Changes of long-term survival of resection and liver transplantation in hepatocellular carcinoma throughout the years: A meta-analysis.

BACKGROUND: Hepatocellular Carcinoma (HCC) still is one of the most detrimental malignant diseases in the world. As two curative surgical therapies exist, the discussion whether to opt for liver resection (LR) or transplantation (LT) is ongoing, especially as novel techniques to improve outcome have emerged for both. The aim of the study was to investigate how the utilization and outcome of the respective modalities changed through time. METHODS: We searched Medline and PubMed for relevant publications comparing LT and LR in HCC patients during the time period from 1990 to 2022, prior to March 31, 2023. A total of 63 studies involving 19,804 patients - of whom 8178 patients received a liver graft and 11,626 underwent partial hepatectomy - were included in this meta-analysis. RESULTS: LT is associated with significantly better 5-year overall survival (OS) (64.83%) and recurrence-free survival (RFS) (70.20%) than LR (OS: 50.83%, OR: 1.79, p < 0.001; RFS: 34.46%, OR: 5.32, p < 0.001). However, these differences are not as evident in short-term intervals. Older cohorts showed comparable disparities between the outcome of the respective modalities, as did newer cohorts after 2005. This might be due to the similar improvement in survival rates that were observed for both, LT (15-23%) and LR (12-20%) during the last 30 years. CONCLUSION: LT still outperforms LR in the therapy of HCC in terms of long-term survival rates. Yet, LR outcome has remarkably improved which is of major importance in reference to the well-known limitations that occur in LT.

A Novel Deep Learning Model as a Donor-Recipient Matching Tool to Predict Survival after Liver Transplantation.

BACKGROUND: The "digital era" in the field of medicine is the new "here and now". Artificial intelligence has entered many fields of medicine and is recently emerging in the field of organ transplantation. Solid organs remain a scarce resource. Being able to predict the outcome after liver transplantation promises to solve one of the long-standing problems within organ transplantation. What is the perfect donor recipient match? Within this work we developed and validated a novel deep-learning-based donor-recipient allocation system for liver transplantation. METHOD: In this study we used data collected from all liver transplant patients between 2004 and 2019 at the university transplantation centre in Munich. We aimed to design a transparent and interpretable deep learning framework to predict the outcome after liver transplantation. An individually designed neural network was developed to meet the unique requirements of transplantation data. The metrics used to determine the model quality and its level of performance are accuracy, cross-entropy loss, and F1 score as well as AUC score. RESULTS: A total of 529 transplantations with a total of 1058 matching donor and recipient observations were added into the database. The combined prediction of all outcome parameters was 95.8% accurate (cross-entropy loss of 0.042). The prediction of death within the hospital was 94.3% accurate (cross-entropy loss of 0.057). The overall F1 score was 0.899 on average, whereas the overall AUC score was 0.940. CONCLUSION: With the achieved results, the network serves as a reliable tool to predict survival. It adds new insight into the potential of deep learning to assist medical decisions. Especially in the field of transplantation, an AUC Score of 94% is very valuable. This neuronal network is unique as it utilizes transparent and easily interpretable data to predict the outcome after liver transplantation. Further validation must be performed prior to utilization in a clinical context.

Expression of CIB1 correlates with colorectal liver metastases but not with peritoneal carcinomatosis.

BACKGROUND: Molecular differences in colorectal cancer (CRC) are associated with the metastatic route. Patient survival is mainly driven by metastatic spread thus it is imperative to understand its key drivers to develop biomarkers for risk stratification, follow-up protocols and personalized therapy. Thus, this study aimed to identify genes associated with the metastatic route in CRC. MATERIAL AND METHODS: CRC patients resected at our clinic from 2005 to 2014 and with a minimum 5-year follow-up were included in this analysis and grouped into CRC with hepatic (HEP), peritoneal (PER) or without distant metastases (M0), and HEP/PER. Firstly, tumor RNA of 6 patients each was isolated by microdissection from formalin-fixed paraffin-embedded specimens and analyzed by a NanoString analysis. Subsequently, these results were validated with immunohistochemistry and correlated to clinicopathological parameters in a larger collective of CRC patients (HEP n = 51, PER n = 44, M0 n = 47, HEP/PER n = 28). RESULTS: Compared to M0, HEP tumors showed 20 differentially expressed genes associated with epithelial-mesenchymal transition (EMT) and angiogenesis. Compared to M0, PER tumors had 18 differentially expressed genes. The finding of different gene signatures was supported by the multidimensional principal component clustering analysis. Tumor perforation did not influence the metastatic route. CIB1 was homogenously and significantly overexpressed in HEP compared to M0 (p < 0.001), but not in PER. Furthermore, immunohistochemical validation demonstrated that the mean CIB1 expression in HEP was 80% higher than in M0 (p < 0.001). CONCLUSION: Gene expression analysis revealed that CIB1 is significantly overexpressed in CRC leading to liver metastases compared to M0 and PER. Thus, the present results suggest that CIB1 may play a crucial role for hematogenous spread to the liver but not for peritoneal carcinomatosis. Consequently, CIB1 seems to be a promising prognostic marker and a potential tool for future targeted therapies as well as early diagnostics and follow-up.

Chances, challenges and outcomes of patients with complex bilobar colorectal liver metastases approached by a combined multimodal therapy with liver resection and local ablative therapy.

BACKGROUND AND OBJECTIVES: In treatment of colorectal liver metastases (CRC-LM), liver surgery combined with systemic therapies and local ablation (LAT) allows improved survival. This study aims at the outcomes of patients with complex bilobar CRC-LM who were intended to undergo multimodal therapy with liver resection and LAT. METHODS: Forty-three CRC-LM patients with recommendation for multimodal treament were extracted from 5878 tumor board decisions between 2014 and 2017. Outcome variables included patient survival, as well as completion of hepatic clearance. Prognostic factors were identified by correlation and a Cox proportional hazards model. RESULTS: Out of 43 patients only 23 achieved complete clearance of CRC-LM. One- and 3-year overall survival of patients with cleared liver disease was 100% and 91.7%, respectively, as compared to 83.8% and 12.1%. Incomplete hepatic clearance was the strongest independent risk factor for overall survival (hazards ratio [HR], 5.86; p = .009). Risk factors for incomplete clearance were higher age (r = .34; p = .026), comorbidities (r = .40; p = .008), major complications (r = .34; p = .024), and prolonged intensive care unit stay (r = .41; p = .017). CONCLUSION: Completion of hepatic clearance is crucial to achieve long-term survival in patients with complex bilobar CRC-LM. Careful patient selection and treatment planning should avoid treatment failure before completing the intended therapy plan when multimodal treatments are planned.

Prognostic Impact of Pedicle Clamping during Liver Resection for Colorectal Metastases.

Pedicle clamping (PC) during liver resection for colorectal metastases (CRLM) is used to reduce blood loss and allogeneic blood transfusion (ABT). The effect on long-term oncologic outcomes is still under debate. A retrospective analysis of the impact of PC on ABT-demand regarding overall (OS) and recurrence-free survival (RFS) in 336 patients undergoing curative resection for CRLM was carried out. Survival analysis was performed by both univariate and multivariate methods and propensity-score (PS) matching. PC was employed in 75 patients (22%). No increased postoperative morbidity was monitored. While the overall ABT-rate was comparable (35% vs. 37%, p = 0.786), a reduced demand for more than two ABT-units was observed (p = 0.046). PC-patients had better median OS (78 vs. 47 months, p = 0.005) and RFS (36 vs. 23 months, p = 0.006). Multivariate analysis revealed PC as an independent prognostic factor for OS (HR = 0.60; p = 0.009) and RFS (HR = 0.67; p = 0.017). For PC-patients, 1:2 PS-matching (N = 174) showed no differences in the overall ABT-rate compared to no-PC-patients (35% vs. 40%, p = 0.619), but a trend towards reduced transfusion requirement (>2 ABT-units: 9% vs. 21%, p = 0.052; >4 ABT-units: 2% vs. 11%, p = 0.037) and better survival (OS: 78 vs. 44 months, p = 0.088; RFS: 36 vs. 24 months; p = 0.029). Favorable long-term outcomes and lower rates of increased transfusion demand were observed in patients with PC undergoing resection for CRLM. Further prospective evaluation of potential oncologic benefits of PC in these patients may be meaningful.

Prognostic Impact of Tumor-Infiltrating Lymphocytes and Neutrophils on Survival of Patients with Upfront Resection of Pancreatic Cancer.

In patients with pancreatic ductal adenocarcinoma (PDAC), the tumor microenvironment consists of cellular and stromal components that influence prognosis. Hence, tumor-infiltrating lymphocytes (TILs) may predict prognosis more precisely than conventional staging systems. Studies on the impact of TILs are heterogeneous and further research is needed. Therefore, this study aims to point out the importance of peritumoral TILs, tumor-infiltrating neutrophils (TINs), and immune subtype classification in PDAC. Material from 57 patients was analyzed with immunohistochemistry performed for CD3, CD8, CD20, CD66b, α-sma, and collagen. Hot spots with peritumoral TILs and TINs were quantified according to the QTiS algorithm and the distance of TILs hot spots to the tumor front was measured. Results were correlated with overall (OS) and progression-free survival (PFS). High densities of peritumoral hot spots with CD3⁺, CD8⁺, and CD20⁺ TILs correlated significantly with improved OS and PFS. Combined immune cell subtypes predicted improved OS and PFS. High infiltration of CD3⁺ TILs predicted progression after 12 months. The location of TILs' hot spots and their distance to the tumor front did not correlate with patient survival. Peritumoral TILs and the composition of the stroma predict OS and PFS in PDAC.

Resection or Transplant in Early Hepatocellular Carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) has an incidence of 5-10 per 100 000 persons per year in the Western world. In 20% of cases, surgical liver resection (LR) or liver transplantation (LT) can be performed. LT results in longer survival, as it involves resection not only of the tumor, but of pre - cancerous tissue as well. The optimal allocation of donor organs depends on the identification of patients for whom LR is adequate treatment. In this meta-analysis, we compare LT and LR for patients with early HCC and wellcompensated cirrhosis. METHODS: A systematic review of the pertinent literature was followed by a subgroup analysis of the studies in which patients with early HCC and wellcompensated cirrhosis were followed up after either LR or LT. Overall survival at 1, 3, and 5 years, as well as morbidity and mortality, were compared in a random effects meta-analysis. RESULTS: 54 studies with a total of 13 794 patients were included. Among patients with early HCC, the overall survival after LT became higher than the overall survival after LR 5 years after surgery (66.67% versus 60.35%, odds ratio 0.60 [0.45; 0.78], p <0.001); there was no significant difference 1 year or 3 years after surgery. Nor was there any significant difference in morbidity or mortality between the two types of treatment in this subgroup. These findings contrast with the results obtained in all of the studies, which documented significantly better survival 3 years after LT. CONCLUSION: Three years after surgery, the survival rates and complication rates of patients with early HCC treated with either LR or LT are comparable. Resection should therefore be the preferred form of treatment if the prerequisites for it are met. In case of recurrent tumor, these patients can still be evaluated for liver transplantation. This strategy could improve the allocation of donor organs.

Hybrid transgastric appendectomy is feasible but does not offer advantages compared with laparoscopic appendectomy: Results from the transgastric appendectomy study.

BACKGROUND: Very few transgastric procedures, the original objective of natural orifice translumenal surgery, have been reported in the international Natural Orifice Translumenal Surgery registers. In addition, most cases were controlled mainly by laparoscopy. To show the feasibility of hybrid transgastric appendectomy and to compare results with laparoscopic a prospective, nonrandomized study was conducted. METHODS: From October 2010 to May 2013, patients with acute appendicitis were screened. If the patients met the inclusion criteria, transgastric appendectomy was offered. If the patient decided on laparoscopy, the consenting patients took part in the observational part of the study. The transgastric appendectomy procedure was controlled completely by the gastroscope, although a 3 mm grasper was used to tauten the appendix. Demographic and clinical parameters were collected. Quality of life and pain were measured with a Short Form-8 questionnaire and the Visual Analogue Scale. RESULTS: Of the 273 patients who underwent an appendectomy, 65 agreed to take part in this study. Out of these, 30 (46.15%) underwent transgastric appendectomy and 35 (53.85%) underwent laparoscopy. No intraoperative complications were recorded. The operation duration rate was greater in the transgastric appendectomy group (94.5 minutes vs 69 minutes; P < .001). Conversions to open appendectomy and complications were the same. There were no differences in pain preoperatively or postoperatively. In both the transgastric appendectomy and laparoscopic groups, the quality of life of all the subscales increased markedly after successful resection of the pathology. CONCLUSION: These preliminary results demonstrate the feasibility of transgastric appendectomy. The postoperative course and quality of life are comparable with laparoscopic appendectomy, but no improvement due to transgastric appendectomy could be demonstrated.

Orthotopic liver transplantation for giant liver haemangioma: A case report.

In liver haemangiomas, the risk of complication rises with increasing size, and treatment can be obligatory. Here we present a case of a 46-year-old female who suffered from a giant haemangioma causing severe portal hypertension and vena cava compression, leading to therapy refractory ascites, hyponatremia and venostasis-associated thrombosis with pulmonary embolism. The patients did not experience tumour rupture or consumptive coagulopathy. Surgical resection was impossible because of steatosis of the non-affected liver. Orthotopic liver transplantation was identified as the only treatment option. The patient's renal function remained stable even though progressive morbidity and organ allocation were improbable according to the patient's lab model for end-stage liver disease (labMELD) score. Therefore, non-standard exception status was approved by the European organ allocation network "Eurotransplant". The patient underwent successful orthotopic liver transplantation 16 mo after admission to our centre. Our case report indicates the underrepresentation of morbidity associated with refractory ascites in the labMELD-based transplant allocation system, and it indicates the necessity of promptly applying for non-standard exception status to enable transplantation in patients with a severe clinical condition but low labMELD score. Our case highlights the fact that liver transplantation should be considered early in patients with non-resectable, symptomatic benign liver tumours.

The collateral caval shunt as an alternative to classical shunt procedures in patients with recurrent duodenal varices and extrahepatic portal vein thrombosis.

Upper gastrointestinal bleeding episodes from variceal structures are severe complications in patients with portal hypertension. Endoscopic sclerotherapy and variceal ligation are the treatment options preferred for upper variceal bleeding owing to extrahepatic portal hypertension due to portal vein thrombosis (PVT). Recurrent duodenal variceal bleeding in non-cirrhotic patients with diffuse porto-splenic vein thrombosis and subsequent portal cavernous transformation represent a clinical challenge if classic shunt surgery is not possible or suitable.In this study, we represent a case of recurrent bleeding of duodenal varices in a non-cirrhotic patient with cavernous transformation of the portal vein that was successfully treated with a collateral caval shunt operation.

Laparoscopic Heller myotomy versus endoscopic balloon dilatation for the treatment of achalasia: a network meta-analysis.

OBJECTIVE: Comparison of short- and long-term effects after laparoscopic Heller myotomy (LHM) and endoscopic balloon dilation (EBD) considering the need for retreatment. BACKGROUND: Previously published studies have indicated that LHM is the most effective treatment for Achalasia. In contrast to that a recent randomized trial found EBD equivalent to LHM 2 years after initial treatment. METHODS: A search in Medline, PubMed, and Cochrane Central Register of Controlled Trials was conducted for prospective studies on interventional achalasia therapy with predefined exclusion criteria. Data on success rates after the initial and repeated treatment were extracted. An adjusted network meta-analysis and meta-regression analysis was used, combined with a head-to-head comparison, for follow-up at 12, 24, and 60 months. RESULTS: Sixteen studies including results of 590 LHM and EBD patients were identified. Odds ratio (OR) was 2.20 at 12 months (95% confidence interval: 1.18-4.09; P = 0.01); 5.06 at 24 months (2.61-9.80; P < 0.00001) and 29.83 at 60 months (3.96-224.68; P = 0.001). LHM was also significantly superior for all time points when therapy included re-treatments [OR = 4.83 (1.87-12.50), 19.61 (5.34-71.95), and 17.90 (2.17-147.98); P ≤ 0.01 for all comparisons) Complication rates were not significantly different. Meta-regression analysis showed that amount of dilations had a significant impact on treatment effects (P = 0.009). Every dilation (up to 3) improved treatment effect by 11.9% (2.8%-21.8%). CONCLUSIONS: In this network meta-analysis, LHM demonstrated superior short- and long-term efficacy and should be considered first-line treatment of esophageal achalasia.

Absorbable ligation loops for flexible endoscopy: a necessary tool for natural orifice transluminal endoscopic surgery.

BACKGROUND: One of the main challenges of natural orifice transluminal endoscopic surgery (NOTES) remains the development of safe and reliable tools. In this study, we introduce the first absorbable ligatures specifically designed for NOTES. OBJECTIVE: To determine the feasibility of a new absorbable ligation loop (NOTES loop) and to compare this new type of suture with the nonabsorbable loop (Endoloop) most commonly used until now. DESIGN: Prospective, comparative animal trial/survival animal study (observation period 21 days) with subsequent histopathological assessment (blinded observer design). SETTING: Veterinarian center. SUBJECTS: This study used 12 female domestic piglets. INTERVENTION: Every pig underwent two transgastric uterine horn ligations, one with an absorbable loop and one with a nonabsorbable loop. Additional uterine horn resections on both sides were done on 6 pigs. MAIN OUTCOME MEASUREMENTS: Intervention success, loop reliability, foreign-body reaction, extent of inflammatory response (µm). RESULTS: Transgastric flexible intra-abdominal ligation of the uterine horns was performed safely with both loops in all cases. During a 3-week observation period, 11 of 11 NOTES loops and 10 of 11 Endoloops were reliable. Microscopically, foreign-body reaction was minimal around both sutures (P = .303). The overall inflammatory response was larger around the Endoloops (P = .046). Uterine horn resection had an influence on the extent of inflammation. LIMITATIONS: Animal study. CONCLUSION: Ligation was feasible with both loops. The absorbable loops were reliable during a 3-week observation period and can be recommended for use during NOTES appendectomies.