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Purpose Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a new, palliative approach for patients with peritoneal surface malignancies (PSMs). Its main goals are to control symptoms and ascites. For this experimental procedure, treatment efficacy and patient safety need to be closely monitored. Methods We performed a prospective registry study for patients with PSMs. Cisplatin (C) (7.5 mg/m2 body surface) and doxorubicin (D) (1.5 mg/m2) were administered laparoscopically via PIPAC. Results Between November 2015 and June 2020, we recorded data from 108 patients and 230 scheduled procedures. Tumor burden, patient fitness, quality of life, operating time and in-hospital stay remained stable over consecutive procedures. We recorded 21 non-access situations and 14 intraoperative complications (11 intestinal injuries, and three aspirations while inducing anesthesia). Three or more previous abdominal surgeries or cytoreductive surgery (CRS) with intraperitoneal hyperthermic chemoperfusion (HIPEC) were risk factors for non-access and intestinal injuries (χ2, p ≤ 0.01). Five Grade IV and three Grade V postoperative complications according to the Clavien–Dindo Classification (CDC) occurred. Median overall survival was 264 days (interquartile range 108–586). Therapies were primarily discontinued because of death (34%), progressive (26%), or regressive (16%) disease. Conclusion PIPAC is effective in stabilizing PSMs and retaining quality of life in selected patients. Earlier abdominal surgeries and CRS with HIPEC should be considered when determining the indication for PIPAC. Randomized controlled studies are needed to evaluate PIPAC’s therapeutic benefits compared to systemic chemotherapy (sCHT) alone. Trial registration NCT03100708 (April 2017).

Das Ideal eines Instituts fur Pathologie bestand aus dem grosen Sektionsbereich und einer breiten Praparatesammlung fur die Ausbildung von Studenten und klinisch tatigen Arzten. Zusatzliche Abteilungen, die den Sektionsbereich unterstutzten, waren ein chemisches und bakteriologisches Labor. In weiteren Abteilungen waren experimentelle Labors fur Biologie, Immunologie, Zellforschung und Tierstalle angesiedelt. Ein Hauptpfeiler des Medizinstudiums stellte die Pathologie fur das Verstandnis des Krankheitsbegriffs und der Krankheitsentstehung dar. In diesem Zusammenhang wurde meist der Endzustand einer Erkrankung im Rahmen einer Sektion erfasst. Der Sonderverdienst Virchows war die zusatzliche Betrachtung der zellularen Ebene unter Hinzuziehung mikroskopischer Praparate. Im Gegensatz dazu wurden in Grosbritannien und USA in den Instituten neben den Sektionen klinisch relevante Arbeiten durchgefuhrt. Die Analyse von Zeitschriftartikeln aus den Jahren 1920 bis 1940 von zwei deutschsprachigen Zeitschriften, Virchows Archiv und Naunyn-Schmiedebergs Archiv fur experimentelle Pathologie und Pharmakologie (heute: Naunyn-Schmiedeberg’s Archives of Pharmacology), sowie zwei englischsprachigen Zeitschriften, Journal of Pathology and Bacteriology sowie American Journal of Pathology, zeigte stark schwankende Veroffentlichungszahlen. Anhand von Publikationen konnte nachvollzogen werden, dass in deutschen Zeitschriften der Pathologie uberwiegend Erkrankungen groser Bandbreite beschrieben und auch haufig erstbeschrieben wurden. In der britischen Zeitschrift fur Pathologie wurden vor allem infektiologische Themen sowie zahlreiche Tierexperimente veroffentlicht. In der amerikanischen Zeitschrift war ein sehr breites Spektrum – von klinisch relevanten Tatigkeitsfeldern des Pathologen einschlieslich klinischer Chemie bis tierexperimentellen Arbeiten – abgebildet, unter anderem viele Ausfuhrungen zu histologischen Techniken.

ZusammenfassungPembrolizumab ist ein monoklonaler Antikörper, der an den PD-1-Rezeptor auf T-Zellen bindet und die Interaktion mit den Liganden PD-L1 und PD-L2 auf Krebszellen hemmt. Pembrolizumab wird zunehmend für die Behandlung von fortgeschrittenen Tumorerkrankungen, v. a. für metastasierte maligne Melanome, aber auch für nicht-kleinzelliges Lungenkarzinom, Urothelkarzinom und Nierenkarzinom angewendet. Trotz der beeindruckenden klinischen Wirkungen sind die Checkpoint-Inhibitoren mit einer Reihe von Nebenwirkungen verbunden, die als immunbezogene unerwünschte Ereignisse bekannt sind. Zu den bekannten Nebenwirkungen dieser Therapie gehören neben kutanen Nebenwirkungen wie Hautausschlag auch Müdigkeit, Schilddrüsendysfunktion, immunvermittelte Pneumonitis und Kolitis. Zu den kutanen unerwünschten Ereignissen gehören u. a. Pruritus, lichenoide Dermatitis, Psoriasis sowie blasenbildende Erkrankungen wie bullöses Pemphigoid. Die Nebenwirkungen werden durch die immunoregulatorischen Mechanismen des Medikaments erklärt. Hier berichten wir über den Fall eines 72-jährigen Patienten mit metastasiertem malignen Melanom und Prostatakarzinom als Zweittumor, der unter einer Therapie mit Pembrolizumab rasch sowohl eine stabile Erkrankung des Tumors hatte, aber auch zuerst eine immunvermittelte Pneumonitis und im Verlauf dann auch ein bullöses Pemphigoid entwickelte. Dieser Fall ergänzt die Liste möglicher kutaner Nebenwirkungen einer PD-1-Inhibitor-Therapie.

Die WHO-Klassifikation von 2014 nimmt eine Unterteilung in verschiedene Subtypen des muzinosen Adenokarzinoms vor. Kurzlich beschrieben wurde der gastrische Subtyp, der keine Assoziation zu einer High-risk-HPV-Infektion (humane Papillomviren) zeigt, prognostisch ungunstig ist sowie bevorzugt bei Asiatinnen auftritt und beim Peutz-Jeghers-Syndrom vorkommen kann. Mittelfristig ist zu erwarten, dass sich beim Adenokarzinom der Cervix uteri ein auf verschiedenen Invasionsmustern beruhendes Grading etabliert. Die tiefe Stromainfiltration makroinvasiver Karzinome ist definiert als eine Infiltration von >66 % des zervikalen Stromas. Zukunftig konnte eine maximale Tumorgrose von 2 cm ein Parameter zur Planung einer eingeschrankt-radikalen Operation sein. Parameter des histopathologischen Befundberichts, die relevant fur die Prognoseabschatzung und Auswahl der adjuvanten Therapie sind und als Qualitatsindikatoren im Rahmen von Zertifizierungen dienen, werden beschrieben. Der histologische Typ Adenokarzinom hat fur sich allein genommen keine pradiktive bzw. prognostische Bedeutung bei Patientinnen mit primar operativer Therapie, einer neoadjuvanten Chemotherapie, einer kombinierten Radiochemotherapie bzw. dem Einsatz von Angiogeneseinhibitoren. Molekulare Parameter und Biomarker besitzen derzeit keine Relevanz.

Die Mehrzahl der Prakanzerosen (intraepitheliale Neoplasien, IN) des Plattenepithels des unteren weiblichen Genitaltrakts beruht auf einer HPV-Infektion (humane Papillomviren). Diese fuhrt zum Auftreten zellularer Atypien mit der Folge eines gestorten geweblichen Aufbaus. In Abhangigkeit von ihrer Pathogenese werden bei den vulvaren intraepithelialen Neoplasien (VIN) die HPV-high-risk-assoziierte klassische VIN („usual“, u‑VIN) und die mit einem Lichen sclerosus assoziierte differenzierte VIN („differentiated“, d‑VIN) mit p53-Alteration unterschieden. In der aktuellen WHO-Klassifikation wird fur die plattenepithelialen Prakanzerosen des unteren weiblichen Genitaltrakts ein neues System zur Graduierung vorgeschlagen mit Unterteilung in L‑SIL („low-grade squamous intraepithelial lesions“; Kondylome/HPV-assoziierte Veranderungen plus VIN 1, vaginale intraepitheliale Neoplasie 1 [VaIN 1] bzw. zervikale intraepitheliale Neoplasie 1 [CIN 1]) und H‑SIL („high-grade squamous intraepithelial lesions“; VIN 2 und 3, VAIN 2 und 3 bzw. CIN 2 und 3). Bei der Unterscheidung kann die p16-Immunhistochemie hilfreich sein. Diese binare Einteilung lauft jedoch der zytologischen Nomenklatur in Deutschland (Munchner Nomenklatur III) zuwider, die zur Vermeidung einer Ubertherapie von Patientinnen mit einer masiggradigen intraepithelialen Neoplasie eine Unterteilung in 3 Dysplasiegrade vornimmt. Die einzelnen Nomenklaturen werden einander gegenuber gestellt. Es wird empfohlen, zusatzlich zur SIL-Klassifikation der WHO den Grad der jeweiligen Prakanzerosen anzugeben.

Histopathological assessment of the tumor grade and cell type is central to the management and prognosis of various gynecological malignancies. Conventional grading systems for squamous carcinomas and adenocarcinomas of the vulva, vagina and cervix are poorly defined. For endometrioid tumors of the female genital tract as well as for mucinous endometrial, ovarian and seromucinous ovarian carcinomas, the 3-tiered FIGO grading system is recommended. For uterine neuroendocrine tumors the grading system of the gastrointestinal counterparts has been adopted. Uterine leiomyosarcomas are not graded. Endometrial stromal sarcomas are divided into low and high grades, based on cellular morphology, immunohistochemical and molecular findings. A chemotherapy response score was established for chemotherapeutically treated high-grade serous pelvic cancer. For non-epithelial ovarian malignancies, only Sertoli-Leydig cell tumors and immature teratomas are graded. At this time molecular profiling has no impact on the grading of tumors of the female genital tract.

Symptome Eine Patientin stellt sich mit seit uber 20 Jahren bestehenden neuralgiformen Schmerzen im Bereich des medialen Fusrands vor.

The majority of precancerous lesions of the lower female genital tract (intraepithelial neoplasia, IN) are caused by human papillomavirus (HPV) infections resulting in cellular atypia and in turn an altered tissue architecture. Depending on the pathogenesis, a distinction is made between vulvar intraepithelial neoplasia (VIN) classified as classical VIN associated with high-risk HPV infections (u-VIN) and differentiated VIN (d-VIN), which is associated with lichen sclerosus et atrophicus and p53 alterations. In the current World Health Organization (WHO) classification a novel grading system for squamous cell precancerous lesions of the lower female genital tract has been proposed, differentiating low grade squamous intraepithelial lesions (L-SIL) including condyloma and HPV-associated alterations plus VIN 1, vaginal intraepithelial neoplasia (VaIN 1) and cervical intraepithelial neoplasia (CIN 1) from high grade squamous intraepithelial lesions (H-SIL) with VIN 2 and 3, VaIN 2 and 3 as well as CIN 2 and 3. The use of p16 immunohistochemistry can assist the differentiation. The new binary classification, however, contradicts the German cytological nomenclature (Munich nomenclature III), which differentiated three grades of dysplasia in order to avoid overtreatment of patients with moderate IN. The individual nomenclatures are compared to each other. It is recommended to report the grade of precancerous lesions in addition to the SIL classification of the WHO.

The World Health Organization (WHO) classification from 2014 differentiates between different subtypes of mucinous adenocarcinoma of the uterine cervix. A gastric subtype was recently described that showed no association with high-risk human papillomavirus (HPV) infections, has a poor prognosis, is mainly diagnosed in women of Asian origin and can occur in patients with Peutz-Jeghers syndrome. Although no clear grading system has been recommended in the WHO classification, it is likely that grading of adenocarcinomas of the uterine cervix will partly be based on the different patterns of invasion. Deep stromal infiltration of macroinvasive carcinomas is defined as an infiltration of66 % of the cervical stroma. In the near future a maximum tumor size of 2 cm could act as a discriminator for planning of less radical surgery. Parameters of the histopathological report that are relevant for the prognostic assessment as well as the choice of adjuvant treatment and function as quality indicators during certification are described. The histological type of an adenocarcinoma alone is of no predictive or prognostic relevance for patients undergoing primary surgical treatment, neoadjuvant chemotherapy, combined chemo-radiotherapy or treatment with angiogenesis inhibitors. Currently, molecular parameters and biomarkers are of no relevance.

Histopathological assessment of the tumor grade and cell type is central to the management and prognosis of various gynecological malignancies. Conventional grading systems for squamous carcinomas and adenocarcinomas of the vulva, vagina and cervix are poorly defined. For endometrioid tumors of the female genital tract as well as for mucinous endometrial, ovarian and seromucinous ovarian carcinomas, the 3‑tiered FIGO grading system is recommended. For uterine neuroendocrine tumors the grading system of the gastrointestinal counterparts has been adopted. Uterine leiomyosarcomas are not graded. Endometrial stromal sarcomas are divided into low and high grades, based on cellular morphology, immunohistochemical and molecular findings. A chemotherapy response score was established for chemotherapeutically treated high-grade serous pelvic cancer. For non-epithelial ovarian malignancies, only Sertoli-Leydig cell tumors and immature teratomas are graded. At this time molecular profiling has no impact on the grading of tumors of the female genital tract.

A multitude of factors influence the state of tissue samples on their way from the biopsy site in the body to the pathologist's microscope. Some of these factors can be influenced by surgeons, while others are dealt with in pathology departments, but surgeons should know potential pitfalls and caveats and their influence on the pathohistological diagnosis. These factors influence diagnoses made on conventional stains, but even more so the results of immunohistochemical stains and molecular pathology examinations. Therefore, the work-up of tissue samples should be standardised. This is of utmost importance for biobank tissue samples, especially those for which a tissue treatment protocol is recommended.

Numerous recent studies of endometrial and cervical carcinomas as well as malignant mixed mullerian tumors (MMMT) of the uterus have made a revision of the FIGO/TNM classification necessary, effective as of January 1st, 2010. There will be a new subclassification of carcinoma of the uterine cervix with proximal vaginal infiltration, using the same cut-off for the tumor extension as used for stage FIGOIB/T1b (≤/>4 cm), resulting in stage FIGO IIA1/T2a1 and FIGO IIA2/T2a2. In endometrial carcinoma, the previous FIGO IA/pT1a and FIGO IB/pT1b will be merged to FIGO IA/pT1a. The former category FIGO IC/T1c will be changed into FIGO IB/T1b. The category FIGO IC/pT1c will not longer been used. Additionally, there will be no separate classification for the involvement of the endocervical glands by endometrial carcinoma. This feature will be incorporated in stage FIGO I/T1 disease. The new category FIGO II/T2 will be defined as endocervical stromal involvement. There will be a new category, termed T3c/IIIC, which includes regional lymph node involvement. Stage T3c1/IIIC1 will be defined as pelvic lymph node involvement and stage T3c2/IIIC2 para-aortal lymph node involvement with or without pelvic lymph node disease. In the TNM system, regional lymph node involvement can alternatively be classified as N1. The MMMT will be staged like endometrial carcinoma.

Recent studies of endometrial and cervical carcinomas have shown that the FIGO/TNM classification of malignant tumors in these organs must be revised. Molecular data found that malignant mixed Mullerian tumors (MMMT) are, in fact, epithelial in origin. Starting from January 1, 2010, a new FIGO/TNM classification will be used. There will be a new subclassification of carcinomas of the uterine cervix with proximal vaginal infiltration, using the same cut-off for tumor extension as has been used for stage FIGO IB/T1b ( 4 cm), resulting in stage FIGO IIA1/T2a1 and FIGO IIA2/T2a2. In endometrial carcinoma, the previous FIGO IA/pT1a and FIGO IB/pT1b will be merged into FIGO IA/pT1a. The former category FIGO IC/T1c will change to FIGO IB/T1b. The category FIGO IC/pT1c will no longer be used. Additionally, there will be no separate classification for the involvement of the endocervical glands by endometrial carcinoma. This feature will be incorporated in stage FIGO I/T1 disease. The new category FIGO II/T2 will be defined as endocervical stromal involvement. There will be a new category, termed T3c/IIIC, which will include regional lymph node involvement. Stage T3c1/IIIC1 will be defined as pelvic lymph node involvement and stage T3c2/IIIC2 as para-aortal lymph node involvement with or without pelvic lymph node disease. In the TNM system, regional lymph node involvement can alternatively be classified as N1. MMMT will be staged like endometrial carcinoma.

Aufgrund einer differenten Pathogenese und Morphologie werden prinzipiell 2 Arten der vulvaren intraephithelialen Neoplase (VIN) definiert: Die haufigste Form ist mit 98% die klassische VIN (mittleres Erkrankungsalter 30 bis 40 Jahre, Multifokalitat, in etwa 90% Nachweis von „High-risk-HPV“). Die differenzierte VIN („simplex type“) ist mit 2–5% deutlich seltener. Sie wird in der Regel postmenopausal diagnostiziert (mittleres Erkrankungsalter etwa 65 Jahre), weist keine HPV-Assoziation, jedoch eine Alteration des p53-Tumorsuppressorgens auf. Sie wird meist im Zusammenhang mit einem (verhornenden) Vulvakarzinom diagnostiziert.

Das Vaginal- und das Vulvakarzinom sind mit jeweils ca. 1% aller malignen Tumoren des weiblichen Genitales selten. In Analogie zum Dysplasiekonzept bei der Cervix uteri werden die Prakanzerosen der Vagina als vaginale intraepitheliale Neoplasien (VAIN) und die der Vulva als vulvare intraepitheliale Neoplasien (VIN) bezeichnet. Aufgrund einer differenten Pathogenese und Morphologie werden prinzipiell zwei Arten der VIN definiert: Die klassische VIN ist durch eine Assoziation zu High-Risk-HPV charakterisiert, einem Auftreten bei jungen Frauen und einer Multifokalitat. Die differenzierte VIN („simplex“ bzw. „differentiated type“) ist deutlich seltener, wird in der Regel bei postmenopausalen Patientinnen diagnostiziert, weist keine Assoziation zu einer HPV-Infektion auf, jedoch eine Alteration von p53. Die meisten der invasiven Vaginal- bzw. Vulvakarzinome sind Plattenepithelkarzinome, gefolgt von den Adenokarzinomen. Die Datenlage zu prognostisch relevanten Faktoren beim Vaginalkarzinom ist eingeschrankt. Gut etabliert ist das Tumorstadium und bei radiotherapierten Karzinomen die Tumorgrose. Das Ausmas des Befalls der Scheide durch den Tumor (befallene Drittel) wird ebenso kontrovers diskutiert wie die Bedeutung einer proximalen bzw. distalen vaginalen Lokalisation des Karzinoms. Relevante Prognosefaktoren beim Vulvakarzinom sind das Tumorstadium, der Nachweis (inguinaler) Lymphknotenmetastasen (LKM), die Grose der LKM sowie der Nachweis eines Kapseldurchbruchs, die Invasionstiefe des Karzinoms und der Abstand zum Resektionsrand. Kontrovers werden das Grading und der Nachweis von Lymphgefaseinbruchen diskutiert. Voraussetzung fur die adaquate Erhebung prognostisch und therapeutisch relevanter Faktoren ist eine sorgfaltige pathologisch-anatomische Befundung.

A patient presented suffering from neural pain in the medial foot for a period of over 20 years.Diagnostic showed a widely spread soft-tissue tumor consisting of confluent glomuvenous malformations that was responsible for the immense pain syndrome.The solitary or multiform-appearing knots are not compressible and manifest as the characteristic syndromes of regional pain, sensitivity to coldness, or local pressure pain. Alternatively, the patient could also be completely symptom-free.Because of the dimension of the tumor and the degree of suffering, a radical resection with simultaneous microsurgical reconstruction was carried out. Twelve weeks postoperatively, healing of the flap stabilized, the foot is fully weight-bearing, and the patient is pain-free.

The generation of metal–organic framework (MOF) coordination polymers enables the tailoring of novel solids with regular porosity from the micro to nanopore scale. Since the discovery of this new family of nanoporous materials and the concept of so called ‘reticular design’, nowadays several hundred different types of MOF are known. The self assembly of metal ions, which act as coordination centres, linked together with a variety of polyatomic organic bridging ligands, results in tailorable nanoporous host materials as robust solids with high thermal and mechanical stability. Describing examples of different zinc-containing structures, e.g. MOF-2, MOF-5 and IRMOF-8 verified synthesis methods will be given, as well as a totally novel electrochemical approach for transition metal based MOFs will be presented for the first time. With sufficient amounts of sample now being available, the testing of metal–organic frameworks in fields of catalysis and gas processing is exemplified. Report is given on the catalytic activation of alkynes (formation of methoxypropene from propyne, vinylester synthesis from acetylene). Removal of impurities in natural gas (traces of tetrahydrothiophene in methane), pressure swing separation of rare gases (krypton and xenon) and storage of hydrogen (3.3 wt% at 2.0 MPa/77 K on Cu-BTC-MOF) will underline the prospective future industrial use of metal–organic frameworks in gas processing. Whenever possible, comparison is made to state-of-art applications in order to outline possibilities which might be superior by using MOFs.

Numerous recent studies of endometrial and cervical carcinomas as well as malignant mixed müllerian tumors (MMMT) of the uterus have made a revision of the FIGO/TNM classification necessary, effective as of January 1st, 2010. There will be a new subclassification of carcinoma of the uterine cervix with proximal vaginal infiltration, using the same cut-off for the tumor extension as used for stage FIGOIB/T1b (≤/4 cm), resulting in stage FIGO IIA1/T2a1 and FIGO IIA2/T2a2. In endometrial carcinoma, the previous FIGO IA/pT1a and FIGO IB/pT1b will be merged to FIGO IA/pT1a. The former category FIGO IC/T1c will be changed into FIGO IB/T1b. The category FIGO IC/pT1c will not longer been used. Additionally, there will be no separate classification for the involvement of the endocervical glands by endometrial carcinoma. This feature will be incorporated in stage FIGO I/T1 disease. The new category FIGO II/T2 will be defined as endocervical stromal involvement. There will be a new category, termed T3c/IIIC, which includes regional lymph node involvement. Stage T3c1/IIIC1 will be defined as pelvic lymph node involvement and stage T3c2/IIIC2 para-aortal lymph node involvement with or without pelvic lymph node disease. In the TNM system, regional lymph node involvement can alternatively be classified as N1. The MMMT will be staged like endometrial carcinoma.

On the basis of varying morphology and pathogenesis, two types of vulvar intraepithelial neoplasias (VIN) have been defined: the common type (approximately 98%), classic VIN, is characterised by strong association to high-risk HPV infection (up to 90%), occurrence at younger age (median age 30-40 years) and multifocality. The differentiated (or simplex) type is rare (1%-2%) and is associated with older age (median age 65 years) and p53 alterations. It is usually diagnosed in combination with vulvar (keratinizing) squamous cell carcinoma. The classification currently preferred by the WHO in which VIN are classified into VIN 1-3 is to be replaced due to new data and according to a proposal by the International Society for the Study of Vulvovaginal Diseases (ISSVD) which eliminates VIN 1 and combines VIN 2 and 3 to VIN of common or, depending on histopathology, differentiated type. Prognostically relevant factors in vulvar cancer include stage of disease, inguinal lymph node involvement, size of metastatic deposits and presence of extracapsular extension, depth of invasion and distance of the tumor from resection margins. Tumor grade and the presence of lymphovascular space involvement are controversially discussed.

The generation of metal–organic framework (MOF) coordination polymers enables the tailoring of novel solids with regular porosity from the micro to nanopore scale. Since the discovery of this new family of nanoporous materials and the concept of so called ‘reticular design’, nowadays several hundred different types of MOF are known. The self assembly of metal ions, which act as coordination centres, linked together with a variety of polyatomic organic bridging ligands, results in tailorable nanoporous host materials as robust solids with high thermal and mechanical stability. Describing examples of different zinc-containing structures, e.g. MOF-2, MOF-5 and IRMOF-8 verified synthesis methods will be given, as well as a totally novel electrochemical approach for transition metal based MOFs will be presented for the first time. With sufficient amounts of sample now being available, the testing of metal–organic frameworks in fields of catalysis and gas processing is exemplified. Report is given on the catalytic activation of alkynes (formation of methoxypropene from propyne, vinylester synthesis from acetylene). Removal of impurities in natural gas (traces of tetrahydrothiophene in methane), pressure swing separation of rare gases (krypton and xenon) and storage of hydrogen (3.3 wt% at 2.0 MPa/77 K on Cu-BTC-MOF) will underline the prospective future industrial use of metal–organic frameworks in gas processing. Whenever possible, comparison is made to state-of-art applications in order to outline possibilities which might be superior by using MOFs.