Sphingosine-1-phosphate receptor type 4 is critically involved in the regulation of peritoneal B-1 cell trafficking and distribution in vivo.

B-1 cells are crucially involved in immune defense and regulation of inflammation and autoimmunity. B-1 cells are predominantly located in the peritoneal and pleural cavities, although body cavity B-1 cells recirculate systemically under steady-state conditions. The chemokines CXCL12 and CXCL13 have been identified as the main regulators of peritoneal B-cell trafficking. In mice deficient for sphingosine-1-phosphate receptor 4 (S1PR4), B-1a and B-1b cell numbers are reduced in the peritoneal cavity by an unknown mechanism. In this study, we show that S1PR4-mediated S1P signaling modifies the chemotactic response of peritoneal B cells to CXCL13 and CXCL12 in vitro. In vivo, S1PR4-mediated S1P signaling affects both immigration into and emigration from the peritoneal cavity. Long-term reconstitution experiments of scid mice with wt or s1pr4 -/- peritoneal B cells revealed a distinct distributional pattern in secondary lymphoid organs. As a functional consequence, both plasmatic and mucosal IgM levels, the main product of B-1a cells, are reduced in mice reconstituted with s1pr4 -/- peritoneal cells. In summary, our data identify S1PR4 as the second S1P receptor (besides S1PR1), which is critically involved in the regulation of peritoneal B-1 cell function.

Gas plasma-oxidized sodium chloride acts via hydrogen peroxide in a model of peritoneal carcinomatosis.

Gas plasma technology generates reactive oxygen and nitrogen species (ROS/RNS), inducing lethal oxidative damage in tumor cells. The transfer of gas plasma-derived ROS/RNS into liquids has been proposed as an innovative anti-cancer strategy targeting peritoneal carcinomatosis (PC). However, the mechanism of action is under debate. To this end, we compared gas plasma-oxidized medical-grade sodium chloride (oxNaCl) with a concentration-matched control (cmc) of NaCl enriched with equivalent concentrations of H2O2 and NO3- in several cell lines and models of PC. Strikingly, oxNaCl and cmc performed equally well in oxidation and cytotoxic activity in tumor cells in two-dimensional cultures, three-dimensional (3D) tumor spheroids, vascularized 3D tumors grown on chicken-embryo chorioallantoic membranes, and a syngeneic PC mouse model in vivo. Given the importance of immunotherapies in oncology today, we focused on immunological consequences of the treatment. Again, to a similar extent, oxNaCl and cmc increased tumor cell immunogenicity and enhanced uptake by and maturation of peripheral blood monocyte-derived dendritic cells together with an inflammatory secretion profile. Furthermore, NanoString gene expression profiling revealed immune system processes and unfolded protein response-related pathways as being linked to the observed anti-tumor effects for both oxNaCl and cmc. In conclusion, gas plasma-generated oxNaCl and cmc showed equal therapeutic efficacy in our PC-related models. In light of the many promising anti-cancer studies of gas plasma-oxidized liquids and the convenient production of corresponding cmcs in large quantities as needed in clinics, our findings may spur research lines based on low-dose oxidants in peritoneal cancer therapy.

Biomarker-stratified first-line treatment of right-sided metastatic colon cancer with interdisciplinary collaboration in the IVOPAK II trial.

Patients with right-sided metastatic colon carcinoma have a significantly worse prognosis than those with left-sided colorectal cancer (CRC), regardless of treatment. The aim of the prospective IVOPAK II study was to implement an interdisciplinary guideline-conform personalized CRC palliative therapy of metastatic colorectal carcinoma and to improve the overall survival (OS) by multidisciplinary approach via secondary metastatic resection. We present the efficacy data of first-line treatment and the benefit of interdisciplinary collaboration of right-sided metastatic colon carcinoma patients: n  = 25. RAS mutation: n  = 20 (80%): received systemic first-line treatment: FOLFIRI plus bevacizumab. All-RAS-wildtype: n  = 5 (20%): received systemic first-line treatment: FOLFIRI plus cetuximab. Last date evaluation: 31 January 2024. Median age: 59.6 years (range 42-71), men/women: 14/11. Eastern Cooperative Oncology Group (ECOG) index: 0/1/2 : 11/10/4. Evaluable for response: n  = 25. Complete response: n  = 0, partial response: n  = 14 (56%), stable disease: n  = 8 (32%), progressive disease: n  = 3 (12%), early tumor shrinkage: n  = 13 (52%), estimates progression-free survival: 13 months (95% CI 8-17 months), estimated OS: 48 months (95% CI 25-71 months), median follow-up: 26 months (1-61 months), no evidence of disease: n  = 4 (16%). A chemotherapy doublette regimen with FOLFIRI plus a biological as first-line treatment shows promising efficacy and secondary metastatic resection after interdisciplinary discussion was associated with a survival benefit in right-sided metastatic colon carcinoma.

Antibiotic treatment after appendectomy for acute complicated appendicitis to prevent intrabdominal abscess and wound infections.

INTRODUCTION: The purpose of this analysis was to investigate the most appropriate duration of postoperative antibiotic treatment to minimize the incidence of intraabdominal abscesses and wound infections in patients with complicated appendicitis. MATERIALS AND METHODS: In this retrospective study, which included 396 adult patients who underwent appendectomy for complicated appendicitis between January 2010 and December 2020 at the University Hospital Erlangen, patients were classified into two groups based on the duration of their postoperative antibiotic intake: ≤ 3 postoperative days (group 1) vs. ≥ 4 postoperative days (group 2). The incidence of postoperative intraabdominal abscesses and wound infections were compared between the groups. Additionally, multivariate risk factor analysis for the occurrence of intraabdominal abscesses and wound infections was performed. RESULTS: The two groups contained 226 and 170 patients, respectively. The incidence of postoperative intraabdominal abscesses (2% vs. 3%, p = 0.507) and wound infections (3% vs. 6%, p = 0.080) did not differ significantly between the groups. Multivariate analysis revealed that an additional cecum resection (OR 5.5 (95% CI 1.4-21.5), p = 0.014) was an independent risk factor for intraabdominal abscesses. A higher BMI (OR 5.9 (95% CI 1.2-29.2), p = 0.030) and conversion to an open procedure (OR 5.2 (95% CI 1.4-20.0), p = 0.016) were identified as independent risk factors for wound infections. CONCLUSION: The duration of postoperative antibiotic therapy does not appear to influence the incidence of postoperative intraabdominal abscesses and wound infections. Therefore, short-term postoperative antibiotic treatment should be preferred.

Prevalence and characteristics of the 'bad feeling' among healthcare professionals in the context of emergency situations: A Bi-Hospital Survey.

INTRODUCTION: Clinical decision-making is based on objective and subjective criteria, including healthcare workers impressions and feelings. This research examines the perception and implications of a 'bad feeling' experienced by healthcare professionals, focusing on its prevalence and characteristics. METHODS: A cross-sectional paper-based survey was conducted from January to July 2023 at the University Medicine Greifswald and the hospital Sömmerda involving physicians, nurses, medical students and trainees from various specialties. With ethics committee approval, participants were recruited and surveyed at regular clinical events. Data analysis was performed using SPSS® Statistics. The manuscript was written using the Strobe checklist. RESULTS: Out of 250 questionnaires distributed, 217 were valid for analysis after a 94.9% return rate and subsequent exclusions. Sixty-five per cent of respondents experience the 'bad feeling' occasionally to frequently. There was a significant positive correlation between the frequency of 'bad feeling' and work experience. The predominant cause of this feeling was identified as intuition, reported by 79.8% of participants, with 80% finding it often helpful in their clinical judgement. Notably, in 16.1% of cases, the 'bad feeling' escalated in the further clinical course into an actual emergency. Furthermore, 60% of respondents indicated that this feeling occasionally or often serves as an early indicator of a potential, yet unrecognised, emergency in patient care. CONCLUSIONS: This study demonstrates the relevance of clinical experience to decision-making. As an expression of this, there is a correlation between the frequency of a 'bad feeling' and the number of years of experience. It is recommended that the 'bad feeling' be deliberately acknowledged and reinforced as an early warning signal for emergency situations, given its significant implications for patient safety. Future initiatives could include advanced training and research, as well as tools such as pocket maps, to better equip healthcare professionals in responding to this intuition.

Metagenomic Identification of Microbial Signatures Predicting Pancreatic Cancer From a Multinational Study.

BACKGROUND & AIMS: To identify gut and oral metagenomic signatures that accurately predict pancreatic ductal carcinoma (PDAC) and to validate these signatures in independent cohorts. METHODS: We conducted a multinational study and performed shotgun metagenomic analysis of fecal and salivary samples collected from patients with treatment-naïve PDAC and non-PDAC controls in Japan, Spain, and Germany. Taxonomic and functional profiles of the microbiomes were characterized, and metagenomic classifiers to predict PDAC were constructed and validated in external datasets. RESULTS: Comparative metagenomics revealed dysbiosis of both the gut and oral microbiomes and identified 30 gut and 18 oral species significantly associated with PDAC in the Japanese cohort. These microbial signatures achieved high area under the curve values of 0.78 to 0.82. The prediction model trained on the Japanese gut microbiome also had high predictive ability in Spanish and German cohorts, with respective area under the curve values of 0.74 and 0.83, validating its high confidence and versatility for PDAC prediction. Significant enrichments of Streptococcus and Veillonella spp and a depletion of Faecalibacterium prausnitzii were common gut signatures for PDAC in all the 3 cohorts. Prospective follow-up data revealed that patients with certain gut and oral microbial species were at higher risk of PDAC-related mortality. Finally, 58 bacteriophages that could infect microbial species consistently enriched in patients with PDAC across the 3 countries were identified. CONCLUSIONS: Metagenomics targeting the gut and oral microbiomes can provide a powerful source of biomarkers for identifying individuals with PDAC and their prognoses. The identification of shared gut microbial signatures for PDAC in Asian and European cohorts indicates the presence of robust and global gut microbial biomarkers.

The role of intraoperative swab during appendectomy in patients with uncomplicated and complicated appendicitis.

INTRODUCTION: Bacteria play an important role not only in pathogenesis of appendicitis but also in the postoperative course of patients. However, the usefulness of an intraoperative swab during appendectomy is controversial. The primary aim of this study was to investigate the impact of intraoperative swab during appendectomy on the postoperative outcome in patients with uncomplicated and complicated appendicitis. METHODS: A retrospective analysis was conducted on a consecutive series of 1570 adult patients who underwent appendectomy for acute appendicitis at the University Hospital Erlangen between 2010 and 2020. Data regarding the intraoperative swab were collected and analyzed for the entire cohort as well as for patients with uncomplicated and complicated appendicitis. RESULTS: An intraoperative swab was taken in 29% of the cohort. The bacterial isolation rate in the obtained intraoperative swabs was 51%, with a significantly higher rate observed in patients with complicated appendicitis compared to those with uncomplicated appendicitis (79% vs. 35%, p < 0.001). The presence of a positive swab was significantly associated with worse postoperative outcomes, including higher morbidity, increased need for re-surgery, and longer hospital stay, when compared to patients without a swab or with a negative swab. A positive swab was an independent risk factor for postoperative morbidity (OR 9.9 (95% CI 1.2-81.9), p = 0.034) and the need for adjustment of postoperative antibiotic therapy (OR 8.8 (95% CI 1.1-72.5), p = 0.043). However, a positive swab resulted in postoperative antibiotic therapy adjustment in only 8% of the patients with bacterial isolation in the swab. CONCLUSION: The analysis of swab samples obtained during appendectomy for acute appendicitis can help identify patients at a higher risk of a worse postoperative outcome. However, the frequency of antibiotic regime changes based on the swab analysis is low.

Colon Cancer Microbiome Landscaping: Differences in Right- and Left-Sided Colon Cancer and a Tumor Microbiome-Ileal Microbiome Association.

In the current era of precision oncology, it is widely acknowledged that CRC is a heterogeneous disease entity. Tumor location (right- or left-sided colon cancer or rectal cancer) is a crucial factor in determining disease progression as well as prognosis and influences disease management. In the last decade, numerous works have reported that the microbiome is an important element of CRC carcinogenesis, progression and therapy response. Owing to the heterogeneous nature of microbiomes, the findings of these studies were inconsistent. The majority of the studies combined colon cancer (CC) and rectal cancer (RC) samples as CRC for analysis. Furthermore, the small intestine, as the major site for immune surveillance in the gut, is understudied compared to the colon. Thus, the CRC heterogeneity puzzle is far from being solved, and more research is necessary for prospective trials that separately investigate CC and RC. Our prospective study aimed to map the colon cancer landscape using 16S rRNA amplicon sequencing in biopsy samples from the terminal ileum, healthy colon tissue, healthy rectal tissue and tumor tissue as well as in preoperative and postoperative stool samples of 41 patients. While fecal samples provide a good approximation of the average gut microbiome composition, mucosal biopsies allow for detecting subtle variations in local microbial communities. In particular, the small bowel microbiome has remained poorly characterized, mainly because of sampling difficulties. Our analysis revealed the following: (i) right- and left-sided colon cancers harbor distinct and diverse microbiomes, (ii) the tumor microbiome leads to a more consistent cancer-defined microbiome between locations and reveals a tumor microbiome-ileal microbiome association, (iii) the stool only partly reflects the microbiome landscape in patients with CC, and (iv) mechanical bowel preparation and perioperative antibiotics together with surgery result in major changes in the stool microbiome, characterized by a significant increase in the abundance of potentially pathogenic bacteria, such as Enterococcus. Collectively, our results provide new and valuable insights into the complex microbiome landscape in patients with colon cancer.

A faecal microbiota signature with high specificity for pancreatic cancer.

BACKGROUND: Recent evidence suggests a role for the microbiome in pancreatic ductal adenocarcinoma (PDAC) aetiology and progression. OBJECTIVE: To explore the faecal and salivary microbiota as potential diagnostic biomarkers. METHODS: We applied shotgun metagenomic and 16S rRNA amplicon sequencing to samples from a Spanish case-control study (n=136), including 57 cases, 50 controls, and 29 patients with chronic pancreatitis in the discovery phase, and from a German case-control study (n=76), in the validation phase. RESULTS: Faecal metagenomic classifiers performed much better than saliva-based classifiers and identified patients with PDAC with an accuracy of up to 0.84 area under the receiver operating characteristic curve (AUROC) based on a set of 27 microbial species, with consistent accuracy across early and late disease stages. Performance further improved to up to 0.94 AUROC when we combined our microbiome-based predictions with serum levels of carbohydrate antigen (CA) 19-9, the only current non-invasive, Food and Drug Administration approved, low specificity PDAC diagnostic biomarker. Furthermore, a microbiota-based classification model confined to PDAC-enriched species was highly disease-specific when validated against 25 publicly available metagenomic study populations for various health conditions (n=5792). Both microbiome-based models had a high prediction accuracy on a German validation population (n=76). Several faecal PDAC marker species were detectable in pancreatic tumour and non-tumour tissue using 16S rRNA sequencing and fluorescence in situ hybridisation. CONCLUSION: Taken together, our results indicate that non-invasive, robust and specific faecal microbiota-based screening for the early detection of PDAC is feasible.

A Possible Distinct Molecular Subtype (Quintuple-Wildtype) of Metastatic Colorectal Cancer in First-Line Anti-EGFR Therapy with Cetuximab Plus FOLFIRI - Palliative Precision Therapy and a Multidisciplinary Treatment Approach: Interim Analysis of the IVOPAK II Trial with Early Results.

OBJECTIVE: The study aimed to prospectively evaluate a new molecular biomarker panel (KRAS, NRAS, BRAF, PIK3CA, and ERBB2) for palliative first-line treatment of colorectal cancer (CRC), including a multidisciplinary treatment approach. The rate of secondary metastasis resections was assessed. PATIENTS AND METHODS: A total of 40 patients with definitively nonresectable metastatic CRC were enrolled from 10 centers before the interim analysis (June 2019) of the IVOPAK II trial (Interdisciplinary Care with Quality Control in Palliative Treatment of Colorectal Cancer). After determination of 5 molecular biomarkers in the tumor (KRAS, exons 2-4; NRAS, exons 2-4; BRAF V600E; PIK3CA; and ERBB2), patients in the IVOPAK II study received FOLFIRI plus cetuximab for all-RAS/quintuple-wildtype disease and FOLFIRI plus bevacizumab in the case of RAS mutations. The current article presents the early description of the clinical outcome of the interim analysis of IVOPAK II comparing the all-RAS/quintuple-wildtype and RAS-mutations populations, including a multidisciplinary-treated case report of a quintuple-wildtype patient. RESULTS: The quintuple-wildtype population treated with FOLFIRI plus cetuximab in first-line exhibited a significantly higher response rate and enhanced early tumor shrinkage in the interim analysis than the RAS-mutations population, as well as a high rate of secondary metastatic resections. CONCLUSION: Initial results of this new biomarker panel (quintuple-wildtype) are promising for anti-EGFR therapy with cetuximab plus doublet chemotherapy (FOLFIRI) in first-line treatment of metastatic CRC. These results warrant confirmation with higher case numbers in the IVOPAK II trial.

The use of single-stapling techniques reduces anastomotic complications in minimal-invasive rectal surgery.

BACKGROUND: Leakage of rectal anastomoses is one of the most important and feared complications in colorectal surgery. Apart from patient-specific risk factors, technical aspects may influence the occurrence of anastomotic complications. This study investigated whether using single-stapling techniques (SST) instead of the double-stapling technique (DST) for minimal-invasive rectal anastomosis is associated with a lower rate of anastomotic complications. METHODS: A retrospective review of 272 patients who received a minimally invasive stapled rectal anastomosis (3-16 cm from the anal verge) at our institution from 2015 to 2020 was performed. In 131 patients, rectal anastomosis was created by SST (SST group), while 141 patients received a rectal anastomosis with crossing stapler lines (DST group). The impact of the anastomotic technique on patient outcomes was determined by uni- and multivariate analyses. RESULTS: Overall anastomotic leakage rate was 6%. Patients with SST anastomoses had a lower leakage rate than patients with DST anastomoses (3% vs. 9% in the DST group, p = 0.045). The rate of anastomotic stenosis was lower in the SST group than in the DST group (1% vs. 6%, p = 0.037). Overall morbidity and mortality did not differ between the two groups. Multivariate analysis showed that single-stapling techniques significantly reduce the risk of anastomotic leakage (OR 3.5 [1.0-11.5], p = 0.043). CONCLUSION: The use of SST for rectal anastomosis may help to reduce anastomotic complications. This finding should be confirmed by a randomized controlled trial.

[Palliative Surgery in Colorectal Cancer - Which Factors Should Influence the Choice of the Surgical Procedure?] / Palliativchirurgie beim kolorektalen Karzinom ­ welche Faktoren können bei der Wahl des operativen Vorgehens helfen?

BACKGROUND: The surgical procedure for patients with colorectal cancer (CRC) in the palliative situation cannot be adequately standardised. The present study was initiated to identify criteria for the decision for resection of the malignancy with or without anastomosis. PATIENTS/MATERIAL AND METHODS: In a unicentric retrospective analysis, 103 patients after palliative resection with or without anastomosis due to CRC were examined. Using univariate and logistic regression analysis, the influence of a total of 40 factors on postoperative morbidity and mortality was assessed. RESULTS: In 46 cases, resection with primary anastomosis and in 57 cases a discontinuity resection was performed. Postoperative morbidity was 44.7% and mortality 17.5%. After one-stage resection with anastomosis, nicotine abuse (OR 4.2; p = 0.044), hypalbuminaemia (OR 4.0; p = 0.012), ASA score > 2 (OR 3.7; p = 0.030) and liver remodelling/cirrhosis (OR 3.6; p = 0.031) increased the risk for postoperative complications. Hypalbuminaemia (OR 1.8; p = 0.036), cachexia (OR 1.8; p = 0.043), anaemia (OR 1.5; p = 0.038) and known alcohol abuse (OR 1.9; p = 0.023) were identified as independent risk factors for early postoperative mortality. After discontinuity resection, renal failure (OR 2.1; p = 0.042) and cachexia (OR 1.5; p = 0.045) led to a significant increase in the risk of postoperative morbidity, alcohol abuse (OR 1.8; p = 0.041) in mortality. Hypalbuminaemia (OR 2.8; p = 0.019) and an ASA score > 2 (OR 2.6; p = 0.004) after resection and reconstruction increased the risk of major complications according to Clavien-Dindo, while pre-existing renal failure (OR 1.6; p = 0.023) increased the risk after discontinuity resection. In univariate analysis, an ASA score > 2 (p = 0.038) after simultaneous tumour resection and reconstruction, and urgent surgery in both groups with or without primary anastomosis were additionally identified as significant parameters with a negative influence on mortality (p = 0.010 and p = 0.017). CONCLUSION: Palliative resections of colorectal carcinomas have high morbidity and mortality. Especially in cases of pre-existing alcohol abuse and/or urgent indication for surgery, more intensive monitoring should be performed. In the case of anaemia, cachexia, hypalbuminemia and an ASA score > 2, discontinuity resection may be the more appropriate procedure.

Oncological colorectal surgery during the COVID-19pandemic-a national survey.

PURPOSE: The aim of this study was to clarify the surgical supply situation of oncological colorectal patients in Germany during limitations of the OR caseload due to the COVID-19 pandemic. METHODS: Between 11th and 19th April 2020, all members of a consortium of German colorectal cancer centers were invited to participate in a web-based survey on the current status of surgical care situation of colorectal cancer patients in Germany. RESULTS: A total of 112 colorectal surgeons of 101 German hospitals participated in the survey. Eighty-seven percent of the participating hospitals had to reduce their total surgical caseload and 34% their surgical volume for oncological colorectal patients during COVID-19 pandemic. Restrictions of the surgical caseload were independent of the size of the hospital and the number of cases of COVID-19 in the federal state of the hospital. Sixteen percent of colorectal surgeons consider surgical limitations to be not justified and 78% to be justified only if the care of oncological patients is ensured. Ninety-five percent of the colorectal surgeons interviewed stated that all oncological colorectal patients with an indication for surgery should be operated in time, despite the current reservations for COVID-19 patients. For the majority of the respondents (63% and 51%, respectively), an extended waiting time for surgery of up to 2 weeks was acceptable for non-metastatic and metastatic patients, respectively. CONCLUSION: In Germany, there is a temporarily relevant reduction of surgical volume in oncological colorectal patients. Most colorectal surgeons stated that oncological colorectal surgery should not be compromised despite the measures taken during the COVID-19 pandemic.

Risk factors for appendiceal neoplasm and malignancy among patients with acute appendicitis.

PURPOSE: Non-operative management of acute uncomplicated appendicitis has shown promising results but might carry the risk of delayed diagnosis of premalignant or malignant appendiceal tumors found by chance in 0.7-2.5% of appendiceal specimen after appendectomy. Purpose of this study was to analyze whether appendiceal tumors are associated with a complicated appendicitis and to determine risk factors for appendiceal neoplasm and malignancy in patients with acute appendicitis. METHODS: We performed a retrospective analysis of 1033 adult patients, who underwent appendectomy for acute appendicitis from 2010 to 2016 at the University hospital Erlangen. Data included patients' demographics; comorbidities; pre-, intra- and postoperative findings; and histopathological results. Complicated appendicitis was defined in the presence of perforation or abscess. RESULTS: Appendiceal neoplasm respectively malignancy rate was 2.8% respectively 1.5%. Using univariate analysis, we identified seven risk factors at least for appendiceal neoplasm or malignancy: age, ASA, C-reactive protein, appendiceal diameter, perforation, intraoperative perithyphilitic abscess, and complicated appendicitis. Risk for appendiceal neoplasm or malignancy was 4.4% respectively 2.7% in complicated acute appendicitis compared to 2.0% respectively 1.0% in uncomplicated appendicitis (p = 0.043 respectively p = 0.060). In multivariate analysis, age ≥ 50 years and a diameter of the appendix in the sonography ≥ 13 mm were independent risk factors predicting the presence of appendiceal neoplasm and malignancy. CONCLUSION: Among patients with appendicitis, there are relevant risk factors predicting appendiceal tumors, especially age and appendiceal diameter in sonography. But the identified risk factors have a low sensitivity and specificity, so obtaining a confident preoperative diagnosis is challenging.

In-hospital mortality and failure to rescue following hepatobiliary surgery in Germany - a nationwide analysis.

BACKGROUND: Recent observational studies on volume-outcome associations in hepatobiliary surgery were not designed to account for the varying extent of hepatobiliary resections and the consequential risk of perioperative morbidity and mortality. Therefore, this study aimed to determine the risk-adjusted in-hospital mortality for minor and major hepatobiliary resections at the national level in Germany and to examine the effect of hospital volume on in-hospital mortality, and failure to rescue. METHODS: All inpatient cases of hepatobiliary surgery (n = 31,114) in Germany from 2009 to 2015 were studied using national hospital discharge data. After ranking hospitals according to increasing hospital volumes, five volume categories were established based on all hepatobiliary resections. The association between hospital volume and in-hospital mortality following minor and major hepatobiliary resections was evaluated by multivariable regression methods. RESULTS: Minor hepatobiliary resections were associated with an overall mortality rate of 3.9% and showed no significant volume-outcome associations. In contrast, overall mortality rate of major hepatobiliary resections was 10.3%. In this cohort, risk-adjusted in-hospital mortality following major resections varied widely across hospital volume categories, from 11.4% (95% CI 10.4-12.5) in very low volume hospitals to 7.4% (95% CI 6.6-8.2) in very high volume hospitals (risk-adjusted OR 0.59, 95% CI 0.41-0.54). Moreover, rates of failure to rescue decreased from 29.38% (95% CI 26.7-32.2) in very low volume hospitals to 21.38% (95% CI 19.2-23.8) in very high volume hospitals. CONCLUSIONS: In Germany, patients who are undergoing major hepatobiliary resections have improved outcomes, if they are admitted to higher volume hospitals. However, such associations are not evident following minor hepatobiliary resections. Following major hepatobiliary resections, 70-80% of the excess mortality in very low volume hospitals was estimated to be attributable to failure to rescue.

Upregulation of CD20 Positive B-Cells and B-Cell Aggregates in the Tumor Infiltration Zone is Associated with Better Survival of Patients with Pancreatic Ductal Adenocarcinoma.

Patients with pancreatic ductal adenocarcinoma (PDAC) normally have a poor long-term prognosis. However, some rare cases of long-term survivors have been reported. The tumor microenvironment, consisting of cellular and stromal components, possibly plays an important role and might influence prognosis. In this context, the role of tumor-infiltrating B-cells and its impact on the survival in patients with PDAC remains controversial. We therefore aimed to assess the prognostic value of CD20-positive B-cells and CD20-positive B-cell aggregates as well as CD138, IgM, Pax5, and Ki67 on the survival of patients with PDAC using immunohistochemistry of FFPE pancreatectomy tissue sections from patients that underwent primary surgery for pT3- and R0-pancreatic adenocarcinoma between 1995 and 2016. Patients with PDAC were matched and grouped in 16 long-term-survivors (LTS, median overall survival (OS): 96 months [range: 61-177 months]) and 16 short-term-survivors (STS, median OS: 16 months [range: 7-32 months]). CD20-positive B-cells and B-cell aggregates in the tumor infiltration zone were significantly upregulated in the LTS-group compared to the STS-group (p = 0.0499 respectively p = 0.0432). Regarding the entire patient cohort (n = 32) CD20 positive B-cell aggregates in the tumor infiltration zone were an independent prognostic marker for overall survival in multivariate analysis (HR 9.2, CI 1.6-51.4, p = 0.012). These results underline the importance of tumor-associated B-cells for prognosis of patients with PDAC. The detailed role of B cells in the pathomechanism of PDAC should be further investigated for predicting outcome, identifying appropriate treatment regimens, and developing novel therapeutic options.

[The Critical View of Safety to Avoid Biliary Complications in Laparoscopic Cholecystectomy]. / Der "critical view of safety" zur Vermeidung von Gallengangskomplikationen bei der laparoskopischen Cholezystektomie.

Laparoscopic cholecystectomy is one of the most frequently performed procedures worldwide. Therefore, iatrogenic injury to the choledochal duct, although rare, remains a surgical risk that should not be underestimated. Over the years, various methods have been described to avoid this serious complication, with its high morbidity and even mortality. One of the safest methods to avoid bile duct lesions is to establish the so called "critical view of safety" before cutting any structures. This method shall be demonstrated in this instructional video.

[Laparoscopic Right Hemicolectomy with Complete Mesocolic Excision (CME)]. / Laparoskopische Hemikolektomie rechts mit kompletter mesokolischer Exzision (CME).

INTRODUCTION: Complete mesocolic excision (CME) is considered as good clinical practice according to the German S3 Guideline for colorectal cancer. This recommendation is based on evidence showing improved histopathological quality criteria of specimens taken and better oncological outcomes following CME surgery compared to conventional colon resections. However, CME surgery, especially of the right colon, is more complex - due to the high variability of the vascular structures (e.g. Truncus Henle) and the anatomical proximity to the stomach, duodenum and pancreas. To increase safety of laparoscopic right hemicolectomy with CME and to improve surgical education of this procedure, a German expert group has developed a standardised procedure with critical safety assessment. This video shows the technique of laparoscopic right hemicolectomy with complete mesocolic excision (CME), according to the concept first described by the German expert group on Lap-CME. INDICATION: Carcinoma of the ascending colon. PROCEDURE: Laparoscopic right hemicolectomy with complete mesocolic excision (CME). CONCLUSION: The proposed standardisation of laparoscopic right hemicolectomy with complete mesocolic excision accommodates the increased complexity of the right colon and structures it into well-defined steps with critical safety assessments, which may result in minimised intraoperative complications and increased patient safety and should improve training.

Effects of regional anesthesia techniques on local anesthetic plasma levels and complications in carotid surgery: a randomized controlled pilot trial.

BACKGROUND: The ultrasound guided intermediate cervical plexus block with perivascular infiltration of the internal carotid artery (PVB) is a new technique for regional anesthesia in carotid endarterectomy (CEA). We conducted a pilot study investigating the effects of deep cervical block (DCB), intermediate cervical block alone (ICB) and PVB on perioperative complications in patients undergoing elective CEA. We hypothesized, that the ropivacaine plasma concentration is higher in patients receiving DCB compared to PVB and ICB. METHODS: In a randomized controlled pilot study thirty patients scheduled for elective CEA were randomly assigned into three groups: DCB receiving 20 mL ropivacaine 0.5% (n = 10), ICB receiving 20 mL ropivacaine 0.5% (n = 10) and PVB receiving 20 mL ropivacaine 0.5% and 10 mL ropivacaine 0,3% (n = 10). As primary outcome, plasma levels of ropivacaine were measured with high performance liquid chromatography before, 5, 10, 20, 60, and 180 min after the injection of ropivacaine. Secondary outcomes were vascular and neurological complications as well as patients' and surgeons' satisfaction. All analyses were performed on an intention-to-treat basis. Statistical significance was accepted at p < 0.05. RESULTS: No conversion to general anesthesia was necessary and we observed no signs of local anesthetic intoxication or accidental vascular puncture. Plasma concentration of ropivacaine was significantly higher in the DCB group compared to PVB and ICB (p < 0.001) and in the PVB group compared to ICB (p = 0.008). Surgeons' satisfaction was higher in the PVB group compared to ICB (p = 0.003) and patients' satisfaction was higher in the PVB group compared to ICB (p = 0.010) and DCB group (p = 0.029). Phrenic nerve paralysis was observed frequently in the DCB group (p < 0.05). None of these patients with hemi-diaphragmatic paralysis showed signs of respiratory distress. CONCLUSION: The ultrasound guided PVB is a safe and effective technique for CEA which is associated with lower plasma levels of local anesthetic than the standard DCB. Considering the low rate of complications in all types of regional anesthesia for CEA, larger randomized controlled trials are warranted to assess potential side effects among the blocks. TRIAL REGISTRATION: The trial was registered at German Clinical Trials Register (DRKS) on 04/05/2019 (DRKS00016705, retrospectively registered).

[Educational Video: Hemithyreoidectomy with Neuromonitoring of the Recurrent Laryngeal Nerve]. / Lehrfilm Facharztweiterbildung: Hemithyreoidektomie mit Neuromonitoring des N. laryngeus recurrens.

INTRODUCTION: The mean prevalence of thyroid nodules in adults is about 20% and increases with age. Most of the thyroid nodules are benign, and are rarely malignant. However, malignancy can often only be conclusively determined after resection. Therefore, it is essential that the surgical technique should be free of complications. Despite all published minimally invasive techniques, the open procedure via a Kocher incision is still standard and commonly used in a teaching setting. This standardised technique is presented step-by-step in the video. INDICATION: Sonographic and MIBI-scintigraphic possibly malignant solitary node in the right thyroid lobe. PROCEDURE: Hemithyreoidectomy with neuromonitoring of recurrent laryngeal nerve. CONCLUSION: Hemithyroidectomy is an adequate primary therapy for a solitary possibly malignant thyroid nodule. Intraoperative neuromonitoring to identify and protect the recurrent laryngeal nerve, visualisation and protection of the parathyroid glands without compromising blood circulation and careful hemostasis are the main pillars of low risk surgery of the thyroid.