Novel Benchmark Values for Open Major Anatomic Liver Resection in Non-cirrhotic Patients: A Multicentric Study of 44 International Expert Centers.

OBJECTIVE: This study aims at establishing benchmark values for best achievable outcomes following open major anatomic hepatectomy for liver tumors of all dignities. BACKGROUND: Outcomes after open major hepatectomies vary widely lacking reference values for comparisons among centers, indications, types of resections, and minimally invasive procedures. METHODS: A standard benchmark methodology was used covering consecutive patients, who underwent open major anatomic hepatectomy from 44 high-volume liver centers from 5 continents over a 5-year period (2016-2020). Benchmark cases were low-risk non-cirrhotic patients without significant comorbidities treated in high-volume centers (≥30 major liver resections/year). Benchmark values were set at the 75th percentile of median values of all centers. Minimum follow-up period was 1 year in each patient. RESULTS: Of 8044 patients, 2908 (36%) qualified as benchmark (low-risk) cases. Benchmark cutoffs for all indications include R0 resection ≥78%; liver failure (grade B/C) ≤10%; bile leak (grade B/C) ≤18%; complications ≥grade 3 and CCI ® ≤46% and ≤9 at 3 months, respectively. Benchmark values differed significantly between malignant and benign conditions so that reference values must be adjusted accordingly. Extended right hepatectomy (H1, 4-8 or H4-8) disclosed a higher cutoff for liver failure, while extended left (H1-5,8 or H2-5,8) were associated with higher cutoffs for bile leaks, but had superior oncologic outcomes, when compared to formal left hepatectomy (H1-4 or H2-4). The minimal follow-up for a conclusive outcome evaluation following open anatomic major resection must be 3 months. CONCLUSION: These new benchmark cutoffs for open major hepatectomy provide a powerful tool to convincingly evaluate other approaches including parenchymal-sparing procedures, laparoscopic/robotic approaches, and alternative treatments, such as ablation therapy, irradiation, or novel chemotherapy regimens.

Perihilar Cholangiocarcinoma - Novel Benchmark Values for Surgical and Oncological Outcomes From 24 Expert Centers.

OBJECTIVE: The aim of this study was to define robust benchmark values for the surgical treatment of perihilar cholangiocarcinomas (PHC) to enable unbiased comparisons. BACKGROUND: Despite ongoing efforts, postoperative mortality and morbidity remains high after complex liver surgery for PHC. Benchmark data of best achievable results in surgical PHC treatment are however still lacking. METHODS: This study analyzed consecutive patients undergoing major liver surgery for PHC in 24 high-volume centers in 3 continents over the recent 5-year period (2014-2018) with a minimum follow-up of 1 year in each patient. Benchmark patients were those operated at high-volume centers (≥50 cases during the study period) without the need for vascular reconstruction due to tumor invasion, or the presence of significant co-morbidities such as severe obesity (body mass index ≥35), diabetes, or cardiovascular diseases. Benchmark cutoff values were derived from the 75th or 25th percentile of the median values of all benchmark centers. RESULTS: Seven hundred eight (39%) of a total of 1829 consecutive patients qualified as benchmark cases. Benchmark cut-offs included: R0 resection ≥57%, postoperative liver failure (International Study Group of Liver Surgery): ≤35%; in-hospital and 3-month mortality rates ≤8% and ≤13%, respectively; 3-month grade 3 complications and the CCI: ≤70% and ≤30.5, respectively; bile leak-rate: ≤47% and 5-year overall survival of ≥39.7%. Centers operating mostly on complex cases disclosed better outcome including lower post-operative liver failure rates (4% vs 13%; P = 0.002). Centers from Asia disclosed better outcomes. CONCLUSION: Surgery for PHC remains associated with high morbidity and mortality with now the availability of benchmark values covering 21 outcome parameters, which may serve as key references for comparison in any future analyses of individuals, group of patients or centers.

Repeated resection for recurrent intrahepatic cholangiocarcinoma: A retrospective German multicentre study.

BACKGROUND: Tumour recurrence is common after resection of intrahepatic cholangiocarcinoma (ICC). Repeated resection is a potential curative treatment, but outcomes are not well-defined thus far. The aim of this retrospective multicentre cohort study was to show the feasibility and survival of repeated resection of ICC recurrence. METHODS: Data were collected from 18 German hepato-pancreatico-biliary centres for patients who underwent repeated exploration of recurrent ICC between January 2008 and December 2017. Primary end points were overall (OS) and recurrence-free survival from the day of primary and repeated resection. RESULTS: Of 156 patients who underwent repeated exploration for recurrent ICC, 113 underwent re-resection. CA19-9 prior to primary resection, R status of first liver resection and median time to recurrence were significant determinants of repeated resectability. Median OS in the repeated resection group was 65.2 months, with consecutive 1-, 3- and 5-year OS of 98%, 78% and 57% respectively. After re-exploration, median OS from primary resection was 46.7 months, with a consecutive 1-, 3- and 5-year OS of 95%, 55% and 22% respectively. From the day of repeated resection, the median OS was 36.8 months, with a consecutive 1-, 3- and 5-year OS of 86%, 51% and 34% respectively. Minor morbidity (grade I+II) was present in 27%, grade IIIa-IVb morbidity in 20% and mortality in 3.5% of patients. CONCLUSION: Repeated resection of ICC has acceptable morbidity and mortality and seems to be associated with improved long-term survival. Structured follow-up after resection of ICC is necessary for early identification of these patients.

Intrahepatic cholangiocarcinoma: Introducing the preoperative prediction score based on preoperative imaging.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) still has a poor long-term outcome, even after complete resection. We investigated different parameters gathered in preoperative imaging and analyzed their influence on resectability, recurrence, and survival. METHODS: All patients who underwent exploration due to ICC between January 2008 and June 2018 were analyzed retrospectively. Kaplan-Meier model, log-rank test and Cox regression were used. RESULTS: Out of 184 patients, 135 (73.4%) underwent curative intended resection. Median overall survival (OS) was 22.2 months with a consecutive 1-, 3- and 5-year OS of 73%, 29%, and 17%. Median recurrence-free survival (RFS) was 9.3 months with a consecutive 1-, 3- and 5-year RFS of 36%, 15%, and 11%. Site of tumor, parenchymal localization, tumor configuration/dissemination, and estimated tumor volume had significant influence on resectability. Univariate analyses showed that site of tumor, tumor configuration/dissemination, number of nodules, and estimated tumor volume had predictive values for OS and RFS. Together with tumor size the preoperative prediction (POP) score was created showing significance for OS and RFS (all P < 0.001). In multivariate analysis, POP score (HR = 1.779; 95% CI: 1.268-2.495; P = 0.001), T stage (HR = 1.255; 95% CI: 1.040-1.514; P = 0.018) and N stage (HR = 1.334; 95% CI: 1.081-1.645; P = 0.007) were the independent predictors for OS. For RFS, POP score (HR = 1.733; 95% CI: 1.300-2.311; P < 0.001) and M stage (HR = 3.036; 95% CI: 1.376-6.697; P = 0.006) were the independent predictors. CONCLUSIONS: The POP score showed to have a highly significant influence on OS and RFS. The score is easy to assess through preoperative imaging. For patients in the high risk group at least staging laparoscopy or preoperative chemotherapy should be evaluated, because they showed equal outcome compared to the irresectable group.

The MEGNA Score and Preoperative Anemia are Major Prognostic Factors After Resection in the German Intrahepatic Cholangiocarcinoma Cohort.

BACKGROUND: Surgical resection is associated with the best long-term results for intrahepatic cholangiocarcinoma (ICC); however, long-term outcomes are still poor. OBJECTIVE: The primary aim of this study was to validate the recently proposed MEGNA score and to identify additional prognostic factors influencing short- and long-term survival. PATIENTS AND METHODS: This was a retrospective analysis of a German multicenter cohort operated at 10 tertiary centers from 2004 to 2013. Patients were clustered using the MEGNA score and overall survival was analyzed. Cox regression analysis was used to identify prognostic factors for both overall and 90-day survival. RESULTS: A total of 488 patients undergoing liver resection for ICC fulfilled the inclusion criteria and underwent analysis. Median age was 67 years, 72.5% of patients underwent major hepatic resection, and the lymphadenectomy rate was 86.9%. Median overall survival was 32.2 months. The MEGNA score significantly discriminated the long-term overall survival: 0 (68%), I (48%), II (32%), and III (19%) [p <0.001]. In addition, anemia was an independent prognostic factor for overall survival (hazard ratio 1.78, 95% confidence interval 1.29-2.45; p <0.01). CONCLUSION: Hepatic resection provides the best long-term survival in all risk groups (19-65% overall survival). The MEGNA score is a good discriminator using histopathologic items and age for stratification. Correction of anemia should be attempted in every patient who responds to treatment. Perioperative liver failure remains a clinical challenge and contributes to a relevant number of perioperative deaths.

Quality-based assessment of camera navigation skills for laparoscopic fundoplication.

Laparoscopic fundoplication is considered the gold standard surgical procedure for the treatment of symptomatic hiatus hernia. Studies on surgical performance in minimally invasive hiatus hernia repair have neglected the role of the camera assistant so far. The current study was designed to assess the applicability of the structured assessment of laparoscopic assistance skills (SALAS) score to laparoscopic fundoplication as an advanced and commonly performed laparoscopic upper GI procedure. Randomly selected laparoscopic fundoplications (n = 20) at a single institute were evaluated. Four trained reviewers independently assigned SALAS scoring based on synchronized video and voice recordings. The SALAS score (5-25 points) consists of five key aspects of laparoscopic camera navigation as previously described. Experience in camera assistance was defined as at least 100 assistances in complex laparoscopic procedures. Nine different surgical teams, consisting of five surgical residents, three fellows, and two attending physicians, were included. Experienced and inexperienced camera assistants were equally distributed (10/10). Construct validity was proven with a significant discrimination between experienced and inexperienced camera assistants for all reviewers (P < 0.05). The intraclass correlation coefficient of 0.897 demonstrates the score's low interrater variability. The total operation time decreases with increasing SALAS score, not reaching statistical significance. The applied SALAS score proves effective by discriminating between experienced and inexperienced camera assistants in an upper GI surgical procedure. This study demonstrates the applicability of the SALAS score to a more advanced laparoscopic procedure such as fundoplication enabling future investigations on the influence of camera navigation on surgical performance and operative outcome.

Relevance of suspicious lymph nodes in preoperative imaging for resectability, recurrence and survival of intrahepatic cholangiocarcinoma.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is often diagnosed at an advanced stage resulting in a low resectability rate. Even after potentially curative resection the risk for tumor recurrence is high. Although the extent and value of lymphadenectomy is part of ongoing discussion, the role of preoperative imaging for assessment of suspicious lymph nodes (suspLN) has only been studied modestly. Aim of this study is to demonstrate the influence of suspicious lymph nodes in preoperative imaging on resectability, recurrence, and long-term outcome. METHODS: All patients who underwent exploration for ICC between January 2008 and June 2018 were included. Preoperative imaging (CT or MRI) was analysed with focus on suspLN at the hepatoduodenal ligament, lesser curvature, interaortocaval, and superior to the diaphragm; suspLN were classified according to the universally accepted RECIST 1.1 criteria; histopathology served as gold standard. RESULTS: Out of 187 patients resection was performed in 137 (73.3%), in 50 patients the procedure was terminated after exploration. Overall, suspLN were found preoperatively in 73/187 patients (39%). Comparing patients who underwent resection and exploration only, suspLN were significantly more common in the exploration group (p = 0.011). Regarding lymph node stations, significant differences could be shown regarding resectability: All tumors with suspLN superior to the diaphragm were irresectable. Preoperative imaging assessment showed a strong correlation with final histopathology, especially of suspLN of the hepatoduodenal ligament and the lesser curvature. Sensitivity of suspLN was 71.1%, specificity 90.8%. Appearance of tumor recurrence was not affected by suspLN (p = 0.289). Using a short-axis cut-off of <> 1 cm, suspLN had significant influence on recurrence-free survival (RFS, p = 0.009) with consecutive 1-, 3-, and 5-year RFS of 41, 21, and 15% versus 29, 0, and 0%, respectively. Similarly, 1-, 3- and 5-year overall survival (OS) was 75, 30, and 18% versus 59, 18, and 6%, respectively (p = 0.040). CONCLUSION: Suspicious lymph nodes in preoperative imaging are predictor for unresectability and worse survival. Explorative laparoscopy should be considered, if distant suspicious lymph nodes are detected in preoperative imaging. Nevertheless, given a sensitivity of only 71.1%, detection of suspicious lymph nodes in the preoperative imaging alone is not sufficient to allow for a clear-cut decision against a surgical approach.

Intrahepatic cholangiocarcinoma - influence of resection margin and tumor distance to the liver capsule on survival.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is often diagnosed in advanced stage. Aim of this study was to analyse the influence of resection margins and tumor distance to the liver capsule on survival and recurrence in a single center with a high number of extended resections. METHODS: From January 2008 to June 2018 data of all patients with ICC were collected and further analysed with Kaplan Meier Model, Cox regression or Chi2 test for categorical data. RESULTS: Out of 210 included patients 150 underwent curative intended resection (71.4%). Most patients required extended resections (n = 77; 51.3%). R0-resection was achieved in 131 patients (87.3%) with minimal distances to the resection margin > 1 cm in 22, 0.5-1 cm in 11, 0.1-0.5 cm in 49 patients, and <  0.1 cm in 49 patients. Overall survival (OS) for margins > 0.5 cm compared to 0.5-0.1 cm or R1 was better, but without reaching significance. All three groups had significantly better OS compared to the irresectable group. Recurrence-free survival (RFS) was also better in patients with a margin > 0.5 cm than in the < 0.5-0.1 cm or the R1-group, but even without reaching significance. Different distance to the liver capsule significantly affected OS, but not RFS. CONCLUSIONS: Wide resection margins (> 0.5 cm) should be targeted but did not show significantly better OS or RFS in a cohort with a high percentage of extended resections (> 50%). Wide margins, narrow margins and even R1 resections showed a significant benefit over the irresectable group. Therefore, extended resections should be performed, even if only narrow margins can be achieved.

The role of sarcopenia in patients with intrahepatic cholangiocarcinoma: Prognostic marker or hyped parameter?

BACKGROUND & AIMS: Sarcopenia has emerged as a prognostic parameter in numerous cancer entities. Current research favours its role as a determining factor for overall survival (OS) in patients with intrahepatic cholangiocarcinoma (ICC); however, it is unclear whether sarcopenia is a truly independent survival predictor if combined with established prognostic factors. METHODS: Between 1997-2018, 417 patients with histopathologically confirmed ICC were referred to our centre, of whom 293 were included in this study. Cross-sectional imaging, laboratory examinations and histopathological reports were retrospectively analysed. Psoas muscle index (PMI) as easy-to-measure marker of sarcopenia was calculated. Using optimal stratification, sex-specific PMI cut-offs were calculated and tested in hazard regression models against previously published risk factors-for the entire cohort, and within resected and non-resected subgroups. RESULTS: Median OS for patients with low respectively high PMI was 23.5 and 34.5 months in the resected subgroup (P = 0.008) and 5.1 and 7.8 months (P = 0.01) in the non-resected subgroup. In multivariate hazard regression models for the entire cohort, low PMI exhibited independent predictive value (P = 0.01) as did translobar tumour spread (P = 0.005), extrahepatic extension (P = 0.03), tumour boundary type (P < 0.001), carbohydrate antigen 19-9 (CA 19-9) levels (P = 0.001), alkaline phosphatase levels (P = 0.001) and distant metastasis (P < 0.001). In subgroup analyses, low PMI remained predictive among non-resected patients (P = 0.03), but lost its predictive value among resected patients (P = 0.15). CONCLUSIONS: Psoas muscle index strongly predicted OS in univariate analysis. However, addition of established risk factors eliminated its predictive value among resected patients. Thus, when resection is deemed oncologically reasonable, patients should not be excluded from surgery because of sarcopenia alone.

Surgical Resection for Recurrent Intrahepatic Cholangiocarcinoma.

BACKGROUND: Although after R0 resection of intrahepatic cholangiocarcinoma (ICC) recurrence is frequent, most guidelines do not address strategies for this. The aim of this study was to analyze the outcome of repeated resection and to determine criteria when repeated resection is reasonable. METHODS: Between 2008 and 2016, we consecutively collected all cases of ICC (n = 176) in a prospective database and further analyzed them with a focus on tumor recurrence, its surgical treatment, overall survival and recurrence-free survival. RESULTS: Overall, a total of 22 explorations were performed for recurrent ICC in 17 patients. Resection rate was 18 repeated resections in 13 patients. Three patients underwent repeated resection twice and one patient three times. Recurrence was solitary in 7 patients and multifocal in 11 re-resected cases. Median overall survival (OS) of patients who underwent repeated resection was 65.2 months (interquartile range 37-126.5) with a 5-year OS rate of 62%, calculated from primary resection. Patients who underwent repeated resections had a significant better OS compared to those receiving chemotherapy, transarterial chemoembolization, selective internal radiotherapy, radiofrequency ablation or best supportive care (p < 0.001). CONCLUSION: Repeated resection of recurrent ICC is reasonable and associated with an improved survival. Re-exploration should be considered as long as resection is technically possible.

Resection of intrahepatic cholangiocarcinoma in elderly patients - is it reasonable?

BACKGROUND: Intrahepatic cholangiocarinoma (ICC) has a rising incidence in western countries. Often major or extended resections are necessary for complete tumor removal. Due to demographical trends the number of elderly patients diagnosed with ICC is rising accordingly. Aim of this study is to show whether resection of ICC in elderly patients is reasonable or not. METHODS: Between January 2008 and June 2018 all consecutive patients with ICC were collected. Analyses were focussed on the performed resection, its extent, postoperative morbidity and mortality as well as survival. Statistics were performed with Chi2 test for categorical data and for survival analyses the Kaplan Meier model with log rank test was used. RESULTS: In total 210 patients underwent surgical exploration with 150 resections (71.4%). Patients were divided in 70-years cut-off groups (> 70 vs < 70 years of age) as well as a young (age 30-50, n = 23), middle-age (50-70, n = 76) and old (> 70, n = 51) group, whose results are presented here. Resectability (p = 0.709), extent of surgery (p = 0.765), morbidity (p = 0.420) and mortality (p = 0.965) was comparable between the different age groups. Neither visceral (p = 0.991) nor vascular (p = 0.614) extension differed significantly, likewise tumor recurrence (p = 0.300) or the localisation of recurrence (p = 0.722). In comparison of patients > or < 70 years of age, recurrence-free survival (RFS) was significantly better for the younger group (p = 0.047). For overall survival (OS) a benefit could be shown, but without reaching significance (p = 0.072). In subgroup analysis the middle-age group had significant better OS (p = 0.020) and RFS (p = 0.038) compared to the old group. Additionally, a better OS (p = 0.076) and RFS (p = 0.179) was shown in comparison with the young group as well, but without reaching significance. The young compared to the old group had analogous OS (p = 0.931) and RFS (p = 0.845). CONCLUSION: Resection of ICC in elderly patients is not associated with an increased perioperative risk. Even extended resections can be performed in elderly patients without obvious disadvantages. Middle-age patients have a clear benefit for OS and RFS, while young and old patients have a comparable and worse long-term outcome.

Transanal total mesorectal excision for restorative coloproctectomy in an obese high-risk patient with colitis-associated carcinoma.

Transanal total mesorectal excision (TaTME) offers great potential for the treatment of malign and benign diseases. However, laparoscopic-assisted TaTME in ulcerative colitis has not been described in more than a handful of patients. We present a 47-year-old highly comorbid female patient with an ulcerative colitis-associated carcinoma of the ascending colon and steroid- refractory pancolitis. A two-stage restorative coloproctectomy including right-sided complete mesocolic excision was conducted. The second step consisted of a successful nerve-sparing TaTME and a handsewn ileal pouch-anal anastomosis. TaTME may extend the possible treatment options in inflammatory bowel disease, especially for high-risk patients.

Responses of intact and injured sural nerve fibers to cooling and menthol.

Intact and injured cutaneous C-fibers in the rat sural nerve are cold sensitive, heat sensitive, and/or mechanosensitive. Cold-sensitive fibers are either low-threshold type 1 cold sensitive or high-threshold type 2 cold sensitive. The hypothesis was tested, in intact and injured afferent nerve fibers, that low-threshold cold-sensitive afferent nerve fibers are activated by the transient receptor potential melastatin 8 (TRPM8) agonist menthol, whereas high-threshold cold-sensitive C-fibers and cold-insensitive afferent nerve fibers are menthol insensitive. In anesthetized rats, activity was recorded from afferent nerve fibers in strands isolated from the sural nerve, which was either intact or crushed 6-12 days before the experiment distal to the recording site. In all, 77 functionally identified afferent C-fibers (30 intact fibers, 47 injured fibers) and 34 functionally characterized A-fibers (11 intact fibers, 23 injured fibers) were tested for their responses to menthol applied to their receptive fields either in the skin (10 or 20%) or in the nerve (4 or 8 mM). Menthol activated all intact (n = 12) and 90% of injured (n = 20/22) type 1 cold-sensitive C-fibers; it activated no intact type 2 cold-sensitive C-fibers (n = 7) and 1/11 injured type 2 cold-sensitive C-fibers. Neither intact nor injured heat- and/or mechanosensitive cold-insensitive C-fibers (n = 25) and almost no A-fibers (n = 2/34) were activated by menthol. These results strongly argue that cutaneous type 1 cold-sensitive afferent fibers are nonnociceptive cold fibers that use the TRPM8 transduction channel.

Computer-assisted intraoperative 3D-navigation for liver surgery: a prospective randomized-controlled pilot study.

Background: Liver surgery is the standard of care for primary and many secondary liver tumors. Due to variability and complexity in liver anatomy preoperative imaging is necessary to determine resectability and for planning the surgical strategy. In the last few years, computer-assisted resection planning has been introduced in liver surgery. Aim of this trial was the evaluation of computer-assisted three-dimensional (3D)-navigation for liver surgery. Methods: This study was a prospective randomized-controlled pilot trial and patients were randomized in navigated or non-navigated group. Primary end point was the quotient of intraoperative resected volume and planned resection volume. Secondary end points included operation time, resection margin and postoperative complications. 3D reconstructions were performed with MeVis Distant Services (MeVis AG, Bremen, Germany). The navigation system CAS-One Liver (CAScination AG, Bern, Switzerland) was used for intraoperative computer-assisted 3D-navigation. Results: The data of 16 patients with 20 liver tumors were used in this analysis. Of these, 8 liver tumors were resected with the utilization of intraoperative navigation. Two postoperative complications were classified grade IIIa or higher. There was no difference in duration of operation (189 vs. 180 min, P=0.970), rate of postoperative complications (n=1 vs. n=1, P=0.696) and length of hospital stay (9 vs. 7 days, P=0.368) between the two groups. Minimal resection margin (0.15 vs. 0.40 cm, P=0.384) and quotient of planned to intraoperative resection volume (0.94 vs. 1.11, P=0.305) were also similar. Conclusions: Intraoperative navigation is a technology that can be safely used during liver resection. Surgical accuracy is not yet superior to the current standard of intraoperative orientation. Further technological advances with suitable deformation algorithms and augmented reality systems will enable a further improvement of the technical feasibility.

Gut Microbiota in Diagnosis, Therapy and Prognosis of Cholangiocarcinoma and Gallbladder Carcinoma-A Scoping Review.

Cancers of the biliary tract are more common in Asia than in Europe, but are highly lethal due to delayed diagnosis and aggressive tumor biology. Since the biliary tract is in direct contact with the gut via the enterohepatic circulation, this suggests a potential role of gut microbiota, but to date, the role of gut microbiota in biliary tract cancers has not been elucidated. This scoping review compiles recent data on the associations between the gut microbiota and diagnosis, progression and prognosis of biliary tract cancer patients. Systematic review of the literature yielded 154 results, of which 12 studies and one systematic review were eligible for evaluation. The analyses of microbiota diversity indices were inconsistent across the included studies. In-depth analyses revealed differences between gut microbiota of biliary tract cancer patients and healthy controls, but without a clear tendency towards particular species in the studies. Additionally, most of the studies showed methodological flaws, for example non-controlling of factors that affect gut microbiota. At the current stage, there is a lack of evidence to support a general utility of gut microbiota diagnostics in biliary tract cancers. Therefore, no recommendation can be made at this time to include gut microbiota analyses in the management of biliary tract cancer patients.

Mixed Hepatocellular Cholangiocarcinoma: A Comparison of Survival between Mixed Tumors, Intrahepatic Cholangiocarcinoma and Hepatocellular Carcinoma from a Single Center.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most frequent primary liver malignancy, followed by intrahepatic cholangiocarcinoma (ICC). In addition, there is a mixed form for which only limited data are available. The aim of this study was to compare recurrence and survival of the mixed form within the cohorts of patients with HCC and ICC from a single center. METHODS: Between January 2008 and December 2020, all patients who underwent surgical exploration for ICC, HCC, or mixed hepatocellular cholangiocarcinoma (mHC-CC) were included in this retrospective analysis. The data were analyzed, focusing on preoperative and operative details, histological outcome, and tumor recurrence, as well as overall and recurrence-free survival. RESULTS: A total of 673 surgical explorations were performed, resulting in 202 resections for ICC, 344 for HCC (225 non-cirrhotic HCC, ncHCC; 119 cirrhotic HCC, cHCC), and 14 for mHC-CC. In addition, six patients underwent orthotopic liver transplant (OLT) in the belief of dealing with HCC. In 107 patients, tumors were irresectable (resection rate of 84%). Except for the cHCC group, major or even extended liver resections were required. Vascular or visceral extensions were performed regularly. Overall survival (OS) was highly variable, with a median OS of 17.6 months for ICC, 26 months for mHC-CC, 31.8 months for cHCC, and 37.2 months for ncHCC. Tumor recurrence was common, with a rate of 45% for mHC-CC, 48.9% for ncHCC, 60.4% for ICC, and 67.2% for cHCC. The median recurrence-free survival was 7.3 months for ICC, 14.4 months for cHCC, 16 months for mHC-CC, and 17 months for ncHCC. The patients who underwent OLT for mHC-CC showed a median OS of 57.5 and RFS of 56.5 months. CONCLUSIONS: mHC-CC has a comparable course and outcome to ICC. The cholangiocarcinoma component seems to be the dominant one and, therefore, may be responsible for the prognosis. 'Accidental' liver transplant for mHC-CC within the Milan criteria offers a good long-term outcome. This might be an option in countries with no or minor organ shortage.

Reduced Lipid Peroxidation Predicts Unfavorable Prognosis in Hepatocellular Carcinoma, but Not Intrahepatic Cholangiocarcinoma.

Primary liver cancer, including hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA), remains a significant contributor to cancer-related mortality worldwide. Oxidative stress and lipid peroxidation play a key role in chronic liver diseases and have been shown to be pivotal for tumor initiation and progression. 4-hydroxy-nonenal (4-HNE), one of the major mediators of oxidative stress and a well-established biomarker for lipid peroxidation, can act as a signal transducer, inducing inflammation and exerting carcinogenic effects. However, the role of 4-HNE in primary liver cancer remains poorly explored. In this study, we investigated 4-HNE levels in 797 liver carcinomas, including 561 HCC and 236 iCCA, by immunohistochemistry. We then correlated 4-HNE levels with comprehensive clinical data and survival outcomes. In HCC, lower expression levels of 4-HNE were associated with vascular invasion, a high tumor grade, a macrotrabecular-massive HCC subtype, and poor overall survival. Concerning iCCA, large duct iCCA showed significantly higher 4-HNE levels when compared to small duct iCCA. Yet, in iCCA, 4-HNE levels did not correlate with known prognostic parameters or survival outcomes. To conclude, in HCC but not in iCCA, low amounts of 4-HNE predict unfavorable survival outcomes and are associated with aggressive tumor behavior. These findings provide insights into the role of 4-HNE in liver cancer progression and may enable novel therapeutic strategies.

Role of associating liver partition and portal vein ligation for staged hepatectomy for advanced colorectal liver disease: indispensable or overstressed?

BACKGROUND: The aim of this study was to analyse the role of associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) for advanced colorectal liver disease. Surgery offers the best long-term survival in patients with colorectal liver metastases (CRLM). To increase the rates of resectability, two-stage procedures (TSH) and ALPPS are established methods in cases of advanced colorectal liver disease to avoid post hepatectomy liver failure (PHLF). There is still a debate of the oncological utility and the surgical ranking of ALPPS in this clinical scenario. The aim of this analysis was to share our ALPPS data of the perioperative and oncological outcome in patients with CRLM and to compare them with regard to recommendations of published data. METHODS: Ten patients (1.1%) out of 881 received a classical ALPPS procedure between January 2008 and November 2021 at our institution. The median volume increase was 76% (range 55-125%) in a median time interval of 7 days. RESULTS: The completion rate was 100% and all resections were R0-situations (100%). No patient developed PHLF. The median overall survival (OS) was 36.7 months and the median recurrence-free survival (RFS) 6.1 months. CONCLUSIONS: The ALPPS procedure is a surgical approach to achieve a R0 situation in patients with an extensive intrahepatic tumor burden. Nevertheless, the use of ALPPS should be allocated for patients who have no other surgical options.

Morbidity and Mortality of Neutropenic Patients in Visceral Surgery: A Narrative Review.

Leukocytes are essential for the function of the immune system and cell-cell interaction in the human body, but hematological diseases as well as chemotherapeutic treatments due to cancer lead to occasionally or even permanent leukocyte deficiency. Normally, more than 50% of leukocytes are neutrophilic granulocytes, and leukopenia is, therefore, mostly characterized by a decrease in neutrophilic granulocytes. The consequence of neutropenia is increased susceptibility to infection, but also healing disorders are suggestable due to the disturbed cell-cell interaction. While there is no surgical treatment for leucocyte disorders, patients suffering from neutropenia are sometimes in need of surgery for other reasons. Less is known about the morbidity and mortality of this patients, which is why this narrative review critically summarizes the results of recent research in this particular field. The results of this review suggest that neutropenic patients in need of emergency surgery have a higher mortality risk compared to non-neutropenic patients. In contrast, in elective surgery, there was not a clear tendency for a higher mortality risk of neutropenic patients. The role of neutrophilic granulocytes in inflammation and immunity in surgical patients is emphasized by the results, but most of the evaluated studies showed methodological flaws due to small sample sizes or risk of bias. Further research has to evaluate the risk for postoperative complications, particularly of infectious complications such as surgical site infections, in neutropenic patients undergoing elective surgery, and should address the role of neutrophilic function in postoperative morbidity and mortality.

Outcome after Resection for Hepatocellular Carcinoma in Noncirrhotic Liver-A Single Centre Study.

Liver cirrhosis is the most common risk factor for the development of hepatocellular carcinoma (HCC). However, 10 to 15% of all HCC arise in a non-cirrhotic liver. Few reliable data exist on outcome after liver resection in a non-cirrhotic liver. The aim of this single-centre study was to evaluate the outcome of resection for HCC in non-cirrhotic liver (NC-HCC) and to determine prognostic factors for overall (OS) and intrahepatic recurrence-free (RFS) survival. From 2008 to 2020, a total of 249 patients were enrolled in this retrospective study. Primary outcome was OS and RFS. Radiological and pathological findings, such as tumour size, number of nodules, Tumour-, Nodes-, Metastases- (TNM) classification and vascular invasion as well as extent of surgical resection and laboratory liver function were collected. Here, 249 patients underwent liver resection for NC-HCC. In this case, 50% of patients underwent major liver resection, perioperative mortality was 6.4%. Median OS was 35.4 months (range 1-151 months), median RFS was 10.5 months (range 1-128 moths). Tumour diameter greater than three centimetres, multifocal tumour disease, vascular invasion, preoperative low albumin and increased alpha-fetoprotein (AFP) values were associated with significantly worse OS. Our study shows that resection for NC-HCC is an acceptable treatment approach with comparatively good outcome even in extensive tumours.