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Liver cirrhosis is an established high-risk factor for HCC and the majority of patients diagnosed with HCC have cirrhosis. However, HCC also arises in non-cirrhotic livers in approximately 20 %of all cases. HCC in non-cirrhotic patients is often clinically silent and surveillance is usually not recommended. HCC is often diagnosed at an advanced stage in these patients. Current information about HCC in patients with non-cirrhotic liver is limited. Here we review the current knowledge on epidemiology, clinical features and imaging features of those patiens.

Objective The aim of this study was to characterize duodenal mast cell (MC) and eosinophil (EO) numbers, their distribution within the lamina propria and possible impact on disease severity of paediatric celiac patients compared to children without celiac disease (CD). Methods We analysed duodenal samples of 215 children (109 CD, 106 controls) who underwent esophagogastroduodenoscopy from 2010 to 2018. After immunohistochemical staining, average MC and EO counts were histologically examined in ten high-power-fields. Additionally, cell-distribution within the lamina propria was analysed. Possible influence of relevant clinical parameters was evaluated. Statistics Student's-t-test, Mann-Whitney U-test, Chi-square-test, ANOVA, significance-level Results MC-density was higher in CD-patients compared to the control-group (23.7 (±12.1)/HPF versus 19.7 (±9.1)/HPF; p = .008), varying in number interindividually. Eosinophils were also increased in the duodenum of celiac patients (23.3 (±9.3)/HPF versus 12.2 (±6.3)/HPF; p= Conclusion MC- and EO-numbers were increased in the duodenum of CD-patients and MCs showed a different distribution-pattern in the lamina propria of celiac patients. These findings support the concept that both cell-types contribute to disease-pathogenesis. However, functional studies highlighting both cell-types' and their mediators' role regarding mucosal alterations during the course of the inflammatory process in celiac patients are needed. Trial registration number and url DRKS00024669; https://www.drks.de/drks_web/.

Die histopathologische Beurteilung neoadjuvant therapierter Tumoren erfolgt durch Tumorregressionsgradingsysteme, die den Anteil des vitalen Restprimartumors im Verhaltnis zum ehemaligen Gesamttumor wiedergeben. Das WHO(Weltgesundheitsorganisation)-Tumorgrading wird in der Tumorklassifikation durch das Tumorregressionsgrading (TRG) ersetzt. Die histopathologische Aufarbeitung eines Tumors richtet sich auch nach neoadjuvanter Therapie nach den Kriterien der TNM-Klassifikation. Ein einheitliches TRG existiert nicht. Es sind fur verschiedene Tumoren auf die Tumorentitat bezogene TRG erstellt worden, die aus einem 3‑ oder 5‑stufigen System bestehen. Eine komplette histopathologische Tumorregression liegt nur dann vor, wenn keine vitalen Tumorzellen bei der histopathologischen Untersuchung des Primartumorresektates (Primartumor und mitresezierte lokoregionare Lymphknoten) nachweisbar sind und keine Fernmetastasierung besteht.

In Germany pancreas transplants are performed in only a few selected and specialized centres, usually combined with a kidney transplant. Knowlegde of the indications for and techniques of transplantation as well as of the histopathological assessment for rejection in pancreas and duodenal biopsies is not very widespread.To give an overview of the development and status quo in pancreas-kidney-transplantation in Germany summarizing the experience of the largest German pancreas transplant centre and to give a résumé of the results of histological diagnoses of biopsy specimens submitted between 06/2017 and 12/2020. Moreover, a detailed description and illustration of histological findings is included.A thorough literature search for aspects of the history, technique and indication for pancreas transplantation was performed and discussed in the context of the local experience and technical particularities specific for the transplant centre in Bochum. The occurrence of complications was compared with international reports. Results of pancreas and duodenal biopsies submitted to Erlangen between 06/2017 and 12/2020 for histological evaluation, which were evaluated according to the Banff classification, were summarized. For a better understanding key histological findings of pancreas rejection and differential diagnoses were illustrated and discussed.A total of 93 pancreas transplant specimens and 3 duodenal biopsies were included. 34.4% of pancreas specimens did not contain representative material for a diagnosis. In the remaining 61 biopsies 24.6% showed no rejection, 62.3% were diagnosed with acute T-cell mediated rejection (TCMR) and 8.2% with signs suspicious of antibody-mediated rejection (ABMR). Acute acinary epithelial injury was seen in 59%, pancreatitis in 8.2% and allograft fibrosis was reported in as many as 54.1%. Calcineurin-inhibitor toxicity was discussed in only 4.9%.Pancreas-kidney-transplantation and standardized histological assessment of the transplanted pancreas or rarely duodenum with reporting according to the updated Banff classification of pancreas transplants or previous reports of duodenal rejection are important mainstays in the management of patients with diabetes.HINTERGRUND: Die Pankreastransplantation wird in Deutschland nur in wenigen ausgewählten Zentren durchgeführt, üblicherweise in Kombination mit einer Niere. Die Kenntnis von Indikationen und Techniken der Transplantation selbst als auch der histopathologischen Abstoßungsdiagnostik mittels Pankreas- oder selten Duodenalbiopsie ist nicht sehr weit verbreitet.Darstellung der Entwicklung und des aktuellen Stands der Pankreas-Nieren-Transplantation in Deutschland anhand der Erfahrungen des größten deutschen Zentrums und Analyse der Ergebnisse der zwischen 06/2017 und 12/2020 durchgeführten Abstoßungsbiopsien inklusive ausführlicher Darstellung und Bebilderung der verschiedenen Abstoßungskategorien MATERIAL UND METHODE: Es wurde eine ausführliche Literaturrecherche zur Historie, Technik und Indikation der Pankreastransplantation durchgeführt und die technischen Besonderheiten und Erfahrungen am Bochumer Zentrum, insbesondere auch die Komplikationen, im internationalen Vergleich dargestellt. Desweiteren wurden alle im Zeitraum zwischen 06/2017 und 12/2020 durchgeführten Pankreas- oder Duodenalbiopsien, die zur Abstoßungsdiagnostik nach Erlangen gegangen waren und mittels der Banff-Klassifikation standardisiert bearbeitet wurden, anhand der vorliegenden Befunde ausgewertet und zusammenfassend dargestellt. Zum besseren Verständnis wurden die wichtigsten histologischen Entitäten bildhaft dargestellt und differenzialdiagnostische Aspekte diskutiert.Insgesamt wurden 93 Pankreastransplantat- und 3 Duodenalbiopsien untersucht. In 32 Pankreasbiopsien, d.h. 34,4 %, war kein diagnostisch verwertbares Material enthalten. Bei den verbliebenen 61 Pankreasbiopsien fanden sich bei 24,6 % keine Abstoßungszeichen, 62,3 % eine akute T-Zell-vermittelte Abstoßungsreaktion (TCMR) und 8,2 % Hinweise auf eine aktive Antikörper-vermittelte Abstoßung (ABMR). Ein akuter Azinuszellschaden wurde in 59 % der Biopsien gesehen, eine Pankreatitis in 8,2 % und eine Allograft-Fibrose in immerhin 54,1 %. Die Calcineurin-Inhibitor (CNI) Toxizität war mit 4,9% eher selten.Die Pankreas-Nieren-Transplantation inklusive der Biopsie des transplantierten Pankreas oder in seltenen Fällen auch des Spenderduodenums mit anschließender standardisierter Beurteilung entsprechend der aktuellen international gültigen Banff-Klassifikation der Pankreasabstoßung und der Empfehlungen zur Beurteilung von Duodenalbiopsien hat ihren festen Stellenwert in der Behandlung von Diabetikern.

Background Current guidelines discourage surgery for serous cystic neoplasms (SCN) of the pancreas, because of their benign character, slow growth, and excellent prognosis. Nevertheless, SCN continue to contribute up to 30% of resected cystic pancreatic lesions worldwide. Methods Spectrum of indications and outcomes of surgery were analysed in a retrospective series of 133 SCN at a single high-volume center in Germany between 2004 and 2019. Results Relevant symptoms justified surgery in 60% of patients with SCN, while 40% underwent surgery because of preoperative diagnostic uncertainty about suspected malignancy. There were 4 malignant SCN (3%). Ninety-day mortality was 0.75%, major morbidity - 15%, 10-year survival - 95%. Risks of malignant transformation and of postoperative mortality were similarly low. Conclusions Surgery is reasonable and safe for symptomatic patients with SCN. Preoperative diagnostic uncertainty is the main reason for futile resections of benign asymptomatic SCN. Conservative management with close initial surveillance should be the first choice for this population. Surgery for supposed SCN without symptoms is justified only in carefully selected patients with suspected malignancy.

In 2017, ovarian cancer due to asbestos exposure was designated a new, and thereby the first, gynaecological occupational disease in Germany. Asbestos is a naturally occurring mineral fibre with an annual usage in Germany of 160 000 – 180 000 metric tonnes in the 1960s and 1970s. The carcinogenicity of asbestos for the target organs lungs, larynx, pleura including pericardium, and peritoneum including tunica vaginalis testis has been clearly established for many years. Recent meta-analyses of data from cohort studies have demonstrated that the risk of ovarian cancer roughly doubles in women with occupational exposure to asbestos. Since the group of people with double the risk of developing lung cancer due to work-related asbestos exposure has a 2.25-fold increased risk of mortality from ovarian cancer on average, work-related ovarian cancer has been assigned the same recognition requirements as in occupational lung (and laryngeal) cancer. Thus, gynaecologists must obtain a thorough history of occupational exposure to asbestos, even if it may have taken place long in the past. The law mandates that suspected such cases must be reported to the Statutory Accident Insurance carrier or the State Occupational Safety and Health Agency.

Nach R0-Resektion eines Kolonkarzinoms im Stadium II und III gemas UICC (Union for International Cancer Control) soll die Indikation zur adjuvanten Therapie gepruft werden. Die Empfehlungen richten sich bislang nach klinischen und histopathologischen Kriterien. Im Stadium II soll die hochgradige Mikrosatelliteninstabilitat (MSI-H) bei der Therapieentscheidung einbezogen werden. Auserdem soll das Risiko fur eine erhohte Toxizitat, wie das Vorliegen von Begleiterkrankungen, eine eingeschrankte Dihydropyrimidindehydrogenase(DPD)-Funktion oder das Alter des Patienten beachtet werden. Immunonkologische Ansatze fur MSI-H-Tumoren oder molekular zielgerichtete Ansatze bei BRAF-mutierten Tumoren werden in lokalisierten Stadien perioperativ in Studien gepruft. Weitere molekulare Parameter, u. a. die zirkulierende Tumor-DNA (ctDNA), werden auf ihre prognostische und pradiktive Wertigkeit hin getestet. Die Gruppe der alteren Patienten wird perspektivisch das groste Kollektiv darstellen und sollte zunehmend beachtet werden.

Unter dem Begriff „Polypen des Gastrointestinaltrakts“ wird eine ganze Reihe von epithelialen und nichtepithelialen tumorartigen Veranderungen zusammengefasst. Generell werden reaktiv-entzundliche Veranderungen von neoplastischen Lasionen unterschieden. Die haufigsten Polypen sind epitheliale Lasionen. Im oberen Gastrointestinaltrakt dominieren reaktiv-entzundliche Veranderungen und hyperplastische Polypen, wahrend echte neoplastische Polypen wie Adenome viel haufiger im Kolorektum auftreten. Neben echten Neoplasien wie Adenomen konnen auch nichtneoplastische Polypen wie hyperplastische Polypen des Magens mit einem erhohten malignen Potenzial assoziiert sein. Das maligne Potenzial eines „Polypen“ wird durch den histologischen Typ bestimmt. Handelt es sich um eine Neoplasie, definiert das Ausmas der Dysplasie und auch die Grose der Lasion das maligne Potenzial. Der Begriff der „Dysplasie“ wurde fur Adenome in der aktuellen Klassifikation der Weltgesundheitsorganisation (WHO) von 2019 wiedereingefuhrt und ersetzt die „intraepitheliale Neoplasie“. Eine weitere Neuerung ist der Begriff „sessile serratierte Lasion“ mit und ohne Dysplasie, der dem fruheren „sessilen serratierten Adenom“ entspricht.

ZusammenfassungEin 47-jähriger Patient mit langjährig bekanntem Asthma bronchiale, chronischer Rhinosinusitis und langjähriger Epilepsie stellte sich aufgrund von progredienter Dyspnoe und Abgeschlagenheit in der pneumologischen Praxis vor. In einer thorakalen Röntgenaufnahme und einer nachfolgend durchgeführten thorakalen Computertomografie zeigten sich multiple pulmonale Rundherde.Eine Bronchoskopie mit bronchoalveolärer Lavage und transbronchialer Biopsie erbrachte den Befund einer eosinophilen Bronchitis und Alveolitis ohne Nachweis maligner Zellen. Nach Einleitung einer immunsuppressiven Therapie mit oralem Prednisolon und Umstellung der antikonvulsiven Therapie von Valproinsäure auf Levetiracetam besserten sich Dyspnoe und Belastbarkeit des Patienten binnen weniger Monate, einhergehend mit einem Regress der pulmonalen Rundherde und der peripheren Eosinophilie.Eine pulmonale Eosinophilie erfordert eine gründliche differenzialdiagnostische Aufarbeitung. Bei diesem Patienten ist am ehesten von einer eosinophilen Granulomatose mit Polyangiitis auszugehen. In der Literatur finden sich aber auch Fallberichte zu Valproinsäure-induzierten eosinophilen Lungenerkrankungen, sodass auch hier eine Assoziation denkbar ist.

Die Leber ist eine der haufigsten Lokalisationen beim CUP(„cancer of unknown primary“)-Syndrom. Die haufigsten Tumore, die in die Leber metastasieren, sind Karzinome und maligne Melanome. Die meisten Karzinommetastasen stammen von Adenokarzinomen des Gastrointestinaltraktes bzw. sind Metastasen von Lungen- und Mammakarzinomen. Das hepatische CUP-Syndrom ist somit als Ausschlussdiagnose zu betrachten. Ein wichtiger Bestandteil der histopathologischen Diagnose sind immunhistochemische und molekularpathologische Untersuchungen. Sie dienen nicht nur zur Identifizierung des histologisch determinierten Ausgangsgewebes bzw. des moglichen Primarorgans, sondern tragen im Rahmen des interdisziplinaren Managements zur Auswahl einer personalisierten zielgerichteten Therapie durch die Detektierung sog. Druggable Targets bei.

Purpose In mCRC, disease dynamics may play a critical role in the understanding of long-term outcome. We evaluated depth of response (DpR), time to DpR, and post-DpR survival as relevant endpoints. Methods We analyzed DpR by central review of computer tomography images (change from baseline to smallest tumor diameter), early tumor shrinkage (≥ 20% reduction in tumor diameter at first reassessment), time to DpR (study randomization to DpR-image), post-DpR progression-free survival (pPFS = DpR-image to tumor progression or death), and post-DpR overall survival (pOS = DpR-image to death) with special focus on BRAF status in 66 patients and primary tumor site in 86 patients treated within the VOLFI-trial, respectively. Results BRAF wild-type (BRAF-WT) compared to BRAF mutant (BRAF-MT) patients had greater DpR (− 57.6% vs. − 40.8%, p = 0.013) with a comparable time to DpR [4.0 (95% CI 3.1–4.4) vs. 3.9 (95% CI 2.5–5.5) months; p = 0.8852]. pPFS was 6.5 (95% CI 4.9–8.0) versus 2.6 (95% CI 1.2–4.0) months in favor of BRAF-WT patients (HR 0.24 (95% CI 0.11–0.53); p p Conclusions BRAF-MT patients derive a less profound treatment response compared to BRAF-WT patients. The difference in outcome according to BRAF status is evident after achievement of DpR with BRAF-MT patients hardly deriving any further disease control beyond DpR. Our observations hint towards an aggressive tumor evolution in BRAF-MT tumors, which may already be molecularly detectable at the time of DpR.

Fibrolamellar hepatocellular carcinoma (f-HCC) is a rare primary liver tumor. Imaging plays an important role in diagnosis. The aim of this retrospective study was to analyze contrast-enhanced ultrasound (CEUS) features of histologically proven f-HCC in comparison to benign focal nodular hyperplasia (FNH). 16 patients with histologically proven f-HCC lesions and 30 patients with FNH lesions were retrospectively reviewed regarding CEUS features to determine the malignant or benign nature of the focal liver lesions (FLL). Five radiologists assessed the CEUS enhancement pattern and came to a consensus using the EFSUMB (European Federation of Societies for Ultrasound in Medicine and Biology) guideline criteria. Fibrolamellar hepatocellular carcinoma manifested as a single and huge FLL. On CEUS, f-HCC showed heterogeneous hyperenhancement in the arterial phase and hypoenhancement (16/16, 100 %) in the portal venous and late phases (PVLP) as a sign of malignancy. In contrast to the hypoenhancement of f-HCC in the PVLP, all patients with FNH showed hyperenhancement as the most distinctive feature (P 0.01). 8 f-HCC lesions showed a central scar as an unenhanced area (8/16, 50.0 %), which could also be detected in 53.3 % (16/30) of FNH lesions (P 0.05). By analyzing the hypoenhancement in the PVLP, CEUS imaging reliably diagnosed f-HCC as a malignant FLL. CEUS also showed differentiation between f-HCC and FNH lesions, showing similar non-enhanced central scars, whereas f-HCC lesions showed peripheral hyperenhancement in the arterial phase and early washout in the PVLP.ZIEL: Das fibrolamelläre hepatozelluläre Karzinom (f-HCC) ist ein seltener primärer Lebertumor. Die Bildgebung spielt bei der Diagnose eine wichtige Rolle. Ziel dieser retrospektiven Studie war es, die Merkmale im kontrastverstärkten Ultraschall (CEUS) bei histologisch nachgewiesenem f-HCC im Vergleich zur benignen fokalen nodulären Hyperplasie (FNH) zu analysieren. 16 Patienten mit histologisch nachgewiesenen f-HCC-Läsionen und 30 Patienten mit FNH-Läsionen wurden retrospektiv auf CEUS-Merkmale untersucht, um die maligne oder benigne Natur der fokalen Leberläsionen (FLL) zu bestimmen. 5 Radiologen bewerteten das CEUS-Enhancement-Muster und kamen zu einem Konsens unter Verwendung der Kriterien der EFSUMB (European Federation of Societies for Ultrasound in Medicine and Biology) -Richtlinien. Das fibrolamelläre Leberzellkarzinom manifestierte sich als eine einzige und große FLL. Im CEUS zeigte das f-HCC ein heterogenes Hyperenhancement in der arteriellen Phase und ein Hypoenhancement (16/16, 100 %) in der portalvenösen und späten Phase (PVLP) als Marker für Malignität. Im Gegensatz zum Hypoenhancement des f-HCC in der PVLP zeigten alle Patienten mit FNH ein Hyperenhancement als auffälligstes Merkmal (p 0,01). 8 f-HCC-Läsionen zeigten eine zentrale Narbe als Bereich ohne Anreicherung (8/16; 50,0 %), welche auch bei 53,3 % (16/30) der FNH-Läsionen nachgewiesen werden konnte (p 0,05). Durch die Untersuchung des Hypoenhancements in der PVLP konnte die CEUS-Bildgebung f-HCC zuverlässig als maligne FLL diagnostizieren. Außerdem konnte CEUS zwischen f-HCC und FNH-Läsionen differenzieren und zeigte ähnliche zentrale Narben ohne Anreicherung, wobei f-HCC-Läsionen ein peripheres Hyperenhancement in der arteriellen Phase und ein frühes Wash-out in der PVLP zeigten.

Schnellschnittuntersuchungen konnen das Ergebnis zahlreicher viszeralchirurgischer Operationen deutlich verbessern. Dabei ist eine enge Zusammenarbeit zwischen Chirurgie und Pathologie Grundvoraussetzung. Hauptindikationen sind die Klarung unklarer intraoperativer Befunde sowie die Beurteilung von Absetzungsrandern. Wie jedes andere Verfahren gibt es auch bei Schnellschnittuntersuchungen limitierende Faktoren, die es zu beachten gilt.

BACKGROUND: Aberrant right hepatic arteries (aRHA) are frequently encountered during pancreaticoduodenectomy (PD). Their effects on surgical morbidity and resection margin are still debated. This study aimed to compare the short term and long term outcomes in patients with and without aRHA. METHODS: A single-center retrospective analysis of 353 consecutive PD during a 5-year period was done. The type of arterial supply was determined preoperatively by CT and confirmed at surgery. Hiatt types III–VI included some type of aRHA and comprised the study group. Hiatt types I and II were considered irrelevant for PD and used as controls. Primary endpoints were the rates of major postoperative complications and the rate of R0-resection in cases of malignant disease. Secondary endpoints included duration of surgery, postoperative stay, number of harvested lymph nodes and survival in patients with pancreatic cancer. Own results were compared to existent data using a systematic review of the literature. RESULTS: No aRHA had to be sacrificed or reconstructed. Surgical morbidity and specific complications such as post-pancreatectomy hemorrhage (PPH), pancreatic fistula and bile leak were the same in patients with and without aRHA. There was no significant difference in operative time, blood loss, length of ICU- and hospital stay. Patients with malignancy had similar high rates of R0-resection and identical number of harvested lymph nodes. Survival of patients with pancreatic cancer was not affected by aRHA. CONCLUSIONS: aRHA may be preserved in virtually all cases of PD for resectable pancreatic head lesions without increasing surgical morbidity and without compromising oncological radicality in patients with cancer, provided the variant anatomy is being recognised on preoperative CT and a meticulous surgical technique is used.

PURPOSE This trial investigated the addition of panitumumab to triplet chemotherapy with fluorouracil/folinic acid, oxaliplatin, and irinotecan (FOLFOXIRI) in a two-to-one randomized, controlled, open-label, phase II trial in patients with untreated RAS wild-type (WT) metastatic colorectal cancer. PATIENTS AND METHODS The primary end point was objective response rate (ORR) according to RECIST (version 1.1). The experimental arm (modified FOLFOXIRI [mFOLFOXIRI] plus panitumumab) was considered active if the ORR was ≥ 75%. The experimental ORR was compared with an estimated ORR of 60% based on historical data, verified by a randomized control group (FOLFOXIRI). The power of the trial was 80%, with a potential type I error of 0.05. Secondary end points included secondary resection rate, toxicity, progression-free survival, and overall survival. RESULTS A total of 63 patients were randomly assigned to the experimental arm and 33 patients to the control arm. The ORR of the mFOLFOXIRI plus panitumumab arm exceeded 75% and was higher when compared with that of FOLFOXIRI (87.3% v 60.6%; odds ratio, 4.469; 95% CI, 1.61 to 12.38; P = .004). The secondary resection rate was improved with the addition of panitumumab (33.3% v 12.1%; P = .02). Progression-free survival was similar in the study arms, whereas overall survival showed a trend in favor of the panitumumab-containing arm (hazard ratio for death, 0.67; 95% CI, 0.41 to 1.11; P = .12). CONCLUSION The addition of panitumumab to mFOLFOXIRI in patients with RAS WT metastatic colorectal cancer improved the ORR and rate of secondary resection of metastases and represents a treatment option in selected and fit patients in need of highly active first-line therapy. Future studies should determine whether the addition of panitumumab to mFOLFOXIRI prolongs survival.

BACKGROUND Secondary lymphedema is a leading sequela of cancer surgery and radiotherapy. The microsurgical transfer of lymph node flaps (LNFs) to affected limbs can improve the symptoms. The intra-abdominal cavity contains an abundant heterogenic source. The aim of this study is to aid selection among intra-abdominal LNFs. METHODS Eight LNFs were harvested in a microsurgical fashion at five sites in 16 cadavers: gastroepiploic, jejunal, ileal, ileocolic, and appendicular. These flaps were compared regarding size, weight, arterial diameter, and lymph node (LN) count after histologic verification. RESULTS One hundred and sixteen flaps were harvested. The exposed area correlated with the flap weight and volume (r2 = 0.86, r = 0.9). While gastroepiploic LNFs (geLNFs) showed the highest median weight of 99 ml, the jejunal LNFs (jLNFs) had the highest density with 3.8 LNs per 10 ml. The most reliable jLNF was 60 cm from the ligament of Treitz. Three or more LNs were contained in 94% of the jejunal, 88% of the ileal/ileocolic, and 63% of the omental LNs. The ileocolic LNF had the largest arterial diameter of 3 mm, yet the smallest volume. CONCLUSIONS jLNF and ileal LNF provide a reliable, high LN density for simultaneous, smaller recipient sites. geLNFs are more suitable for larger recipient sites.

Primary cutaneous anaplastic large cell lymphoma (pcALCL) belongs to the primary cutaneous CD30+ T cell lymphoproliferative disorders.1 Systemic involvement is relatively rare and rather confined to the regional lymph nodes.1We describe a patient with recurrent pcALCL and diffuse lung manifestation which spontaneously regressed after one SARS‐CoV‐2 vaccination. We report a 57‐year‐old male patient with a 10‐year history of biopsy‐proven (CD30+, CD3+, CD4+, ALK‐, clonal T cell receptor gamma chain rearrangement) pcALCL with frequent local relapses predominantly affecting his scalp and neck.

To evaluate the diagnostic performance of PET-MR enterography in detecting histological active inflammation in patients with ulcerative colitis and the impact of bowel purgation on diagnostic accuracies of PET-MR parameters. Fifty patients were enrolled in this randomized controlled trial (clinicaltrials.gov [NCT03781284]). Forty patients were randomized in two study arms, in which bowel purgation was performed either before or after PET-MR enterography. All patients underwent ileocolonoscopy with mucosal biopsies after PET-MR within 24 h. Diagnostic performance of MR morphological parameters (MRmorph), diffusion-weighted imaging (DWI), and PET in detecting histological inflammation determined by the Nancy index was compared with each other and between study arms. Correlation between PET and histological inflammatory severity was calculated. In study arm without previous bowel purgation, SUVmax ratio of bowel segment (relative to SUVmax of the liver) facilitated the highest specificity and diagnostic accuracy compared with MRmorph and DWI. Bowel cleansing led to markedly increased metabolic activity of bowel segments, resulting in significantly reduced specificity of PET compared with study arm without purgation (0.808 vs. 0.966, p = 0.007, respectively). Inter-observer concordance for assessing MRmorph was clearly increased after bowel cleansing (Cohen’s κ, 0.847 vs. 0.665; p = 0.013, respectively), though diagnostic performance of MRmorph was not significantly improved. Our findings suggested that the change of metabolic status was mainly associated with the grade of neutrophil infiltrate and less dependent on chronic infiltrate. PET-MR enterography was an excellent non-invasive diagnostic method in the assessment of histological active inflammation in ulcerative colitis without the need of previous bowel purgation. https://clinicaltrials.gov/ct2/show/NCT03781284

In der pathologischen Diagnostik finden monoklonale Antikorper ganz uberwiegend immunhistochemisch Anwendung. Nach primarer Evaluation des Materials im histologischen Schnitt wird je nach Fragestellung ein moglichst prazises Panel von Antikorpern ausgewahlt. Die Schnitte werden dann mittels einer indirekten Immunmarkierung gefarbt. Die haufigsten Fragestellungen sind die Klarung des Primartumors bei Metastase, die Diagnostik konventionell-histologisch undifferenzierter Tumoren, die Subtypisierung von lymphoproliferativen Erkrankungen und Weichteiltumoren und die immunhistochemische Beurteilung der Proliferationsrate mithilfe von Ki-67. Einen immer groseren Stellenwert nimmt die Bestimmung pradiktiver Biomarker ein (Hormonrezeptoren und HER2/neu, Mismatch-repair-Proteine und „programmed death ligand 1“ [PD-L1]). Deren Auswertung erfolgt anhand verschiedener Scores, die aufgrund der unmittelbar resultierenden Therapieoptionen auch dem klinisch tatigen Arzt gelaufig sein mussen.

Eine deutschstammige 65-jahrige Frau stellte sich mit seit mehreren Wochen bestehenden und sich verschlimmernden Ruckenschmerzen in der Notaufnahme vor. Wenige Tage spater verstarb sie unter dem Bilde einer Sepsis, dessen sehr seltene Ursache durch eine Obduktion erkannt wurde. Mit diesem Fallbericht wird die Wichtigkeit von Obduktionen aufgezeigt und in Zusammenhang mit den aktuellen Diskussionen im Rahmen des Qualitatsmanagements gebracht.

Hypereosinophilic syndrome (HES) is a complex multisystem disease characterized by sustained overproduction of eosinophils. A 40-year-old woman presented with digital ischemia and gangrene on her distal fingers and toes. We diagnosed HES on the basis of marked eosinophilia, accumulation of eosinophils in organs, and cutaneous eosinophilic vasculitis after having excluded all differential diagnoses. On digital subtraction angiography, occlusion of several arteries of both lower legs was noted. HES may be associated with severe vascular damage including gangrene. The occurrence of digital gangrene is a differential diagnostic challenge that should also include investigations of blood parameters, such as eosinophils.

Das kolorektale Karzinom (KRK) ist noch immer eine der haufigsten Tumorerkrankungen in der westlichen Welt. Frauen sind spater und seltener betroffen als Manner, das Uberleben ist nicht signifikant unterschiedlich. In der Krankheitsentstehung scheinen Ostrogene protektiv zu wirken, wobei der genaue Mechanismus unklar ist. Abweichungen zwischen den Geschlechtern sind bezuglich der Primartumorlokalisation sowie der Molekulargenetik beschrieben. Vor allem rechtsseitige Tumoren und Tumoren mit einer hochgradigen Mikrosatelliteninstabilitat (MSI-H) treten bei Frauen ofter auf. Frauen nehmen offenbar etwas haufiger an Vorsorgeprogrammen teil, allerdings ist die Effektivitat des Screenings bei Mannern hoher. Weder zu geschlechtsspezifischen Unterschieden in der Toxizitat noch zur Wirksamkeit einer Systemtherapie gibt es in der adjuvanten oder palliativen Therapiesituation prospektive geschlechtsspezifische Daten. Retrospektive Auswertungen kontrollierter Studien ergeben hier vor allem Unterschiede in der 5‑Fluorouraci- und Irinotecantoxizitat. In der Wirksamkeit mag es gewisse geschlechtsspezifische Unterschiede fur Antikorper gegen den epidermalen Wachstumsfaktorrezeptor (EGFR) zu geben, wobei Frauen weniger von dieser Substanzgruppe zu profitieren scheinen als Manner.

Zusammenfassung Anamnese und klinischer Befund Wir berichten von einer 72–jährigen Patientin mit einer therapieresistenten Diarrhö. Untersuchungen Bei negativem Keimnachweis und unauffälliger Bildgebung erfolgte eine endoskopische Diagnostik. Histologisch imponierte das Bild einer Zöliakie im Duodenum sowie einer lymphozytären Kolitis bis in das terminale Ileum und eine mikroskopische Kolitis. Bei negativem Antikörpernachweis für eine Zöliakie ergab sich die Verdachtsdiagnose einer Medikamentennebenwirkung. Therapie und Verlauf Nach Absetzen des Sartans Olmesartan kam es zu einer raschen Besserung der Symptomatik. Folgerung und Diagnose Für den AT1-Rezeptorantagonisten Olmesartan ist in seltenen Fällen das Auftreten einer Sprue-ähnlichen Enteropathie beschrieben. Mikroskopische Kolitiden sind Ausnahmen.

Background: Currently, patients with breast cancer (BC) with hormone receptor (HR) immunohistochemical expression between 1-9% are eligible to receive endocrine therapy. However, recent data suggest that these tumors express a basal-like molecular phenotype associated with triple negative BC (TNBC) rather than luminal phenotype associated with HR positive BC. Here, we aimed to determine the differences between strong HR positive, low HR positive and negative HR BC, in regard to responsiveness to neoadjuvant chemotherapy (NACT) and disease free survival (DFS) in large cohorts from GBG clinical trials. Methods: In this retrospective analysis of data from women with BC treated in the neoadjuvant GeparQuinto (n=2572), GeparSixto (n=588) and GeparSepto (n=1206) clinical trials, we compared patients with three HR phenotypes: low positive (ER and/or PR= 1-9%), strong positive (ER or PR= 10-100%), and negative (ER and PR= Results: Patients median age was 49 years, the majority had clinical tumor stage 2 (54.1%), negative nodal status (54.7%), and Her2 negative tumors (72.4%). 85.1% of women had BC classified as no special histological type. The pCR rate across the studies was 26.2%. 145 (3.4%) patients had low HR positive, 2417 (57.3%) strong HR positive and 1658 (39.3%) HR negative tumors. After NACT, 16.3% of patients with strong HR positive BC achieved a pCR, while among those with HR negative and low HR positive tumors, pCR rates were 40.2% and 37.9%, respectively (p Conclusions: Similarly to patients with negative HR tumors, patients with low HR positive tumors have a better responsiveness to NACT and worse survival rates, compared to patients with strongly HR positive BC. We suggest that studies on treatment options for basal-like/TNBC, should also consider including patients with low HR positive tumors. Citation Format: Villegas SL, Lederer B, Untch M, Holms F, Ulmer H-U, Diebold K, Fasching PA, Weber K, Schmitt WD, Tesch H, Rezai M, Marmé F, Sinn B, Hackmann J, Schneeweiss A, Tannapfel A, Nekljudova V, Denkert C, Loibl S. Similarities between low hormone receptor positive and hormone receptor negative breast cancer: An analysis of 4366 patients from multicenter clinical trials [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-08-10.

Intraductal papillary neoplasms of the biliary tract (IPNB) are rare tumors originating from the bile duct epithelium. Metastatic disease of IPNB is extremely rare and only reported in a small number of cases worldwide. Due to this limitation in number, the treatment of IPNB mainly relies on retrospective case series. We reported three cases of IPNB, one benign, one carcinoma with lymph node metastasis, and one case with histologically proven metachronous pulmonary metastasis. We correlated our findings with the existing data found in the literature. All patients underwent hemihepatectomy and complete tumor resection was achieved. Diagnosis of IPNB can be challenging due to varying presentation. The treatment of choice is surgical oncological resection in an early tumor stage. Long-term outcome highly depends on the underlying grade of dysplasia, multiplicity, and tumor-free margins. Aggressive tumor invasion is reported in up to 72% of cases in IPNB. Furthermore, the recurrence rate of IPNB is high with up to 22%. Further factors associated with an impaired survival are incomplete resection, lymph node involvement, and MUC1 expression. High potential for dysplasia and proof of invasive carcinoma upon diagnosis are hallmarks of IPNB. Metastatic disease in IPNB is reported only in small numbers. IPNB is an aggressive tumor entity with impaired long-term outcomes. A drawback for interpretation of current data is the fact that they rely on case series and reports and are not validated through more powerful randomized multicentric trials.

Background Even clearly resectable pancreatic cancer still has an unfavorable prognosis. Neoadjuvant or perioperative therapies might improve the prognosis of these patients. Thus, evaluation of perioperative chemotherapy in resectable pancreatic cancer in a prospective, randomized trial is warranted. A substantial improvement in overall survival of patients with metastatic pancreatic cancer with FOLFIRINOX and nab-paclitaxel/gemcitabine vs standard gemcitabine has been demonstrated in phase III-trials. Indeed nab-paclitaxel/gemcitabine has a more favorable toxicity profile compared to the FOLFIRINOX protocol and appears applicable in a perioperative setting. Methods NEONAX is an interventional, prospective, randomized, controlled, open label, two sided phase II study with an unconnected analysis of the results in both experimental arms against a fixed survival probability (38% at 18 months with adjuvant gemcitabine), NCT02047513. NEONAX will enroll 166 patients with resectable pancreatic ductal adenocarcinoma (≤ cT3, N0 or N1, cM0) in two arms: Arm A (perioperative arm): 2 cycles nab-paclitaxel (125 mg/m2)/gemcitabine (1000 mg/m2, d1, 8 and 15 of an 28 day-cycle) followed by tumor surgery followed by 4 cycles nab-paclitaxel/gemcitabine, Arm B (adjuvant arm): tumor surgery followed by 6 cycles nab-paclitaxel/gemcitabine. The randomization (1:1) is eminent to avoid allocation bias between the groups. Randomization is stratified for tumor stage (ct1/2 vs. cT3) and lymph node status (cN0 vs. cN1). Primary objective is disease free survival (DFS) at 18 months after randomization. Key secondary objectives are 3-year overall survival (OS) rate and DFS rate, progression during neoadjuvant therapy, R0 and R1 resection rate, quality of life and correlation of DFS, OS and tumor regression with pharmacogenomic markers, tumor biomarkers and molecular analyses (ctDNA, transcriptome, miRNA-arrays). In addition, circulating tumor-DNA will be analyzed in patients with the best and the worst responses to the neoadjuvant treatment. The study was initiated in March 2015 in 26 centers for pancreatic surgery in Germany. Discussion The NEONAX trial is an innovative study on resectable pancreatic cancer and currently one of the largest trials in this field of research. It addresses the question of the role of intensified perioperative treatment with nab-paclitaxel plus gemcitabine in resectable pancreatic cancers to improve disease-free survival and offers a unique potential for translational research. Trial registration ClinicalTrials.gov : NCT02047513, 08/13/2014. Open-Access-Publikationsfonds 2018

Numerous trials have examined the prognostic and predictive value of localization of the primary tumor (LPT) in metastastic colorectal cancer, there is limited information about the predictive value of LPT on different maintenance strategies.We analyzed progression-free survival (PFS)/overall survival (OS) on maintenance therapy according to LPT and mutational subgroups (BRAF/RAS) in patients from the AIO (Arbeitsgemeinschaft Internistische Onkologie) 0207 trial. Following induction, 471 patients were randomized to fluoropyrimidine (FU)/bevacizumab (Bev), Bev, or no treatment. Data on LPT were available in 414 (91%) patients.A total of 291 patients were left-sided (LPTl, 70%), and 123 were right-sided (LPTr, 30%). The median PFS was 3.9 months for LPTr and 5.3 months for LPTl (P = .11; hazard ratio [HR], 1.19; 95% confidence interval [CI], 0.96-1.48). There was no predictive impact of LPT on the maintenance strategies. The pairwise comparison of treatment arms showed a better PFS for FU/Bev versus no treatment independent from LPT (left, P .0001; HR, 2.39; 95% CI, 1.73-3.31; right, P = .011; HR, 1.78; 95% CI, 1.14-2.80). Analysis for OS (429 patients) confirmed the strong prognostic impact of LPT (left vs. right: 24.0 vs. 16.7 months; P .0001; HR, 1.65; 95% CI, 1.32-2.06), but also without major interaction between the LPT and maintenance arms. The strong negative prognostic impact of BRAF mutation was confirmed in right-/left-sided metastastic colorectal cancer, reaching significance in LPTl. In patients with RAS mutational status, the negative prognostic impact of the mutation remains, but its effect is stronger in LPTl (P .0001).The strong prognostic factor of LPT is confirmed undergoing oxaliplatin/FU/Bev induction therapy, whereas there seems to be no major predictive impact of LPT on different maintenance strategies.

Background : Guidance regarding adjuvant treatment decisions in stage II colorectal cancer (CRC) remains uncertain due to lack of predictive clinical or molecular markers. Recently, postoperative circulating tumour (ct)DNA has been demonstrated to be a strong prognostic marker in early colon cancer. Patients and Methods : CIRCULATE enrols patients with stage II microsatellite stable CRC in Germany (AIO) and Austria (ABCSG). Within the AIO, screening is supported by ColoPredict Plus 2.0, a molecular registry and screening platform for interventional trials. Patient-specific mutations are centrally analysed by next generation sequencing in the resected primary tumour. A postoperative plasma sample subsequently screened for the specific mutation(s). ctDNA positive (ctDNApos) patients are randomised (1:2) to control (follow up) or chemotherapy (capecitabine, oxaliplatin added a investigator's choice). ctDNA negative (ctDNAneg) patients are randomised (1:4) to be followed-up within CIRCULATE (control group) or outside the trial. Patients in the control group remain blinded to the ctDNA results. The primary objective is to compare disease free survival (DFS) of ctDNApos patients with chemotherapy or control. To demonstrate a treatment effect with a hazard ratio of 0.617 (3 year DFS rates 42.5 % vs. 25 %), 231 ctDNApos and estimated 2079 ctDNAneg patients are randomised. Secondary aims include to compare overall survival and DFS in the ctDNApos and ctDNAneg patient cohorts and ctDNA kinetics. Conclusion : The CIRCULATE trial may establish ctDNA for adjuvant treatment decision in stage II colon cancer – and with the secondary objectives – support a ctDNA guided follow up in colon cancer stage II and beyond. Micro Abstract Circulating tumour DNA (ctDNA) is a prognostic biomarker of recurrence in patients with early stage and resected colorectal cancer. The CIRCULATE study evaluates the predictive value of ctDNA with respect to adjuvant treatment in colon cancer stage II. In total, 231 patients with detectable ctDNA (ctDNApos) post resection are randomised 2:1 to chemotherapy or to control (follow-up). Patients without detectable ctDNA (approx. 2079 patients) are randomized 1:4 into control or off-study. The primary endpoint is the disease free survival.

Objective To identify patients at risk for biochemical recurrence (BCR) of prostate cancer (PCa) after radical prostatectomy (RP) with intra-operative whole-mount frozen section (FS) of the prostate. Material and methods We examined differences in BCR between patients with initial negative surgical margins at FS, patients with final negative surgical margins with initial positive margins at FS without residual PCa after secondary tumour resection, and patients with final negative surgical margins with initially positive margins at FS with residual PCa in the secondary tumour resection specimen. Institutional data of 883 consecutive patients undergoing RP were collected. Intra-operative whole-mount FS was routinely used to check for margin status and, if necessary, to resect more periprostatic tissue in order to achieve negative margins. Patients with lymph node-positive disease or final positive surgical margins were excluded from the analysis. Kaplan-Meier curves and multivariable Cox proportional hazards regression analyses adjusting for clinical covariates were employed to examine differences in biochemical recurrence-free survival (BRFS) according to the resection status mentioned above. Results The median follow-up was 22.4 months. The 1- and 2-year BRFS rates in patients with (81.0% and 72.9%, respectively; P = 0.001) and without residual PCa (90.3% and 82.3%, respectively; P = 0.033) after secondary tumour resection were significantly lower compared to patients with initial R0 status (93.4% and 90.9%, respectively). On multivariable Cox regression only residual PCa in the secondary tumour resection was associated with a higher risk of BCR compared to initial R0 status (hazard ratio 1.99, 95% confidence interval 1.01-3.92; P = 0.046). Conclusion Despite being classified as having a negative surgical margin, patients with residual PCa in the secondary tumour resection specimen face a high risk of BCR. These findings warrant closer post-RP surveillance of this particular subgroup. Further research of this high-risk subset of patients should focus on examining whether these patients benefit from early salvage therapy and how resection status impacts oncological outcomes in the changing landscape of PCa treatment.

Patients with muscle-invasive bladder cancer (MIBC) that underwent neoadjuvant chemotherapy (NAC) prior to radical cystectomy (RC) show improved overall survival, especially those with pathological complete response (pCR). The response to NAC according to molecular subtypes has been discussed. Molecular targets such as estrogen receptor (ESR1) and human epidermal growth factor receptor 2 (ERBB2) play an important role in breast cancer management and have also been associated with urothelial bladder cancer. Hence, the association of Keratin 20 (KRT20) Keratin 5 (KRT5), ESR1, and ERBB2 mRNA expression in MIBC at transurethral resection (TUR-BT) with pCR after NAC was analyzed retrospectively. Formalin-fixed paraffin-embedded tumour tissue samples from TUR-BT of 54 patients (42 males, 12 females, median age of 64) with MIBC were analyzed for KRT20, KRT5, ESR1, and ERBB2 mRNA expression. After NAC, RC was performed, and the specimens were evaluated for pCR. Statistical analyses comprised nonparametric and chi2 testing, partition models, and Spearman correlation analyses. After NAC, 22 out of 54 patients (40.7%) had pCR. Tumours with an elevated expression of markers associated with luminal differentiation (KRT20, ERBB2, ESR1) were associated with a higher chance of pCR (55% vs. 15.8%, p = 0.009). Elevated ERBB2 expression was positively correlated with luminal expression features such as KRT20, and negatively with basal characteristics such as KRT5. Patients with MIBC showing a high expression of ERBB2, ESR1, or KRT20 have a significantly higher chance of pCR following NAC. These findings might improve patient selection for NAC in MIBC., publishedVersion

A malignant ureteral obstruction is most often due to primary tumors of the ureter. However, it can occur secondary due to external tumor compression or metastatic infiltration. Distant metastases to the ureter are extremely rare. We present a case of a rare double distant metachronic metastasis to the right ureter as well as to the right renal pelvis in a 58-year-old female with a history of anterior resection for rectal cancer 2 years earlier. She presented with recurrent urinary tract infection and right hydronephrosis caused by an ureteral mass. The patient underwent a right nephroureterectomy via laparotomy. Two metastases of the rectal cancer in the ureteral mucosa were verified at histology. On account of the infiltration of the right ureteral orifice, a completion transurethral resection of the tumor was performed. A follow-up 3 and 6 months later showed no signs of tumor relapse and the patient was doing well. The differential diagnosis of malignant ureteral obstruction in patients with history of colorectal cancer should include the rare possibility of distant metastasis from the primary tumor.

ZusammenfassungEs wird über eine 15-jährige Patientin mit chronischen Bauchschmerzen, Übelkeit, stuhlig riechendem Aufstoßen und Durchfällen nach dem Trinken berichtet. Endoskopisch wurden 3 gastrokolische Fisteln entdeckt. Weder laborchemisch noch histologisch ergab sich ein Hinweis auf das Vorliegen eines M. Crohn oder anderer Grunderkrankungen. Histologisch fanden sich in Schleimhautbiopsaten der größten Fistel Zeichen einer geringgradigen chronischen und floriden Gastritis. Nach Therapiebeginn mit Omeprazol kam es zur deutlichen Beschwerdebesserung. Alle Fisteln wurden in einer laparoskopischen Operation mithilfe eines Staplers durchtrennt.

Perioperative chemotherapy with 5-fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT) is a mainstay in the treatment of esophagogastric adenocarcinomas (EGA). Trastuzumab improved survival when added to chemotherapy in patients with HER-2-positive metastatic EGA. We investigated the combination of trastuzumab and FLOT as perioperative treatment in patients with locally advanced EGA. A multicenter phase II study evaluated the efficacy and toxicity of perioperative FLOT (24-hours 5-FU 2600 mg/m2 , leucovorin 200 mg/m2 , oxaliplatin 85 mg/mg2 , docetaxel 50 mg/m2 , trastuzumab 6 mg/kg then 4 mg/kg d1, repeated d15 for four cycles preoperatively and postoperatively followed by 9 cycles of trastuzumab monotherapy) in patients with HER-2 positive EGA. Patients had ≥cT2, any N, M0 EGA. The primary endpoint was the rate of centrally assessed pathological complete response (pCR). Secondary endpoints comprised disease-free (DFS) and overall survival (OS), R0 resection rate, toxicity and surgical morbidity. Fifty-six evaluable patients (median age 62 years) were included; n = 40 had tumors originating from the esophagogastric junction; T stage was (cT2/3/4/unknown): 4/42/8/2; n = 50 patients had cN+ disease. Main adverse events grades 3-4: leukopenia (17.9%), neutropenia (46.6%) and diarrhea (17.0%). All patients underwent tumor resections. R0 resection rate was 92.9%. Eight patients had anastomotic leakage. One postoperative death occurred. pCR was found in 12 patients (21.4%) and a further n = 14 patients (25.0%) had near complete response. Median DFS was 42.5 months and the 3-year OS rate was 82.1%. The primary endpoint of achieving a pCR >20% was reached. No unexpected safety issues were observed. Survival data are promising.

BACKGROUND: Total pancreatectomy (TP) eliminates the risk of postoperative pancreatic fistula (POPF) and its associated secondary complications. Hence, it may theoretically offer advantages over pancreaticoduodenectomy (PD) regarding early postoperative outcome of patients with high-risk pancreatic remnant. METHODS: Ninety-day mortality and morbidity of 100 TP vs. 100 PD for pancreatic head lesions were retrospectively compared. Groups were matched for pancreatic texture, pancreatic duct size, final histology, age, gender and surgeon. Only patients at high risk for POPF due to soft pancreatic texture and small pancreatic duct

BACKGROUND: Mucinous cystic neoplasms (MCN) of the pancreas are rare mucin-producing cystic tumors. As they harbor malignant potential, surgical resection is frequently performed. Current guidelines recommend surgery in asymptomatic patients only for MCN exceeding 4 cm. The aim of this study was to identify radiological and clinical risk factors for malignancy in a single-center cohort of MCN. METHODS: All resected MCN from a single high-volume center between 2004 and 2019 were retrospectively analyzed. Patient characteristics, preoperative findings, histopathological results, and data on the postoperative course were recorded. Variables associated with malignancy were evaluated using χ(2) and Mann-Whitney U test. Receiver operating characteristic (ROC) curves were used to model predictive capabilities of preoperative tumor marker levels. Furthermore uni- and multivariate logistic regression analysis were performed for binary variables. Survival time was plotted as Kaplan-Meier curves and evaluated by log-rank test. RESULTS: A total of 63 patients were included. Median age was 62 years; 51 (81.0%) of them were women; median tumor size was 3.5 cm (range, 0.5–18.5); 16 (25.4%) of tumors harbored invasive carcinoma and 13 presented intraepithelial dysplasia (20.6%); 7 (43.8%) invasive carcinomas were smaller than 4 cm. All malignant MCN were radiologically suspected of malignancy (calcifications, mural nodules, or wall thickness) preoperatively. Elevated levels of carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) were strongly associated with malignancy (odd’s ratio 33.600; 7.000–161.270); P

Acute appendicitis (AA) is amongst the most common causes of acute abdominal pain. In spite of progress based on risk stratifications, “negative” appendectomies are performed in up to 30% of patients whilst the appendix perforates in others. Preoperative classification of AA based on imaging is therefore recommended. The aim was to classify AA based on imaging (ultrasound/US, computed tomography/CT), surgical pathology, and/or histopathology in order to differentiate between complicated and uncomplicated AA. A new classification of acute appendicitis (CAA) shall be illustrated by typical US and CT images and be employed in a diagnostic and therapeutic algorithm. Medline, Embase, and the Cochrane Library were searched. Any study after 1970, which investigated clinical scores, pathology, US, CT, magnetic resonance imaging, and treatment of AA, was included. Typical images were taken from the author’s image database. Five main types of AA are defined, normal appendix (type 0), nonvisualised appendix (type X), uncomplicated AA (type 1), complicated AA without perforation (type 2), and complicated AA with perforation (type 3). The imaging modality is indicated by an additional letter, e.g., type p3b for free perforation on pathology. Standardised reporting of the appendix evaluation by US and CT is presented, as well as algorithms for AA management. Imaging features indicating imminent perforation, as well as likely recurrence, were both classified as complicated AA. Imaging is mandatory in suspected AA. The CAA clearly separates uncomplicated from complicated forms of AA allowing nonoperative management in selected patients with uncomplicated forms of AA.

Background and Aims Histological remission has arisen as the optimal treatment outcome in ulcerative colitis (UC). The aim of this retrospective study was to explore the diagnostic performance of the noninvasive fecal biomarkers calprotectin (FC) and lactoferrin (FL) compared to the histological indices Nancy Index (NI) and Riley Index (RI). Methods This study is a retrospective diagnostic accuracy study based on secondary analysis of patient data from 2002 to 2017 extracted from medical registries of our clinics in Essen-Mitte, Germany. Patients with UC underwent a colonoscopy, with biopsies taken from the rectum and the sigmoid scored by 2 experienced pathologists according to NI and RI and provided a stool sample within 7 days pre- or post-colonoscopy. Diagnostic accuracy of recommended cutoffs for FC (>50 μg/g) and FL (≥7.25 μg/g) were tested against our reference standard (NI ≥2) in terms of specificity, sensitivity, positive predictive value, negative predictive value, and accuracy (effectiveness). Results The number of patients with UC recruited was n = 226, aged 45.2 (SD 13.3). Histological indices were highly correlated (r = 0.980, P < 0.001). Fecal biomarkers correlated moderately with NI (FC: r = 0.383, P < 0.001; FL: r = 0.420, P < 0.001) and RI (FC: r = 0.395, P < 0.001; FL: r = 0.424, P < 0.001). Fecal biomarker concentrations were increased in patients with active histological disease (NI ≥2), median [IQR], FC 69.72 [20.07–254.38], FL 18.59 [6.06–44.42], compared to those with inactive disease (NI ≤1), FC 12.35 [3.89 – 32.16], FL 3.14 [0.75–11.05], z = −6.60, P < 0.001. Fecal biomarker concentrations differed significantly across NI grades 0–4 (FC: H4 = 45.2; FL: H4 = 47.5, both P < 0.001). Patients with grade 0 had significantly lower concentrations of fecal biomarkers than those with grade 3 (median; FC 10.94 vs 72.22; FL 2.30 vs 29.10; both P < 0.001) or grade 4 (FC 10.94 vs 67.00; FL 2.30 vs 27.64; both P < 0.001), as well as grade 2 for FC only (10.94 vs 56.22, P = 0.001). Concentrations were also lower in patients with grade 1 compared to those with grade 3 (FC 17.49 vs 72.22; FL 4.24 vs. 29.10; both P ≤ 0.001) or grade 4 (FC 17.49 vs 67.00; FL 4.24 vs 27.64; both P < 0.001). Receiver operating characteristics area under the curve showed moderate diagnostic accuracy for both FC 0.76 (95% confidence interval [CI] 0.70–0.83) and FL 0.73 (95% CI 0.66–0.80). Optimized cutoffs for both FC (≥34.29) and FL (≥5.85 μg/g) had slightly improved accuracy, compared with the manufacturer’s cutoffs (FC: 69.9% vs 65.9%; FL: 71.7% vs 69.0%). Conclusions Fecal biomarkers calprotectin and lactoferrin correlate with histological disease activity and differentiate between patients in histological remission from those with evidence of moderate to severe disease activity. Their noninvasiveness, in addition to being inexpensive, supports their use in the clinical monitoring of patients with UC.

Colorectal cancer is one of the leading malignancies and still accounts for almost 25 000 deaths in Germany each year. Although there is accumulating data on the molecular basis, treatment and clinical outcome of patients within clinical trials evidence from the real-world setting is mostly lacking. We started the molecular registry trial Colopredict Plus in 2013 to collect clinical and molecular data from a real-world cohort of patients with early colon cancer stage II and III in 70 German colon cancer centers focusing on the prognostic impact of high microsatellite instability. In this interim report, we characterize a clinical cohort of 2615 patients, of whom 1787 tissue probes were analyzed. Microsatellite status was assessed using immunhistochemistry and fragment length analysis, with a concordance of 91.4 %. These established histopathological methods are sensitive and cost-effective. The median age was 72 years, significantly higher compared to clinical trial populations, with a median Charlson Comorbidity Index of 3. The stage-dependent incidence of microsatellite instability was 23.7 % and was associated with female gender, BRAF-mutation, UICC stage II and localization in the right colon. Survival calculated in disease free, relapse free and overall survival significantly differed between MSI-H and MSS, in favor of MSI-H patients. Multivariate age-adjusted analyses of relapse-free survival, disease-free survival, and overall survival highlighted microsatellite instability as a robust and positive prognostic marker for early colon cancer independent of age.Das kolorektale Karzinom ist weiterhin eine der häufigsten Tumorerkrankungen mit einer Mortalität von fast 25 000 pro Jahr in Deutschland. Obwohl wir mehr und mehr Daten zur molekularen Basis, zu neuen Behandlungsmethoden und Verläufen von Patienten im Rahmen klinischer Studien generieren, gibt es nur wenige Informationen aus der klinischen Versorgungsrealität. Wir starteten die molekulare Registerstudie Colopredict Plus im Jahre 2013, um klinische sowie molekulare Daten von einer „Real-World“-Kohorte von Patienten mit Kolonkarzinomen im UICC-Stadium II und III aus 70 deutschen Darmkrebszentren zu dokumentieren. Der Fokus liegt hier auf dem prognostischen Wert einer hochgradigen Mikrosatelliteninstabilität. In dieser Interimsanalyse charakterisieren wir das klinische Kollektiv von 2615 Patienten, von denen 1787 Tumorproben analysiert wurden. Der Mikrosatellitenstatus wurde via Immunhistochemie und Fragmentlängenanalyse mit einer Konkordanz von 91,4 % durchgeführt, was eine kosteneffektive histopathologische Nachweismethodik darstellt. Das mediane Alter lag bei 72 Jahren und damit deutlich höher als üblicherweise in klinischen Studien, der mediane Charlson Comorbidity Index lag bei 3. Die stadienabhängige Mikrosatelliteninstabilität-Inzidenz lag bei 23,7 % und war assoziiert mit dem weiblichen Geschlecht, BRAF-Mutationen, UICC-Stadium II und der Primärtumorlokalisation im rechten Kolon. Das Überleben berechnet in krankheitsfreiem, rezidivfreiem sowie Gesamtüberleben unterschied sich signifikant zugunsten der MSI-H-Patienten. Multivariate altersadjustierte Analysen des rezidivfreien und krankheitsfreien Überlebens sowie des Gesamtüberlebens bestätigten eine hochgradige Mikrosatelliteninstabilität als robusten und positiven prognostischer Marker für frühe Kolonkarzinome unabhängig vom Alter.

Background We assessed the usefulness of circulating tumor DNA (ctDNA) pre- or post-treatment initiation for outcome prediction and treatment monitoring in metastatic colorectal cancer (mCRC). Methods Droplet digital PCR was used to measure absolute mutant V-Ki-ras2 Kirsten rat sarcoma viral oncogene ((mut)KRAS) ctDNA concentrations in 214 healthy controls (plasma and sera) and in 151 tissue-based mutKRAS positive patients with mCRC from the prospective multicenter phase 3 trial AIO KRK0207. Serial mutKRAS ctDNA was analyzed prior to and 2–3 weeks after first-line chemotherapy initiation with fluoropyrimidine, oxaliplatin, and bevacizumab in patients with mCRC and correlated with clinical parameters. Results mut KRAS ctDNA was detected in 74.8% (113/151) of patients at baseline and in 59.6% (90/151) at follow-up. mutKRAS ctDNA at baseline and follow-up was associated with poor overall survival (OS) (hazard ratio [HR] =1.88, 95% confidence interval [CI] 1.20–2.95; HR = 2.15, 95% CI 1.47–3.15) and progression-free survival (PFS) (HR = 2.53, 95% CI 1.44–4.46; HR = 1.90, 95% CI 1.23–2.95), respectively. mutKRAS ctDNA clearance at follow-up conferred better disease control (P = 0.0075), better OS (log-rank P = 0.0018), and PFS (log-rank P = 0.0018). Measurable positive mutKRAS ctDNA at follow-up was the strongest and most significant independent prognostic factor on OS in multivariable analysis (HR = 2.31, 95% CI 1.40–3.25). Conclusions Serial analysis of circulating mutKRAS concentrations in mCRC has prognostic value. Post treatment mutKRAS concentrations 2 weeks after treatment initiation were associated with therapeutic response in multivariable analysis and may be an early response predictor in patients receiving first-line combination chemotherapy. Clinicaltrialsgov Identifier NCT00973609.

Importance Total neoadjuvant therapy has been increasingly adopted for multimodal rectal cancer treatment. The optimal sequence of chemoradiotherapy (CRT) and chemotherapy needs to be established. Objective To report the long-term results of the secondary end points prespecified in the Randomized Phase 2 Trial of Chemoradiotherapy Plus Induction or Consolidation Chemotherapy as Total Neoadjuvant Therapy (CAO/ARO/AIO-12 trial) for Locally Advanced Rectal Cancer. Design, Setting, and Participants This secondary analysis of a randomized clinical trial included 311 patients who were recruited from the accrued CAO/ARO/AIO-12 trial population from June 15, 2015, to January 31, 2018, from 18 centers in Germany. Patients with cT3-4 and/or node-positive rectal adenocarcinoma were included in the analysis. Data were analyzed from June 15, 2015, to January 31, 2018. The follow-up analysis was conducted between January 31, 2018, and November 30, 2020. Interventions Patients were randomly assigned to group A for 3 cycles of fluorouracil, leucovorin, and oxaliplatin before fluorouracil/oxaliplatin CRT (50.4 Gy), or to group B for CRT before chemotherapy. Total mesorectal excision was scheduled on day 123 after the start of total neoadjuvant therapy in both groups. Main Outcomes and Measures The end points assessed in this secondary analysis included long-term oncologic outcomes, chronic toxicity, patient-reported outcome measures for global health status (GHS) and quality of life (QoL), and the Wexner stool incontinence score. Results Of the 311 patients enrolled, 306 were evaluable, including 156 in group A (mean [SD] age, 60 [11] years; 106 men [68%]) and 150 in group B (mean [SD] age, 62 [10] years; 100 men [67%]). After a median follow-up of 43 months (range, 35-60 months), the 3-year disease-free survival was 73% in both groups (hazard ratio, 0.95; 95% CI, 0.63-1.45,P = .82); the 3-year cumulative incidence of locoregional recurrence (6% vs 5%,P = .67) and distant metastases (18% vs 16%,P = .52) were not significantly different. Chronic toxicity grade 3 to 4 occurred in 10 of 85 patients (11.8%) in group A and 8 of 66 patients (9.9%) in group B at 3 years. The GHS/QoL score decreased after total mesorectal excision but returned to pretreatment levels 1 year after randomization with no difference between the groups. Stool incontinence deteriorated 1 year after randomization in both groups and only improved slightly at 3 years, but never reached baseline levels. Conclusions and Relevance This secondary analysis of a randomized clinical trial showed that CRT followed by chemotherapy resulted in higher pathological complete response without compromising disease-free survival, toxicity, QoL, or stool incontinence and is thus proposed as the preferred total neoadjuvant therapy sequence if organ preservation is a priority. Trial Registration ClinicalTrials.gov identifier:NCT02363374

A higher incidence of proximal interval cancers after colonoscopy has been reported in several follow-up studies. One possible explanation for this might be that proximally located adenomas have greater malignant potential. The aim of the present study was to assess the risk of malignancy in proximal versus distal adenomas in patients included in a large screening colonoscopy database; adenoma shape and the patients' age and sex distribution were also analyzed.Data for 2007-2012 from the German National Screening Colonoscopy Registry, including 594,614 adenomas identified during 2,532,298 screening colonoscopies, were analyzed retrospectively. The main outcome measure was the rate of high-grade dysplasia (HGD) in adenomas, used as a surrogate marker for the risk of malignancy. Odds ratios (ORs) for the rate of HGD found in adenomas were analyzed in relation to patient- and adenoma-related factors using multivariate analysis.HGD histology was noted in 20,873 adenomas (3.5%). Proximal adenoma locations were not associated with a higher HGD rate. The most significant risk factor for HGD was adenoma size (OR 10.36 ≥1 cm vs1 cm), followed by patient age (OR 1.26 and 1.46 for age groups 65-74 and 75-84 vs 55-64 years) and sex (OR 1.15 male vs female). In comparison with flat adenomas as a reference lesion, sessile lesions had a similar HGD rate (OR 1.02) and pedunculated adenomas had a higher rate (OR 1.23). All associations were statistically significant (P ≤ .05).In this large screening database, it was found that the rates of adenomas with HGD are similar in the proximal and distal colon. The presence of HGD as a risk marker alone does not explain higher rates of proximal interval colorectal cancer. We suggest that certain lesions (flat, serrated lesions) may be missed in the proximal colon and may acquire a more aggressive biology over time. A combination of endoscopy-related factors and biology may therefore account for higher rates of proximal versus distal interval colorectal cancer.

The major prognostic relevance of primary tumour location (LPT) in advanced colorectal cancer was shown in large retrospective studies, but quantitative estimates are highly heterogeneous, and there is still limited information about its impact within the framework of biomarker-guided treatment strategies. Therefore, we analysed LPT in relation to other clinical and molecular parameters, based on mature survival data from the recent randomised AIO KRK0207 trial.Patients uniformly received first-line induction treatment with a combination of bevacizumab, oxaliplatin and fluoropyrimidine. LPT was retrospectively determined using surgical reports, pathology reports and endoscopy reports. The prognostic analyses were performed using Kaplan-Meier estimations and log-rank tests, while hazard ratios (HRs) and multivariable results were derived from Cox models.Among 754 patients with unequivocal information on LPT, patients with left-sided tumours showed a median overall survival of 24.8 months compared with the right-sided cohort with 18.4 months (HR: 1.54, 95% confidence interval: 1.30-1.81, P 0.0001). In a multivariable model, LPT proved to be the strongest prognosticator (HR 1.60), with performance status, number of metastatic sites, baseline carcinoembryonic antigen (CEA) and platelets independently retaining prognostic significance. In the subgroup of patients with known RAS/BRAF status (n = 567, 75%), a BRAF mutation showed the greatest unfavourable impact (HR 3.16). Although BRAF is strongly correlated to LPT, the latter remained a significant prognosticator in the BRAF wild-type subgroup. In contrast, no major impact of LPT was seen on tumours carrying RAS mutations.Within the framework of a uniform treatment strategy according to the current standards, LPT proved to have an important, although not solely dominating, relevance for survival prognosis. Its impact seems to be low in tumours with a RAS mutation.ClinicalTrials.govNCT00973609.