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.

Influence of perioperative step volume on complication rate and length of hospital stay after colorectal cancer surgery (IPOS trial): study protocol for a randomised controlled single-centre trial at a German university hospital.

BACKGROUND: Perioperative mobilisation and physical activity are critical components of postoperative rehabilitation. Physical inactivity is a significant risk factor for complications and prolonged hospitalisation. However, specific recommendations for preoperative and postoperative physical activity levels are currently lacking. Evidence suggests that daily step count before and after surgery may impact the length of hospital stay and complication rate.The goal of this study is to determine the effectiveness of perioperative step volume recommendations, measured by pedometers, in reducing the length of hospital stay and complication rate for patients undergoing colorectal cancer surgery. METHODS: This study is a single-centre randomised controlled trial with two arms, allocated at a 1:1 ratio. The trial includes individuals undergoing colorectal surgery for either suspected or confirmed colorectal malignancy. A total of 222 patients will be randomly assigned to either an intervention or a control group. Step counts will be measured using a pedometer. Patients assigned to the intervention group will be given a predetermined preoperative and postoperative step count goal. The analysis will be conducted on preoperative and postoperative physical activity, quality of life, health, duration of hospitalisation, complication rate and bowel function, among other factors. ETHICS AND DISSEMINATION: The trial was approved by the ethics committee of the Ludwig-Maximilians-University of Munich, Germany (reference number: 22-0758, protocol version 2022.02). Results will be published in peer-reviewed journals and shared at academic conferences. After the publication of the results, a fully anonymised data set and the statistical code can be made available on justified scientific request and after ethical approval has been granted. TRIAL REGISTRATION NUMBER: DRKS00030017.

Immersive Virtual Reality Fitness Games to Improve Recovery After Colorectal Surgery: A Randomized Single Blind Controlled Pilot Trial.

Introduction: Early mobilization after surgery is crucial for reducing postoperative complications and restoring patients' fitness and ability to care for themselves. Immersive, activity-promoting fitness games in virtual reality (VR) can be used as a low-cost motivational adjunct to standard physiotherapy to promote recovery after surgery. In addition, they have potentially positive effects on mood and well-being, which are often compromised after colorectal surgery. The purpose of this pilot study was to evaluate the feasibility and clinical outcomes of a VR-based intervention that provides additional mobilization. Methods: Patients undergoing curative surgery for colorectal cancer were randomly assigned to an intervention group or a control group. Participants in the intervention group (VR group) received daily bedside fitness exercises using immersive, activity-promoting, virtual reality fitness games in addition to standard care during their postoperative hospital stay. Results: A total of 62 patients were randomized. The feasibility outcomes were in line with the predefined goals. In the VR group, an improvement in overall mood (+0.76 points; 95% confidence interval [CI] 0.39 to 1.12; P < 0.001) and a shift toward positive feelings were observed. The median length of hospital stay was 7.0 days in the VR group compared with 9.0 days in the control group, but the difference (2.0 days) did not reach statistical significance (95% CI -0.0001 to 3.00; P = 0.076). Surgical outcomes, health status, and measures of distress did not differ between groups. Conclusions: The study demonstrated the feasibility of a VR intervention that improved overall mood and showed a desirable effect on feelings and length of hospital stay after colorectal surgery. The results should stimulate further research investigating the potential of VR as an adjunct to physiotherapy to enhance mobilization after surgery.

CHANGES ANALYSIS OF THE HEPATOCYTE APOPTOSIS MARKERS LEVELS IN MALIGNANT OBSTRUCTIVE JAUNDICE COMPLICATED BY CHOLANGITIS.

OBJECTIVE: The aim: To evaluate changes in the levels of hepatocyte apoptosis markers in malignant obstructive jaundice (MOJ) depending on the performance of preoperative biliary decompression (PBD) and the severity degree of primary ascending cholangitis (PAC). PATIENTS AND METHODS: Materials and methods: 136 patients with MOJ complicated by cholangitis were included in the study: group A (n=84) - patients who underwent PBD; group B (n=52) - patients without PBD. The level of CASP3 and Bcl-2 (Human Bcl-2(B-cell Leukemia/Lymphoma 2) in blood serum and bile was assessed according to the principle of Sandwich-ELISA. Material collection for research was performed at the PBD stage and intraoperatively. RESULTS: Results: Comparative analysis of CASP3 levels in patients of the study groups revealed that the level of this indicator in the blood and bile of group A patients was statistically significantly higher compared to group B, p=0,004 and p<0,001, respectively. There was no statistically significant difference between the study groups in the intraoperative levels of blood serum Bcl-2 (p=0,786) and bile Bcl-2 (p=0,439). The presence of a correlation between apoptosis markers in group A patients with I and II degree of PAC at the time of PBD and the main surgical intervention was determined: blood serum CASP3 - r=0,733, p<0,001 and r=0,753, p<0,001; bile CASP3 - r=0,716, p<0,001 and r=0,792, p<0,001; blood serum Bcl-2 - r=0,609, p<0,001 and r=0,495, p=0,002; bile Bcl-2- r=0,744, p<0,001 and r=0,497, p=0,002, respectively. Binary logistic regression analysis showed that the development of grade I and II PAC did not relate with the levels of apoptosis markers (p>0.05). Linear regression analysis revealed a correlation between the levels of Bcl-2 in bile during PBD and intraoperatively in group A patients with moderate grade OJ (R2=0,547, p<0,001) and between the levels of CASP3 in blood serum (R2=0,614, p<0,001), CASP3 in bile (R2=0,603, p<0,001), Bcl-2 in blood serum (R2=0,484, p<0,001) and Bcl-2 in bile (R2=0,485, p<0,001) in PBD and intraoperatively in patients with severe grade OJ. A statistically significant difference in the levels of Bcl-2 in blood serum (p<0,001) and Bcl-2 in bile (p=0,016) was found when comparing apoptosis markers in patients with moderate grade OJ of the study groups. Binary logistic analysis showed that the performance of PBD had a significant (reducing) effect on CASP3 levels in blood serum and bile taken intraoperatively in study groups patients with moderate grade OJ (R2= 0,292, p<0,001; R2= 0,184, p<0,001). CONCLUSION: Conclusions: Prolonged OJ leads to the pathological apoptosis process. The performance of PBD statistically significantly reduces the level of CASP3 in blood serum and bile, which is confirmed by further determination intraoper¬atively in patients with OJ complicated by PAC, p<0,001. Staged surgical intervention with the performance of PBD according to clear indications is a necessary treatment strategy in patients with MOJ complicated by cholangitis.

[Surgical technique of axillary, inguinal and iliac lymph node dissection]. / Operative Technik der axillären, inguinalen und iliakalen Lymphknotendissektion.

BACKGROUND: Systematic lymph node dissection (SLND) plays an important role in the surgical treatment of many tumors. Despite continuous developments in surgical techniques, the morbidity in axillary, inguinal and iliac SLND remains high. OBJECTIVE: Description of the currently existing surgical techniques of axillary, inguinal and iliac SLND with presentation of the possible advantages and disadvantages, also with respect to the oncological results. MATERIAL AND METHODS: Based on the currently available literature reports, study results and own experience, the techniques of SLND and treatment results are presented. RESULTS: SLND in the axillary, inguinal and iliac regions is still a challenging procedure for surgeons and patients. This problem exists due to the complex anatomy and the high morbidity. Modifications of open surgical techniques led to a reduction of postoperative complications only in rare exceptions. Minimally invasive iliac SLND is possible and can be performed both by laparoscopy and retroperitoneoscopy. The application of videoscopic techniques in axillary and inguinal SLND is also possible and the feasibility has been confirmed in different studies. Using minimally invasive approaches a significant reduction in wound complications could be achieved. Nevertheless, up to now the oncological results of minimally invasive surgery are still unclear, especially for malignant melanoma. CONCLUSION: By using minimally invasive SLND in the axillary, inguinal and iliac regions, a significant reduction of wound complications can be achieved. Further prospective studies are needed to confirm the initially promising results, especially with respect to the oncological outcome.

All-Body-Cavity (ABC)-scopy-An approach for a feasible method of minimally invasive autopsy to allow for postmortem tissue sampling in cases where a conventional autopsy is denied.

OBJECTIVES: The decreasing autopsy numbers in many western countries have been partially attributed to the invasiveness of the autopsy, which causes relatives to decline postmortem examination. This issue has been addressed by developing methods of minimally or non-invasive autopsy, which could be shown to increase acceptance for autopsies. The aim of this study is to compare the All-Body-Cavity-scopy (ABC-scopy) to conventional autopsies for diagnostic accuracy. METHODS: The ABC-scopy is an endoscopic approach for minimally invasive autopsy involving laparoscopic and thoracoscopic evaluation of the accessible organs, followed by excision biopsies of relevant organs and conspicuous findings. The method was performed in 10 cases on deceased patients scheduled for autopsy, each followed by a conventional autopsy. RESULTS: The results gathered from ABC-scopy through observation and histopathological evaluation provided an acceptable diagnostic accuracy in 9 out of 10 autopsies when compared to those of the conventional autopsy for diagnostic findings. CONCLUSIONS: The ABC-scopy is a feasible approach for minimally invasive autopsy that provides acceptable diagnostic value. Despite its minimally invasive nature, the procedure enables representative histology through providing large size excision biopsies from intraabdominal and thoracic organs, which is especially useful for examining disseminated diseases such as metastasized tumors.

Immersive virtual reality fitness games for enhancement of recovery after colorectal surgery: study protocol for a randomised pilot trial.

BACKGROUND: Physical inactivity after surgery is an important risk factor for postoperative complications. Compared to conventional physiotherapy, activity-promoting video games are often more motivating and engaging for patients with physical impairments. This effect could be enhanced by immersive virtual reality (VR) applications that visually, aurally and haptically simulate a virtual environment and provide a more interactive experience. The use of VR-based fitness games in the early postoperative phase could contribute to improved mobilisation and have beneficial psychological effects. Currently, there is no data on the use of VR-based fitness games in the early postoperative period after colorectal surgery. METHODS: This pilot trial features a single-centre, randomised, two-arm study design with a 1:1 allocation. Patients undergoing elective abdominal surgery for colorectal cancer or liver metastases of colorectal cancer will be recruited. Participants will be randomly assigned to an intervention group or a control group. Patients randomised to the intervention group will perform immersive virtual reality-based fitness exercises during their postoperative hospital stay. Feasibility and clinical outcomes will be assessed. DISCUSSION: Early mobilisation after surgery is crucial for reducing many postoperative complications. VR-based interventions are easy to use and often inexpensive, especially compared to interventions that require more medical staff and equipment. VR-based interventions could serve as an alternative or complement to regular physiotherapy and enhance mobilisation after surgery. The proposed pilot study will be the first step to evaluate the feasibility of VR-based interventions in the perioperative period, with the aim of improving the postoperative rehabilitation of cancer patients. TRIAL REGISTRATION: The trial has been registered in the German Clinical Trials Register (DRKS) Nr. DRKS00024888 , on April 13, 2021, WHO Universal Trial Number (UTN) U1111-1261-5968.

Continuous and interrupted abdominal-wall closure after primary emergency midline laparotomy (CONIAC-trial): study protocol for a randomised controlled single centre trial.

INTRODUCTION: The optimal closure of the abdominal wall after emergency midline laparotomy is still a matter of debate due to lack of evidence. Although closure of the fascia using a continuous, all-layer suture technique with slowly absorbable monofilament material is common, complications like burst abdomen and hernia are frequent. METHODS AND ANALYSIS: This randomised controlled trial with a 1:1 allocation evaluates the efficacy and safety of a continuous suture with or without additional interrupted retention sutures for closure of the abdominal fascia. Patients with an indication for a primary emergency midline laparotomy are eligible to participate in this study and will be randomised intraoperatively via block randomisation. Fascia closure in the intervention group will be done with a standard continuous suture with slowly absorbable monofilament material (MonoMax 1, B. Braun, Tuttlingen, Germany) and additional interrupted retention sutures every 2 cm of the fascia using rapidly absorbable braided material (Vicryl 2, Ethicon, Norderstedt, Germany). In the control group, the fascia is closed only with the standard continuous suture with slowly absorbable monofilament material. Sample size calculations (n=111 per study arm) are based on the available literature. The primary endpoint is the rate of dehiscence of the abdominal fascia (rate of burst abdomen within 30 days or rate of incisional hernia within 12 months). Secondary endpoints are wound infections, quality of life, length of hospital stay, morbidity and mortality. Patients as well as individuals involved in data collection, endpoint assessment, data analysis and quality of life assessment will be blinded. ETHICS AND DISSEMINATION: The study protocol, the patient information and the informed consent form have been approved by the ethics committee of the Ludwig-Maximilians-University, Munich, Germany (reference number: 20-1041). Study findings will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: DRKS00024802. WHO UNIVERSAL TRIAL NUMBER: U1111-1259-1956.

Concurrent loss of MLH1, PMS2 and MSH6 immunoexpression in digestive system cancers indicating a widespread dysregulation in DNA repair processes.

Immunohistochemical analysis of mismatch repair (MMR) protein expression is widely used to identify tumors with a deficient MMR (dMMR). MMR proteins (MLH1/PMS2 and MSH2/MSH6) work as functional heterodimers, which usually leads to the loss of expression in only one functional MMR heterodimer. Recently, there have been studies showing the simultaneous loss of immunoexpression in proteins of both heterodimers. Yet, this phenomenon has been rarely investigated. In this study, we retrospectively considered cases of different digestive system cancers (gastric cancer, ampullary cancer, small bowel cancer, colorectal cancer), which were immunohistochemically tested for dMMR within a 4-year period at our university hospital (n=352). Of the 103 cases showing dMMR, 5 cases (1.4% of all, 5.1% of dMMR cases) showed a concurrent loss of MLH1, PMS2 and MSH6 immunoexpression, whereas in the other 98 dMMR cases only one MMR heterodimer was affected. MLH1-/PMS2-/MSH6- cancer cases almost arose throughout the entire digestive tract: from the gastric antrum to the left colic flexur. To provide a comprehensive molecular characterization of this MLH1-/PMS2-/MSH6- immunophenotype, tumors were analyzed for microsatellite instability, MLH1 promotor hypermethylation and BRAF exon 15 status. Furthermore, we performed next-generation sequencing focusing on genes related to DNA repair. Here, we could detect pathogenic germline variants as well as multiple sporadic mutations in different genes involved in MMR and homologous recombination repair (HRR) respectively. The affected MMR/HRR-related genes were: ATM, BARD1, BRCA1, CDK12, CHEK1, CHEK2, FANCA, MLH1, MSH6, PALB2, TP53. Considering the biologic function of HRR/MMR proteins as potential drug targets and the low frequency of most of these mutations in digestive system cancers in general, their common occurrence in our MLH1-/PMS2-/MSH6- cases seems to be even more noteworthy, highlighting the need for recognition, awareness and further investigation of this unusual IHC staining pattern.

A randomised pilot trial of virtual reality-based relaxation for enhancement of perioperative well-being, mood and quality of life.

A cancer diagnosis and subsequent treatment can trigger distress, negatively impact coping resources, and affect well-being as well as quality of life. The aim of this pilot study was to investigate feasibility and clinical effects of a VR intervention on quality of life, well-being and mood in cancer patients undergoing surgery compared to a non-VR intervention and a control group. 54 patients with colorectal cancer or liver metastases from colorectal cancer undergoing elective curatively intended surgery were recruited and randomised to one of two intervention groups or a control group receiving standard treatment. Participants assigned to one of the intervention groups either received a VR-based intervention twice daily or listened to music twice daily. Adherence to the intervention was 64.6% in the music group and 81.6% in the VR group. The VR intervention significantly reduced heart rate (- 1.2 bpm; 95% CI - 2.24 to - 0.22; p = 0.02) and respiratory rate (- 0.7 brpm; 95% CI - 1.08 to - 0.25; p = 0.01). Self-reported overall mood improved in both groups (VR: + 0.79 pts; 95% CI 0.37-1.21; p = 0.001; music: + 0.59 pts; 95% CI 0.22-0.97; p = 0.004). There was no difference in quality of life between the three groups. Both interventions groups reported changes in feelings. Adherence rates favoured the VR intervention over the music group. Observed clinical outcomes showed stronger intragroup effects on mood, feelings, and vital signs in the VR group. The study demonstrated feasibility of a VR intervention in cancer patients undergoing surgery and should encourage further research investigating the potential of VR interventions to positively influence well-being and mood in cancer patients.

ALK, NUT, and TRK Do Not Play Relevant Roles in Gastric Cancer-Results of an Immunohistochemical Study in a Large Series.

ALK, NUT, and TRK are rare molecular aberrations that are pathognomonic for specific rare tumors. In low frequencies, however, they are found in a wide range of other tumor entities. This study aimed to investigate the frequency, association with clinicopathological characteristics, and prognosis of the immunohistochemical expressions of ALK, NUT, and TRK in 477 adenocarcinomas of the stomach and gastroesophageal junction. Seven cases (1.5%) showed an expression of TRK. In NGS, no NTRK fusion was confirmed. No case with ALK or NUT expression was detected. ALK, NUT, and NTRK expression does not seem to play an important role in gastric carcinomas.

IgG4-related pseudotumours: a series of 12 cases and a review of the literature.

IgG4-related pseudotumours (IgG4-RPT) represent a distinctive manifestation in the broad spectrum of IgG4-related diseases (IgG4-RD). Due to their wide morphology and rarity, IgG4-RPTs represent a diagnostic challenge in the differential between reactive lesions and a fibrous soft tissue tumours. Thus, our aim was to characterise our cases and review the literature, focusing on the macroscopic and microscopic features of the lesions. In this paper, we summarise the possible presentations and histomorphological features of IgG4-RPT based on data collected from the literature and from cases at our institute and provide an overview of the pathogenesis and histological characteristics based on the knowledge accumulated in recent years. We collected surgical cases with a diagnosis of IgG4-RPT over the period 2013-2020 at two centres and analysed their macroscopic, histological, and immunohistochemical profiles. Furthermore, we performed a literature research in the MEDLINE and EBSCO databases regarding case reports and studies with the explicit diagnosis of IgG4-RPT. Our cases consist of nine men and three women, with an average age of 60±14 years, representing about 0.05% of the lesions evaluated at the two departments. The involved sites include the kidney, lung, gallbladder, pterygopalatine fossa, spleen, tongue, mediastinum, and submandibular gland. Grossly, nine lesions showed sharp margins. On histological examination, all the lesions showed an abundant inflammatory infiltrate with lymphocytes and IgG4-positive plasma cells as well as characteristic fibroblastic storiform proliferation. The literature search revealed 266 cases and similar histomorphological features in 23 locations. In 30 of these cases (11%), IgG4-RPTs were multifocal. IgG4-RPT are exceedingly rare lesions, which makes them challenging to diagnose. They can affect different sites, and the histomorphological presentation may differ.

Acute appendicitis during the COVID-19 pandemic-changes in incidence and clinical presentation but not in patients' outcome.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic is an ongoing severe issue. OBJECTIVE: The aim of this study was to compare the incidence, severity and treatment of acute appendicitis (AA) before and during the COVID-19 pandemic. METHODS: A retrospective cohort analysis was conducted between January 2019 and April 2020 in one high-volume center. A comparison was performed between two groups (Group A: patients admitted with AA before the COVID-19 pandemic; Group B: patients admitted with AA at the beginning of the pandemic) in terms of the incidence of AA and clinical and pathological outcomes. The incidence of AA was also analyzed in six surrounding peripheral hospitals. RESULTS: A total of 94 patients were identified, 54 in Group A and 40 in Group B (57% vs. 43%). Demographic data were comparable between groups. AA in Group B showed a significant higher rate of histological advanced cases (10 (18.5%) Group A vs. 20 (50%) Group B, P = 0.001) and the need for postoperative antibiotic treatment (6 (11.1%) Group A vs. 11 (27.5%) Group B, P = 0.045). During the pandemic, a higher percentage of patients were treated at peripheral hospitals (Group A: 54/111 vs. 40/126). CONCLUSION: During the onset of the COVID-19 pandemic there was a significant decrease of patients with AA in a high-volume center, which showed more advanced disease of AA. This significant decrease in the high-volume center correlates with an increase in patients with AA in peripheral hospitals and represents a change in patient flow during the onset of the pandemic.

Intraoperative endoluminal pyloromyotomy for reduction of delayed gastric emptying after pylorus preserving partial pancreaticoduodenectomy (PORRIDGE trial): study protocol for a randomised controlled trial.

BACKGROUND: Pylorus-preserving pancreaticoduodenectomy (ppPD) is a standard surgical procedure for the treatment of resectable neoplasms of the periampullary region. One of the most common postoperative complications after ppPD is delayed gastric emptying (DGE) which reduces quality of life, prevents a timely return to a solid oral diet and prolongs the length of hospital stay. In a retrospective analysis, intraoperative endoluminal pyloromyotomy was associated with a reduced rate of DGE. The aim of this study is to investigate the effect of intraoperative endoluminal pyloromyotomy on postoperative DGE after ppPD in a randomised and controlled setting. METHODS: This randomised trial features parallel group design with a 1:1 allocation ratio and a superiority hypothesis. Patients with a minimum age of 18 years and an indication for ppPD are eligible to participate in this study and will be randomised intraoperatively to receive either endoluminal pyloromyotomy or atraumatic stretching of the pylorus. The sample size calculation (n=64 per study arm) is based on retrospective data. The primary endpoint is the rate of DGE within 30 days. Secondary endpoints are quality of life, operation time, estimated blood loss, length of hospital stay, morbidity and mortality. DISCUSSION: DGE after ppPD is a common complication with an incomplete understood aetiology. Prevention of DGE could improve outcomes and enhance quality of life after one of the most common procedures in pancreatic surgery. This trial will expand the existing evidence on intraoperative pyloromyotomy, and the results will provide additional data on a simple surgical technique that could reduce the incidence of postoperative DGE. TRIAL REGISTRATION: German Clinical Trials Register DRKS00013503 . Registered on 27 December 2017.

Stroma AReactive Invasion Front Areas (SARIFA) - a new prognostic biomarker in gastric cancer related to tumor-promoting adipocytes.

Compared to other malignancies, there is a lack of easy-to-evaluate biomarkers for gastric cancer, which is associated with an adverse clinical outcome in many cases. Here, we present Stroma AReactive Invasion Front Areas (SARIFA) as a new histological prognostic marker. We defined SARIFA as the direct contact between a cluster of tumor glands/cells comprising at least five tumor cells and inconspicuous surrounding adipose tissue at the invasion front. A total of 480 adenocarcinomas of the stomach and the gastroesophageal junction from two different collections were classified according to SARIFA. To understand the potential underlying mechanisms, a transcriptome analysis was conducted using digital spatial profiling (DSP). It was found that 20% of the tumors were SARIFA-positive. Kappa values between the three pathologists were good in both collections: 0.74 and 0.78. Patients who presented SARIFA-positive tumors had a significantly lower overall survival in Collections A (median: 20.0 versus 44.0 months; p = 0.014, n = 160) and B (median: 15.0 versus 41.0 months; p < 0.0001, n = 320). SARIFA positivity emerged as a negative independent prognostic factor for overall survival (HR 1.638, 95% CI 1.153-2.326, p = 0.006). Using DSP, the most upregulated genes in SARIFA-positive cases were those associated with triglyceride catabolism and endogenous sterols. COL15A1, FABP2, and FABP4 were differentially expressed in positive cases. At the protein level, the expression of proteins related to lipid metabolism was confirmed. SARIFA combines low inter-observer variability, minimal effort, and high prognostic relevance, and is therefore an extremely promising biomarker related to tumor-promoting adipocytes in gastric cancer. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.

Stroma AReactive Invasion Front Areas (SARIFA)-A New Easily to Determine Biomarker in Colon Cancer-Results of a Retrospective Study.

Many studies have used histomorphological features to more precisely predict the prognosis of patients with colon cancer, focusing on tumor budding, poorly differentiated clusters, and the tumor-stroma ratio. Here, we introduce SARIFA: Stroma AReactive Invasion Front Area(s). We defined SARIFA as the direct contact between a tumor gland/tumor cell cluster (≥5 cells) and inconspicuous surrounding adipose tissue in the invasion front. In this retrospective, single-center study, we classified 449 adipose-infiltrative adenocarcinomas (not otherwise specified) from two groups based on SARIFA and found 25% of all tumors to be SARIFA-positive. Kappa values between the two pathologists were good/very good: 0.77 and 0.87. Patients with SARIFA-positive tumors had a significantly shorter colon-cancer-specific survival (p = 0.008, group A), absence of metastasis, and overall survival (p < 0.001, p = 0.003, group B). SARIFA was significantly associated with adverse features such as pT4 stage, lymph node metastasis, tumor budding, and higher tumor grade. Moreover, SARIFA was confirmed as an independent prognostic indicator for colon-cancer-specific survival (p = 0.011, group A). SARIFA assessment was very quick (<1 min). Because of low interobserver variability and good prognostic significance, SARIFA seems to be a promising histomorphological prognostic indicator in adipose-infiltrative adenocarcinomas of the colon. Further studies should validate our results and also determine whether SARIFA is a universal prognostic indicator in solid cancers.

Comprehensive Immunohistochemical Study of the SWI/SNF Complex Expression Status in Gastric Cancer Reveals an Adverse Prognosis of SWI/SNF Deficiency in Genomically Stable Gastric Carcinomas.

The SWI/SNF complex has important functions in the mobilization of nucleosomes and consequently influences gene expression. Numerous studies have demonstrated that mutations or deficiency of one or more subunits can have an oncogenic effect and influence the development, progression, and eventual therapy resistance of tumor diseases. Genes encoding subunits of the SWI/SNF complex are mutated in approximately 20% of all human tumors. This study aimed to investigate the frequency, association with clinicopathological characteristics, and prognosis of immunohistochemical expression of proteins of the SWI/SNF complexes, SMARCA2, SMARCA4 SMARCB1, ARID1A, ARID1B, and PBRM1 in 477 adenocarcinomas of the stomach and gastroesophageal junction. Additionally, the tumors were classified immunohistochemically in analogy to The Cancer Genome Atlas (TCGA) classification. Overall, 32% of cases demonstrated aberrant expression of the SWI/SNF complex. Complete loss of SMARCA4 was detected in three cases (0.6%) and was associated with adverse clinical characteristics. SWI/SNF aberration emerged as an independent negative prognostic factor for overall survival in genomically stable patients in analogy to TCGA. In conclusion, determination of SWI/SNF status could be suggested in routine diagnostics in genomically stable tumors to identify patients who might benefit from new therapeutic options.

Ultrastaging Using Ex Vivo Sentinel Lymph Node Mapping and One-Step Nucleic Acid Amplification (OSNA) in Gastric Cancer: Experiences of a European Center.

BACKGROUND: In this study, the effectiveness of One-step nucleic acid amplification (OSNA) in combination with ex vivo SLN mapping is compared with conventional histology including immunohistochemistry. METHODS: LNs were retrieved from gastrectomy specimens in an unfixed state. After ex vivo SLN mapping using methylene-blue, LNs were sliced to provide samples for histology and OSNA. RESULTS: In total, 334 LNs were retrieved in the fresh state from 41 patients. SLN detection was intended in 40 cases but was successful in only 29, with a correct LN status prediction in 23 cases (79%). Excluding one case out of 41 with a failure likely caused by a processing error, OSNA showed a high effectiveness with sensitivity, specificity, and accuracy rates of 85.4%, 93.5%, and 92.4%, respectively. The LN status could be predicted in all but one case, in which the single positive LN was not eligible for OSNA testing. Moreover, OSNA evaluation led to upstaging from N0 to N+ in three cases (14%). CONCLUSION: The ex vivo SLN protocol used resulted in a relatively poor detection rate. However, the OSNA method was not hampered by this detection rate and proved its potential to increase the sensitivity of metastases detection.

Large Vessel Vasculitis as a Possible Mechanism of Vascular Side Effects of Ponatinib: A Case Report.

Arterial occlusive events (AOEs) such as cerebrovascular, cardiovascular and peripheral arterial events are known side effects of ponatinib, assumed due to the rapid development and increase of arteriosclerosis, while the definitive pathomechanisms therefore are still unclear. We present a case of clinically apparent large vessel vasculitis and discuss this phenomenon as a possible mechanism of AOEs beside arteriosclerosis.