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.

Preoperative Computed Tomography Volumetry and Graft Weight Estimation of Left Lateral Segment in Pediatric Living Donor Liver Transplant.

OBJECTIVES: Liver volumetry based on a computed tomography scan is widely used to estimate liver volume before any liver resection, especially before living donorliver donation. The 1-to-1 conversion rule for liver volume to liver weight has been widely adopted; however, debate continues regarding this approach. Therefore, we analyzed the relationship between the left-lateral lobe liver graft volume and actual graft weight. MATERIALS AND METHODS: This study retrospectively included consecutive donors who underwent left lateral hepatectomy for pediatric living donor liver transplant from December 2008 to September 2020. All donors were healthy adults who met the evaluation criteria for pediatric living donor liver transplant and underwent a preoperative contrast-enhanced computed tomography scan. Manual segmentation of the leftlateral liverlobe for graft volume estimation and intraoperative measurement of an actual graft weight were performed. The relationship between estimated graft volume and actual graft weight was analyzed. RESULTS: Ninety-four living liver donors were included in the study. The mean actual graft weight was ~283.4 ± 68.5 g, and the mean graft volume was 244.9 ± 63.86 mL. A strong correlation was shown between graft volume and actual graft weight (r = 0.804; P < .001). Bland-Altman analysis revealed an interobserver agreement of 38.0 ± 97.25, and intraclass correlation coefficient showed almost perfect agreement(r = 0.840; P < .001). The conversion formula for calculating graft weight based on computed tomography volumetry was determined based on regression analysis: 0.88 × graft volume + 41.63. CONCLUSIONS: The estimation of left liver graft weight using only the 1-to-1 rule is subject to measurable variability in calculated graft weights and tends to underestimate the true graft weight. Instead, a different, improved conversion formula should be used to calculate graft weight to more accurately determine donor graft weight-to-recipient body weightratio and reduce the risk of underestimation of liver graft weightin the donor selection process before pediatric living donor liver transplant.

Lymph Node Staging in Perihilar Cholangiocarcinoma: The Key to the Big Picture.

Klatskin tumors have a bad prognosis despite aggressive therapy. The role and extent of lymph node dissection during surgery is a matter of discussion. This retrospective study analyzes our current experience of surgical treatments in the last decade. Patients and Methods: A retrospective single-center analysis of patients (n = 317) who underwent surgical treatment for Klatskin tumors. Univariable and multivariable logistic regression and Cox proportional analysis were performed. The primary endpoint was to investigate the role of lymph node metastasis for patient survival after complete tumor resection. The secondary endpoint was the prediction of lymph node status and long-term survival from preoperatively available parameters. Results: In patients with negative resection margins, a negative lymph node status was the prognosis-determining factor with a 1-, 3-, and 5-year survival rate of 87.7%, 37%, and 26.4% compared with 69.5%, 13.9%, and 9.3% for lymph-node-positive patients, respectively. Multivariable logistic regression for complete resection and negative lymph node status demonstrated only Bismuth type 4 (p = 0.01) and tumor grading (p = 0.002) as independent predictors. In multivariate Cox regression analysis, independent predictors of survival after surgery were the preoperative bilirubin level (p = 0.03), intraoperative transfusion (p = 0.002), and tumor grading (G) (p = 0.001). Conclusion: Lymph node dissection is of utmost importance for adequate staging in patients undergoing surgery for perihilar cholangiocarcinoma. In spite of extensive surgery, long-term survival is clearly associated with the aggressiveness of the disease.

Optimization of the preoperative requirements of blood units for the surgical treatment of extra-abdominal soft tissue sarcoma: the TRANSAR score.

BACKGROUND AND OBJECTIVES: Excessive preoperative blood orders frequently occur during the preoperative planning of resections of sarcomas. We aimed to develop a prediction score model that would be able to identify a patient cohort in which the cross-matching could be safely evaded. PATIENTS AND METHODS: We retrospectively analyzed data of 309 consecutive patients with extra-abdominal soft tissue sarcomas treated between September 2012 and December 2014. Scorecard scores for variables were calculated and summarized to a total score that can be used for risk stratification. The score was used in a logistic regression model. Results of the optimized model were described as a receiver operating characteristic curve. RESULTS: Preoperative units of red blood cells were requested for 206 (66.7%) patients, of which only 31 (10%) received them. Five parameters were identified with high predictive power. In the visualized barplot, there was an increased risk of blood transfusion with a higher score of TRANSAR. CONCLUSION: A TRANSAR score is a new tool that can predict the probability of transfusion for patients with sarcoma. This may reduce the number of preoperative cross-matching and blood product ordering and associated costs without compromising patient care.

Fully automated preoperative liver volumetry incorporating the anatomical location of the central hepatic vein.

The precise preoperative calculation of functional liver volumes is essential prior major liver resections, as well as for the evaluation of a suitable donor for living donor liver transplantation. The aim of this study was to develop a fully automated, reproducible, and quantitative 3D volumetry of the liver from standard CT examinations of the abdomen as part of routine clinical imaging. Therefore, an in-house dataset of 100 venous phase CT examinations for training and 30 venous phase ex-house CT examinations with a slice thickness of 5 mm for testing and validating were fully annotated with right and left liver lobe. Multi-Resolution U-Net 3D neural networks were employed for segmenting these liver regions. The Sørensen-Dice coefficient was greater than 0.9726 ± 0.0058, 0.9639 ± 0.0088, and 0.9223 ± 0.0187 and a mean volume difference of 32.12 ± 19.40 ml, 22.68 ± 21.67 ml, and 9.44 ± 27.08 ml compared to the standard of reference (SoR) liver, right lobe, and left lobe annotation was achieved. Our results show that fully automated 3D volumetry of the liver on routine CT imaging can provide reproducible, quantitative, fast and accurate results without needing any examiner in the preoperative work-up for hepatobiliary surgery and especially for living donor liver transplantation.

Multi-center living liver donor quality of life survey up to 20 years after donor hepatectomy and association with surgical outcomes.

BACKGROUND: We implemented a multicenter interview with the donors to investigate Quality of Life (QoL) up to 20 years following donation. METHODS: Data were collected retrospectively. Complications were graded by Dindo-Clavien classification. RESULTS: Median follow-up was 16.1 years. Out of 485 donors, 272 responded (56.1%). The majority (>90%) reported they are in excellent/good overall health and positive or no impact of donation on professional life. Length of stay (LOS) was associated with impact on professional life and return to baseline functionality (both p = 0.046). Major complication was not associated with current physical condition or return to baseline normalcy (p = 0.06). Seventy-five (27.5%) reported unsure or no to donate again. None of the parameters were associated with donation again response. Faster return to baseline functionality, and more positive impact on professional life were reported in the last decade, likely secondary to less complication rates (all p < 0.001). CONCLUSION: This the longest follow up reports after living liver donation among German and Turkish populations. Although subject to recall bias, LOS was associated with negative impact on professional life and return to baseline functionality. Regret feelings were higher than literature. These long-term effects should be incorporated into donor discussions.

Outcomes of right lobe donors with BMI≥30 for living donor liver transplantation.

BACKGROUND: Donor BMI above 30 is generally considered contraindication for donor hepatectomy. We compared the donor outcomes based on BMI threshold and weight loss. PATIENTS AND METHODS: All potential donors were identified and data were collected retrospectively. Steatosis was assessed based on liver-spleen Hounsfield unit difference and absolute liver intensity values. We compared BMI≥30 (n = 53) and BMI < 30 (n = 64) donor outcomes. Donors with weight loss (WL) prior to surgery were also analyzed separately. Complications were graded by Clavien-Dindo classification. RESULTS: All donors underwent open right donor hepatectomy. There was no difference between BMI≥30 and < 30 groups except female predominance in BMI≥30 group (P = .006). Both groups had similar rates of complication rates in all categories, similar remnant volume, operative time, length of stay and similar postoperative liver function recovery (all P > .05). On the other hand, donors with WL were more commonly male, had smaller graft size, and higher biliary complications rates compared to no-WL donors (all P < .05). Multivariate binary logistics regression analysis revealed no association between BMI or WL and outcomes. CONCLUSION: We demonstrate that donors with BMI≥30 have similar outcomes compared to BMI < 30 donors with our defined selection criterion, therefore BMI≥30 is not an absolute contraindication to donate right liver, provided that there is no significant steatosis and remnant liver is satisfactory. For potential overweight donors, WL down to BMI < 30 is a reasonable target. Higher biliary complication rates after WL should be investigated further.

Invasive Fungal Infections After Liver Transplantation: A Retrospective Matched Controlled Risk Analysis.

BACKGROUND Invasive fungal infections (IFI) are major risks for mortality after liver transplantation (LT). The aim of this study was to evaluate possible risk factors for the development of IFI after LT. MATERIAL AND METHODS All adult patients with IFI after LT between January 2012 and December 2016 at Essen University were identified. Pre-, intra-, and postoperative data were reviewed. These were compared to a 1-to-3 matched control group. Multinominal univariate and multivariate regression analyses were performed. RESULTS Out of the 579 adults who underwent LT, 33 (5.6%) developed postoperative IFI. Fourteen had invasive aspergillosis with 7 (50%) mortality, and 19 had Candida sepsis with 7 (37%) mortality. The overall mortality due to invasive fungal infections was 42%. Perfusion fluid contamination with yeast was detected in 5 patients (15%). Multivariate regression analyses showed that preoperative dialysis (OR=1.163; CI: 1.038-1.302), Eurotransplant donor risk index (OR=0.04; CI=0.003-0.519), length of hospital stay (OR=25.074; CI: 23.99-26.208), and yeast contamination of the preservation fluid (OR=47.8; CI: 4.77-478, 96) were associated with IFI in the Candida group, whereas duration of surgery (OR=1.013; CI: 1.005-1.022), ventilation hours (OR=0.993; CI=0.986-0.999), and days of postoperative dialysis (OR=1.195; CI: 1.048-1,362) were associated with IFI in the aspergillosis group. CONCLUSIONS Post-LT IFI had 42% mortality in our cohort. Prophylactic antifungal therapy should be expanded to broader risk groups as defined above.

Frailty as a predictive factor for survival after liver transplantation, especially for patients with MELD≤15-a prospective study.

INTRODUCTION: Frailty has been discussed as a predictor of morbidity and mortality for liver cirrhosis. The aim of our study is to evaluate the role of frailty in liver transplantation, particularly for patients with MELD scores < 15. METHODS: All patients listed for liver transplantation between September 2015 and November 2018 were prospectively included in the study. Frailty was assessed by Fried's frailty classification. Pre-, intra-, and postoperative data were prospectively recorded. Univariate and multivariate regression analyses were performed. The ethical approval of the institutional board review was obtained for the study. RESULTS: There were 114 patients included in the study, and their median MELD score was 16. Of these, 86 patients were defined as frail (75.4%). A total of 62 patients (54.4%) underwent liver transplantation, 11 (17.7%) died postoperatively, and 24 patients (21.0%) died while on the waitlist. All postoperative mortality cases were frail, and only 3 patients (12.5%) were non-frail in the waitlist mortality group. There were 14 patients who had MELD scores of <15 (58.3%). The overall survival of non-frail patients was significantly better than that of frail patients. The multivariate regression analyses identified frailty criteria, including unintended weight loss and low hand grip strength, and platelet count and being married or living in a solid partnership were prognostic factors for survival in all patients. CONCLUSION: The addition of frailty assessment can be beneficial for predicting mortality after liver transplantation, especially in patients with low MELD score. Frail patients on the waitlist have significant risk for mortality even with low MELD score.

Inner Abdominal Fat and Psoas Muscle as Predictive Factors for the Outcome After Liver Transplant.

OBJECTIVES: We analyzed the nutritional condition of liver transplant recipients and the body mass index, the inner abdominal fat tissue, the outer abdominal fat tissue, the psoas muscle size, and the psoas muscle index of the recipients and evaluated the effects of these factors on patient outcomes after liver transplant. MATERIALS AND METHODS: We included recipients of liver transplants from January 2009 to December 2018 who had computed tomography at our center < 3 months before transplant. Preoperative, intraoperative, and postoperative data were evaluated. Outer abdominal fat tissue, inner abdominal fat tissue, and psoas muscle area were measured on the computed tomography abdominal images. We used univariate and multi-variate regression analyses to evaluate the data. RESULTS: There were 265 patients; mean age was 54 years (SD, 13 years). The mean value for body mass index, calculated as weight in kilograms divided by height in meters squared, was 25 (SD, 5). The mean score for Model for End-Stage Liver Disease was 17 (SD, 6). All patients underwent orthotopic liver transplant by standard technique. After adjustment for multivariable analysis, the values for psoas muscle size and the psoas muscle index of the recipient were associated as independent factors for postoperative complications and duration of hospital stay. The survival rate at 1 year was 78.5%, and the rate of perioperative mortality was 16.6%. Independent factors associated with survival after liver transplant were inner abdominal fat tissue, etiology, and rate of major postoperative complications. CONCLUSIONS: Inner abdominal fat tissue, psoas muscle size, and the psoas muscle index are significantly associated with postoperative complications and/or survival after liver transplant. Our results suggest that these prognostic factors may be useful to optimize the selection of appropriate candidates for liver transplant.

Splenic Artery Transposition for Arterial Reconstruction in Living Donor Liver Transplantation.

PURPOSE: In living donor liver transplantation, poor compatibility of the recipient hepatic artery remains a technical challenge. Here, we analyzed our 14 years of experience with extra-anatomic hepatic artery reconstruction. METHODS: Between July 2004 and December 2018, there were 1063 liver transplantations at our center. All patients with an extra-anatomic hepatic artery reconstruction were identified. The gastroduodenal artery and the transposed splenic artery were the primary options for extra-anatomic arterial reconstruction. Patient characteristics, operative data, and post-transplant outcome were reviewed retrospectively. RESULTS: There were 22 patients with extra-anatomic hepatic artery reconstruction, 6 with gastroduodenal artery, and 16 with splenic artery. There were 2 major complications: 1 patient underwent early reoperation due to bleeding from the splenic artery trunk and another had an iatrogenic injury to the transposed splenic artery during conversion hepaticojejunostomy. Both were treated successfully with surgery. One patient died perioperatively due to sepsis. The 1- and 3-year graft survival rates of these 16 patients were 93.7% and 87.5%. CONCLUSION: If the hepatic arteries are not suitable for anastomosis, then we consider the gastroduodenal artery and the splenic artery to be the conduits of choice for extra-anatomic arterial reconstruction. The transposed splenic artery is very consistent, easily accessible, and offers adequate length and diameter for successful arterial anastomosis.

Fully automated body composition analysis in routine CT imaging using 3D semantic segmentation convolutional neural networks.

OBJECTIVES: Body tissue composition is a long-known biomarker with high diagnostic and prognostic value not only in cardiovascular, oncological, and orthopedic diseases but also in rehabilitation medicine or drug dosage. In this study, the aim was to develop a fully automated, reproducible, and quantitative 3D volumetry of body tissue composition from standard CT examinations of the abdomen in order to be able to offer such valuable biomarkers as part of routine clinical imaging. METHODS: Therefore, an in-house dataset of 40 CTs for training and 10 CTs for testing were fully annotated on every fifth axial slice with five different semantic body regions: abdominal cavity, bones, muscle, subcutaneous tissue, and thoracic cavity. Multi-resolution U-Net 3D neural networks were employed for segmenting these body regions, followed by subclassifying adipose tissue and muscle using known Hounsfield unit limits. RESULTS: The Sørensen Dice scores averaged over all semantic regions was 0.9553 and the intra-class correlation coefficients for subclassified tissues were above 0.99. CONCLUSIONS: Our results show that fully automated body composition analysis on routine CT imaging can provide stable biomarkers across the whole abdomen and not just on L3 slices, which is historically the reference location for analyzing body composition in the clinical routine. KEY POINTS: • Our study enables fully automated body composition analysis on routine abdomen CT scans. • The best segmentation models for semantic body region segmentation achieved an averaged Sørensen Dice score of 0.9553. • Subclassified tissue volumes achieved intra-class correlation coefficients over 0.99.

Comorbidity Index as a Selection Tool for Living Donor Liver Transplantation in Elderly Patients.

BACKGROUND: Previously published data have shown that age alone is not a contraindication for living donor liver transplantation (LDLT). However, careful evaluation is needed to identify the patients who are unlikely to benefit from LDLT. We hypothesized that the Charlson Comorbidity Index (CCI) could be used as one of the criteria for risk stratification in elderly patients undergoing LDLT. PATIENTS AND METHODS: There were 951 patients who underwent LDLT between October 2004 and February 2018. All recipients who were older than 60 years of age at the time of transplantation were identified. The comorbidity score was retrospectively assessed for each elderly patient according to the Charlson Comorbidity Index. Univariate and multivariate Cox regression analyses were performed to identify independent predictive factors for survival in elderly patients after LDLT. RESULTS: There were 96 patients (10.1%) in the age of > 60 years. All patients received the right lobe of their donor. Out of these patients, 18 (18.7%) died in the median time of 4 months. The remaining 78 patients (81.2%) are alive, with a median survival of 33 months. The CCI of these patients was significantly lower compared to the other 18 patients (2 versus 4). None of the patients with a CCI above 4 survived longer than 12 months. The results of the multivariate Cox regression analyses have shown that pulmonary disease, renal disease, and CCI are independent negative predictive factors for survival. CONCLUSION: The results of our study show clearly that the CCI has a significant influence on survival after LDLT in elderly patients and can be used as one of the selection criteria for LDLT in elderly patients.

Ten-year survival of esophageal cancer after an en-bloc esophagectomy.

BACKGROUND: Esophagectomy with gastric pull-up is the optimal treatment for patients with resectable esophageal cancer. Although the morbidity and mortality of an esophagectomy is reduced, the long-term outcome remains poor. The aim of this study was to evaluate the 10-year survival of a standardized multidisciplinary therapy concept for esophageal cancer. METHODS: Between 1989 and 1999, 114 patients were treated for esophageal cancer at the University of Essen. All patients underwent an en-bloc esophagectomy with systematic lymphadenectomy. Patients with locally advanced disease (stage III) received neoadjuvant therapy. All patients were followed-up for 10 years or more or until death. RESULTS: The 3-year survival was 35%, the 5-year survival 25%, and the 10-year survival was 18%. The recurrence rate was 44% with a median time of 13 months. There was no significant difference in survival between patients with locally advanced disease who received neoadjuvant therapy and patients with early disease (stadium I + II) who underwent surgery alone. Of the patients who achieved 10-year survival, 60% had locally advanced disease and received neoadjuvant therapy. CONCLUSION: Patients with locally advanced disease, managed by a multidisciplinary treatment strategy, achieved a similar long-term survival to patients with early disease (stadium I + II).

Kidney transplantation in patients with diabetes mellitus: surgical complications.

BACKGROUND/AIMS: The aim of this study was to analyze the risk for surgical complications after kidney transplantation in patients with diabetes mellitus (DM) compared to patients without DM. METHODOLOGY: Between January 2002 and December 2005 270 consecutive kidney transplantations from deceased donors in adult recipients were performed. Data of these patients were analyzed on the presence of DM. Recipients with DM (n=32) were compared with patients without DM (n=238) concerning delayed graft function, wound infections, urinary leakage, postoperative bleeding and urinary infections. RESULTS: No statistically significant differences were found in the occurrence of delayed graft function, postoperative bleeding and urinary tract infections between both groups. Although the percentage of postoperative wound infections and urinary leakages was elevated in the DM group it was not statistical significant. CONCLUSION: In patients with terminal kidney insufficiency the presence of DM type II is a frequent co-morbidity and is per se not a contraindication for kidney transplantation. Because of the elevated cardiovascular risk profile patients with DM have to be evaluated very diligent before being listed for kidney transplantation. Nevertheless beside the additional short term risk caused by kidney transplantation it is the only modifiable risk with possible long term reduction for these patients.