Small bowel neuroendocrine tumors (SB-NETs) are increasingly identified and have become the most frequent entity among small bowel tumors. An increasing incidence, a high prevalence, and a prolonged ...survival with optimal modern multidisciplinary management makes SB-NETs a unique set of tumors to consider for surgical oncologists. The major goals of surgical treatment in the setting of SB-NET include control of tumor volume, control of endocrine secretion, and prevention of locoregional complications. Key considerations include assessment of multifocality and resection of mesenteric nodal masses with the use of mesenteric-sparing approaches and acceptance of R1 margins if necessary to clear disease while avoiding short bowel syndrome. A description through eight steps for consideration is presented to allow for systematic surgical planning and execution of resection. Moreover, some controversies and evolving considerations to the surgical principles and technical procedures remain. The role of primary tumor resection in the presence of (unresectable) liver metastasis is still unclear. Reports of feasibility of minimally invasive surgery are emerging, with undetermined selection criteria for appropriateness or long-term outcomes. Resection of SB-NETs should be considered in all patients fit for surgery and should follow principles to achieve surgical oncological control that is appropriate for the stage and tumor burden, considering the age and comorbidity of the individual patient.
Objectives
Non-operative management (NOM) is increasingly utilised in blunt abdominal trauma. The 1994 American Association of Surgery of Trauma grading (1994-AAST) is applied for clinical ...decision-making in many institutions. Recently, classifications incorporating contrast extravasation such as the CT severity index (CTSI) and 2018 update of the liver and spleen AAST were proposed to predict outcome and guide treatment, but validation is pending.
Methods
CT images of patients admitted 2000–2016 with blunt splenic and hepatic injury were systematically re-evaluated for 1994/2018-AAST and CTSI grading. Diagnostic accuracy, diagnostic odds ratio (DOR), and positive and negative predictive values were calculated for prediction of in-hospital mortality. Correlation with treatment strategy was assessed by Cramer V statistics.
Results
Seven hundred and three patients were analysed, 271 with splenic, 352 with hepatic and 80 with hepatosplenic injury. Primary NOM was applied in 83% of patients; mortality was 4.8%. Comparing prediction of mortality in mild and severe splenic injuries, the CTSI (3.1% vs. 10.3%; diagnostic accuracy = 75.4%; DOR = 3.66;
p
= 0.006) and 1994-AAST (3.3% vs. 10.5%; diagnostic accuracy = 77.9%; DOR = 3.45;
p
= 0.010) were more accurate compared with the 2018-AAST (3.4% vs. 8%; diagnostic accuracy = 68.2%; DOR = 2.50;
p
= 0.059). In hepatic injuries, the CTSI was superior to both AAST classifications in terms of diagnostic accuracy (88.7% vs. 77.1% and 77.3%, respectively). CTSI and 2018-AAST correlated better with the need for surgery in severe vs. mild hepatic (Cramer V = 0.464 and 0.498) and splenic injuries (Cramer V = 0.273 and 0.293) compared with 1994-AAST (Cramer V = 0.389 and 0.255; all
p
< 0.001).
Conclusions
The 2018-AAST and CTSI are superior to the 1994-AAST in correlation with operative treatment in splenic and hepatic trauma. The CTSI outperforms the 2018-AAST in mortality prediction.
Key Points
• Non-operative management of blunt abdominal trauma is increasingly applied and correct patient stratification is crucial.
• CT-based scoring systems are used to assess injury severity and guide clinical decision-making, whereby the 1994 version of the American Association of Surgery of Trauma Organ Injury Scale (AAST-OIS) is currently most commonly utilised.
• Including contrast media extravasation in CT-based grading improves management and outcome prediction. While the 2018-AAST classification and the CT-severity-index (CTSI) better correlate with need for surgery compared to the 1994-AAST, the CTSI is superior in outcome-prediction to the 2018-AAST.
To evaluate the efficacy, safety and overall clinical outcome of local treatment for recurrent intrahepatic cholangiocellular carcinoma after hepatic resection.
Between 2007 and 2019 72 consecutive ...patients underwent hepatic resection for primary intrahepatic cholangiocellular carcinoma. If amenable, recurrent tumors were aggressively treated by HR or stereotactic radiofrequency ablation with local curative intent. Endpoints consisted of morbidity and mortality, locoregional and de novo recurrence, disease free survival, and overall survival.
After a median follow-up of 28 months, recurrence of intrahepatic cholangiocellular carcinoma was observed in 43 of 72 patients undergoing hepatic resection (60.3%). 16 patients were subsequently treated by hepatic resection (n = 5) and stereotactic radiofrequency ablation (n = 11) with local curative intention. The remaining 27 patients underwent palliative treatment for first recurrence. Overall survival of patients who underwent repeated aggressive liver-directed therapy was comparable to patients without recurrence (p = 0.938) and was better as compared to patients receiving palliative treatment (p = 0.018). The 5-year overall survival rates for patients without recurrence, the repeated liver-directed treatment group and the palliative treatment group were 54.3%, 47.7% and 12.3%, respectively. By adding stereotactic radiofrequency ablation as an alternative treatment option, the rate of curative re-treatment increased from 11.9% to 37.2%.
Repeated hepatic resection is often precluded due to patient morbidity or anatomical and functional limitations. Due to the application of stereotactic radiofrequency ablation in case of recurrent intrahepatic cholangiocellular carcinoma, the number of patients treated with curative intent can be increased. This leads to favorable clinical outcome as compared to palliative treatment of intrahepatic cholangiocellular carcinoma recurrence.
ERAS
(Enhanced Recovery after Surgery) is an evidence-based multidisciplinary approach focusing on optimizing outcomes after surgery through structured clinical pathways. This study aimed to assess ...patient-reported outcome and experience measures (PROM/PREM), which are not routinely assessed after liver surgery within an ERAS
protocol.
Routine outcome parameters were extracted from clinical documentation. Using qualitative content analysis, PROM and PREM were retrospectively identified in 13 case records. In a prospective survey of 10 participants, PROM was assessed at three timepoints using the EQ-5D-5L questionnaire. PREM were collected at discharge.
The following PROM categories occurred in the retrospective content analysis:
(84.6%),
(76.9%),
(69.2%),
(69.2%), and
(61.5%). The categories of
(92.0%) and
,
,
(69.0%) emerged as PREM. Descriptive changes in health state were shown for all EQ-5D-5L dimensions and timepoints. At discharge,
,
,
, and
tended to be worse, whereas
decreased gradually from preoperatively to the 4 week follow-up. There was high satisfaction with interprofessional care services and experienced cooperation between professionals.
PROM and PREM are helpful to incorporate patients' perspectives after liver surgery within an ERAS
pathway and should be collected routinely in clinical practice.
Colorectal cancer (CRC) represents a major cause for cancer death and every third patient develops liver metastases (CRLM). Several factors including number and size of metastases and primary tumour ...lymph-node status have been linked to survival. The primary tumour location along the colo-rectum continuum (sidedness) was analysed in first-line chemotherapy trials, where right-sided CRCs showed decreased survival. This association has not yet been clearly established in patients undergoing resection for CRLM.
Clinicopathological differences in CRLM resections according to sidedness in two Austrian centres (2003-2016) are described and survival is compared through Kaplan-Meier and multivariable analysis. A risk-score is presented with time-dependent receiver operating curve analysis and international validation in two major hepatobiliary centres. Furthermore, a systematic meta-analysis of studies on primary tumour location and survival after CRLM resection was performed.
259 patients underwent hepatectomy. Right-sided CRC patients (n = 59) more often had positive primary tumour lymph-nodes (76.3%/61.3%;p = 0.043) and RAS-mutations (60%/34.9%;p = 0.036). The median overall and disease-free survival was 33.5 and 9.1 months in right-sided versus 55.5 (p = 0.051) and 12.1 months (p = 0.078) in left-sided patients. In multivariable analysis nodal-status (HR 1.52), right-sidedness (HR 1.53), extrahepatic disease (HR 1.71) and bilobar hepatic involvement (HR 1.41) were significantly associated with overall survival. Sidedness was not independently associated with disease-free survival (HR 1.33; p = 0.099). A clinical risk score including right-sidedness, nodal-positivity and extrahepatic involvement significantly predicted overall (p = 0.005) and disease-free survival (p = 0.027), which was confirmed by international validation in 527 patients (p = 0.001 and p = 0.011). Meta-analysis including 10 studies (n = 4312) showed a significant association of right-sidedness with overall survival after resection (HR 1.55;p<0.001). There was no significant association with disease-free survival (HR 1.22;p = 0.077), except when rectal-cancers were excluded (HR 1.39;p = 0.006).
Patients with liver metastases from right-sided CRC experience worse survival after hepatic resection. Sidedness is a simple yet effective factor to predict outcome.
To evaluate the therapeutic efficacy, safety and overall clinical outcome of multiprobe stereotactic RF ablation (SRFA) as first-line treatment of HCC recurrence after hepatic resection (HR).
In this ...retrospective single-center study, 34 consecutive patients with previous HR were treated by SRFA between 2006 and 2018 for 140 HCCs in 60 ablation sessions.
The median treated tumor size was 3.0 cm (range 0.5–10 cm). SRFA was primarily successful for 133/140 (95%) tumors. Four tumors were successfully retreated, resulting in a secondary technical efficacy rate of 97.9%. Local tumor recurrence developed in 4 of 140 tumors (2.9%). The major complication rate was 4.8% (3 of 60 ablations). No periprocedural deaths occurred.
The overall survival (OS) rates at 1-, 3-, and 5- years from the date of the first SRFA were 94.0%, 70.2%, and 53.3%, respectively, with a median OS of 69.1 months (95% CI 18.8–119.3). The disease-free survival (DFS) was 52.6%, 19.7% and 15.8%, at 1-, 3- and 5- years, respectively, with a median DFS of 12.8 months (95% CI 9.0–28.9).
Stereotactic RFA is a safe, feasible and useful option in the management of recurrent HCC following HR with low morbidity paired with good clinical outcome.
In this retrospective single-center study, we have shown that stereotactic RFA is a safe, feasible and effective option in the management of recurrent HCC after HR with low morbidity paired with good clinical outcome.
Presepsin is involved in binding lipopolysaccharides and previous studies have confirmed its value as a marker for early diagnosis and prediction of severity in sepsis. Comparable studies assessing ...the predictive potential regarding postoperative complications and mortality following pancreatic resection are lacking.
This prospective study included 70 patients undergoing pancreatic resection from December 2017 until May 2019. Presepsin was measured preoperatively, on postoperative day 1, 3 and 8 (POD1/3/8) and correlated with the clinical course and mortality.
Severe complications (Clavien-Dindo ≥3a) occurred in 28 patients (40%), postoperative pancreatic fistula (POPF) grade B/C occurred in 20 patients (28.6%), infectious complications in 28 (40%), and four patients (5.7%) died during hospital stay. Presepsin levels at any timepoint did not correlate with further development of postoperative complications or in-hospital mortality whereas CRP levels on postoperative day (POD) 3 were significantly associated with clinically relevant POPF (AUC 0.664, 95%CI 0.528-0.800; p = 0.033). Preoperative Presepsin levels as well as Presepsin on POD1 were significantly elevated in patients with malignant compared to benign underlying disease (299pg/ml vs. 174pg/ml and 693.5pg/ml vs. 294pg/ml; p = 0.009 and 0.013, respectively).
In our cohort, Presepsin was not eligible to predict the postoperative course following pancreatic resection. However, Presepsin levels were significantly elevated in patients with malignant disease, this finding warrants further investigation.
Epigenetic factors contribute to carcinogenesis, tumor promotion and chemoresistance. Histone deacetylases (HDACs) are epigenetic regulators that primarily cause chromatin compaction, leading to ...inaccessibility of promoter regions and eventually gene silencing. Many cancer entities feature over-expression of HDACs. Currently, the role of HDACs in pancreatic neuroendocrine tumors (pNETs) is unclear. We analyzed expression patterns of all HDAC classes (Class I, IIA, IIB, III & IV) in five human tissue microarrays (TMA) representing 57 pNETs resected between 1997 and 2013 and corresponding control tissue. All pNET cases were characterized clinically and pathologically according to recent staging guidelines. The investigated cases included 32 (56.1%) female and 25 (43.9%) male pNET patients (total n = 57, 47.4% immunohistochemically endocrine positive). Immunohistochemical profiling revealed a significant up-regulation of all HDAC classes in pNET versus control with different levels of intensity and extensity ranging from 1.5 to >7-fold up-regulation. Additionally, expression of several HDACs (HDAC-1, −2, −5, −11 and Sirt 1) was significantly increased in G3 tumors. Correlation analysis showed a significant association between the protein expression of HDAC classes I, III and IV and rate of the pHH3/Ki-67-associated mitotic and proliferation index. Furthermore, especially HDAC-5 proved as a negative predictor of disease-free and overall survival in pNET patients. Overall, we demonstrate that specific members of all four HDAC classes are heterogeneously expressed in pNET. Moreover, expression of HDACs was associated with tumor grading, proliferation markers and patient survival, therefore representing interesting new targets in pNET treatment.
Epigenetic factors are essentially involved in carcinogenesis, tumor promotion, and chemoresistance. Two epigenetic key players are miRNAs and histone deacetylases (HDACs). As previously shown by own ...theoretical databank analysis, the crosstalk between miRNAs and HDACs is relevant in different human chronic diseases and cancerogenic pathways. We aimed to investigate a potential connection between the expression of a well-defined subset of "proliferation-associated" miRNAs and the expression of HDACs as well as clinical parameters in pancreatic neuroendocrine tumors (pNETs).
Expression levels of miRNA132-3p, miRNA145-5p, miRNA183-5p, miRNA34a-5p, and miRNA449a in 57 pNETs resected between 1997 and 2015 were measured and linked to the immunohistochemical expression pattern of members of the four HDAC classes on human tissue microarrays. All pNET cases were clinically and pathologically characterized according to published guidelines. Correlation analysis revealed a significant association between expression of specific miRNAs and two members of the HDAC family (HDAC3 and HDAC4). Additionally, a linkage between miRNA expression and clinico-pathological parameters like grading, TNM-staging, and hormone activity was found. Moreover, overall and disease-free survival is statistically correlated with the expression of the investigated miRNAs. Overall, we demonstrated that specific miRNAs could be linked to HDAC expression in pNETs. Especially miRNA449a (associated with HDAC3/4) seems to play an important role in pNET proliferation and could be a potential prognostic factor for poor survival. These first data could help, to improve our knowledge of the complex interactions of the epigenetic drivers in pNETs for further therapeutic approaches.
A widespread shift to non-operative management (NOM) for blunt hepatic and splenic injuries has been observed in most centers worldwide. Furthermore, many countries introduced safety measures to ...systematically reduce severe traffic and leisure sports injuries. This study aims to evaluate the effect of these nationwide implementations on individual patient characteristics and outcomes through a time-trend analysis over 17 years in an Austrian high-volume trauma center.
A retrospective review of all emergency trauma patients admitted to the Medical University of Innsbruck from 2000 to 2016. Injury severity, clinical data on admission, operative and non-operative treatment parameters, complications, and in-hospital mortality were evaluated.
In total, 731 patients were treated with blunt hepatic and/or splenic injuries. Among these, 368 had a liver injury, 280 splenic injury, and 83 combined hepatic/splenic injury. Initial NOM was performed in 82.6% of all patients (93.5% in hepatic and 71.8% in splenic injuries) with a success rate of 96.7%. The secondary failure rate of NOM was 3.3% and remained consistent over 17 years (
= 0.515). In terms of injury severity, we observed a reduction over time, resulting in an overall mortality rate of 4.8% and 3.5% in the NOM group (decreasing from 7.5 to 1.9% and from 5.6 to 1.3%, respectively). These outcomes confirmed an improved utilization of the NOM approach.
Our cohort represents one of the largest Central European single-center experiences available in the literature. NOM is the standard of care for blunt hepatic and splenic injuries and successful in > 96% of all patients. This rate was quite constant over 17 years (
= 0.515). Overall, national and regional safety measures resulted in a significantly decreased severity of observed injury patterns and deaths due to blunt hepatic or splenic trauma. Although surgery is nowadays only applied in about one third of splenic injury patients in our center, these numbers might further decrease by intensified application of interventional radiology and modern coagulation management.
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