The TGF-ß1 target WISP1 is highly expressed in liver cirrhosis and cirrhotic HCC microenvironment and involved in pro- and anti-tumorigenic effects.

INTRODUCTION: WNT1-inducible signalling pathway protein 1 (WISP1) promotes progression of several tumor entities often correlating with worse prognosis. Here its expression regulation and role in the progression of chronic liver diseases (CLD) was investigated. METHODS: WISP1 expression was analyzed in human HCC datasets, in biopsies and serum samples and an HCC patient tissue microarray (TMA) including correlation to clinicopathological parameters. Spatial distribution of WISP1 expression was determined using RNAscope analysis. Regulation of WISP1 expression was investigated in cytokine-stimulated primary mouse hepatocytes (PMH) by array analysis and qRT-PCR. Outcome of WISP1 stimulation was analyzed by IncuCyte S3-live cell imaging, qRT-PCR, and immunoblotting in murine AML12 cells. RESULTS: In a TMA, high WISP1 expression was positively correlated with early HCC stages and male sex. Highest WISP1 expression levels were detected in patients with cirrhosis as compared to healthy individuals, patients with early fibrosis, and non-cirrhotic HCC in liver biopsies, expression datasets and serum samples. WISP1 transcripts were predominantly detected in hepatocytes of cirrhotic rather than tumorous liver tissue. High WISP1 expression was associated with better survival. In PMH, AML12 and HepaRG, WISP1 was identified as a specific TGF-ß1 target gene. Accordingly, expression levels of both cytokines positively correlated in human HCC patient samples. WISP1-stimulation induced the expression of Bcl-xL, PCNA and p21 in AML12 cells. CONCLUSIONS: WISP1 expression is induced by TGF-ß1 in hepatocytes and is associated with cirrhotic liver disease. We propose a crucial role of WISP1 in balancing pro- and anti-tumorigenic effects during premalignant stages of CLD.

Remote ischemic preconditioning versus sham-control for prevention of anastomotic leakage after resection for rectal cancer (RIPAL trial): a pilot randomized controlled, triple-blinded monocenter trial.

PURPOSE: Remote ischemic preconditioning (RIPC) reportedly reduces ischemia‒reperfusion injury (IRI) in various organ systems. In addition to tension and technical factors, ischemia is a common cause of anastomotic leakage (AL) after rectal resection. The aim of this pilot study was to investigate the potentially protective effect of RIPC on anastomotic healing and to determine the effect size to facilitate the development of a subsequent confirmatory trial. MATERIALS AND METHODS: Fifty-four patients with rectal cancer (RC) who underwent anterior resection were enrolled in this prospectively registered (DRKS0001894) pilot randomized controlled triple-blinded monocenter trial at the Department of Surgery, University Medicine Mannheim, Mannheim, Germany, between 10/12/2019 and 19/06/2022. The primary endpoint was AL within 30 days after surgery. The secondary endpoints were perioperative morbidity and mortality, reintervention, hospital stay, readmission and biomarkers of ischemia‒reperfusion injury (vascular endothelial growth factor, VEGF) and cell death (high mobility group box 1 protein, HMGB1). RIPC was induced through three 10-min cycles of alternating ischemia and reperfusion to the upper extremity. RESULTS: Of the 207 patients assessed, 153 were excluded, leaving 54 patients to be randomized to the RIPC or the sham-RIPC arm (27 each per arm). The mean age was 61 years, and the majority of patients were male (37:17 (68.5:31.5%)). Most of the patients underwent surgery after neoadjuvant therapy (29/54 (53.7%)) for adenocarcinoma (52/54 (96.3%)). The primary endpoint, AL, occurred almost equally frequently in both arms (RIPC arm: 4/25 (16%), sham arm: 4/26 (15.4%), p = 1.000). The secondary outcomes were comparable except for a greater rate of reintervention in the sham arm (9 (6-12) vs. 3 (1-5), p = 0.034). The median duration of endoscopic vacuum therapy was shorter in the RIPC arm (10.5 (10-11) vs. 38 (24-39) days, p = 0.083), although the difference was not statistically significant. CONCLUSION: A clinically relevant protective effect of RIPC on anastomotic healing after rectal resection cannot be assumed on the basis of these data.

Robotic or laparoscopic repeat hepatectomy after open hepatectomy: a cohort study.

BACKGROUND: Repeat hepatectomies are technically complex procedures. The evidence of robotic or laparoscopic (= minimally invasive) repeat hepatectomies (MIRH) after previous open hepatectomy is poor. Therefore, we compared postoperative outcomes of MIRH vs open repeat hepatectomies (ORH) in patients with liver tumors after previous open liver resections. METHODS: Consecutive patients who underwent repeat hepatectomies after open liver resections were identified from a prospective database between April 2018 and May 2023. Postoperative complications were graded in line with the Clavien-Dindo classification. We stratified patients by intention to treat into MIRH or ORH and compared outcomes. Logistic regression analysis was performed to define variables associated with the utilization of a minimally invasive approach. RESULTS: Among 46 patients included, 20 (43%) underwent MIRH and 26 (57%) ORH. Twenty-seven patients had advanced or expert repeat hepatectomies (59%) according to the IWATE criteria. Baseline characteristics were comparable between the study groups. The use of a minimally invasive approach was not dependent on preoperative or intraoperative variables. All patients had negative resection margins on final histology. MIRH was associated with less blood loss (450 ml, IQR (interquartile range): 200-600 vs 600 ml, IQR: 400-1500 ml, P = 0.032), and shorter length of stay (5 days, IQR: 4-7 vs 7 days, IQR: 5-9 days, P = 0.041). Postoperative complications were similar between the groups (P = 0.298). CONCLUSIONS: MIRH is feasible after previous open hepatectomy and a safe alternative approach to ORH. (German Clinical Trials Register ID: DRKS00032183).

Ultra-sensitive CTC-based liquid biopsy for pancreatic cancer enabled by large blood volume analysis.

The limited sensitivity of circulating tumor cell (CTC) detection in pancreatic adenocarcinoma (PDAC) stems from their extremely low concentration in the whole circulating blood, necessitating enhanced detection methodologies. This study sought to amplify assay-sensitivity by employing diagnostic leukapheresis (DLA) to screen large blood volumes. Sixty patients were subjected to DLA, with a median processed blood volume of ~ 2.8 L and approximately 5% of the resulting DLA-product analyzed using CellSearch (CS). Notably, DLA significantly increased CS-CTC detection to 44% in M0-patients and 74% in M1-patients, yielding a 60-fold increase in CS-CTC enumeration. DLA also provided sufficient CS-CTCs for genomic profiling, thereby delivering additional genomic information compared to tissue biopsy samples. DLA CS-CTCs exhibited a pronounced negative prognostic impact on overall survival (OS), evidenced by a reduction in OS from 28.6 to 8.5 months (univariate: p = 0.002; multivariable: p = 0.043). Additionally, a marked enhancement in sensitivity was achieved (by around 3-4-times) compared to peripheral blood (PB) samples, with positive predictive values for OS being preserved at around 90%. Prognostic relevance of CS-CTCs in PDAC was further validated in PB-samples from 228 PDAC patients, consolidating the established association between CTC-presence and reduced OS (8.5 vs. 19.0 months, p < 0.001). In conclusion, DLA-derived CS-CTCs may serve as a viable tool for identifying high-risk PDAC-patients and aiding the optimization of multimodal treatment strategies. Moreover, DLA enables comprehensive diagnostic profiling by providing ample CTC material, reinforcing its utility as a reliable liquid-biopsy approach. This high-volume liquid-biopsy strategy presents a potential pathway for enhancing clinical management in this malignancy.

Structural expression of bovine milk and meat factors in tissues of colorectal, lung and pancreatic cancer patients.

Chronic inflammation, linked to the presence of bovine milk and meat factors (BMMFs) and specific subsets of macrophages, results in oxygen radical synthesis and induction of mutations in DNA of actively replicating cells and replicating single stranded DNA. Cancers arising from this process have been characterized as indirect carcinogenesis by infectious agents (without persistence of genes of the agent in premalignant or cancers cells). Here, we investigate structural properties of pleomorphic vesicles, regularly identified by staining peritumor tissues of colorectal, lung and pancreatic cancer for expression of BMMF Rep. The latter represents a subgroup of BMMF1 proteins involved in replication of small single-stranded circular plasmids of BMMF, but most likely also contributing to pleomorphic vesicular structures found in the periphery of colorectal, lung and pancreatic cancers. Structurally dense regions are demonstrated in preselected areas of colorectal cancer, after staining with monoclonal antibodies against BMMF1 Rep. Similar structures were observed in human embryonic cells (HEK293TT) overexpressing Rep. These data suggest that Rep or Rep isoforms contribute to the structural formation of vesicles.

Intestinal B cells license metabolic T-cell activation in NASH microbiota/antigen-independently and contribute to fibrosis by IgA-FcR signalling.

BACKGROUND & AIMS: The progression of non-alcoholic steatohepatitis (NASH) to fibrosis and hepatocellular carcinoma (HCC) is aggravated by auto-aggressive T cells. The gut-liver axis contributes to NASH, but the mechanisms involved and the consequences for NASH-induced fibrosis and liver cancer remain unknown. We investigated the role of gastrointestinal B cells in the development of NASH, fibrosis and NASH-induced HCC. METHODS: C57BL/6J wild-type (WT), B cell-deficient and different immunoglobulin-deficient or transgenic mice were fed distinct NASH-inducing diets or standard chow for 6 or 12 months, whereafter NASH, fibrosis, and NASH-induced HCC were assessed and analysed. Specific pathogen-free/germ-free WT and µMT mice (containing B cells only in the gastrointestinal tract) were fed a choline-deficient high-fat diet, and treated with an anti-CD20 antibody, whereafter NASH and fibrosis were assessed. Tissue biopsy samples from patients with simple steatosis, NASH and cirrhosis were analysed to correlate the secretion of immunoglobulins to clinicopathological features. Flow cytometry, immunohistochemistry and single-cell RNA-sequencing analysis were performed in liver and gastrointestinal tissue to characterise immune cells in mice and humans. RESULTS: Activated intestinal B cells were increased in mouse and human NASH samples and licensed metabolic T-cell activation to induce NASH independently of antigen specificity and gut microbiota. Genetic or therapeutic depletion of systemic or gastrointestinal B cells prevented or reverted NASH and liver fibrosis. IgA secretion was necessary for fibrosis induction by activating CD11b+CCR2+F4/80+CD11c-FCGR1+ hepatic myeloid cells through an IgA-FcR signalling axis. Similarly, patients with NASH had increased numbers of activated intestinal B cells; additionally, we observed a positive correlation between IgA levels and activated FcRg+ hepatic myeloid cells, as well the extent of liver fibrosis. CONCLUSIONS: Intestinal B cells and the IgA-FcR signalling axis represent potential therapeutic targets for the treatment of NASH. IMPACT AND IMPLICATIONS: There is currently no effective treatment for non-alcoholic steatohepatitis (NASH), which is associated with a substantial healthcare burden and is a growing risk factor for hepatocellular carcinoma (HCC). We have previously shown that NASH is an auto-aggressive condition aggravated, amongst others, by T cells. Therefore, we hypothesized that B cells might have a role in disease induction and progression. Our present work highlights that B cells have a dual role in NASH pathogenesis, being implicated in the activation of auto-aggressive T cells and the development of fibrosis via activation of monocyte-derived macrophages by secreted immunoglobulins (e.g., IgA). Furthermore, we show that the absence of B cells prevented HCC development. B cell-intrinsic signalling pathways, secreted immunoglobulins, and interactions of B cells with other immune cells are potential targets for combinatorial NASH therapies against inflammation and fibrosis.

The Role of Adjuvant Therapy in Duodenal Adenocarcinoma and Intestinal Subtype Ampullary Carcinoma after Curative Resection.

OBJECTIVE: Defining the role of adjuvant therapy in duodenal adenocarcinoma (DAC) and intestinal subtype ampullary carcinoma (iAC). SUMMARY BACKGROUND DATA: DAC and iAC share a similar histological differentiation but the benefit of adjuvant therapy remains unclear. METHODS: Patients undergoing curative-intent surgical resection for DAC and iAC between 2010 and 2021 at five high-volume centers were included. Patient baseline, perioperative and long-term oncological outcomes were evaluated. Statistical testing was performed with SPSS 25 (IBM). RESULTS: A total of 136 patients with DAC and 171 with iAC were identified. Patients with DAC had more advanced tumors than those with iAC. Median overall survival (OS) in DAC patients was 101 months versus 155 months for iAC patients (P=0.098). DAC had a higher rate of local (14.1% vs. 1.2%, P<0.001) and systemic recurrence (30.4% vs. 3.5%, P<0.001). Adjuvant therapy failed to improve overall survival in all patients with DAC and iAC. For DAC, patients with perineural invasion, but not other negative prognostic factors had improved OS rates with adjuvant therapy (72 m vs. 44 m, P=0.044). IAC patients with N+ (190 m vs. 57 m, P=0.003), T3-4 (177 m vs. 59 m, P=0.050) and perineural invasion (150 m vs. 59 m, P=0.019) had improved OS rates with adjuvant therapy. CONCLUSION: While adjuvant therapy fails to improve OS in all patients with DAC and iAC in the current study, it improved overall survival in DAC patients with perineural invasion and in iAC patients with T3-4 tumors, positive lymph nodes, and perineural invasion.

An APRI+ALBI Based Multivariable Model as Preoperative Predictor for Posthepatectomy Liver Failure.

OBJECTIVE AND BACKGROUND: Clinically significant posthepatectomy liver failure (PHLF B+C) remains the main cause of mortality after major hepatic resection. This study aimed to establish an APRI+ALBI, aspartate aminotransferase to platelet ratio (APRI) combined with albumin-bilirubin grade (ALBI), based multivariable model (MVM) to predict PHLF and compare its performance to indocyanine green clearance (ICG-R15 or ICG-PDR) and albumin-ICG evaluation (ALICE). METHODS: 12,056 patients from the National Surgical Quality Improvement Program (NSQIP) database were used to generate a MVM to predict PHLF B+C. The model was determined using stepwise backwards elimination. Performance of the model was tested using receiver operating characteristic curve analysis and validated in an international cohort of 2,525 patients. In 620 patients, the APRI+ALBI MVM, trained in the NSQIP cohort, was compared with MVM's based on other liver function tests (ICG clearance, ALICE) by comparing the areas under the curve (AUC). RESULTS: A MVM including APRI+ALBI, age, sex, tumor type and extent of resection was found to predict PHLF B+C with an AUC of 0.77, with comparable performance in the validation cohort (AUC 0.74). In direct comparison with other MVM's based on more expensive and time-consuming liver function tests (ICG clearance, ALICE), the APRI+ALBI MVM demonstrated equal predictive potential for PHLF B+C. A smartphone application for calculation of the APRI+ALBI MVM was designed. CONCLUSION: Risk assessment via the APRI+ALBI MVM for PHLF B+C increases preoperative predictive accuracy and represents an universally available and cost-effective risk assessment prior to hepatectomy, facilitated by a freely available smartphone app.

E-AHPBA-ESSO-ESSR Innsbruck consensus guidelines for preoperative liver function assessment before hepatectomy.

BACKGROUND: Posthepatectomy liver failure (PHLF) contributes significantly to morbidity and mortality after liver surgery. Standardized assessment of preoperative liver function is crucial to identify patients at risk. These European consensus guidelines provide guidance for preoperative patient assessment. METHODS: A modified Delphi approach was used to achieve consensus. The expert panel consisted of hepatobiliary surgeons, radiologists, nuclear medicine specialists, and hepatologists. The guideline process was supervised by a methodologist and reviewed by a patient representative. A systematic literature search was performed in PubMed/MEDLINE, the Cochrane library, and the WHO International Clinical Trials Registry. Evidence assessment and statement development followed Scottish Intercollegiate Guidelines Network methodology. RESULTS: Based on 271 publications covering 4 key areas, 21 statements (at least 85 per cent agreement) were produced (median level of evidence 2- to 2+). Only a few systematic reviews (2++) and one RCT (1+) were identified. Preoperative liver function assessment should be considered before complex resections, and in patients with suspected or known underlying liver disease, or chemotherapy-associated or drug-induced liver injury. Clinical assessment and blood-based scores reflecting liver function or portal hypertension (for example albumin/bilirubin, platelet count) aid in identifying risk of PHLF. Volumetry of the future liver remnant represents the foundation for assessment, and can be combined with indocyanine green clearance or LiMAx® according to local expertise and availability. Functional MRI and liver scintigraphy are alternatives, combining FLR volume and function in one examination. CONCLUSION: These guidelines reflect established methods to assess preoperative liver function and PHLF risk, and have uncovered evidence gaps of interest for future research.

Liver surgery is an effective treatment for liver tumours. Liver failure is a major problem in patients with a poor liver quality or having large operations. The treatment options for liver failure are limited, with high death rates. To estimate patient risk, assessing liver function before surgery is important. Many methods exist for this purpose, including functional, blood, and imaging tests. This guideline summarizes the available literature and expert opinions, and aids clinicians in planning safe liver surgery.

[Robotic Left Hepatectomy Using the Glissonean Pedicle Approach for the Treatment of Caroli's Syndrome]. / Roboter-assistierte Hemihepatektomie links mittels Glissonean pedicle approach bei Caroli Syndrom.

BACKGROUND: Caroli's syndrome is a rare disease characterised by non-obstructive dilation of intrahepatic bile ducts, hepatic fibrosis, and an increased risk of developing cholangiocarcinoma. Minimally invasive liver resection has recently been increasingly adopted for the treatment of patients with localised Caroli's syndrome. However, robot-assisted liver resection for the treatment of Caroli's syndrome has not been published. MATERIALS AND METHODS: We report a case of a 72-year-old Asian female who was referred to our hospital with multifocal cystic dilation of liver segments II, III, and IV. She had no family history of congenital cysts. Her past medical history was uneventful except for an open appendectomy. The liver function tests were normal, with a negative echinococcus serology test. On MRI, the biliary anatomy at the hilum and right liver appeared to be regular. Therefore, a robotic left hepatectomy was carried out for the unilobar involvement of Caroli's syndrome using the Da Vinci Xi-system. RESULTS: We performed a Glissonean pedicle approach while preserving the caudate lobe. After removing surgical adhesions from the anterior abdominal wall using robotic scissors, a routine cholecystectomy was performed. An aberrant left hepatic artery arising from the left gastric artery was clipped and divided. The left portal pedicle was controlled after lowering the hilar plate. The ischemic demarcation line on the liver surface was followed after clamping the left pedicle, and parenchymal dissection was performed using Maryland bipolar forceps. A Pringle manoeuvre was not applied. The left pedicle and the left hepatic vein were transected using a GIA stapling device while the middle hepatic vein was preserved. Indocyanin green fluorescence imaging confirmed adequate perfusion of the remnant liver tissue including the caudate lobe. The specimen was placed in an extraction bag and removed via a Pfannenstiel incision. The total operation time was 239 min, including a total blood loss of 100 ml. The postoperative course was uneventful. The patient was discharged on postoperative day 5. On 6 months follow-up, the patient had normal liver function and no signs of recurrent disease. CONCLUSION: Robotic left hepatectomy using an extrahepatic Glissonean pedicle approach is technically feasible.

Identification of liver-derived bone morphogenetic protein (BMP)-9 as a potential new candidate for treatment of colorectal cancer.

Colorectal cancer (CRC) is a high-incidence malignancy worldwide which still needs better therapy options. Therefore, the aim of the present study was to investigate the responses of normal or malignant human intestinal epithelium to bone morphogenetic protein (BMP)-9 and to find out whether the application of BMP-9 to patients with CRC or the enhancement of its synthesis in the liver could be useful strategies for new therapy approaches. In silico analyses of CRC patient cohorts (TCGA database) revealed that high expression of the BMP-target gene ID1, especially in combination with low expression of the BMP-inhibitor noggin, is significantly associated with better patient survival. Organoid lines were generated from human biopsies of colon cancer (T-Orgs) and corresponding non-malignant areas (N-Orgs) of three patients. The N-Orgs represented tumours belonging to three different consensus molecular subtypes (CMS) of CRC. Overall, BMP-9 stimulation of organoids promoted an enrichment of tumour-suppressive gene expression signatures, whereas the stimulation with noggin had the opposite effects. Furthermore, treatment of organoids with BMP-9 induced ID1 expression (independently of high noggin levels), while treatment with noggin reduced ID1. In summary, our data identify the ratio between ID1 and noggin as a new prognostic value for CRC patient outcome. We further show that by inducing ID1, BMP-9 enhances this ratio, even in the presence of noggin. Thus, BMP-9 is identified as a novel target for the development of improved anti-cancer therapies of patients with CRC.

Prognosis of patients with hepatocellular carcinoma treated with immunotherapy - development and validation of the CRAFITY score.

BACKGROUND & AIMS: Immunotherapy with atezolizumab plus bevacizumab represents the new standard of care in systemic front-line treatment of hepatocellular carcinoma (HCC). However, biomarkers that predict treatment success and survival remain an unmet need. METHODS: Patients with HCC put on PD-(L)1-based immunotherapy were included in a training set (n = 190; 6 European centers) and a validation set (n = 102; 8 European centers). We investigated the prognostic value of baseline variables on overall survival using a Cox model in the training set and developed the easily applicable CRAFITY (CRP and AFP in ImmunoTherapY) score. The score was validated in the independent, external cohort, and evaluated in a cohort of patients treated with sorafenib (n = 204). RESULTS: Baseline serum alpha-fetoprotein ≥100 ng/ml (hazard ratio [HR] 1.7; p = 0.007) and C-reactive protein ≥1 mg/dl (HR, 1.7; p = 0.007) were identified as independent prognostic factors in multivariable analysis and were used to develop the CRAFITY score. Patients who fulfilled no criterion (0 points; CRAFITY-low) had the longest median overall survival (27.6 (95% CI 19.5-35.8) months), followed by those fulfilling 1 criterion (1 point; CRAFITY-intermediate; 11.3 (95% CI 8.0-14.6) months), and patients meeting both criteria (2 points; CRAFITY-high; 6.4 (95% CI 4.8-8.1) months; p <0.001). Additionally, best radiological response (complete response/partial response/stable disease/progressive disease) was significantly better in patients with lower CRAFITY score (CRAFITY-low: 9%/20%/52%/20% vs. CRAFITY-intermediate: 3%/25%/36%/36% vs. CRAFITY-high: 2%/15%/22%/61%; p = 0.003). These results were confirmed in the independent validation set and in different subgroups, including Child-Pugh A and B, performance status 0 and ≥1, and first-line and later lines. In the sorafenib cohort, CRAFITY was associated with survival, but not radiological response. CONCLUSIONS: The CRAFITY score is associated with survival and radiological response in patients receiving PD-(L)1 immunotherapy. The score may help with patient counseling but requires prospective validation. LAY SUMMARY: The immunotherapy-based regimen of atezolizumab plus bevacizumab represents the new standard of care in systemic first-line therapy of hepatocellular carcinoma (HCC). Biomarkers to predict treatment outcome are an unmet need in patients undergoing immunotherapy for HCC. We developed and externally validated a score that predicts outcome in patients with HCC undergoing immunotherapy with immune checkpoint blockers.

Impact of spleen preservation on the incidence of postoperative pancreatic fistula after distal pancreatectomy: Is less more?

BACKGROUND: Postoperative pancreatic fistula (POPF) remains a major complication after distal pancreatectomy (DP) with a significant impact on patients' quality of life. There is limited evidence that preservation of the spleen reduces the risk of POPF. Therefore, we aimed to investigate the impact of splenectomy on perioperative outcome. METHODS: Data from patients who underwent DP for malignant and benign disease at our institution between 2004 and 2021 were reviewed. Patients were grouped according to spleen preservation (SP-DP) and splenectomy (DPS). Intraoperative parameters and postoperative outcomes were compared between groups. Univariable and multivariable analyses were used to investigate factors that influence the occurrence of clinically relevant (cr)POPF. RESULTS: A total of 199 patients were included, of whom 61 (30.7%) patients underwent SP-DP. Patients who underwent SP-DP had a significantly lower rate of crPOPF (p = 0.022), shorter hospital stay (p = 0.003), and less readmissions (p = 0.012). On multivariate analysis, obesity (OR 2.88, p = 0.021), benign lesions (OR 2.35, p = 0.018), postoperative acute pancreatitis (OR 2.53, p = 0.028), and splenectomy (OR 2.83, p = 0.011) were independent risk factors associated with the onset of crPOPF. DISCUSSION: Preservation of the spleen reduces the risk of crPOPF in patients undergoing distal pancreatectomy for benign and malignant disease.

Quality assurance and quality control in surgical oncology.

Even though surgery has remained a key component within multi-disciplinary cancer care, the expectations have changed. Instead of serving as a modality to free a patient of a mass at all means and at the risk of high morbidity, modern cancer surgery is expected to provide adequate tumor clearance with lowest invasiveness. This review summarizes the evidence on quality assurance in surgical oncology and gives a comprehensive overview of quality improvement tools.

Endoscopic papillectomy or pancreaticoduodenectomy for ampullary lesions: a single center retrospective cohort study.

BACKGROUND: This study aimed to compare post-operative morbidity, mortality, and completeness of resection following endoscopic vs. radical surgical resection for ampullary lesions. METHODS: A retrospective analysis of the prospectively collected data from a surgical database for patients with ampullary lesions at our institution was performed. All consecutive patients undergoing endoscopic papillectomy (EP) or pancreaticoduodenectomy (PD) for ampullary lesions between 2007 and 2021 were eligible for this analysis. RESULTS: A total of 85 patients were included of whom 42 underwent EP whereas 43 received a PD. The resected lesion was a tubulovillous adenoma in 26 patients (61.9%) in the EP cohort, and 37 patients (86.0%) in the PD cohort had adenocarcinomas. The completeness of resection was equal in both cohorts. Significantly more patients of the PD cohort had to undergo reinterventions. After a mean follow up of 36 months (EP) vs. 16 months (PD), the rate of tumor recurrence did not differ between both groups. CONCLUSION: Equivalently high completeness of resection rates and correspondingly low recurrence rates can be achieved after EP and PD. Our results regarding residual tumor and recurrence rates show that even large tumors can be resected endoscopically with high primary success and completeness of resection rates.

Minimally invasive mesohepatectomy for centrally located liver lesions-a case series.

BACKGROUND: Resection of centrally located liver lesions remains a technically demanding procedure. To date, there are limited data on the effectiveness and safety of minimally invasive mesohepatectomy for benign and malignant lesions. It was therefore the objective of this study to evaluate the perioperative outcomes of minimally invasive mesohepatectomy for liver tumors at a tertiary care hospital. METHODS: Consecutive patients who underwent a minimally invasive anatomic mesohepatectomy using a Glissonean pedicle approach from April 2018 to November 2021 were identified from a prospective database. Demographics, operative details, and postoperative outcomes were analyzed using descriptive statistics for continuous and categorical variables. RESULTS: A total of ten patients were included, of whom five patients had hepatocellular carcinoma, one patient had cholangiocarcinoma, three patients had colorectal liver metastases, and one patient had a hydatid cyst. Two and eight patients underwent robotic-assisted and laparoscopic resections, respectively. The median operative time was 393 min (interquartile range (IQR) 298-573 min). Conversion to laparotomy was required in one case. The median lesion size was 60 mm and all cases had negative resection margins on final histopathological analysis. The median total blood loss was 550 ml (IQR 413-850 ml). One patient had a grade III complication. The median length of stay was 7 days (IQR 5-12 days). Time-to-functional recovery was achieved after a median of 2 days (IQR 1-4 days). There were no readmissions within 90 days after surgery. CONCLUSION: Minimally invasive mesohepatectomy is a feasible and safe approach in selected patients with benign and malignant liver lesions.

Using a Reinforced Stapler Decreases the Incidence of Postoperative Pancreatic Fistula After Distal Pancreatectomy: A Systematic Review and Meta-Analysis.

BACKGROUND: There is no consensus on the pancreatic transection during distal pancreatectomy (DP) to reduce postoperative pancreatic fistula (POPF). This meta-analysis aimed to evaluate the effects of a reinforced stapler on the postoperative outcomes of DP. METHODS: We systematically searched electronic databases and bibliographic reference lists in The PubMed/MEDLINE, Google Scholar, Cochrane Library's Controlled Trials Registry and Database of Systematic Reviews, Embase, and Scopus. Review Manager Software was used for pooled estimates. RESULTS: Seven eligible studies published between 2007 and 2021 were included with 553 patients (267 patients in the reinforced stapler group and 286 patients in the standard stapler group). The reinforced stapler reduced the POPF grade B and C (OR = 0.33; 95% CI [0.19, 0.57], p < 0.01). There was no difference between the reinforced stapler group and standard stapler group in terms of mortality rate (OR = 0.39; 95% CI [0.04, 3.57], p = 0.40), postoperative haemorrhage (OR = 0.53; 95% CI [0.20, 1.43], p = 0.21), and reoperation rate (OR = 0.91; 95% CI [0.40, 2.06], p = 0.82). CONCLUSIONS: Reinforced stapling in DP is safe and seems to reduce POPF grade B/C with similar mortality rates, postoperative bleeding, and reoperation rate. The protocol of this systematic review with meta-analysis was registered in PROSPERO (ID: CRD42021286849).

Intraoperative Increase of Portal Venous Pressure is an Immediate Predictor of Posthepatectomy Liver Failure After Major Hepatectomy: A Prospective Study.

OBJECTIVES: The aim of this study was to assess intraoperative changes of hepatic macrohemodynamics and their association with ascites and posthepatectomy liver failure (PHLF) after major hepatectomy. SUMMARY OF BACKGROUND DATA: Large-scale ascites and PHLF remain clinical challenges after major hepatectomy. No study has concomitantly evaluated arterial and venous liver macrohemodynamics in patients undergoing liver resection. METHODS: Portal venous pressure (PVP), portal venous flow (PVF), and hepatic arterial flow (HAF) were measured intraoperatively pre- and postresection in 67 consecutive patients with major hepatectomy (ie, resection of ≥3 liver segments). A group of 30 patients with minor hepatectomy served as controls. Liver macrohemodynamics and their intraoperative changes (ie, Δ) were analyzed as predictive biomarkers of ascites and PHLF using Fisher exact, t test, or Wilcoxon rank sum test for univariate and logistic regression for multivariate analyses. RESULTS: Major hepatectomy increased PVP by 26.9% (P = 0.001), markedly decreased HAF by 40.7% (P < 0.001), and slightly decreased PVF by 13.4% (P = 0.011). Minor resections had little effects on hepatic macrohemodynamics. There was no significant association of liver macrohemodynamics with ascites. While middle hepatic vein resection caused higher postresection PVP after right hepatectomy (P = 0.04), the Pringle maneuver was associated with a significant PVF (P = 0.03) and HAF reduction (P = 0.03). Uni- and multivariate analysis revealed an intraoperative PVP increase as an independent predictor of PHLF (P = 0.025). CONCLUSION: Intraoperative PVP kinetics serve as independent predictive biomarker of PHLF after major hepatectomy. These data highlight the importance to assess intraoperative dynamics rather than the pre- and postresection PVP values.

Outcomes of non-metastatic poorly differentiated gastroenteropancreatic neuroendocrine neoplasms treated with surgery: a real-world population-based study.

OBJECTIVE: To assess the outcomes of non-metastatic poorly differentiated gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) treated with radical surgery. METHODS: Surveillance, Epidemiology, and End Results (SEER) database (1998-2015) was accessed, and patients with non-metastatic poorly differentiated/undifferentiated GEP-NENs were reviewed. Multivariable Cox regression analysis was used to evaluate factors affecting overall survival (OS) and cancer-specific survival (CSS). Patients treated with radical surgery were matched to those who did not undergo surgery through propensity score matching and Kaplan-Meier survival estimates were used to evaluate the impact of surgery in the post-propensity cohort. RESULTS: A total of 1517 patients were included. Within multivariable Cox regression models and compared to no surgery, radical surgery was associated with improved OS (HR: 0.41; 95% CI: 0.34-0.50) and CSS (HR: 0.37; 95% CI: 0.29-0.47). A total of 233 patients who underwent no surgery were then matched to 233 patients who underwent radical surgery. Within the post-propensity cohort, radical surgery was associated with improved OS (P < 0.001). CONCLUSIONS: Radical surgery is associated with improved survival outcomes in patients with non-metastatic poorly differentiated GEP-NENs. Further studies are required to better identify the best timing of radical surgery within the context of multimodal management.