Liver Fibrosis Is Associated with Poorer Overall Survival and Higher Recurrence Rate in Patients with Cholangiocarcinoma.

INTRODUCTION: Cholangiocarcinoma is the second most common primary liver tumour worldwide with an increasing incidence in recent decades. While the effects of fibrosis on hepatocellular carcinoma have been widely demonstrated, the impact on cholangiocarcinoma remains unclear. The aim of this study was to evaluate the impact of liver fibrosis on overall survival (OS) and disease-free survival (DFS) in patients who have undergone liver resection for cholangiocarcinoma. METHODS: Eighty patients with cholangiocarcinoma who underwent curatively intended liver surgery between January 2007 and December 2020 were included in this retrospective single-centre study. Clinical and histopathological features were analysed. The primary endpoint was cause-specific survival. Secondary endpoints were DFS and identification of prognostic factors. RESULTS: The present study shows that the median OS is significantly reduced in patients with fibrosis (p < 0.001). The median OS in patients with fibrosis was three times shorter than in the group without fibrosis. In addition, a significantly shorter DFS was observed in patients with fibrosis (p < 0.002). Multivariate analysis showed that fibrosis is the strongest independent factor with a negative impact on OS and DFS. CONCLUSION: Liver fibrosis has a significant impact on OS and DFS in patients with cholangiocarcinoma. Patients with known liver fibrosis require thorough perioperative care and postoperative follow-up.

Lymph node examination and survival in resected pancreatic ductal adenocarcinoma: retrospective study.

BACKGROUND: The minimum number of examined lymph nodes (ELN) required for adequate staging and best prediction of survival has not been established in pancreatic ductal adenocarcinoma (PDAC). The aim of the study was to investigate the influence of ELN on staging and survival in PDAC. METHODS: Patients undergoing partial or total pancreatectomy for PDAC at two European university hospitals between 2007 and 2018 were retrospectively reviewed. Multivariate Cox regression model and survival analyses were performed to verify adequate staging. RESULTS: Overall 341 (73 per cent) patients showed lymph node metastasis (N1/N2), whereas 125 (27 per cent) patients had no lymph node involvement (N0). With increasing number of ELN, the proportion of positive lymph nodes increased. The minimum number of ELN needed to detect lymph node involvement was 21. In multivariate analysis, examination of <21 lymph nodes was a significant negative predictor for survival. Examination of ≥21 ELN reversed this effect and ruled out possible misclassification. CONCLUSION: The number of ELN affects survival in PDAC. Possible misclassification was identified when <21 lymph nodes were examined. Therefore, at least 21 lymph nodes must be examined to avoid false lymph node classification in all types of resection.

A Modern Series of Secondary Aortoenteric Fistula - A 19-Year Experience.

OBJECTIVES: Secondary aortoenteric fistula is a rare and life-threatening condition. Clear evidence on the ideal therapeutic approach is largely missing. This study aims to analyze symptoms, etiology, risk factors, and outcomes based on procedural details. PATIENTS AND METHODS: All patients with secondary aortoenteric fistula admitted between 2003 and 2021 were included. Patient characteristics, surgical procedure details, and postoperative outcomes were analyzed. Outcomes were stratified and compared according to the urgency of operation and the procedure performed. Descriptive statistics were used. The primary endpoint was in-hospital mortality. RESULTS: A total of twentytwo patients (68% male, median age 70 years) were identified. Main symptoms were gastrointestinal bleeding, pain, and fever. From the twentytwo patients ten patients required emergency surgery and ten urgent surgery. Emergency patients were older on average (74 vs 63 years, P = .015) and had a higher risk of postoperative respiratory complications (80% vs 10%, P = .005). Primary open surgery with direct replacement of the aorta or an extra-anatomic bypass with an additional direct suture or resection of the involved bowel was performed in sixteen patients. In four patients underwent endovascular bridging treatment with the definitive approach as a second step. Other two patients died without operation (1x refusal; 1x palliative cancer history). In-hospital mortality was 27%, respectively. Compared to patients undergoing urgent surgery, those treated emergently showed significantly higher in-hospital (50% vs 0%, P = .0033) mortalities. CONCLUSION: Despite rapid diagnosis and treatment, secondary aortoenteric fistula remains a life-threatening condition with 27% in-hospital mortality, significantly increased upon emergency presentation.

Stroma AReactive Invasion Front Areas (SARIFA) proves prognostic relevance in gastric carcinoma and is based on a tumor-adipocyte interaction indicating an altered immune response.

BACKGROUND: Recently, we presented Stroma AReactive Invasion Front Areas (SARIFA) as a new histomorphologic negative prognostic biomarker in gastric cancer. It is defined as direct contact between tumor cells and fat cells. The aim of this study was to further elucidate the underlying genomic, transcriptional, and immunological mechanisms of the SARIFA phenomenon. METHODS: To address these questions, SARIFA was classified on H&E-stained tissue sections of three cohorts: an external cohort (n = 489, prognostic validation), the TCGA-STAD cohort (n = 194, genomic and transcriptomic analysis), and a local cohort (n = 60, digital spatial profiling (whole transcriptome) and double RNA in situ hybridization/immunostaining of cytokines). RESULTS: SARIFA status proved to be an independent negative prognostic factor for overall survival in an external cohort of gastric carcinomas. In TCGA-STAD cohort, SARIFA is not driven by distinct genomic alterations, whereas the gene expression analyses showed an upregulation of FABP4 in SARIFA-positive tumors. In addition, the transcriptional regulations of white adipocyte differentiation, triglyceride metabolism, and catabolism were upregulated in pathway analyses. In the DSP analysis of SARIFA-positive tumors, FABP4 and the transcriptional regulation of white adipocyte differentiation were upregulated in macrophages. Additionally, a significantly lower expression of the cytokines IL6 and TNFα was observed at the invasion front. CONCLUSIONS: SARIFA proves to be a strong negative prognostic biomarker in advanced gastric cancer, implicating an interaction of tumor cells with tumor-promoting adipocytes with crucial changes in tumor cell metabolism. SARIFA is not driven by tumor genetics but is very likely driven by an altered immune response as a causative mechanism.

Low microsatellite instability: A distinct instability type in gastric cancer?

PURPOSE: We recently showed that low microsatellite instability (MSI-L) is associated with a good response to platinum/5-fluorouracil (5-FU) neoadjuvant chemotherapy (CTx) in gastric cancer. The purpose of this study was to characterize the instability pattern and to investigate an association of MSI-L tumors with mutations in genes of DNA repair pathways and with total tumor mutation burden (TMB). METHODS: MSI patterns were compared between 67 MSI high (-H) and 35 MSI-L tumors. Whole-exome sequencing was performed in 34 microsatellite stable (MSS) and 20 MSI-L tumors after or without neoadjuvant CTx. RESULTS: Of the 35 MSI-L tumors, 33 tumors had instability at a dinucleotide repeat marker. In the homologous recombination (HR) pathway, 10 of the 34 (29%) MSS and 10 of the 20 (50%) MSI-L tumors showed variants (p = 0.154). In the DNA damage tolerance pathway, 6 of the 34 (18%) MSS and 7 of the 20 (35%) MSI-L tumors had variants (p = 0.194). The HR deficiency score was similar in both tumor groups. TMB was significantly higher in MSI-L compared to MSS tumors after CTx (p = 0.046). In the MSS and MSI-L tumors without CTx no difference was observed (p = 1.00). CONCLUSION: MSI-L due to instability at dinucleotide repeat markers was associated with increased TMB after neoadjuvant CTx treatment, indicating sensitivity to platinum/5-FU CTx. If confirmed in further studies, this could contribute to refined chemotherapeutic options including immune-based strategies for GC patients with MSI-L tumors.

Study protocol for a multicenter randomized controlled pilot study on decompressive laparotomy vs. decompressive craniectomy for intractable intracranial pressure after traumatic brain injury: The SCALPEL study.

Introduction: Decompressive craniectomy (DC) is the ultimate intervention to lower intracranial pressure (ICP) following severe traumatic brain injury (TBI). However, this intervention is associated with considerable adverse events and a higher proportion of survivors with poor functional outcomes. Research question: In a multicompartment system ICP is associated with intraabdominal pressure (IAP) due to cerebral venous outflow from the brain. This is the rationale for decompressive laparotomy (DL) to control ICP after TBI as reported by experimental and retrospective clinical data. The safety profile of DL is superior to DC. This study aims to randomly assign patients with intractable high ICP after severe TBI to DL or DC. Material and methods: Among other inclusion criteria, ICP must be above 20 mmHg (1-12 h) despite sedation and all other measures according to current guidelines. The primary outcome is the Extended Glasgow Outcome Scale assessed after twelve months. Further secondary outcome measures are compartmental pressure values, complications, etc. After 20 initial patients, results will be reviewed by the ethics committees and safety monitoring board to decide on the enrolment of 80 additional patients. Results: The study is designed to provide not only high-quality prospective data for the first time on this treatment approach, its two-stage design (20 + 80 pts) also provides maximum patient safety. This protocol conforms with the SPIRIT 2013 Statement. Ethics approval was granted by our but also 5 other university ethics committees (registration 473/18S). Conclusion: Registration was performed prior to study initiation in November 2021 (registration number NCT05115929).

Arterial Resection for Pancreatic Cancer: Feasibility and Current Standing in a High-Volume Center.

Background: Arterial resection (AR) during pancreatectomy for curative R0 resection of pancreatic ductal adenocarcinoma (PDAC) remains a controversial procedure with high morbidity. Objective: To investigate the feasibility and oncological outcomes of pancreatectomy combined with AR at a high-volume center for pancreatic surgery. Methods: We retrospectively analyzed our experience in PDAC patients, who underwent pancreatic resection with AR and/or venous resection (VR) between 2007 and 2021. Results: In total 259 PDAC patients with borderline resectable (n = 138) or locally advanced (n = 121) PDAC underwent vascular resection during tumor resection. From these, 23 patients had AR (n = 4 due to intraoperative injury, n = 19 due to suspected arterial infiltration). However, 12 out of 23 patients (52.2%) underwent simultaneous VR including 1 case with intraoperative arterial injury. In comparison, 11 patients (47.8%) underwent AR only including 3 intraoperative arterial injury patients. Although the operation time and bleeding rate of patients with AR were respectively longer and higher than in VR, no significant difference was detected in postoperative complications between VR and AR (P = 0.11). The final histopathological findings of PDAC patients were similar, including M stage, regional lymph node metastases, and R0 margin resection. The mortality of the entire cohort was 6.2% (16/259), with a tendency to increase mortality in the AR cohort, yet without statistical significance (VR: 5% vs AR: 21.1%; P = 0.05). Although 19 (82.6%) patients had PDAC in the final histopathology, only 6 were confirmed to have infiltrated arteria. The microscopic distribution of PDAC in these infiltrated arterial walls on hematoxylin-eosin staining was classified into 3 patterns. Strikingly, the perivascular nerves frequently exhibited perineural invasion. Conclusions: AR can be performed in high-volume centers for pancreatic surgery with an acceptable morbidity, which is comparable to that of VR. However, the likelihood of arterial infiltration seems to be rather overestimated, and as such, AR might be avoidable or replaced by less invasive techniques such as divestment during PDAC surgery.

Microsatellite instability and sex-specific differences of survival in gastric cancer after neoadjuvant chemotherapy without and with taxane: An observational study in real world patients.

PURPOSE: To investigate the prognostic role of microsatellite instability (MSI) in association with sex of patients treated with platinum/fluoropyrimidine neoadjuvant chemotherapy (CTx) with or without a taxane-containing compound. METHODS: Of the 505 retrospectively analyzed patients with gastric or gastroesophageal adenocarcinoma, 411 patients were treated without taxane and 94 patients with a taxane-containing compound. MSI was determined using standard assays. RESULTS: Females demonstrated a better overall survival (OS) than males in the non-taxane group (HR, 0.59; 95% CI 0.41-0.86; p = 0.005), whereas no significant difference was found in the taxane group (HR 1.22; 95% CI 0.55-2.73, p = 0.630). MSI-High (-H) was associated with a better prognosis in both groups (without taxane: HR 0.56; 95% CI 0.33-0.97; p = 0.038; with taxane: HR 0.28; 95% CI 0.04-2.02, p = 0.204). In the non-taxane group, female MSI-H patients showed the best OS (HR 0.18, 95% CI 0.05-0.73; p = 0.016), followed by the female microsatellite stable (MSS) (HR 0.67, 95% CI 0.46-0.98, p = 0.040) and the male MSI-H group (HR 0.76; 95% CI 0.42-1.37, p = 0.760) taken the male MSS group as reference. In the taxane group, female and male MSI-H patients demonstrated the best OS (female MSI-H: HR 0.05, 95% CI 0.00-240.46; male MSI-H: HR 0.45, 95% CI 0.61-3.63, p = 0.438), whereas the female MSS group showed a decreased OS (HR 1.39 95% CI 0.62-3.12, p = 0.420) compared to male MSS patients. CONCLUSION: OS in gastric/gastroesophageal cancer after CTx might depend on sex and MSI status and may differ between patients treated with or without a taxane compound in the chemotherapeutic regimen.

Significant Tumor Regression after Neoadjuvant Chemotherapy in Gastric Cancer, but Poor Survival of the Patient? Role of MHC Class I Alterations.

We aimed to determine the clinical and prognostic relevance of allelic imbalance (AI) of the major histocompatibility complex (MHC) class I genes, encompassing the human leukocyte antigen (HLA) class I and beta-2 microglobulin (B2M) genes, in the context of neoadjuvant platinum/fluoropyrimidine chemotherapy (CTx). Biopsies before CTx were studied in 158 patients with adenocarcinoma of the stomach or gastroesophageal junction. The response was histopathologically evaluated. AI was detected by multiplex PCRs analysis of four or five microsatellite markers in HLA and B2M regions, respectively. AI with no marker was significantly associated with response or survival. However, subgroup analysis revealed differences. AI at marker D6S265, close to the HLA-A gene, was associated with an obvious increased risk in responding (HR, 3.62; 95% CI, 0.96-13.68, p = 0.058) but not in non-responding patients (HR, 0.92; 95% CI, 0.51-1.65, p = 0.773). Markers D6S273 and D6S2872 showed similar results. The interaction between AI at D6S265 and response to CTx was significant in a multivariable analysis (p = 0.010). No associations were observed for B2M markers. Our results underline the importance of intact neoantigen presentation specifically for responding patients and may help explain an unexpectedly poor survival of a patient despite significant tumor regression after neoadjuvant platinum/fluoropyrimidine CTx.

Non-invasive multispectral optoacoustic tomography resolves intrahepatic lipids in patients with hepatic steatosis.

Hepatic steatosis is characterized by intrahepatic lipid accumulation and may lead to irreversible liver damage if untreated. Here, we investigate whether multispectral optoacoustic tomography (MSOT) can offer label-free detection of liver lipid content to enable non-invasive characterization of hepatic steatosis by analyzing the spectral region around 930 nm, where lipids characteristically absorb. In a pilot study, we apply MSOT to measure liver and surrounding tissues in five patients with liver steatosis and five healthy volunteers, revealing significantly higher absorptions at 930 nm in the patients, while no significant difference was observed in the subcutaneous adipose tissue of the two groups. We further corroborated the human observations with corresponding MSOT measurements in high fat diet (HFD) - and regular chow diet (CD)-fed mice. This study introduces MSOT as a potential non-invasive and portable technique for detecting/monitoring hepatic steatosis in clinical settings, providing justification for larger studies.

Meta-analysis of reported presacral myelolipomas, including a report of a new case.

BACKGROUND: Presacral myelolipomas form a rare disease and are often found incidentally in imaging diagnostics. CASE PRESENTATION: In this study, we report the case of a 71-year-old caucasian female with an incidental finding of a retroperitoneal tumor on magnetic resonance imaging scan. This report aimed at presenting the clinical course of this patient with emphasis on analysis of pathological, clinical, and epidemiological features in a meta-analysis of reported cases. CONCLUSION: Presacral myelolipomas are rare and its etiology remains unclear. Surgical resection is indicated in symptomatic lesions and lesions > 4 cm. More clinical and pathological research on this rare entity is warranted.

UICC Staging after Neoadjuvant/Perioperative Chemotherapy Reveals No Significant Survival Differences Compared to Primary Surgery for Locally Advanced Gastric Cancer.

Background: The applicability of UICC TNM staging for gastric cancer (GC) patients treated with neoadjuvant chemotherapy (nCTX) and surgery was not yet analyzed in comparison to patients undergoing primary surgery (PS). The purpose of this analysis was to analyze if the prognostic impact of TNM staging after nCTx is comparable with PS. Methods: Data for patients having been treated for GC with or without nCTx between 1990 and 2016 were analyzed. Uni-(URA) and multivariable regression analyses (MRA) were performed to identify predictors. Survival according to the UICC 8th edition stages was analyzed by the Kaplan−Meier method and cox regression analysis. Propensity score matching (PSM) was performed to balance for confounders. Results: 1149 patients with GC were eligible for primary analysis. URA demonstrated age (p < 0.0001), tumor localization (p < 0.0001), clinical UICC-stage, complications, UICC stage 0, IIB-IIIC, Lauren subtype, grading, and R-stage to be significantly associated with OS. MRA revealed that age, distal tumor localization, more than 25 dissected lymph nodes, UICC stage 0, IIB-IIIC, and Lauren subtype were significantly and independently related to OS. After PSM, survival analyses revealed only a significant difference for pN2/ypN2 (p = 0.03), while all other T and N stages were comparable. Conclusion: UICC dependent survival stages do not change significantly after nCTx treatment for GC. Therefore, UICC staging in its present version is applicable to patients undergoing nCTx.

Peritoneal antiseptic irrigation to prevent surgical site infection after laparotomy for hepatobiliary or gastrointestinal surgery (PAISI)-protocol for a randomized controlled study.

BACKGROUND: Postoperative surgical site infections (SSIs) remain common after laparotomy for resections of the gastrointestinal or hepatobiliary tract. Especially organ/space infections (CDC class III SSI) can be life-threatening, require relaparotomy, intensive care or interventional drainage of intraabdominal abscesses. The PAISI study aims to investigate whether the use of prophylactic peritoneal irrigation with NaOCl/HOCl solution can reduce the SSI rates following laparotomy for resections of the gastrointestinal or hepatobiliary tract, compared to standard irrigation with physiological electrolyte solution (Ringer's solution). Secondarily, to evaluate whether the use of prophylactic peritoneal irrigation with NaOCl/HOCl solution can reduce postoperative morbidity and mortality as well as the rate of re-operations and length of hospital stay. METHODS: PAISI is a prospective, randomized, observer- and patient-blinded, monocentric, two-arm surgical study in an adaptive parallel groups design, comparing peritoneal and wound irrigation with NaOCl/HOCl (50/50ppm) solution to irrigation with Ringer's solution. The primary endpoint of the study is the SSI rate within 30 days postoperatively. Since there is no data on incidence rates from randomized clinical trials, the rates for sample size calculation were estimated according to the clinical experience at our institution. Therefore, the study design includes one unblinded look at the data by a second statistician, which will be performed after half of the patients reached the primary endpoint. This interim information will be used to check the assumptions and if needed, the sample size will be adjusted. The O'Brien-Fleming spending function is used to determine the efficacy test boundary and the non-binding futility boundary. The one-sided z-test (Group sequential test of two proportions) at the 2.5% significance level with a total of two looks at the data will have overall 80% power. DISCUSSION: The results of this study will provide high-level evidence for future research and clinical recommendations regarding the use of NaOCl/HOCl solution in abdominal surgery and provide the participating patients the opportunity of a potentially improved treatment. TRIAL REGISTRATION: German Clinical Trials Register (DRKS) DRKS00028037. Registered on 27 May 2022.

Bacterial content of the human pancreatic duct: An observational study.

Background: Pancreatic fistula/PF is a challenging surgical complication. We could recently show that intestinal bacteria such as Enterobacterales colonize the PF fluid even after a "sterile" operation like distal pancreatectomy/DP. Therefore, we explored the bacterial flora of the human pancreatic duct in a patient collective undergoing pancreatic surgery. Methods: In this observational study, upon transection of the pancreas during surgery, a swab was inserted into the main duct, and the micro-organismal content was correlated with clinical characteristics. Results: Between February 2017 and February 2020, an intraoperative swab from the pancreatic duct was obtained from a total of 54 patients who underwent pancreatico-duodenectomy/PD or DP. The swabs were sterile in 39 cases (72.2%), detected intestinal bacteria in 10 cases (18.5%), and other bacteria in 5 cases (9.3%). There was no correlation of the micro-organismal content of the pancreatic duct swab with bacteria detected in the PF fluid or bile. Preoperative ERCP was associated with a higher frequency of bacterial colonization of the pancreatic duct (33.3% vs. 6.7%, p = 0.005). There was no correlation of the pancreatic duct swabs with postoperative complications. Discussion: The human main pancreatic duct is usually sterile, and its bacterial colonization does not correlate with the occurrence of PF. Therefore, the mechanisms leading to infection of PF warrant in-depth, mechanistic investigation.

Post-neoadjuvant assessment of tumour budding according to ITBCC subgroups delivers stage- and regression-grade independent prognostic information in intestinal-type gastric adenocarcinoma.

Tumour budding (TB) has been associated with adverse clinicopathological factors and poor survival in a plethora of therapy-naïve carcinoma entities including gastric adenocarcinoma (GC). As conventional histopathological grading is usually omitted in the post-neoadjuvant setting of GC, our study aimed to investigate the prognostic impact of TB in GCs resected after neoadjuvant therapy. We evaluated TB according to the criteria from the International Tumour Budding Consensus Conference (ITBCC) in 167 post-neoadjuvant resections of intestinal-type GC and correlated the results with overall survival (OS) and clinicopathological parameters. GCs were categorised into Bd1 (0-4 buds, low TB), Bd2 (5-9 buds, intermediate TB), and Bd3 (≥10 buds, high TB). Carcinomas with intermediate and high TB were significantly enriched in higher ypTNM stages and strongly associated with reduced 5-year OS in univariable analyses (p < 0.001). In multivariable analyses including sex, age, resection status, UICC stage, and tumour regression grading, TB remained a stage-independent predictor of survival (p < 0.001, hazard ratio Bd2: 2.60, Bd3: 4.74). The assessment of TB according to the ITBCC criteria provides valuable prognostic information in the post-neoadjuvant setting of intestinal-type GC and may be a considerable substitute for the conventional grading system in GCs after neoadjuvant therapy.

Serum albumin at resection predicts in-hospital death, while serum lactate and aPTT on the first postoperative day anticipate anastomotic leakage after Ivor-Lewis-esophagectomy.

BACKGROUND: Anastomotic leakage (AL) is a major complication after esophagectomy, potentiating morbidity and mortality. There are several patient risk factors associated with AL, but high-fidelity postoperative predictors are still under debate. The aim was to identify novel reliable predictors for AL after esophagectomy. METHODS: A high-volume single-center database study, including 138 patients receiving Ivor-Lewis-esophagectomy between 2017 and 2019, was performed. Serum levels of albumin, aPTT, and lactate before and after surgery were extracted to assess their impact on AL and in-hospital mortality. RESULTS: High serum lactate on postoperative day 1 (POD1) could be shown to predict AL after esophagectomy [AL vs. no AL: 1.2 (0.38) vs. 1.0 (0.37); p < 0.001]. Accordingly, also differences of serum lactate level between end (POD0-2) and start of surgery (POD0-1) (p < 0.001) as well as between POD1 and POD0-1 (p < 0.001) were associated with AL. Accordingly, logistic regression identified serum lactate on POD 1 as an independent predictor of AL [HR: 4.37 (95% CI: 1.28-14.86); p = 0.018]. Further, low serum albumin on POD0 [2.6 (0.53) vs. 3.1 (0.56); p = 0.001] and high serum lactate on POD 0-1 [1.1 (0.29) vs. 0.9 (0.30); p = 0.043] were associated with in-hospital death. Strikingly, logistic-regression (HR: 0.111; p = 0.008) and cox-regression analysis (HR: 0.118; p = 0.003) showed low serum albumin as an independently predictor for in-hospital death after esophagectomy. CONCLUSIONS: This study identified high serum lactate as an independent predictor of AL and low serum albumin as a high-fidelity predictor of in-hospital death after esophagectomy. These parameters can facilitate improved postoperative treatment leading to better short-term as well as long-term outcomes.

softALPPS - A novel, individual procedure for patients with advanced liver tumors.

BACKGROUND: The first-line therapy for liver malignancies is a radical extended liver resection. This high-risk operation has a high incidence of post-hepatectomy liver failure (PHLF) due to a small future liver remnant (FLR). One of the procedures to increase the FLR is the associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) which is still associated with high morbidity and mortality. Here, we present a new, less invasive ALPPS variant that may be associated with lower morbidity. METHODS: SoftALPPS is characterized by reduced trauma to the liver tissue and individual adaptation to the patient's health constitution. In softALPPS, portal vein embolization (PVE) is performed instead of portal vein ligation (PVL) after complete recovery of liver function. In addition, a non-absorbable foil was avoided in order to be able to extend the interval to step two or skip step two when required. RESULTS: Four patients successfully underwent softALPPS. Two of these patients have been followed-up for over a year (one patient with Klatskin tumor, one patient with extensive HCC). Both patients show no evidence of recurrence after 12 months and are in good medical condition. The other two patients who recently had surgery are also doing well. CONCLUSION: SoftALPPS offers the chance to curatively resect patients with high tumor burden of the liver even when the FLR is inadequate. This individual therapy method can give patients the possibility of complete tumor resection and can help to reduce perioperative morbidity.

Elevated microsatellite instability at selected tetranucleotide (EMAST) repeats in gastric cancer: a distinct microsatellite instability type with potential clinical impact?

We investigated the clinical impact of elevated microsatellite instability at selected tetranucleotide (EMAST) repeats in the context of neoadjuvant chemotherapy (CTx) in gastric/gastro-oesophageal adenocarcinomas. We analysed 583 resected tumours (272 without and 311 after CTx) and 142 tumour biopsies before CTx. If at least two or three of the five tetranucleotide repeat markers tested showed instability, the tumours were defined as EMAST (2+) or EMAST (3+), respectively. Expression of mismatch repair proteins including MSH3 was analysed using immunohistochemistry. Microsatellite instability (MSI) and Epstein-Barr virus (EBV) positivity were determined using standard assays. EMAST (2+) and (3+) were detected in 17.8 and 11.5% of the tumours, respectively. The frequency of EMAST (2+) or (3+) in MSI-high (MSI-H) tumours was 96.2 or 92.5%, respectively, demonstrating a high overlap with this molecular subtype, and the association of EMAST and MSI status was significant (each overall p < 0.001). EMAST (2+ or 3+) alone in MSI-H and EBV-negative tumours demonstrated only a statistically significant association of EMAST (2+) positivity and negative lymph node status (42.3% in EMAST (2+) and 28.8% in EMAST negative, p = 0.045). EMAST alone by neither definition was significantly associated with overall survival (OS) of the patients. The median OS for EMAST (2+) patients was 40.0 months (95% confidence interval [CI] 16.4-63.6) compared with 38.7 months (95% CI 26.3-51.1) for the EMAST-negative group (p = 0.880). The median OS for EMAST (3+) patients was 46.7 months (95% CI 18.2-75.2) and 38.7 months (95% CI 26.2-51.2) for the negative group (p = 0.879). No statistically significant association with response to neoadjuvant CTx was observed (p = 0.992 and p = 0.433 for EMAST (2+) and (3+), respectively). In conclusion, our results demonstrate a nearly complete intersection between MSI-H and EMAST and they indicate that EMAST alone is not a distinct instability type associated with noticeable clinico-pathological characteristics of gastric carcinoma patients.

Drain use in pancreatic surgery: Results from an international survey among experts in the field.

BACKGROUND: Drain use in pancreatic surgery remains controversial. This survey sought to evaluate habits, experiences, and opinions of experts in the field on the use of drains to provide interesting insights for pancreatic surgeons worldwide. METHODS: An online survey designed via Google Forms was sent in December 2020 to experienced surgeons of the International Study Group for Pancreatic Surgery. RESULTS: Forty-two surgeons (42/63, 67%) completed the survey. During their career, 74% (31/42) performed personally >500 pancreatic resections; of these, 9 (21%) >1,500. Sixty-nine percent of the respondents (29/42) declared to always use drains during pancreatic resections and 17% (7/42) in >50% of the operations. For these participants, the use of drains does not increase but reduces the risk of pancreatic fistula and other complications, and more importantly, helps to detect them earlier and manage them better. By contrast, 2 surgeons (5%) declared to never apply drains, whereas other 4 (10%) use drains only in selective cases, deeming that drains increase the risk of infection and other complications. When applied, drains are managed very heterogeneously as for the type of drains, enzyme testing, and removal schedules. Four participants declared to practice continuous irrigation. Twenty-two surgeons (55%) remove drains routinely within the third postoperative day, other 11 (27.5%) only in selected cases, whereas 7 (17.5%) normally keep drains longer. CONCLUSION: Despite plenty of publications on this topic, drain management in pancreatic surgery remains very heterogeneous. Safety and the surgeon´s personal experience seem to play a determining role.

Kidney Transplantation After Rescue Allocation-the Eurotransplant Experience: A Retrospective Multicenter Outcome Analysis.

BACKGROUND: At Eurotransplant (ET), kidneys are transferred to "rescue allocation" (RA), whenever the standard allocation (SA) algorithms Eurotransplant Kidney Allocation System (ETKAS) and Eurotransplant Senior Program (ESP) fail. We analyzed the outcome of RA. METHODS: Retrospective patient clinical and demographic characteristics association analyses were performed with graft outcomes for 2422 recipients of a deceased donor renal transplantation (DDRT) after RA versus 25 481 after SA from 71 centers across all ET countries from 2006 to 2018. RESULTS: Numbers of DDRTs after RA increased over the time, especially in Germany. RA played a minor role in ESP versus ETKAS (2.7% versus 10.4%). RA recipients and donors were older compared with SA recipients and donors, cold ischemia times were longer, waiting times were shorter, and the incidence of primary nonfunction was comparable. Among ETKAS recipients, HLA matching was more favorable in SA (mean 3.7 versus 2.5). In multivariate modeling, the incidence of graft loss in ETKAS recipients was reduced in RA compared with SA (subdistribution hazard ratio, 0.80; 95% confidence interval [0.70-0.91], P < 0.001), whereas other outcomes (mortality, death with functioning graft (DwFG)) were not significantly different. None of the 3 outcomes were significantly different when comparing RA with SA within the ESP program. CONCLUSIONS: Facing increased waiting times and mortality on dialysis due to donor shortage, this study reveals encouragingly positive DDRT outcomes following RA. This supports the extension of RA to more patients and as an alternative tool to enable transplantation in patients in countries with prohibitively long waiting times or at risk of deterioration.