Validation of the Estimation of Physiologic Ability and Surgical Stress (E-PASS) Score in Liver Surgery

Background: The estimation of physiologic ability and surgical stress (E-PASS) has been used to produce a numerical estimate of expected mortality and morbidity after elective gastrointestinal surgery. The aim of this study was to validate E-PASS in a selected cohort of patients requiring liver resections (LR). Methods: In this retrospective study, E-PASS predictor equations for morbidity and mortality were applied to the prospective data from 243 patients requiring LR. The observed rates were compared with predicted rates using Fisher's exact test. The discriminative capability of E-PASS was evaluated using receiver-operating characteristic (ROC) curve analysis. Results: The observed and predicted overall mortality rates were both 3.3% and the morbidity rates were 31.3 and 26.9%, respectively. There was a significant difference in the comprehensive risk scores for deceased and surviving patients (p=0.043). However, the scores for patients with or without complications were not significantly different (p=0.120). Subsequent ROC curve analysis revealed a poor predictive accuracy for morbidity. Conclusions: The E-PASS score seems to effectively predict mortality in this specific group of patients but is a poor predictor of complications. A new modified logistic regression might be required for LR in order to better predict the postoperative outcom

Long-Term Quality of Life After Hepatic Resection: Health Is not Simply the Absence of Disease

Background: Due to advances in operative methods and perioperative care, mortality and morbidity following major hepatic resection have decreased substantially, making long-term quality of life (QoL) an increasingly prominent issue. We evaluated whether postoperative diagnosis was associated with long-term QoL and health in patients requiring hepatic surgery for benign or malignant disease. Methods: QoL was evaluated using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 and the liver-specific QLQ-LMC21 module. Results: Between 2002 and 2006, 249 patients underwent hepatic surgery for malignant (76%) and benign (24%) conditions. One hundred thirty-five patients were available for QoL analysis after a mean of 26.5months. There was no statistical difference in global QoL scores between patients with malignant and benign diseases (p=0.367). Neither the extent of the resection (≥2 segments vs. <2 segments; p=0.975; OR=0.988; 95% CI=0.461-2.119) nor patient age had a significant influence on overall QoL (p=0.092). Conclusions: These results indicate that long-term QoL for patients who underwent liver resection for malignant disease is quite good and that a poor clinical prognosis does not seem to correlate with a poor Qo

Diagnosis and Management of the Symptomatic Duodenal Diverticulum: a Case Series and a Short Review of the Literature

Introduction: The incidence of duodenal diverticula (DD) found at autopsy may be as high as 22%. Perforation is the least frequent but also the most serious complication. This case series gives an overview of the management of this rare entity. Methods: This study is a case series of eight patients treated for symptomatic DD. Results: Two patients had a perforated DD. One perforation was in segments III-IV, which to our knowledge is the first published case; the other perforation was in segment II. A segmental duodenectomy was performed in the first patient and a pylorus-preserving duodeno-pancreatectomy (pp-Whipple) in the second. A third patient with chronic complaints and recurring episodes of fever required an excision of the DD. In a fourth patient with biliary and pancreatic obstruction, a pp-Whipple was carried out, and a DD was discovered as the underlying cause. Four patients (one small perforation, one hemorrhage, and two recurrent cholangitis/pancreatitis caused by a DD) were treated conservatively. Conclusions: Symptomatic DD and, in particular, perforations are rare, encompass diagnostic challenges, and may require technically demanding surgical or endoscopic interventions. The diagnostic value of forward-looking gastroduodenoscopy in this setting seems limited. If duodenoscopy is performed at all, the use of a side-viewing endoscope is mandator

Bilateral total extraperitoneal inguinal hernia repair (TEP) has outcomes similar to those for unilateral TEP: population-based analysis of prospective data of 6,505 patients

Background: Whether bilateral total extraperitoneal (TEP) inguinal hernia repair is associated with worse outcomes than unilateral TEP continues to be a matter of debate. This study aimed to compare different outcomes of large cohorts of patients undergoing bilateral versus unilateral TEP. Methods: Based on prospective data of the Swiss Association of Laparoscopic and Thoracoscopic Surgery (SALTS), all patients undergoing elective unilateral or bilateral TEP from 1995 to 2006 were included in the study. The outcomes compared included conversion rates; intraoperative, surgical, and general postoperative complications; duration of operation; and length of hospital stay (LOS). Unadjusted and risk-adjusted multivariable analyses were performed. Results: Data for 6,505 patients undergoing unilateral (n=3,457) and bilateral (n=3,048) TEP were prospectively collected. The average age and the American Society of Anesthesiologists (ASA) score were similar in the two groups. The patients undergoing bilateral TEP repair had a slightly increased rate of intraoperative complications (bilateral, 3.1% vs. unilateral, 1.9%) and surgical postoperative complications (bilateral, 3.2% vs. unilateral, 2.3%). The operation time was longer for bilateral TEP repair (86 vs. 67min). No significant differences in postoperative LOS, general postoperative complications, or conversion rates were found. Conclusions: This is the first population-based analysis in the literature to compare different outcomes in a prospective cohort of more than 6,500 patients undergoing bilateral versus unilateral TEP. Although the rates for intraoperative and surgical postoperative complications were slightly higher for the patients undergoing bilateral TEP repair, the absolute differences were small and of minor clinical relevance. Bilateral TEP repair is associated with a minimal increase in operating time and similar LOS, general postoperative complications, and conversion rates. Therefore, for patients with bilateral inguinal hernia, a simultaneous endoscopic approach represents an excellent therapeutic optio

COVID-19 in Liver Transplant Recipients: A Systematic Review.

Liver transplant (LT) recipients are considered a vulnerable population amidst the COVID-19 pandemic. To date, available data have been heterogeneous and scarce. Therefore, we conducted a systematic literature review identifying English-language articles published in PubMed between November 2019 and 30 May 2021. We aimed to explore three areas: (1) outcome and clinical course; (2) immunological response after COVID-19 in LT recipients; and (3) vaccination response. After systematic selection, 35, 4, and 5 articles, respectively, were considered suitable for each area of analysis. Despite the heterogeneity of the reports included in this study, we found that gastrointestinal symptoms were common in LT recipients. The outcome of the LT population was not per se worse compared to the general population, although careful management of immunosuppressive therapy is required. While a complete therapy discontinuation is not encouraged, caution needs to be taken with use of mycophenolate mofetil (MMF), favoring tacrolimus (TAC) use. Although data conflicted about acquired immunity after SARS-CoV-2 infection, vaccine immunogenicity appeared to be low, suggesting that the level of surveillance should be kept high in this population

TAPP or TEP? Population-Based Analysis of Prospective Data on 4,552 Patients Undergoing Endoscopic Inguinal Hernia Repair

Background: Whether total extraperitoneal inguinal hernia repair (TEP) is associated with worse outcomes than transabdominal preperitoneal inguinal hernia repair (TAPP) continues to be a matter of debate. The objective of this large cohort study is to compare outcomes between patients undergoing TEP or TAPP. Methods: Based on prospective data of the Swiss association of laparoscopic and thoracoscopic surgery, all patients undergoing unilateral TEP or TAPP between 1995 and 2006 were included. The following outcomes were compared: conversion rates, intraoperative and postoperative complications, duration of operation. Results: Data on 4,552 patients undergoing TEP (n=3,457) and TAPP (n=1,095) were collected prospectively. Average age and American Society of Anesthesiologists score were similar in the two groups. Patients undergoing TEP had a significantly higher rate of intraoperative complications (TEP 1.9% vs. TAPP 0.9%, p=0.029) and surgical postoperative complications (TEP: 2.3% vs. TAPP: 0.8%, p=0.003). The postoperative length of stay was longer for patients undergoing TAPP (2.9 vs. 2.3days, p=0.002), whereas the duration of the operation was longer for TEP (66.6 vs. 59.0min, p<0.001) and the conversion rate was higher (TEP 1.0% vs. TAPP 0.2%, p=0.011). Conclusions: This study is one of the first population-based analyses comparing TEP and TAPP in a prospective cohort of more than 4,500 patients. Intraoperative and surgical postoperative complications were significantly higher in patients undergoing TEP. TEP is also associated with longer operating times and higher conversion rates. Therefore, on a population-based level, the TAPP technique appears to be superior to the TEP repair in patients undergoing unilateral inguinal hernia repai

Hepatocellular Carcinoma in Cirrhotic Versus Non-Cirrhotic Patients: A Retrospective Study of 483 Patients

Background and Aim: Although cirrhosis is a classical risk factor for the development of hepatocellular carcinoma (HCC), its absence does not exclude this risk. We aimed to assess the clinical characteristics and outcomes of cirrhotic HCC (C-HCC) and non-cirrhotic HCC (NC-HCC) patients. Methods: Patients consecutively included in a prospective HCC cohort (University Hospital Bern) were analysed. They were categorised into two groups, based on the basis of histology or combined radiological and laboratory characteristics. Results: 20.4% of patients were NC-HCC. This group was characterized by a higher median age and a higher female prevalence compared to the C-HCC group. Non-alcoholic fatty liver disease (NAFLD) (25.7%) and HBV infection (14.9%) were the main risk factors in this group, whereas alcohol abuse (26%) and HCV (21.6%) in C-HCC, P<0.001. 19.4% of them were diagnosed during a screening programme. Resection was performed in 54.5% of NC HCC patients despite the advanced stage (BCLC stage B and C). No statistically significant difference in survival rate was observed between C and NC-HCC patients (24 months vs. 33.9 months, P=0.162). In multivariate analysis, in the NC-HCC group each unit increase in BMI was associated with mortality while liver transplantation and resection were positively associated with survival. In the C-HCC group, the BCLC stage C was negatively associated with survival while all the therapeutic lines were negative factors for mortality. Conclusion: NC-HCC patients were diagnosed more often outside a screening programme. The patients were older, with a higher female prevalence and despite an advanced stage, were often amenable to surgery

Investigation of Different Library Preparation and Tissue of Origin Deconvolution Methods for Urine and Plasma cfDNA Methylome Analysis.

Methylation sequencing is a promising approach to infer the tissue of origin of cell-free DNA (cfDNA). In this study, a single- and a double-stranded library preparation approach were evaluated with respect to their technical biases when applied on cfDNA from plasma and urine. Additionally, tissue of origin (TOO) proportions were evaluated using two deconvolution methods. Sequencing cfDNA from urine using the double-stranded method resulted in a substantial within-read methylation bias and a lower global methylation (56.0% vs. 75.8%, p ≤ 0.0001) compared to plasma cfDNA, both of which were not observed with the single-stranded approach. Individual CpG site-based TOO deconvolution resulted in a significantly increased proportion of undetermined TOO with the double-stranded method (urine: 32.3% vs. 1.9%; plasma: 5.9% vs. 0.04%; p ≤ 0.0001), but no major differences in proportions of individual cell types. In contrast, fragment-level deconvolution led to multiple cell types, with significantly different TOO proportions between the two methods. This study thus outlines potential limitations of double-stranded library preparation for methylation analysis of cfDNA especially for urinary cfDNA. While the double-stranded method allows jagged end analysis in addition to TOO analysis, it leads to significant methylation bias in urinary cfDNA, which single-stranded methods can overcome

Comparison of methods for donor-derived cell-free DNA quantification in plasma and urine from solid organ transplant recipients.

In allograft monitoring of solid organ transplant recipients, liquid biopsy has emerged as a novel approach using quantification of donor-derived cell-free DNA (dd-cfDNA) in plasma. Despite early clinical implementation and analytical validation of techniques, direct comparisons of dd-cfDNA quantification methods are lacking. Furthermore, data on dd-cfDNA in urine is scarce and high-throughput sequencing-based methods so far have not leveraged unique molecular identifiers (UMIs) for absolute dd-cfDNA quantification. Different dd-cfDNA quantification approaches were compared in urine and plasma of kidney and liver recipients: A) Droplet digital PCR (ddPCR) using allele-specific detection of seven common HLA-DRB1 alleles and the Y chromosome; B) high-throughput sequencing (HTS) using a custom QIAseq DNA panel targeting 121 common polymorphisms; and C) a commercial dd-cfDNA quantification method (AlloSeq® cfDNA, CareDx). Dd-cfDNA was quantified as %dd-cfDNA, and for ddPCR and HTS using UMIs additionally as donor copies. In addition, relative and absolute dd-cfDNA levels in urine and plasma were compared in clinically stable recipients. The HTS method presented here showed a strong correlation of the %dd-cfDNA with ddPCR (R 2 = 0.98) and AlloSeq® cfDNA (R 2 = 0.99) displaying only minimal to no proportional bias. Absolute dd-cfDNA copies also correlated strongly (τ = 0.78) between HTS with UMI and ddPCR albeit with substantial proportional bias (slope: 0.25; 95%-CI: 0.19-0.26). Among 30 stable kidney transplant recipients, the median %dd-cfDNA in urine was 39.5% (interquartile range, IQR: 21.8-58.5%) with 36.6 copies/μmol urinary creatinine (IQR: 18.4-109) and 0.19% (IQR: 0.01-0.43%) with 5.0 copies/ml (IQR: 1.8-12.9) in plasma without any correlation between body fluids. The median %dd-cfDNA in plasma from eight stable liver recipients was 2.2% (IQR: 0.72-4.1%) with 120 copies/ml (IQR: 85.0-138) while the median dd-cfDNA copies/ml was below 0.1 in urine. This first head-to-head comparison of methods for absolute and relative quantification of dd-cfDNA in urine and plasma supports a method-independent %dd-cfDNA cutoff and indicates the suitability of the presented HTS method for absolute dd-cfDNA quantification using UMIs. To evaluate the utility of dd-cfDNA in urine for allograft surveillance, absolute levels instead of relative amounts will most likely be required given the extensive variability of %dd-cfDNA in stable kidney recipients