Defining distal splenopancreatectomy by the mesopancreas.

BACKGROUND: The implementation of the pathologic CRM (circumferential resection margin) staging system for pancreatic head ductal adenocarcinomas (hPDAC) resulted in a dramatic increase of R1 resections at the dorsal resection margin, presumably because of the high rate of mesopancreatic fat (MP) infiltration. Therefore, mesopancreatic excision (MPE) during pancreatoduodenectomy has recently been promoted and has demonstrated better local disease control, fueling the discussion of neoadjuvant downsizing regimes in MP + patients. However, it is unknown to what extent the MP is infiltrated in patients with distal pancreatic (tail/body) carcinomas (dPDAC). It is also unknown if the MP infiltration status affects surgical margin control in distal pancreatectomy (DP). The aim of our study was to histopathologically analyze MP infiltration and elucidate the influence of resection margin clearance on recurrence and survival in patients with dPDAC. Furthermore, the results were compared to a collective receiving MPE for hPDAC. METHOD: Clinicopathological and survival parameters of 295 consecutive patients who underwent surgery for PDAC (n = 63 dPDAC and n = 232 hPDAC) were evaluated. The CRM evaluation was performed in a standardized fashion and the specimens were examined according to the Leeds pathology protocol (LEEPP). The MP area was histopathologically evaluated for cancerous infiltration. RESULTS: In 75.4% of dPDAC patients the MP fat was infiltrated by vital tumor cells. The rates of MP infiltration and R0CRM- resections were similar between dPDAC and hPDAC patients (p = 0.497 and 0.453 respectively). MP- infiltration status did not correlate with CRM implemented resection status in dPDAC patients (p = 0.348). In overall survival analysis, resection status and MP status remained prognostic factors for survival. In follow up analysis. surgical margin clearance in dPDAC patients was associated with a significant improvement in local recurrence rates (5.2% in R0CRM- resected vs. 33.3 in R1/R0CRM + resected, p = 0.002). CONCLUSION: While resection margin status was not affected by the MP status in dPDAC patients, the high MP infiltration rate, as well as improved survival in MP- dPDAC patients after R0CRM- resection, justify mesopancreatic excision during splenopancreatectomy. Larger scale studies are urgently needed to validate our results and to study the effect on neoadjuvant treatment in dPDAC patients.

MRI in-bore biopsy following MRI/US fusion-guided biopsy in patients with persistent suspicion of clinically significant prostate cancer.

PURPOSE: Patients with suspicion of clinically significant prostate cancer (csPC) on multiparametric prostate MRI (mpMRI) but negative or inconclusive MRI/US fusion-guided biopsy (FB) can be challenging in clinical practice. To assess the utility of MRI in-bore biopsy (IB) in patients with discordant imaging and histopathological findings after FB. METHODS: Consecutive patients with Prostate Imaging Reporting and Data System (PI-RADS) category 4 or 5 on mpMRI at 3T after FB without histologically confirmed csPC who underwent IB between 01/2014 and 05/2022, were retrospectively included. The primary objective was to assess the detection rate of csPC. Secondary objectives were to analyze clinical parameters, MRI parameters, and lesion localization. RESULTS: In the final cohort of 51 patients, the IB resulted in an overall detection rate of 71% for PC and 47% for csPC. Furthermore, in 55% of cases with initial low-grade PC, the Gleason score was upgraded after IB. CsPC was often detected apical and/or anterior. The detection rate for PC was 58% in PI-RADS category 4 and 94% in PI-RADS category 5 (csPC 39% and 61%, respectively). Patients with csPC had statistically significant smaller prostate volumes, a higher PI-RADS category, a higher prostate-specific antigen density (PSAD), and were older. CONCLUSIONS: For a relevant proportion of patients with PI-RADS category 4 or 5 and negative or inconclusive findings on previous FB, but with persistent suspicion of csPC, a subsequent IB verified the presence of csPC. Therefore, IB can be a backup in cases of uncertainty.

Multiparametric MRI characteristics of prostatitis and atrophy in the peripheral zone in men without prostate cancer.

PURPOSE: To analyse multiparametric magnetic resonance imaging (mpMRI) characteristics and appearance of histopathologically proven non-cancerous intraprostatic findings focussing on quantity of prostatitis and atrophy in the peripheral zone. METHOD: In this retrospective analysis consecutive patients with mpMRI followed by MRI/TRUS-fusion biopsy comprising targeted (TB) and systematic biopsy (SB) cores without prostate cancer (PC) at histopathology were included. Subgroup analysis was performed in younger men (≤50 years). The proportions of prostatitis and atrophy were quantified for each biopsy core based on histopathology. MRI findings in the peripheral zone (PZ) and index lesions (IL, most suspicious/representative lesion) were characterized regarding changes in T2w, ADC value, and enhancement of dynamic contrast enhancement (DCE) and correlated with quantity of prostatitis and atrophy. RESULTS: Seventy-two patients were analysed. The median baseline characteristics were PSA 5.4 ng/ml (4.0-7.9), PI-RADS classification 3 (2-4), prostate volume 43 ml (33-57), and PSA density 0.13 ng/ml2 (0.10-0.19). Prostatitis was found in 44 % (n = 32) and atrophy in 65 % (n = 47) of cases. The quantity of atrophy demonstrated a significant correlation to T2w changes, ADC increase and DCE enhancement (p = 0.05, p = 0.05, p = 0.01), whereas quantity of prostatitis did not show any significant correlation to the MRI changes (p = 0.68, p = 0.58, p = 0.95). Quantity of prostatitis and atrophy increased with PI-RADS classification. Younger men had lower PSA (4.4 vs. 7.8 ml/ng; p < 0.001), smaller prostate volume (40 vs. 59 ml; p = 0.001), and lower PI-RADS classification (2-3 vs. 3-4; p = 0.005) and prostatitis and atrophy were less frequently observed (p ≤ 0.01, p = 0.03). CONCLUSIONS: Quantity of atrophy and prostatitis had different influence on MRI characteristics and increased within higher PI-RADS classification. Younger men had diffuse hypointense changes at T2w images, but less quantity of prostatitis and atrophy.

Data on the detection of clinically significant prostate cancer by magnetic resonance imaging (MRI)-guided targeted and systematic biopsy.

This is a data article from the original publication "Reasons for missing clinically significant prostate cancer by targeted magnetic resonance imaging/ultrasound fusion-guided biopsy" [1]. From January 2014 to April 2019 a sample collective of 785 patients with 3T multiparametric magnetic resonance imaging (mp-MRI) of the prostate and subsequent combined systematic biopsy (SB) and magnetic resonance imaging/ultrasound (US) fusion-guided biopsy (TB) was retrospectively analyzed. Prostate cancer (PCa) detection by TB and/or additional SB was analyzed.

Pre-operative magnetic resonance imaging can predict prostate cancer with risk for positive surgical margins.

PURPOSE: Analysis of patients with pre-operative 3 T multiparametric prostate MRI (mpMRI) to determine reliable MRI-based risk predictors of patients at risk for positive surgical margins (PSM) in robotic assisted radical prostatectomy (RPE). METHODS: Consecutive patients with 3 T mpMRI and subsequent RPE from 01/2015 to 12/2018 were retrospectively included. Patients were compared regarding clinical and MRI related parameters such as length of capsular tumor contact (LCC) and distance to the membranous urethra (UD). RESULTS: Forty-nine of 179 patients (27%) had PSM in 70 different localizations, with the majority located at the capsule (57%, 40/70), mostly apical and/or posterior. The second most often PSM occurred at the apical urethra (22%, 15/70). PCA was visible on mpMRI at the localization of PSM in 93% at the capsule and in 80% at the urethra. PSA, PI-RADS classification, extraprostatic extension (EPE), and seminal vesicles infiltration (SVI) on MRI were significantly higher / more frequent in patients with PSM. LCC (AUC 0.710), EPE (AUC 0.693), and UD (1-AUC 0.673) predicted PSM (overall). An UD of ≤ 3.5 mm showed the highest accuracy of 95% (J = 0.946) for PSM at the urethra and a LCC of ≥ 22.5 mm with 77% (J = 0.378) for PSM at the capsule. CONCLUSION: PSM occurred mostly in the apex and/or posteriorly at the capsule or at the apical urethra. LCC was the best MRI predictor for PSM at the capsule and UD for tumors with PSM at the apical urethra. Using these MRI parameters readers might pre-operatively determine PCA localizations at risk for PSM.

Treatment outcome of atypical EGFR mutations in the German National Network Genomic Medicine Lung Cancer (nNGM).

BACKGROUND: Atypical EGFR mutations occur in 10%-30% of non-small-cell lung cancer (NSCLC) patients with EGFR mutations and their sensitivity to classical epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKI) is highly heterogeneous. Patients harboring one group of uncommon, recurrent EGFR mutations (G719X, S768I, L861Q) respond to EGFR-TKI. Exon 20 insertions are mostly insensitive to EGFR-TKI but display sensitivity to exon 20 inhibitors. Clinical outcome data of patients with very rare point and compound mutations upon systemic treatments are still sparse to date. PATIENTS AND METHODS: In this retrospective, multicenter study of the national Network Genomic Medicine (nNGM) in Germany, 856 NSCLC cases with atypical EGFR mutations including co-occurring mutations were reported from 12 centers. Clinical follow-up data after treatment with different EGFR-TKIs, chemotherapy and immune checkpoint inhibitors were available from 260 patients. Response to treatment was analyzed in three major groups: (i) uncommon mutations (G719X, S7681, L861Q and combinations), (ii) exon 20 insertions and (iii) very rare EGFR mutations (very rare single point mutations, compound mutations, exon 18 deletions, exon 19 insertions). RESULTS: Our study comprises the largest thus far reported real-world cohort of very rare EGFR single point and compound mutations treated with different systemic treatments. We validated higher efficacy of EGFR-TKI in comparison to chemotherapy in group 1 (uncommon), while most exon 20 insertions (group 2) were not EGFR-TKI responsive. In addition, we found TKI sensitivity of very rare point mutations (group 3) and of complex EGFR mutations containing exon 19 deletions or L858R mutations independent of the combination partner. Notably, treatment responses in group 3 (very rare) were highly heterogeneous. Co-occurring TP53 mutations exerted a non-significant trend for a detrimental effect on outcome in EGFR-TKI-treated patients in groups 2 and 3 but not in group 1. CONCLUSIONS: Based on our findings, we propose a novel nNGM classification of atypical EGFR mutations.

MRI grading for the prediction of prostate cancer aggressiveness.

OBJECTIVES: T o evaluate the value of multiparametric MRI (mpMRI) for the prediction of prostate cancer (PCA) aggressiveness. METHODS: In this single center cohort study, consecutive patients with histologically confirmed PCA were retrospectively enrolled. Four different ISUP grade groups (1, 2, 3, 4-5) were defined and fifty patients per group were included. Several clinical (age, PSA, PSAD, percentage of PCA infiltration) and mpMRI parameters (ADC value, signal increase on high b-value images, diameter, extraprostatic extension [EPE], cross-zonal growth) were evaluated and correlated within the four groups. Based on combined descriptors, MRI grading groups (mG1-mG3) were defined to predict PCA aggressiveness. RESULTS: In total, 200 patients (mean age 68 years, median PSA value 8.1 ng/ml) were analyzed. Between the four groups, statistically significant differences could be shown for age, PSA, PSAD, and for MRI parameters cross-zonal growth, high b-value signal increase, EPE, and ADC (p < 0.01). All examined parameters revealed a significant correlation with the histopathologic biopsy ISUP grade groups (p < 0.01), except PCA diameter (p = 0.09). A mixed linear model demonstrated the strongest prediction of the respective ISUP grade group for the MRI grading system (p < 0.01) compared to single parameters. CONCLUSIONS: MpMRI yields relevant pre-biopsy information about PCA aggressiveness. A combination of quantitative and qualitative parameters (MRI grading groups) provided the best prediction of the biopsy ISUP grade group and may improve clinical pathway and treatment planning, adding useful information beyond PI-RADS assessment category. Due to the high prevalence of higher grade PCA in patients within mG3, an early re-biopsy seems indicated in cases of negative or post-biopsy low-grade PCA. KEY POINTS: • MpMRI yields relevant pre-biopsy information about prostate cancer aggressiveness. • MRI grading in addition to PI-RADS classification seems to be helpful for a size independent early prediction of clinically significant PCA. • MRI grading groups may help urologists in clinical pathway and treatment planning, especially when to consider an early re-biopsy.

Comparison of 3 T mpMRI and pelvic CT examinations for detection of lymph node metastases in patients with prostate cancer.

PURPOSE: This study investigates preoperative lymph node metastases (LNM) detection accuracy by MRI and CT in patients with prostate cancer (PCA). METHODS: All patients with preoperative MRI, CT or both and subsequent radical prostatectomy (RPE) and lymphadenectomy (LA) were included in this retrospective cohort study. Prostate specific antigen (PSA), PI-RADS, ISUP grade group, clinical and pathological tumor (T) stage was compared between negative and positive nodal (N) stage. LNM were assessed with size and localization and weather they were preoperatively detected or not. In patients with preoperative CT and MRI, the results were compared intermodally. The reference standard was the histopathological results after RPE and LA. RESULTS: A total of 228 patients were analysed including 24 patients with confirmed LNM (N1; 11%). PSA (median 9.7 vs. 14 ng/ml), PI-RADS (median 4 vs. 5), ISUP (median 2 vs. 4), and cT/pT-stage (median T2 vs. T3) was significantly higher in patients with LNM. No LNM were found in patients with ISUP-1-PCA. MRI was able to detect 67% of patients with LNM. Lymph node metastases presented on MRI predominantly small, round-shaped, located parailiacally with a minimum SAD of 4 mm (vs. CT SAD of 8 mm). In comparison, MRI was superior to CT in the detection of LNM (sensitivity 81% vs. 33%; specificity 99% vs. 97). CONCLUSION: LNM were very rare in patients with PSA < 10 ng/ml, PI-RADS ≤ 4, and ≤ cT2. MRI could detect LNM up to 4 mm with a moderate sensitivity and high specificity. Thus, MRI might optimise the preoperative diagnostic and therapy planning of patients with PCA, whereas CT was clearly limited for N-stage assessment.

Mesopancreatic excision for pancreatic ductal adenocarcinoma improves local disease control and survival.

BACKGROUND: Survival in ductal adenocarcinoma of the pancreatic head (hPDAC) is poor. After implementation of the circumferential resection margin (CRM) into standard histopathological evaluation, the margin negative resection rate has drastically dropped. However, the impact of surgical radicality on survival and the influence of malignant infiltration of the mesopancreatic fat remains unclear. At our institution, a standardized dissection of the mesopancreatic lamina and peri-pancreatic vessels are obligatory components of radical pancreatoduodenectomy. The aim of our study was to histopathologically analyze mesopancreatic tumor infiltration and the influence of CRM-evaluated resection margin on relapse-free and overall survival. METHOD: Clinicopathological and survival parameters of 264 consecutive patients who underwent surgery for hPDAC were evaluated. RESULTS: The rate of R0 resection R0(CRM-) was 48.5%, after the implementation of CRM. Mesopancreatic fat infiltration was evident in 78.4% of all consecutively treated patients. Patients with mesopancreatic fat infiltration were prone to lymphatic metastases (N1 and N2) and had a higher rate of positive resection margin (R1/R0(CRM+)). In multivariate analysis, only R0 resection was shown to be an independent prognostic parameter. Local recurrence was diagnosed in only 21.1% and was significantly lower in patients with R0(CRM-) resected hPDACs (10.9%, p < 0.001). CONCLUSION: Mesopancreatic excision is justified, since mesopancreatic fat invasion was evident in the majority of our patients. It is associated with a significantly improved local tumor control as well as longer relapse-free and overall survival.

Reasons for missing clinically significant prostate cancer by targeted magnetic resonance imaging/ultrasound fusion-guided biopsy.

OBJECTIVES: This study evaluates cases with clinically significant prostate cancer (csPCa) missed by targeted biopsy (TB) and analyzes the diagnostic impact of an additional systematic biopsy (SB) in a large patient collective. METHODS: Consecutive patients with a 3 T multiparametric prostate MRI (mpMRI) and a subsequent MRI/US fusion-guided TB plus 12-core US-guided SB from 01/2014 to 04/2019 were included in this study. Primary study endpoint was the analysis of cases with a csPCa missed by TB and detected by SB. Secondary study objectives were the PCa detection and the correlation with clinical and MRI parameters. RESULTS: In total 785 patients met the inclusion criteria. 342 patients had a csPCa (median PSAD 0.29 ng/mL/cm3). In 42 patients (13 %), a csPCa was detected only by SB. In 36 of these cases, the localization of the positive SB cores matched with the cancer suspicious region described on mpMRI (mCSR). Cases with a csPCA missed by TB showed either an insufficient MRI segmentation (prostate boundary correlation) (31 %) and/or insufficient lesion registration (lesion transfer, tracking, and/or matching) (48 %), a missed small lesion (14 %), or a failed center of a large lesion (10 %). Median PSAD of patients with non-significant PCa detected by SB was 0.15 ng/mL/cm3. CONCLUSIONS: Main reasons for missing a csPCa by TB were insufficient prostate segmentation or imprecise lesion registration within MRI/US fusion-guided biopsy. Consequently, verification of MRI quality, exact mCSR assessment, and advanced biopsy experience may improve accuracy. Altogether, an additional SB adds limited clinical benefit in men with PSAD ≤ 0.15 ng/mL/cm3.

Dusseldorf autopsies 1914-1918.

This article presents an evaluation of 4255 autopsy cases recorded at the Dusseldorf Pathology Institute in the years 1914 to 1918. Diagnoses were coded according to the International Classification of Diseases, 10th edition (ICD-10), and the contemporaneous history of the Pathology Institute was reviewed. We found a proportion of 54.1% adults and 45.5% children in our cohort, with a male predominance of 63.9%. Infectious diseases account for the majority of all cases (35.5%), among which tuberculosis is the most frequent, reported in 22.7% of all cases. The second largest diagnosis group is the one of respiratory diseases (16.9%), including pneumonia and influenza. Cases of perinatal conditions account for 10.5% of the collective, followed by neoplasms, injuries, intoxications, or external causes, each representing 6.6%. Cardiovascular diseases account for 5.3% of the cases. In 4.4% of the pediatric and 0.8% of adult cases, a diagnosis of the ICD-10 group "nutritional and endocrine diseases" was made. No diagnosis of hunger edema is reported. Parts of the cohort are 272 war pathology cases (6.4%), made up by soldiers who mainly had died of shotgun injuries. The whole cohort represents the disease spectrum of a German big city population at times of World War I. The data exemplify the epidemiological shift that has occurred in industrialized countries over the last 100 years, from infectious to neoplastic and cardiovascular diseases.

Magnetic resonance imaging improves the prediction of tumor staging in localized prostate cancer.

OBJECTIVES: The aim of this study was to investigate 3 Tesla multiparametric magnetic resonance imaging (mpMRI)-based predictors for the pretherapeutic T staging of prostate cancer and their accuracy. METHODS: Consecutive patients with 3 Tesla mpMRI, positive systematic and MR-targeted biopsy, and subsequent radical prostatectomy (RPE) between 01/2016 and 12/2017 were included. MRI parameters such as measurable extraprostatic extension (EPE) (≥ 3 mm), length of (pseudo)capsular contact (LCC), invasion of neurovascular bundle (NVBI), and/or seminal vesicles lesion contact (SVC) or infiltration (SVI) were assessed and correlated to clinical and histopathological results. RESULTS: 136 men were included. In 76 cases, a pT2 stage was determined, in 29 cases a pT3a, and in 31 a pT3b stage. The positive and negative predictive values (PPV, NPV) for the detection of T3 by measurable EPE on MRI was 98% (CI 0.88-1) and 81% (CI 0.72-0.87). No visible NVBI was found in pT2 patients (NPV 100%; CI 0.95-1). ROC analysis for T3a prediction with LCC (AUC 0.81) showed a sensitivity of 87% and a specificity of 62% at a threshold of 12.5 mm (J = 0.485) and 93% and 58% at 11 mm (Jmax = 0.512). All patients with pT3a had a LCC > 5 mm. In case of pT3b, 29/31 patients showed a SVC (PPV 76%, CI 0.61-0.87; NPV 98%, CI 0.93-0.99), and 23/31 patients showed a SVI (PPV 100%, CI 0.86-1; NPV 93%, CI 0.87-0.96). EPE (p < 0.01), LCC (p = 0.05), and SVC (p = 0.01) were independent predictors of pT3. CONCLUSIONS: MRI-measurable EPE, LCC, and SVC were reliable, independent, preoperative predictors for a histopathological T3 stage. A LCC ≥ 11 mm indicated a pT3a stage, whereas a LCC < 5 mm excluded it. On MRI, visible SVI or even SVC of the PCa lesion was reliable preoperative predictors for a pT3b stage.

[Status of the availability and use of next generation sequencing (NGS) in bladder cancer-a questionnaire within the uropathology working group]. / Status der Verfügbarkeit und Anwendung von "next generation sequencing" (NGS) beim Harnblasenkarzinom ­ eine Umfrage in der Arbeitsgemeinschaft Uropathologie.

BACKGROUND: Technical advancement and availability of high-throughput analysis has advanced molecular subtyping of most cancers. Thus, new possibilities for precision oncology have emerged. AIM: Therefore, we aimed to collect data regarding availability and use of next generation sequencing (NGS) for urothelial cancer within the uropathology working group of the German Society of Pathology. METHODS: We collected data by questionnaires and additionally asked for sequencing results of bladder cancers in the participating institutions. RESULTS: A total of 13 university-affiliated institutes of pathology took part in the survey. All university institutes offer NGS-based molecular panel diagnostics and provide panels covering between 15 and 170 genes. Altogether, only 20 bladder cancers were sequenced in routine diagnostics and for 10 cancers potential targeted treatment options were available. DISCUSSION: So far, despite availability of NGS diagnostics at university institutes of pathology, only few bladder cancer samples have been sequenced. Based on current data from the molecular subtyping of bladder cancers, we recommend a step-by-step protocol with basic immunohistochemistry analysis and subsequent subtype-dependent analyses, e.g., alterations of the fibroblast growth factor receptors (FGFR) or comprehensive gene panel analyses.

Apparent Diffusion Coefficient (ADC) predicts therapy response in pancreatic ductal adenocarcinoma.

Recent advances in molecular subtyping of Pancreatic Ductal Adenocarcinoma (PDAC) support individualization of therapeutic strategies in this most aggressive disease. With the emergence of various novel therapeutic strategies and neoadjuvant approaches in this quickly deteriorating disease, robust approaches for fast evaluation of therapy response are urgently needed. To this aim, we designed a preclinical imaging-guided therapy trial where genetically engineered mice harboring endogenous aggressive PDAC were treated with the MEK targeting drug refametinib, which induces rapid and profound tumor regression in this model system. Multi-parametric non-invasive imaging was used for therapy response monitoring. A significant increase in the Diffusion-Weighted Magnetic Resonance Imaging derived Apparent Diffusion Coefficient (ADC) was noted already 24 hours after treatment onset. Histopathological analyses showed increased apoptosis and matrix remodeling at this time point. Our findings suggest the ADC parameter as an early predictor of therapy response in PDAC.