of all studies performing quantitative indocyanine green evaluation in general, visceral, and transplant surgeries should be conducted. Free term and medical subject heading (MeSH) term searches were performed in the Medline and Cochrane databases until October 2022. The main categories of ICG quantification were esophageal surgery (24.6%), reconstructive surgery (24.6%), and colorectal surgery (21.3%). Concordantly, anastomotic leak (41%) was the main endpoint, followed by the assessment of flap perfusion (23%) and the identification of structures and organs (14.8%). Most studies examined open surgery (67.6%) or laparoscopic surgery (23.1%). The analysis was mainly carried out using manufacturer software (44.3%) and open-source software (15.6%). The most frequently analyzed parameter was intensity over time for blood flow assessment, followed by intensity alone or intensity-to-background ratios for structure and organ identification. Intraoperative ICG quantification could become more important with the increasing impact of robotic surgery and machine learning algorithms for image and video analysis.

Hybrid laparoscopic versus fully robot-assisted minimally invasive esophagectomy: an international propensity-score matched analysis of perioperative outcome.

BACKGROUND: Currently, little is known regarding the optimal technique for the abdominal phase of RAMIE. The aim of this study was to investigate the outcome of robot-assisted minimally invasive esophagectomy (RAMIE) in both the abdominal and thoracic phase (full RAMIE) compared to laparoscopy during the abdominal phase (hybrid laparoscopic RAMIE). METHODS: This retrospective propensity-score matched analysis of the International Upper Gastrointestinal International Robotic Association (UGIRA) database included 807 RAMIE procedures with intrathoracic anastomosis between 2017 and 2021 from 23 centers. RESULTS: After propensity-score matching, 296 hybrid laparoscopic RAMIE patients were compared to 296 full RAMIE patients. Both groups were equal regarding intraoperative blood loss (median 200 ml versus 197 ml, p = 0.6967), operational time (mean 430.3 min versus 417.7 min, p = 0.1032), conversion rate during abdominal phase (2.4% versus 1.7%, p = 0.560), radical resection (R0) rate (95.6% versus 96.3%, p = 0.8526) and total lymph node yield (mean 30.4 versus 29.5, p = 0.3834). The hybrid laparoscopic RAMIE group showed higher rates of anastomotic leakage (28.0% versus 16.6%, p = 0.001) and Clavien Dindo grade 3a or higher (45.3% versus 26.0%, p < 0.001). The length of stay on intensive care unit (median 3 days versus 2 days, p = 0.0005) and in-hospital (median 15 days versus 12 days, p < 0.0001) were longer for the hybrid laparoscopic RAMIE group. CONCLUSIONS: Hybrid laparoscopic RAMIE and full RAMIE were oncologically equivalent with a potential decrease of postoperative complications and shorter (intensive care) stay after full RAMIE.

Struggle in the bubble - a prospective study on the effect of remote learning and distance education on confidence in practical surgical skills acquired during COVID-19.

BACKGROUND: The coronavirus disease (COVID-19) has significantly changed healthcare systems and medical education. Universities were required to develop innovative curricula based on remote and distance education to continue medical education. This prospective questionnaire-based study aimed to investigate the impact of COVID-19-associated remote learning on the surgical training of medical students. METHODS: A 16-item questionnaire-based survey was distributed to medical students at the University Hospital of Münster before and after a surgical skills laboratory (SSL). Two cohorts were included: summer semester 2021 (COV-19), with rigorous social-distancing restrictions requiered SSL to be remotely, and winter semester 2021 (postCOV-19), in which the SSL was provided as a face-to-face, hands-on course. RESULTS: Both, cohorts showed a significant improvement in self-assessment of pre- and post-course confidence. While no significant difference in the average gain in self-confidence for sterile working was observed between the two cohorts, improvement in self-confidence was significantly higher in the COV-19 cohort regarding skin suturing and knot tying (p < 0.0001). However the average improvement regarding history and physical was significantly higher in the postCOV-19 cohort (p < 0.0001). In subgroup analysis, gender-associated differences varied in the two cohorts and were not related to specific subtasks, while age-stratified analysis revealed superior results for younger students. CONCLUSION: The results of our study underline the usability, feasibility, and adequacy of remote learning for the surgical training of medical students. The on-site distance education version, presented in the study, allows the continuing of hands-on experience in a safe environment in compliance with governmental social-distancing restrictions.

Worldwide Techniques and Outcomes in Robot-assisted Minimally Invasive Esophagectomy (RAMIE): Results From the Multicenter International Registry.

OBJECTIVE: This international multicenter study by the Upper GI International Robotic Association aimed to gain insight in current techniques and outcomes of RAMIE worldwide. BACKGROUND: Current evidence for RAMIE originates from single-center studies, which may not be generalizable to the international multicenter experience. METHODS: Twenty centers from Europe, Asia, North-America, and South-America participated from 2016 to 2019. Main endpoints included the surgical techniques, clinical outcomes, and early oncological results of ramie. RESULTS: A total of 856 patients undergoing transthoracic RAMIE were included. Robotic surgery was applied for both the thoracic and abdominal phase (45%), only the thoracic phase (49%), or only the abdominal phase (6%). In most cases, the mediastinal lymphadenectomy included the low paraesophageal nodes (n=815, 95%), subcarinal nodes (n = 774, 90%), and paratracheal nodes (n = 537, 63%). When paratracheal lymphadenectomy was performed during an Ivor Lewis or a McKeown RAMIE procedure, recurrent laryngeal nerve injury occurred in 3% and 11% of patients, respectively. Circular stapled (52%), hand-sewn (30%), and linear stapled (18%) anastomotic techniques were used. In Ivor Lewis RAMIE, robot-assisted hand-sewing showed the highest anastomotic leakage rate (33%), while lower rates were observed with circular stapling (17%) and linear stapling (15%). In McKeown RAMIE, a hand-sewn anastomotic technique showed the highest leakage rate (27%), followed by linear stapling (18%) and circular stapling (6%). CONCLUSION: This study is the first to provide an overview of the current techniques and outcomes of transthoracic RAMIE worldwide. Although these results indicate high quality of the procedure, the optimal approach should be further defined.

Microsurgical training course for clinicians and scientists: a 10-year experience at the Münster University Hospital.

BACKGROUND: Microsurgical techniques are an important part of clinical and experimental research. Here we present our step-by-step microsurgery training course developed at the Münster University Hospital. The goal of this course was to create a short, modular curriculum with clearly described and easy to follow working steps in accordance with the Guidelines for Training in Surgical Research in Animals by the Academy of Surgical Research. METHODS: Over the course of 10 years, we conducted an annual 2.5 day (20 h) microsurgical training course with a total of 120 participants. RESULTS: Prior to the course, 90% of the participants reported to have never performed a microanastomosis before. During the 10 years a total of 84.2% of the participants performed microanastomoses without assistance, 15% required assistance and only 0.8% failed. CONCLUSIONS: Our step-by-step microsurgery training course gives a brief overview of the didactic basics and the organization of a microsurgical training course and could serve as a guide for teaching microsurgical skills. During the 2.5-day curriculum, it was possible to teach, and for participants to subsequently perform a microsurgical anastomosis. The independent reproducibility of the learned material after the course is not yet known, therefore further investigations are necessary. With this step-by-step curriculum, we were able to conduct a successful training program, shown by the fact that each participant is able to perform microvascular anastomoses on a reproducible basis.

Robotic Liver Surgery - Current Standards and Future Perspectives.

BACKGROUND: Robotic liver surgery is emerging as the future of minimal invasive surgery. The robotic surgical system offers a stable camera platform, elimination of physiologic tremor, augmented surgical dexterity as well as improved ergonomics because of a seated operating position. Due to the theoretical advantages of the robotic assisted system, complex liver surgery might be an especially interesting indication for a robotic approach since it demands delicate tissue dissection, precise intracorporeal suturing as well as difficult parenchymal transection with subsequent need for meticulous hemostasis and biliostasis. MATERIAL AND METHODS: An analysis of English and German literature on open, laparoscopic and robotic liver surgery was performed and this review provides a general overview of the existing literature along with current standards and aims to specifically point out future directions of robotic liver surgery. RESULTS: Robotic liver surgery is safe and feasible compared to open and laparoscopic surgery, with improved short-term postoperative outcomes and at least non-inferior oncological outcomes. CONCLUSION: In complex cases including major hepatectomies, extended hepatectomies with biliary reconstruction and difficult segmentectomies of the posterior-superior segments, robotic surgery appears to emerge as a reasonable alternative to open surgery rather than being an alternative to laparoscopic procedures.

Cytomegalovirus Treatment Strategy After a Liver Transplant: Preemptive Therapy or Prophylaxis for Cytomegalovirus Seropositive Donor and Recipient.

OBJECTIVES: Cytomegalovirus infections cause the most frequent infection after solid-organ transplant. While Cytomegalovirus prophylaxis is established in high-risk patients (donor+/ recipient-), data on Cytomegalovirus prophylaxis in other serostatus constellation are rare. The aim of this study was to evaluate the influence of Cytomegalovirus treatment strategy after a liver transplant (preemptive therapy vs general prophylaxis) in the largest group of patients: Cytomegalovirus seropositive donor and recipient. MATERIALS AND METHODS: Forty-seven seropositive recipients of seropositive donor liver transplants (D+/R+, 2005-2012) were included in this retrospective study. Twenty-one patients received oral valganciclovir as Cytomegalovirus prophylaxis 100 days after transplant. Cytomegalovirus infection and Cytomegalovirus disease were monitored during the first 6 months. RESULTS: A Cytomegalovirus infection could be detected in 4 out of 47 patients (8.5%), including Cytomegalovirus disease in 2 patients (Cytomegalovirus pneumonia and Cytomegalovirus-CNS disease). Three of these patients received no Cytomegalovirus prophylaxis (P = .408). Eight patients developed a graft failure; this occurred more frequently among patients without Cytomegalovirus prophylaxis (P = .044). Patients receiving Cytomegalovirus prophylaxis more often developed leukopenia. No difference was seen regarding the number of platelets, hemoglobin, and creatinine. CONCLUSIONS: Cytomegalovirus prophylaxis can minimize the risk of Cytomegalovirus reactivation and graft failure. However, disadvantages of the prophylaxis as leukopenia should be considered.

Prognostic factors for kidney allograft survival in the Eurotransplant Senior Program.

BACKGROUND: The shortage of organ donors has led to the introduction of the Eurotransplant Senior Program (ESP) to optimize the allocation of kidneys from elderly donors by age-matching. In the face of a rapidly aging population, identification of prognostic factors for kidney allograft survival within the ESP population will be of enormous significance. MATERIAL AND METHODS: Donor and recipient data from 89 patients transplanted under the ESP protocol between 1999 and 2007 were retrospectively analyzed. Data were correlated with initial graft function, graft survival, acute rejection episodes, serum creatinine levels, glomerular filtration rates, and patient survival using univariate and multivariate analysis. Maximum follow-up was 5 years. RESULTS: Cold ischemia time (CIT) >16 hours, body mass index (BMI) ≥25 kg/m(2), and kidney re-transplantation were significant risk factors for delayed graft function (DGF). Odds ratio for primary non-function was significantly increased with prolonged CIT, BMI ≥25 kg/m(2), and duration of renal replacement therapy >69 months. CIT >15 h, DGF, and kidney re-transplantation were associated with poor graft survival (P<0.05). CONCLUSIONS: Risk reduction (e.g., aiming at CIT <15 h) and close surveillance of patients at risk appear to be crucial for allograft survival in the ESP.

Course of a HBsAg positive liver transplantation in a hepatitis B and D virus coinfected recipient.

The increasing demand for transplantation has led to consideration of liver grafts from donors exposed to hepatitis B virus (HBV). Six transplantations of liver grafts from hepatitis B surface antigen (HBsAg) positive donors have been reported; two recipients suffered from HBV/HDV (hepatitis Delta virus) coinfection and were followed up for 10-12 months. Here, we report a 56 months follow-up of a HBV/HDV-coinfected recipient of a HBsAg positive liver graft. Posttransplant combination prophylaxis consisted of hepatitis immunoglobulin, lamivudine and adefovir dipivoxil. HBsAg remained positive during stable posttransplant follow-up and subclinical HDV reinfection with low replication rate was detected at 1 month. Pegylated interferon therapy was introduced after documentation of histological evidence of mild chronic hepatitis, but without virological response after 48 weeks. Finally, antiviral treatment was switched to tenofovir disoproxil fumarate. More than 50 months posttransplant the recipient revealed clinical symptoms of decompensated liver cirrhosis and has been relisted for liver transplantation. In conclusion HBsAg positive liver grafts in HBsAg positive recipients with HDV coinfection may result in virological recurrence and rapid development of liver cirrhosis.

Role of angiotensin-1 receptor blockade in cirrhotic liver resection.

BACKGROUND: The regeneration capacity of cirrhotic livers might be affected by angiotensin-1 (AT1) receptors located on hepatic stellate cells (HSC). The effect of AT1 receptor blockade on microcirculation, fibrosis and liver regeneration was investigated. MATERIALS AND METHODS: In 112 Lewis rats, cirrhosis was induced by repetitive intraperitoneal injections of CCl(4) . Six hours, 3, 7 and 14 days after partial hepatectomy or sham operation, rats were sacrificed for analysis. Animals were treated with either vehicle or 5 mg/kg body weight losartan pre-operatively and once daily after surgery by gavage. Microcirculation and portal vein flow were investigated at 6 h. The degree of cirrhosis was assessed by Azan Heidenhein staining, activation of HSC by desmin staining, apoptosis by ssDNA detection and liver regeneration by Ki-67 staining. Changes in expression of various genes important for liver regeneration and fibrosis were analysed at 6 h and 3 days. Haemodynamic parameters and liver enzymes were monitored. RESULTS: Losartan treatment increased sinusoidal diameter, sinusoidal blood flow and portal vein flow after partial hepatectomy (P<0.05), but not after sham operation. AT1 receptor blockade resulted in increased apoptosis early after resection. HSC activation was reduced and after 7 days, a significantly lower degree of cirrhosis in resected animals was observed. Losartan increased the proliferation of hepatocytes at late time-points and of non-parenchymal cells early after partial hepatectomy (P<0.05). Tumour necrosis factor (TNF)-α was significantly upregulated at 6 h and stem cell growth factor (SCF) was downregulated at 3 days (P<0.05). CONCLUSION: Losartan increased hepatic blood flow, reduced HSC activation and liver fibrosis, but interfered with hepatocyte proliferation after partial hepatectomy in cirrhotic livers.

Influence of heme oxygenase-1 on microcirculation after kidney transplantation.

BACKGROUND: Cytoprotective proteins, such as heme oxygenase-1 (HO-1), play a decisive role in ischemia-reperfusion injury during kidney transplantation. The aim of this study was to investigate the impact of heme oxygenase-1 on microcirculation and on ischemia-reperfusion injury in an isogenic kidney transplantation rat model. MATERIALS AND METHODS: Seventy male Lewis rats were distributed into three groups. In Group 1(control), the kidneys were only mobilized. In Groups 2 and 3, bilateral nephrectomy was performed, and a kidney from another Lewis rat was orthotopically transplanted on the left side. The donor animals in Group 3 received preconditioning with the HO-1 inductor hemin. 24 h after reperfusion graft function and morphology were examined. Microcirculation was investigated by in vivo microscopy of the renal surface 1 h after reperfusion. RESULTS: HO-1 preconditioning led to significantly lower serum creatinine and serum urea, as well as less histological damage and inducible nitric oxide synthase expression. Microcirculation was improved by a significant enlargement of the vascular diameter and an increase of the capillary flow. CONCLUSIONS: Treatment with hemin improves microcirculation by induction of HO-1 and reduces ischemia-reperfusion injury after kidney transplantation. HO-1 induction was shown to be a promising approach in the preconditioning of donor kidneys.

Impact of rapamycin on liver regeneration.

The remarkable capacity of the liver to regenerate after injury and the prospects of organ self-renewal have attracted much interest in the understanding and modulation of the underlying molecular events. We investigated the effect of mammalian target of rapamycin (mTOR) inhibitor rapamycin (RAPA) on liver by correlating intravital microscopy, immunohistochemistry, and reverse transcriptase polymerase chain reaction in a rat model of 2/3 hepatectomy. RAPA significantly retarded proliferation of hepatocytes, endothelial cells, and hepatic stellate cells (HSCs) mostly between days 2 and 4 after hepatectomy and downregulated major cytokines and growth factors (tumor necrosis factor alpha, hepatocyte growth factor, platelet-derived growth factor, platelet-derived growth factor receptor, insulin-like growth factor-1, transforming growth factor beta 1) important for liver regeneration. These effects were almost absent at later time points. RAPA also had a transient, but broad effect on angiogenesis, and impaired sinusoidal density as well as mRNA levels of vascular endothelial growth factor, vascular endothelial growth factor receptor 1, vascular endothelial growth factor receptor 2, and angiopoietin-1. Activation of HSC was also transiently suppressed as observed by smooth muscle protein 1 alpha protein expression and intercellular adhesion molecule-1 mRNA levels. The rate of apoptosis in liver was significantly increased by RAPA between day 3 and day 7. The effect of RAPA on liver repair, angiogenesis, and HSC activation is confined to the phase of active cell proliferation. This transient effect might allow further exploration of mTOR inhibitors in clinical situations that involve liver regeneration, and seems to have implications beyond immunosuppression.

Organ-specific metastatic tumor cell adhesion and extravasation of colon carcinoma cells with different metastatic potential.

Adhesive and invasive characteristics appear to be crucial for organ-specific metastasis formation. Using intravital microscopy we investigated the relation between the metastatic potential of colon carcinoma cells and their adhesive and invasive behavior during early steps of metastasis within microvasculatures of rat liver, lung, intestine, skin, muscle, spleen, and kidney in vivo. Colon carcinoma cells with low (HT-29P), intermediate (KM-12C), and high (HT-29LMM, KM-12L4) metastatic potential were injected into nude or Sprague-Dawley rats. Initial interactions with host organ microvasculatures were semiquantitatively analyzed throughout 20 to 30 minutes. Circulating cells passed microvessels in all observed organs without size restriction. All cell lines showed high adhesion rates, independent from their metastatic potential, within liver and lung but very rarely in other organs. Diameters of involved microvessels were larger than diameters of adherent tumor cells. Cell extravasation of highly metastatic HT-29LMM and KM-12L4 cells into liver parenchyma was significantly higher compared to low metastatic cells (P<0.05). Our results indicate that colon carcinoma cells can arrest in target organs without size restriction. Cell adhesion of circulating tumor cells occurred in metastatic target organs only, likely attributable to specific interactions. Migration into target organs correlated with their metastatic potential.

Microsurgical training curriculum for learning kidney and liver transplantation in the rat.

During the education of the next generation of scientists in experimental research, careful instruction in surgical techniques is of major importance. This applies in particular to complicated microsurgical models, which require a structured teaching concept with clearly laid-down working steps and adequate didactic resources. Transplantations in rats are undoubtedly among the most difficult models in experimental surgery. Because completely sutured orthotopic liver transplantation and kidney transplantation have been practiced for many years in our Surgical Research Unit, techniques must be transmitted to future generations. A microsurgical training program has been set up with the aim of being efficient, transparent, and motivating. Simply learning-by-doing in the sense of "laissez-faire" is ineffective and costly. Our training program is based on "three-phase didactics," in which the learning targets are presented in sequence and are clearly defined. This report is intended to give a brief overview of the principal transplantation models and to serve as a guide for teaching these models.